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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 45 (1989), S. 171-173 
    ISSN: 1420-9071
    Keywords: Estrogen receptor ; homogenization ; temperature ; nucleus ; uterus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Homogenization of rat uterus at elevated temperatures results in an increased nuclear localization of unoccupied estrogen receptor. This is a nonlinear effect which is accounted for by an increased population of KCl-resistant nuclear binding sites at the elevated homogenization temperatures.
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  • 2
    Electronic Resource
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    Springer
    Cellular and molecular life sciences 45 (1989), S. 349-351 
    ISSN: 1420-9071
    Keywords: Spermatogenesis ; temperature ; brain ; hibernation ; Helix aspersa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ablation of the brain from hibernatingHelix aspersa maintained at 25°C causes a significant increase in the proliferation of male cells in the gonad, whereas the ablation of the optic tentacles has no effect. The brain, therefore, produces a factor which specifically inhibits the multiplication of spermatogonia and spermatocytes.
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  • 3
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    Cellular and molecular life sciences 45 (1989), S. 102-103 
    ISSN: 1420-9071
    Keywords: Djungarian hamster ; photoperiod ; temperature ; T3 ; T4 ; testosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of photoperiod, temperature and testosterone treatment on plasma T3 and T4 levels were investigated in the Djungarian hamster. Plasma T3 level was affected by temperature (25°C〈7°C) but not by photoperiod. Plasma T4 level was affected by photoperiod (short day 〈 long day) at 25°C. Administration of testosterone increased plasma T4 level under short photoperiod at 25°C. Thus, higher plasma T4 level under long photoperiod at 25°C might be induced by testosterone.
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  • 4
    ISSN: 1432-1041
    Keywords: ramipril ; renal insufficiency ; hypertension ; pharmacokinetics ; ramiprilat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1–2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5–15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15–40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40–80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex. The study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min) smaller doses of ramipril are required than in patients with normal or borderline renal function.
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  • 5
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    Springer
    European journal of clinical pharmacology 36 (1989), S. 575-578 
    ISSN: 1432-1041
    Keywords: bunazosin ; hypertension ; alpha1-adrenoceptor blocker ; blood pressure ; renal blood flow ; renal function ; renin ; aldosterone ; atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal and hormonal effects of the α1-adrenoceptor blocker bunazosin were examined in 6 patients with essential hypertension. Oral bunazosin for 4 to 12 weeks significantly decreased mean blood pressure by 10%, increased effective renal blood flow and creatinine clearance by 34% and 37%, respectively, the plasma norepinephrine concentration was elevated by 60%, and the plasma atrial natriuretic peptide level was lowered by 22%. The plasma renin activity and aldosterone concentration were unchanged. Thus, a moderate reduction in blood pressure was produced by bunazosin treatment while maintaining renal perfusion.
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  • 6
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
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  • 7
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    European journal of clinical pharmacology 36 (1989), S. 229-234 
    ISSN: 1432-1041
    Keywords: enalapril ; hydrochlorothiazide ; hypertension ; side-effects ; Africans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy both of angiotensin converting enzyme (ACE) inhibitors and thiazide diuretics has been claimed to be influenced by plasma renin activity, which declines with age and is low in blacks. In a double-blind, placebo-controlled, double-dummy, randomized, parallel-group preliminary study, the antihypertensive efficacy and tolerability of the ACE inhibitor enalapril (20 mg day−1) and hydrochlorothiazide (50 mg day−1) were evaluated and compared for 4 weeks in 20 African patients with essential hypertension. The two groups had similar baseline clinical features and serum Na+ and K+ levels. Hydrochlorothiazide caused a significant and sustained fall in erect blood pressure with a reflex tachycardia. Enalapril exerted only a modest antihypertensive action, but significantly reduced erect heart rate. Direct comparison of hydrochlorothiazide — and enalapril — induced hypotension suggested a greater fall in subjects on the thiazide. The 95% confidence limits for the thiazide-enalapril difference in antihypertensive action at the end of the study was 39.5 to −7.5 mm Hg systolic and 22.0 to −6.6 mm Hg diastolic. The maximal blood pressure fall after hydrochlorothiazide was positively correlated with age (r=0.50;p〈0.05), whilst that of enalapril was inversely related age to (r=−0.57,p〈0.05). The results are compatible with the notion that ACE inhibitor monotherapy may be less effective than thiazide diuretic treatment in African and black patients with essential hypertension. The findings also support the concept that age and racial factors may influence the response to antihypertensive treatment.
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  • 8
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    European journal of clinical pharmacology 36 (1989), S. 567-573 
    ISSN: 1432-1041
    Keywords: isradipine ; hypertension ; blood pressure ; calcium entry blockade ; renin angiotensin system ; aldosterone plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng · kg−1 · min−1 was given before (control) and 30 min after the oral administration either of IS or P. After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II. In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.
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  • 9
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; ambulatory blood pressure monitoring ; slow-release formulation ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the duration of the antihypertensive effect of the dihydropiridine calcium antagonist felodipine in conventional (C-F) and slow-release (ER-F) formulations, 12 patients with essential hypertension underwent ambulatory blood pressure monitoring (ABPM) at the end of a 2-week treatment period with C-F 5 mg b.d., ER-F 10 mg once daily (o.d.) and placebo. C-F, ER-F and placebo were given in a double-blind 3×3 latin square design 4 times replicated. There was no systematic change in the ABP profile over the three study periods regardless of the treatment. In comparison to placebo, the mean 24-h systolic and diastolic blood pressures showed a significant and similar reduction after both formulations of F. Compared to placebo, C-F and ER-F induced a significant reduction in systolic blood pressure for 15 and 21 h, respectively, and of diastolic blood pressure for 16 and 21 h, respectively. Three patients complained of headache (mild in 2, moderately severe in 1), and two patients of nocturia, with either formulation of F.
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  • 10
    ISSN: 1432-1041
    Keywords: nicardipine ; insulin ; glucose ; diabetes ; hypertension ; metabolic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v. GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl·90 min on placebo, 33.1 mg/dl·90 min acutely and 31.4 mg/dl·90 min on chronic administration of nicardipine; insulin 2.08 µU/ml·90 min on placebo, 1.87 µU/ml·90 min acutely and 1.93 µU/ml·90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v. GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%. min−1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.
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  • 11
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; once-daily administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve patients with essential hypertension receiving captopril monotherapy or captopril in conjunction with a diuretic had their 24-h blood pressure profiles monitored using an automatic, non-invasive ambulatory method. The study examined the efficacy of once a day versus twice a day administration of the ACE inhibitor in controlling blood pressure. Six untreated subjects with borderline hypertension were also studied using the same monitoring equipment and with the same frequency, to act as controls because of the possibility of repeated use of the device causing a ‘familiarisation’ effect. The results obtained indicated that if anything, the once daily dosing produced marginally better blood pressure values. The amplitude of the diurnal blood pressure variation was reduced on a ‘second-wearing’ of the monitoring equipment suggesting some degree of familiarisation with the apparatus.
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  • 12
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    European journal of clinical pharmacology 36 (1989), S. 83-86 
    ISSN: 1432-1041
    Keywords: carteolol ; hypertension ; chronic renal failure ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of short- and long-term administration of carteolol on renal function has been examined in healthy subjects and in hypertensive patients with or without renal failure. In healthy subjects neither a single dose of 10 mg carteolol nor continuous administration of 20 mg/day for 7 days had any effect on creatinine clearance and renal blood flow. In all subjects the clearance rate of carteolol was about 400 ml/min and its fractional excretion of carteolol exceeded 300%, suggesting that the drug is secreted actively from renal tubules. Twenty-three hypertensive patients with or without renal dysfunction were given carteolol 10 to 20 mg/day for more than 50 weeks in addition to their standard antihypertensive regimens, which were left changed. Laboratory results were compared with the mean values of 50 weeks before and after the addition of carteolol, and none, including plasma creatinine, blood urea nitrogen and electrolytes, were significantly changed. Neither the estimated glomerular filtration rate nor the effect of the drug on blood pressure changed significantly during this prolonged treatment. It is concluded that carteolol had no effect on renal function in healthy subjects and in hypertensive patients with or without renal failure.
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  • 13
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    European journal of clinical pharmacology 36 (1989), S. 119-125 
    ISSN: 1432-1041
    Keywords: co-dergocrine ; hypertension ; presynaptic dopamine2-receptors ; norepinephrine ; haemodynamic effects ; side-effects ; renin-angiotensin-aldosterone system ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by −7% and the upright plasma NE level by −24%. Supine plasma NE also fell (−24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by −6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL − cholesterol fraction.
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  • 14
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    European journal of clinical pharmacology 36 (1989), S. 223-227 
    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; hypertension ; uric acid excretion ; metabolic effects ; cardiovascular risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine. Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed. Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.
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  • 15
    ISSN: 1432-1041
    Keywords: metoprolol ; pindolol ; renal haemodynamics ; salt-water handling ; hypertension ; beta-adrenoceptor blockade ; ISA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective β-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) β-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1–2 hypertensive men. M lowered pulse rate more than P. Systolic pressure was equally reduced by both agents, and diastolic and mean pressures were decreased only after P. Glomerular filtration rate was not significantly altered by either antagonist, and renal blood flow decreased by approximately 11% both after M and P. Renal vascular resistance was unchanged after P, and was increased by 10% after M. It is concluded that, like the effects on central haemodynamics, ISA is more important in the renal response to β-adrenoceptor blockade than is β-receptor selectivity.
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  • 16
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    European journal of clinical pharmacology 36 (1989), S. 347-350 
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; hyperlipidaemia ; chronic treatment ; cholesterol ; HDL ; LDL ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension. Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension. Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year. The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol · l−1 during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year. It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment.
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  • 17
    ISSN: 1432-1041
    Keywords: calcium antagonists ; nicardipine ; hypertension ; placebo effect ; slow-release preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the anti-hypertensive effect of slow-release nicardipine (SR-Nicardipine) have been compared with placebo in 36 uncomplicated essential hypertensives (diastolic BP 95 to 115 mm Hg after 1-month placebo washout). According to a double-blind, randomized, cross-over design they received SR-Nicardipine 40 mg b.d. and placebo for 1 month. At the end of each treatment period, blood pressure and heart rate were measured 12 h after the evening dose and 1, 2, 3 and 4 h after the morning dose. SR-Nicardipine significantly reduced systolic (SBP) and diastolic (DBP) blood pressure at each time after dosing. The absolute decrements peaked 4 h after dosing (−18.3 and −11.7 mm Hg, respectively) and more than 90% of the peak effect persisted 12 h after dosing, both for SBP and DBP. The heart rate was slightly increased by SR-Nicardipine. Adverse effects monitored with a check-list occurred in 31% of patients during SR-Nicardipine treatment and in 28% on placebo. Thus, SR-Nicardipine 40 mg b.d. has a maintained and significant antihypertensive effect lasting up to 12 h in essential hypertension.
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  • 18
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    European journal of clinical pharmacology 37 (1989), S. 333-335 
    ISSN: 1432-1041
    Keywords: diabetes mellitus ; nifedipine ; hypertension ; oedema ; vasodilator ; blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied the incidence of oedema 2 weeks following initation of nifedipine therapy for hypertension in a group of 10 diabetic subjects, and also measured skin blood flow (SBF) with a laser Doppler flowmeter, before and after lowering the foot. SBF with the foot horizontal increased after nifedipine from 0.31V (arbitrary units of flow) to 0.51V (NS). The postural fall in blood flow in dependency was significantly attenuated by nifedipine from 64.4 to 24.0%. Five patients developed ankle oedema. Results were similar in a small group of non-diabetic subjects starting nifedipine. The attenuation of reflex postural vasoconstriction is therefore likely to contribute to development of the oedema associated with starting nifedipine therapy, which should be monitored carefully in diabetic patients.
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  • 19
    ISSN: 1432-1041
    Keywords: ketanserin ; ritanserin ; hypertension ; haemodynamics ; alpha1-adrenoceptor blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of ketanserin (40 mg p.o.) on blood pressure and brachial haemodynamics (brachial artery diameter, brachial blood velocity and blood flow) have been compared in a double-blind study with those of ritanserin (10 mg p.o.) and placebo. Haemodynamic parameters were measured before and 1 h after treatment. Patients with mild to moderate essential hypertension participated in this study, 6 each on ketanserin, ritanserin and placebo. Placebo significantly reduced heart rate and did not modify the other parameters. Compared to placebo, ketanserin significantly reduced systolic and diastolic blood pressure, increased brachial blood velocity and flow, and decreased forearm vascular resistance. Compared to placebo, ritanserin slightly decreased blood pressure and slightly increased blood flow, but neither effect was significant. When blood circulation to the hand was excluded, neither ketanserin nor ritanserin modified the proximal arterial resistance or blood flow. It is concluded that the actions of ketanserin and ritanserin essentially occurred in the distal part of the upper limb, and alpha1-receptor blockade is probably involved.
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  • 20
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; renal function/-impairment ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of nisoldipine on renal function after 6 weeks treatment was investigated in hypertensive patients with and without renal impairment. Nisoldipine was well tolerated and an effective antihypertensive agent when administered over a period of 6 weeks. There were no significant changes in glomerular filtration, cardiac output, plasma renin activity or serum biochemistry during nisoldipine administration. Effective renal plasma flow was unaffected by treatment in the patients with normal renal function, but in the patients with renal insufficiency, the value decreased by a mean of 12%. Nisoldipine had no major untoward effects on renal function after 6 weeks administration, but minor changes in renal haemodynamics in the patients with renal insufficiency would suggest that careful monitoring of renal function is indicated in such patients.
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  • 21
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    European journal of clinical pharmacology 37 (1989), S. 551-554 
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; ambulatory monitoring ; cuff blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cuff blood pressure data has suggested that the calcium channel antagonist nisoldipine has full twenty four hour efficacy. To test this, 24 h ambulatory intra-arterial blood pressure monitoring was performed on 18 untreated hypertensive subjects (12 men, 6 women) (cuff blood pressure 〉150/95 mm Hg) before and after chronic treatment with 10–20 mg oral nisoldipine taken daily at 08.00 h. Twelve patients completed the study, six being withdrawn, four because of side-effects. After baseline intra-arterial monitoring patients were started on 10 mg nisoldipine daily. Response was assessed by cuff pressures taken 24 h after dosing at fortnightly intervals, and if not controlled (〈150/95 or at least 10 mm Hg reduction in diastolic BP) the dose was increased to 20 mg. All patients received at least six weeks' therapy before the second intra-arterial blood pressure monitoring. There was a slight but insignificant reduction in mean daytime heart rate of 3 beats·min−1. Mean significant reduction in daytime systolic and diastolic BP was 19 mm Hg and 13 mm Hg respectively but there was no significant mean night-time reduction. By comparison 8 out of 12 patients were apparently controlled more than 24 h post dose according to cuff pressures. This study suggests that this formulation of nisoldipine does not control blood pressure over a full 24-h period, and emphasises the importance of 24 h ambulatory monitoring in assessing the efficacy of once-daily antihypertensive agents.
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  • 22
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    Molecular and cellular biochemistry 91 (1989), S. 3-11 
    ISSN: 1573-4919
    Keywords: calcium ATPase ; glucose transport ; herpes virus ; hypertension ; leaks ; pore-formation ; sodium channels ; stress ; toxins ; transport ; viruses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Four situations in which membrane transport is altered by disease are discussed: (a) non-specific leaks induced by poreforming agents; (b) glucose transport and cellular stress; (c) Ca+-ATPase and hypertension; (d) Na− channels and HSV infection.
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  • 23
    ISSN: 1432-0878
    Keywords: Corpora allata ; Ultrastructure ; Precocenes ; Juvenile hormone ; Blattella germanica (Insecta)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructural studies on corpora allata (CA) from different stages during the first gonadotropic cycle of the cockroach Blattella germanica have shown well defined changes which have a correspondence with oocyte length, CA volume and juvenile hormone (JH) biosynthesis. The most significant variations concern the mitochondria and the endoplasmic reticulum. Topically applied precocene II (P II) at a dose of 200 ⧎g induced a transient arrest of CA function, although cytotoxic effects were occasionally observed. When CA were maintained in vitro with 10-3 M of P II, a relationship between the time of treatment (3, 6 or 9 h) and the intensity of the effects was apparent. The 9-h treatment led to an irreversible inhibition of JH production which parallels the severe damages observed in the CA (membrane lysis, nuclear pyknosis, vacuolization). Equivalent studies performed with the chroman derivative 3,4-dihydroprecocene II (DHP II) showed that it is less active than P II. Only treatments as severe as 12 h of incubation with a 10-3 M concentration elicited cytotoxic effects which could be due to radical species involved in the in situ oxidative bioactivation of DHP II. Thus, this compound could be regarded as a new type of pro-allatocidin.
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  • 24
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    Cell & tissue research 258 (1989), S. 203-210 
    ISSN: 1432-0878
    Keywords: Epididymis ; Histology ; Ultrastructure ; Antechinus stuartii (Marsupialia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ductus epididymidis of the marsupial mouse Antechinus stuartii was divided into caput, corpus, and caudal regions using several constant morphological landmarks. Tubule diameter and epithelial height increased gradually from caput to cauda. In contrast, the surface area of the lumen of the ductus epididymidis increased to a maximum in the distal caput region, but decreased markedly in the distal cauda in association with characteristic changes in lumen shape (from circular to slit-shaped) and epithelial height. Epithelial cells of the ductus epididymidis were generally similar in structure to those described in other mammalian species. Principal and basal cells were common throughout the epithelium. Clear and mitochondria-rich cells were also identified, but occurred less frequently. Regional variations in cell ultrastructure were observed only in principal cells. Numerous vesicular inclusions occurred in the apical cytoplasm of cells in caput segments, membrane-bounded, electron-dense bodies were common in distal corpus regions, and a brush border of microvilli characterized the luminal surface of principal cells in caudal segments. Sperm index increased in the proximal caput, declined to basal levels in the distal caput and proximal corpus, and then increased to a maximum in segment 9 of the distal corpus and remained at about this level throughout the cauda epididymidis. Nuclear rotation, loss of cytoplasmic droplets, and other sperm maturational changes were observed along the epididymis. Discarded cytoplasmic droplets collected in large masses interspersed between aggregates of spermatozoa throughout the distal regions of the duct. There was no evidence of phagocytosis by principal cells of cytoplasmic droplets. The epididymis of A. stuartii differs from that of other mammals. The unusual caudal region, which has little storage capacity for sperm, is an unusual adaptation in a species in which the male is known to be polygamous.
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  • 25
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    Cell & tissue research 258 (1989), S. 247-257 
    ISSN: 1432-0878
    Keywords: Zinc ; Timm method ; Ultrastructure ; Synapses ; Avian brain ; Domestic fowl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The brain of young domestic chicks was investigated using a Timm sulfide silver method. Serial Vibratome sections were analyzed under the light microscope, and the localization of zinc-positive structures in selected areas was determined at the ultrastructural level. Both strong and differential staining was visible in the avian telencephalon whereas most subtelencephalic structures showed a pale reaction. The highest staining intensity was found in the nonprimary sensory regions of the telencephalon such as the hyperstriatum dorsale, hyperstriatum ventrale, hippocampus, palaeostriatum augmentatum, lobus parolfactorius and caudal parts of neostriatum. There was an overall gradient of staining intensity in neostriatal areas from rostral to caudal with the heaviest zinc deposits in the caudal neostriatum. Primary sensory projection areas, such as the ectostriatum (visual), hyperstriatum intercalatum superius (visual), nucleus basalis (beak representation), the input layer L2 of the auditory field L and the somatosensory area rostral to field L were selectively left unstained. Fiber tracts throughout the brain were free of zinc deposits except for glial cells. In electron micrographs of stained regions, silver grains were localized in some presynaptic boutons of asymmetric synapses (Gray type I), within the cytoplasm of neuronal somata and sporadically in the nucleus. The possible involvement of zinc in synaptic transmission and other processes is discussed.
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  • 26
    ISSN: 1432-0878
    Keywords: Enterochromaffin-like cells ; Ultrastructure ; Hypertrophy ; Hypergastrinaemia ; Gastrin infusion ; Omeprazole ; Rat (Sprague Dawley) ; Syrian hamster ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present report describes the ultrastructure of the enterochromaffin-like (ECL) cells in the stomach of the rat, hamster and guinea pig, and the ultrastructural consequences of long-term hypergastrinaemia evoked either by continuous infusion of synthetic human (Leu15)-gastrin-17 for 4 weeks (rats) or by daily treatment with large doses of the antisecretory agent omeprazole for 2–10 weeks (rats, hamsters and guinea pigs). As a result, the ECL cells increased greatly in size (maximal effect after 2 weeks of omeprazole treatment, no further gain in size after 4 or 10 weeks). Also the endoplasmic reticulum and Golgi area were enlarged. The most conspicuous feature of the ECL cells is the cytoplasmic vesicles, which are of varying size and either devoid of a dense core or with a small, often eccentrically located dense core. The vesicles probably represent the main storage site of the secretory products of the ECL cell. In addition, the cytoplasm contains granules, which differ from the vesicles in that they possess a more or less electron-dense core, surrounded by a narrow halo. The size of the vesicles ranged from small to very large, while the granules were uniformly small. Many vesicles were seen to lie very close together, some displaying an irregular outline (vacuole-like vesicles), at times giving the impression that they were undergoing fusion. The profile size (median value) of the vesicles was unaffected by gastrin infusion for 4 weeks. However, there was a tendency to a relative increase in the number of very small vesicles. In contrast, the vesicles became larger during the omeprazole treatment. Also, the number of vesicles that seemed to be engaged in fusion increased after omeprazole treatment but not after gastrin infusion. The observations support the view that ECL cells are influenced by gastrin. The effects of gastrin infusion and of omeprazole treatment on ECL cell ultrastructure were not completely identical. It cannot be excluded that the omeprazole-evoked achlorhydria evokes effects unrelated to those of hypergastrinaemia on the ECL cells, or that endogenous gastrins may evoke effects that are in some ways distinct from those of synthetic human (Leu15)-gastrin-17. Alternatively, the additional effects seen after long-term omeprazole treatment may reflect simply the duration of the hypergastrinaemic stimulus.
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  • 27
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    Cell & tissue research 256 (1989), S. 303-307 
    ISSN: 1432-0878
    Keywords: Arachnoid cells ; Tight and gap junctions ; Cold injury ; Ultrastructure ; Freeze-fracture technique ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The junctional complexes of cells in the outer arachnoid layer overlying the cerebral cortex of 2-week-old rats were examined with freeze-fracture electron microscopy up to 60 min after transcranial cold injury to the dorsal surface of the brain. Within 30 min after injury, areas of gap and tight junctions with morphological features characteristic of junction formation and/or junction disruption were found scattered among normal junctional complexes in some arachnoid cells. Within 60 min after injury, tight junctions with features typical of less leaky zonulae occludentes were present in all arachnoid cells examined. These morphological features include increases in the number of tight junctional strands and the number of strand-to-strand anatomoses. Gap junctions were interspersed among the tight junctional strands, and many were completely encircled by the strands. The increase in the number and complexity of the tight junctional strands in response to brain injury may be the morphological basis for the maintenance of the cerebrospinal fluid-blood dural barrier.
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  • 28
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Differentiation ; Tissue culture ; Steroids ; Ultrastructure ; Lipoproteins ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We studied the effects of lipoprotein-derived cholesterol on the ACTH-induced differentiation of cultured fetal rat adrenocortical cells. For this purpose human plasma high-density lipoprotein3 (HDL3) or low-density lipoprotein (LDL) was added to culture media devoid of cholesterol, and thereafter the morphological changes in cells were monitored and the amounts of steroids synthesized were measured. It could be demonstrated that, ultrastructurally, upon ACTH-stimulation the adrenocortical cells differentiated into fasciculata-like cells even in the absence of lipoproteins in the culture medium. The addition of either HDL3 or LDL caused an increase in the number and size of cytoplasmic lipid droplets suggesting uptake and deposition of lipoprotein-derived cholesterol into the differentiating cells. The amount of steroids secreted from cells differentiating in media devoid of cholesterol was only half that observed in cells differentiating in serum-supplemented medium. Addition of either HDL3 or LDL increased the ACTH-stimulated steroid synthesis to the levels observed in serum-supplemented medium. This study demonstrates that both HDL3 and LDL are able to provide cholesterol for steroid synthesis accompanying the ACTH-induced differentiation of fetal rat adrenocortical cells.
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  • 29
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    Cell & tissue research 255 (1989), S. 405-410 
    ISSN: 1432-0878
    Keywords: Pituitary gland, pars intermedia ; Bromocriptine ; Secretory granules ; Golgi apparatus ; Ultrastructure ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The morphological effect of chronic synthetic and secretory inhibition of the intermediate lobe of the rat pituitary induced by bromocriptine treatment was studied using morphometric techniques in combination with electron microscopy. On the basis of granule diameters, a heterogeneous cell population was shown in the normal intermediate lobe. Bromocriptine treatment did not induce any change in the volume fraction, number or location of electron-dense secretory granules. Instead, there was a shift toward a more homogeneous cell population containing smaller granules, the mean granule volume being reduced by ∼30%. The volume fraction of electron-lucent granules or vacuoles was markedly reduced, indicating a functional significance of these organelles. The volume of the Golgi apparatus was not significantly altered, but the number of condensing granules within the Golgi area was reduced. The volume of the intermediate lobe was decreased, apparently due to a decrease in the mean cell volume.
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  • 30
    ISSN: 1432-0878
    Keywords: Endostyle ; Peroxidase cytochemistry ; Autora diography ; Ultrastructure ; Oikopleura albicans, Oikopleura longicauda (Appendicularia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Oikopleura albicans and O. longicauda belong to the two subgenera Vexillaria and Coecaria, respectively. The morphology and ultrastructure of their endostyles were investigated with conventional microscopic procedures as well as with DAB cytochemistry and 125I autoradiography at both light- and electron-microscopic levels. As expected, the general morphology of these endostyles is similar to all hitherto examined endostyles. They possess a ventral portion consisting of alternating glandular and ciliated cell zones, probably serving food capture, and a dorsal region, the corridor. Autoradiographic grains were found mainly in the corridor lumen associated with the apical surface of the two central rows of corridor cells. The same cells also gave strong positive reactions for peroxidase, the iodinating enzyme. Peroxidase activity was found in the apical plasma membrane as well as in the nuclear envelope, rough endoplasmic reticulum, Golgi area and cytoplasmic vesicles. Definitive conclusions concerning an apical uptake and subsequent release into the body fluid of iodinated material could not be made from the present experiments. Our investigations indicate that the two central rows of corridor cells in both subgenera of oikopleurids constitute the protothyroid region, possibly homologous to the vertebrate thyroid gland.
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  • 31
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    Cell & tissue research 257 (1989), S. 207-216 
    ISSN: 1432-0878
    Keywords: Morphogenesis ; Meninges ; Mesenchyme ; Ultrastructure ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The meninges of albino Wistar rat embryos, aged between the 11th embryonic day (ED) and birth, were sectioned using a specially constructed device. This technique permits optimal microanatomical preservation of all tissues covering the convexity of the brain: skin, muscle, cartilage or bone, and the meninges. At ED11, the zone situated between the epidermis and the brain is occupied by a mesenchymal network. At ED12, part of this delicate network develops as a dense outer cellular layer, while the remainder retains its reticular appearance, thus forming an inner layer (the future meningeal tissue). At ED13, the dura mater starts to differentiate. At ED14, the bony anlage of the skull can be identified, and along with the proceeding maturation of dura mater some fibrillar structures resembling skeletal muscle fibers appear in the developing arachnoid space. At ED15–17, a primitive interface zone — dura mater/ arachnoid — is formed, comprised by an outer electronlucent and an inner electron-dense layer marking the outer aspect of the arachnoidal space. At ED18–19, the innermost cellular row of the inner durai layer transforms into neurothelium, which is separated from the darker arachnoidal cells by an electron-dense band. The arachnoidal trabecular zone with the leptomeningeal cells is formed at ED19. By the end of the prenatal period (ED20–21), its innermost part organizes into an inner arachnoidal layer and an outer and inner pial layer. The results from this study indicate (i) that dura mater and leptomeninges develop from an embryonic network of connective tissue-forming cells, and (ii) that the formation of cerebrospinal fluid (CSF)-containing spaces accompanies the differentiation of the meningeal cellular layers.
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  • 32
    ISSN: 1432-0878
    Keywords: Serotonin-containing cells ; Urophysis ; Spinal Cord ; Ultrastructure ; Leptomeninges ; Poecilia latipinna (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The caudal neurosecretory complex of poeciliids has previously been shown to be innervated by extranuclear and intrinsic serotonergic projections. In the present study, immunohistochemical techniques were used to characterize fibers originating from serotonin neurons intrinsic to the caudal spinal cord. Bipolar and multipolar neurons were oriented ventromedially, and contained numerous large granular vesicles. Three types of serotonergic fibers were distinguished based on their distribution and morphology. Intrinsic Type-A fibers branched into varicose segments near the ventrolateral surface of the spinal cord and contacted the basal lamina beneath the leptomeninges. Type-B fibers coursed longitudinally to enter the urophysis, where they diverged and terminated around fenestrated capillaries. Labelled vesicles in Type-A and Type-B terminals were the same size as those in labelled cells and in unlabelled neurosecretory terminals in the urophysis. Type-C small varicose fibers branched within the neuropil of the caudal neurosecretory complex. Serotonin may be secreted into the submeningeal cerebrospinal fluid, the urophysis, and the caudal vein by Type-A and Type-B fibers, whereas, Type-C fibers may be processes of serotonergic interneurons in the neuroendocrine nucleus. The possibility that urotensins I and II or arginine vasotocin were colocalized in the processes of the intrinsic serotonin neurons was investigated immunohistochemically. The negative results of these experiments suggest that serotonin-containing neurons may represent a neurochemically distinct subpopulation in the caudal neurosecretory complex.
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  • 33
    ISSN: 1432-0878
    Keywords: Insect muscle ; Denervation ; Ultrastructure ; Development, ontogenetic ; Neoconocephalus robustus (Insecto)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The singing muscles of the katydid Neoconocephalus robustus develop adult ultrastructure late in the last nymphal instar and during the first few days of adult life. The ultrastructural changes during early adulthood were not affected by unilateral axotomy shortly after the adult molt. Both denervated and innervated muscles developed adult proportions of mitochondria, myofibril, and sarcoplasmic reticulum and transverse tubules.
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  • 34
    ISSN: 1432-0878
    Keywords: Zona pellucida ; Ovarian follicles ; Atresia ; Ultrastructure ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present study provides further details on the fine-structural three-dimensional architecture of the zona pellucida (ZP) in growing and atretic follicles of mice by use of ruthenium red in combination with the detergents Triton X100 and saponin. These detergents were used for extraction of the “soluble” fraction of the zonal proteins in an attempt to expose the “structural” zonal glycoproteins, which in turn can be viewed as minute three-dimensional networks upon transmission- and scanning electron-microscopic examination. By use of these methods, the ZP of growing follicles appeared to be formed by interconnected filaments which also bind to globular structures building up a three-dimensional lattice. In contrast, the ZP of stage I as well as other (II and III) stages of atretic follicles showed a structure characterized by the presence of closely packed granules connected with short filaments to form a close-mesh reticulum. This structural change of the ZP, which in the present study is also associated with the disappearance of “gap junctions” within the granulosa and cumulus cell population, might represent one of the early events involved in the onset of atresia. These changes, most probably depending on an altered secretory activity of both oocytes and follicle cells, might lead to a degradation of the ZP network structure and to its subsequent increased density (condensation). All these morphodynamic events eventually contribute to a sequestration of the oocyte in the early stage of atresia.
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  • 35
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    Cell & tissue research 257 (1989), S. 405-414 
    ISSN: 1432-0878
    Keywords: Mollusc ; Ultrastructure ; Musculature ; Hydroskeleton ; Retraction reflex ; Clione limacina (Mollusca)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Wing (parapodial) retraction in the pteropod mollusc Clione limacina is a reflex triggered by tactile stimulation. Light and transmission electron microscopy revealed three groups of smooth muscles in the wing hemocoel that participate in retraction movements: transverse, longitudinal, and dorsoventral. Among these, two subtypes of muscle cells were identified. The first (type A) appears in all three groups and forms a well-organized lattice-like structure. The second (type B) is the major component of transverse muscles and runs in one direction only. Quantitative ultrastructural comparisons of dimensions, abundance, and organization of dense bodies, thick and thin filaments, membrane invaginations, sarcoplasmic reticulum, and mitochondria suggest that type A cells are able to contract and relax more quickly with less endurance whereas type B cells are capable of generating stronger contractions with more endurance and slower relaxation speed. Furthermore, type A cells have a unique pattern of thick filament organization, here referred to as pseudosarcomeres. The roles played by the different cell types in wing retraction are discussed.
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  • 36
    ISSN: 1432-0878
    Keywords: Hippocampus ; Mossy fibers ; Picrotoxin ; Ultrastructure ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ultrastructural changes in hippocampal granule cells, mossy fibers and mossy fiber boutons were examined following the administration of picrotoxin in adult rats. Generalized seizures occurred within 5–10 min after the intraperitoneal injection of picrotoxin. The electron-microscopic examination of hippocampal tissues from rats that had been perfused with fixative during the seizure revealed that the large dense-core vesicles increased in number and accumulated on the presynaptic membranes of mossy fiber boutons; some of these vesicles appeared to be fused with the membranes, and omega-shaped exocytotic profiles were frequently seen. Furthermore, greatly increased numbers of coated vesicles (60–90 nm in diameter) were observed on the maturing faces of Golgi fields of granule cells. Thus, our study not only indicates an increased incidence of exocytosis of large dense-core vesicles during picrotoxin-induced seizures, but also suggests that these vesicles are replaced in excess from the perikaryon of the granule cell.
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  • 37
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    Neuroscience and behavioral physiology 19 (1989), S. 399-407 
    ISSN: 1573-899X
    Keywords: hemodynamics ; stress ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In the article, we present experimental data indicating that negative emotional states evoked by electrical stimulation of the ventromedial hypothalamus or by behavioral conflicts are accompanied by a predominance of vascular responses of a presser character possessing the property of summation. In contrast, positive emotional states during a self-stimulation reaction or when animals attain behavioral results satisfying their major biological demands are accompanied by a predominance of pressor-depressor vascular reactions. In individual animals under conditions of experimental emotional stress in conflicting situations of a prolonged character, pronounced disturbances of cardiac-vascular functions occur. Predominantly pressor vascular reactions arise in response to forced stimulation of the ventromedial hypothalamus in such cases. It is shown that changes in vascular tonus plays a leading role in disturbances of AP regulation during stress of immobilization. The most frequent cause of death in animals under such conditions is a progressive fall of AP due to an abrupt decrease in the total peripheral resistance. The resistance of the cardiac-vascular functions to emotional stress is determined to a significant degree by genetic mechanisms.
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  • 38
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    Bulletin of experimental biology and medicine 107 (1989), S. 200-202 
    ISSN: 1573-8221
    Keywords: hypertension ; platelets ; sodium-proton exchange
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  • 39
    ISSN: 1573-8221
    Keywords: hypertension ; erythrocyte membrane permeability ; electron microscopy ; erythrocyte transformation
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  • 40
    ISSN: 1573-8221
    Keywords: wound healing ; morphine ; hypertension ; substance P
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  • 41
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    European journal of clinical pharmacology 34 (1988), S. 513-515 
    ISSN: 1432-1041
    Keywords: methyldopa ; prolactin ; hypertension ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.
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  • 42
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    European journal of clinical pharmacology 34 (1988), S. 605-611 
    ISSN: 1432-1041
    Keywords: oxprenolol ; hypertension ; osmotic delivery system ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS. At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses. However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade. The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration. These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.
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  • 43
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; controlled-release metoprolol ; systolic and diastolic blood pressure ; heart rate ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained ≥95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure 〈95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.
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  • 44
    ISSN: 1432-1041
    Keywords: felodipine ; propranolol ; hydrochlorothiazide ; hypertension ; general practice ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]≧95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not ≦90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients. Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP ≦ 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm). In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.
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  • 45
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    European journal of clinical pharmacology 34 (1988), S. 411-413 
    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-adrenoceptor blocker ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients (mean age 53 years) with essential hypertension have been studied at rest and during exercise following oral treatment for 6 weeks with a new beta-adrenoceptor blocking agent, bopindolol. The treatment caused a significant decrease in systolic and diastolic arterial blood pressure and heart rate, both at rest and during exercise. Stroke volume fell, too, and therefore so did cardiac output, whereas the systemic vascular resistance was increased. Left ventricular filling pressure was elevated both at rest and during exercise following bopindolol therapy. However, a different haemodynamic pattern was noted in patients with elevated total peripheral resistance prior to therapy (Group 1) compared to patients with normal or subnormal peripheral resistance (Group 2). A decrease in systemic vascular resistance seemed to be the cause of the fall in blood pressure in Group 1, as the expected increase in vascular resistance did not occur, whereas a reduction in cardiac output was of greater importance in Group 2. During exercise the lowering of arterial blood pressure in both groups was mediated by a reduction in cardiac output.
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  • 46
    ISSN: 1432-1041
    Keywords: atenolol ; nifedipine ; hypertension ; adverse effects ; fixed combination ; drug efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily. The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components. Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately. A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.
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  • 47
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    European journal of clinical pharmacology 35 (1988), S. 21-24 
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
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  • 48
    ISSN: 1432-1041
    Keywords: metoprolol ; hydralazine ; hypertension ; pregnancy ; pharmacokinetics ; drug interactions
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the plasma concentrations levels of metoprolol after its twice daily administration in a dose of 50 mg for 4 days in ten, hypertensive pregnant women to the during monotherapy and in combination with 25 mg of hydralazine given twice daily. Hydralazine increased the median AUC and Cmax of metoprolol by 38% and 88% respectively, and decreased the tmax from 1.5 h to 1.0 h. Hydralazine had no effect on the plasma concentrations of alpha-OH-metoprolol. These results suggest that the effect of hydralazine on metoprolol plasma concentrations is primarily due to a reduction in first-pass elimination.
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  • 49
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    European journal of clinical pharmacology 35 (1988), S. 431-432 
    ISSN: 1432-1041
    Keywords: rifampicin ; enalapril ; hypertension ; drug interaction ; case report
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary When a 35-year-old man with essential hypertension was treated with antibiotics for brucellosis his blood pressure rose significantly. While all other treatment was kept constant rifampicin was discontinued. On rechallenge rifampicin did not alter serum concentrations of enalapril or the area under the curve (AUC) between 0 and 7 h, but it did reduce the AUC of the active metabolite enalaprilat by 31%. These observations suggest that there may be an interaction between rifampicin and enalapril, causing reduced hypotensive efficacy of enalapril. The mechanism of such an interaction merits further study, but it could be due to enhanced renal clearance of enalaprilat.
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  • 50
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    European journal of clinical pharmacology 33 (1988), S. 549-555 
    ISSN: 1432-1041
    Keywords: verapamil ; sustained release formulation ; hypertension ; renal disease ; kidney function ; angiotensin II ; aldosterone ; arginine vasopressin ; atrial natriuretic peptide ; lipids and lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r=−0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.
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  • 51
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; hydrochlorothiazide ; hypertension ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained ≥95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective ‘calcium antagonist’ felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metroprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if ‘control’ of BP (dBP 〈90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.
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  • 52
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    European journal of clinical pharmacology 34 (1988), S. 61-65 
    ISSN: 1432-1041
    Keywords: lisinopril ; renal failure ; half-life ; drug dose ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function. In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h. It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.
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  • 53
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
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  • 54
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    European journal of clinical pharmacology 35 (1988), S. 571-572 
    ISSN: 1432-1041
    Keywords: cadralazine ; pharmacokinetics ; hypertension
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  • 55
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; combination therapy ; diuretic ; beta-adrenergic blocker ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mm Hg to 156/91 mm Hg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats·min−1 was observed with the ketanserin + β-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mm Hg to 146/92 mm Hg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.
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  • 56
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; tolerability ; exercise ; once-daily dosing ; controlled-release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily, was compared with conventional metoprolol tablets, 100 mg once daily, in 27 patients with primary hypertension. Exercise tests on a bicycle ergometer were undertaken 24 h after intake of the last dose of the drug following a four-week placebo run-in period and after four weeks of active treatment. Heart rate, measured in the supine position and during exercise at the highest comparable workload, was reduced significantly more by metoprolol CR (p〈0.05), thus indicating a higher degree of β1-blockade at the end of the dose interval with metoprolol CR. There was a greater reduction in supine systolic pressure (p〈0.05) but not in supine diastolic pressure after metoprolol CR than after conventional tablets at 24 h. There was no significant difference between the two groups with respect to reduction in systolic blood pressure during exercise. The 24-h plasma concentrations of metoprolol CR and conventional tablets correlated with the effects on heart rate, but not with blood pressure. The tolerability of metoprolol CR was comparable with that of metoprolol administered as conventional tablets. In conclusion, there was significantly greater β1-blockade 24 h after the intake of drug after metoprolol CR compared with conventional tablets.
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  • 57
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    European journal of clinical pharmacology 34 (1988), S. 125-128 
    ISSN: 1432-1041
    Keywords: celiprolol ; acebutolol ; hypertension ; beta-blockers ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the new cardioselective beta-blocker celiprolol and acebutolol have been compared. Thirty patients with arterial hypertension WHO Grade I–II were treated in a double-blind fashion with celiprolol or acebutolol. Before starting the treatment and on Days 15 and 29, before the morning dose, blood samples were taken for measurement of the plasma level of celiprolol. At the same times physical examinations, and clinical and urine chemistry analyses were performed. At the 99% probability level both drugs had significantly lowered the systolic and diastolic blood pressures to normal values at the end of the second and fourth weeks. There was no significant difference between their antihypertensive efficacy. The decrease in diastolic blood pressure at the end of the second week was significantly correlated with the reciprocal of the plasma celiprolol concentration at steady-state at the end of the dosage interval.
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  • 58
    ISSN: 1432-1041
    Keywords: dilevalol ; hypertension ; labetolol R-R-isomer ; renal function ; plasma renin activity ; plasma aldosterone ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new β-adrenoceptor blocker with β2-receptor stimulating and α-recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks. Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study. Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA. The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.
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  • 59
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    European journal of clinical pharmacology 35 (1988), S. 25-30 
    ISSN: 1432-1041
    Keywords: alfuzosin ; alpha1-adrenoceptor blockers ; hypertension ; adverse reactions ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week runin placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was 〉90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypothensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml. Nine of the 11 patients reached the end-point (supine diastolic BP≤90 mm Hg) at the end of 28 days: 1 at the dose of 5 mg b.d., 6 at 10 mg b.d. and 2 at 20 mg q.i.d. At the high dose they both complained of palpitations. Two other patients complained of mild and transient palpitations at lower doses.
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  • 60
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; obesity ; betaendorphin ; ACTH ; cortisol ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of alpha2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.
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  • 61
    ISSN: 1432-1041
    Keywords: ritanserin ; hypertension ; serotonin ; (5 HT) ; blood pressure ; platelet aggregation ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have given the selective 5 HT2 antagonist ritanserin in a dose of 10 mg twice daily for 4 weeks in a double-blind, randomized, placebocontrolled, parallel group study of 18 patients with untreated essential hypertension. The fall in single platelet count due to 5 HT-induced platelet aggregation was significantly reduced by ritanserin compared with placebo (p〈0.05). There were no significant changes in supine or erect blood pressure or heart rate after ritanserin compared to placebo. Forearm blood flow, measured by mercury-in-strain gauge venous occlusion plethysmography, was not significantly altered by ritanserin. Ritanserin caused prolongation of the QTc interval by 41 (SEM 11) ms (p〈0.05 compared to placebo) but had no detectable effect on QRS duration, features suggestive of Class III antiarrhythmic activity. These findings do not support an independent role of the 5 HT2 receptor in maintaining raised arterial pressure in essential hypertension.
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  • 62
    ISSN: 1432-1041
    Keywords: aldosterone ; DA2-receptor ; co-dergocrine ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. The PAC response to sodium depletion was reduced to 155 (29) pg/ml by co-dergocrine. No significant PAC changes were found in patients maintained on a normal sodium intake. In addition the drug did not significantly modify plasma renin activity (PRA) in either experimental group. These results suggest that the dopaminergic inhibition of aldosterone secretion in man is mediated by DA2-receptors in the adrenal cortex.
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  • 63
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; sustained-release formulation ; handgrip test ; pressor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a new formulation of verapamil sustained release (SR) 240 mg tablets on resting blood pressure (BP) and on the pressor response to isometric exertion have been examined in a single-blind, placebo-controlled, cross-over study in 12 hypertensive patients (mean age 45 years). SR verapamil and placebo were administered every 12 h for 6 consecutive weeks. At the end of each period of treatment BP and heart rate (HR) were measured at rest and during isometric exercise, performed as a handgrip (HG) test for 3 min at 30% of the maximum voluntary contraction. There was a significant reduction in resting systolic and diastolic BP, with no change in HR. BP and HR at peak exercise were lower after verapamil than after placebo, but the maximal absolute increase did not change during verapamil therapy. The results are compatible with a role of SR verapamil b.d. in reducing resting BP in hypertension, and in lowering very high pressure at the peak of a HG test, without modifying the physiological reactivity of cardiovascular system.
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  • 64
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    European journal of clinical pharmacology 34 (1988), S. 601-604 
    ISSN: 1432-1041
    Keywords: cyclosporin A ; uveitis ; renal function ; creatinine clearance ; hypertension ; corticosteroids ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal function has been evaluated in 21 patients treated with cyclosporin A (CyA) for 9 months for idiopathic uveitis. Serum creatinine, which was 82 µmol·l−1 before treatment, was significantly elevated after 1 month (111 µmol·l−1). After 9 months of treatment, and despite a decrease in CyA dosage, the mean plasma creatinine remained elevated at 132 µmol·l−1. Hypertension developed in 6 patients, five of them being concomitantly treated with corticosteroids. In 8 patients serum creatinine 3 months after CyA had been stopped had decreased from 148 to 93 µmol·l−1. Two of those patients remained hypertensive 3 months after CyA treatment had ceased. In patients with idiopathic uveitis CyA induces a reversible increase in serum creatinine. However the reversibility of such a biochemical marker does not preclude a histopathological lesion. Chronic renal damage may be responsible for the persistance of hypertension after cessation of CyA treatment
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  • 65
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    European journal of clinical pharmacology 34 (1988), S. 249-253 
    ISSN: 1432-1041
    Keywords: verapamil ; bendrofluazide ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of verapamil and bendrofluazide used singly and in combination were examined in patients with primary hypertension in a patient blind, partly observer blind placebo controlled study of parallel group design; there were ten subjects in each arm of the trial. Verapamil 160 mg twice daily caused supine mean arterial pressure to fall by 21 mm Hg; this reduction was significantly greater (p〈0.05) than that induced by bendrofluazide 5 mg daily which caused a fall of only 10 mm Hg. The addition of verapamil 160 mg twice daily to bendrofluazide 5 mg daily caused a further fall in pressure of 18 mm Hg (p〈0.005), but the reduction in pressure when bendrofluazide was added to verapamil was only 1 mm Hg and not significant. Bendrofluazide therapy caused a fall in plasma potassium concentration and an increase in plasma urate concentration; urinary calcium excretion was reduced. Verapamil caused no detectable biochemical alterations in plasma or urine.
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  • 66
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    European journal of clinical pharmacology 34 (1988), S. 613-618 
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; adverse effects ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy of the new, once daily, alpha1-adrenoceptor inhibitor, doxazosin, was compared with placebo in 40 patients with mild to moderate hypertension. Following a dose titration the mean final daily doxazosin dose in 20 patients was 13.1 mg. Through-the-day blood pressure control was assessed by frequent measurements during 24 h hospitalisation in the 9 th week of double-blind treatment compared with similar measurements made during a 2 week single-blind placebo run-in. Mean reductions in standing and supine systolic and diastolic blood pressure during doxazosin treatment were statistically significantly greater than during placebo treatment at most hourly time points during the 24 h post-dose period. Twenty-four post-dose the mean falls in standing and supine diastolic blood pressure during doxazosin treatment were statistically significant when compared with placebo. Adverse effects during doxazosin treatment were generally minor and were tolerated or disappeared with continued therapy. No patients were withdrawn from the study due to adverse effects. We conclude that once daily doxazosin provides smooth and effective blood pressure control throughout a 24 h post-dose period.
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  • 67
    ISSN: 1432-0878
    Keywords: Basement membrane ; Lipids ; Ultrastructure ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Developing rat incisors were treated with malachite green-aldehyde fixative solution (MGA), which retains and stains lipids. We observed positive staining occurring as dots in the basement membrane. Most of these dots (2–3.5 nm in diameter) were grouped in the lamina densa but some were also present in the lamina lucida and the lamina fibroreticularis. These data provide evidence for the existence of lipids in the dental basement membrane and suggest that they are distributed together with the various groups of proteins so far detected.
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  • 68
    ISSN: 1432-0878
    Keywords: Adrenergic nerves ; Steroidogenic cells ; Embryonic ovary ; β 2Adrenoceptors ; Cytochemistry ; Ultrastructure ; Chicken
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The present study investigates the innervation of the embryonic chick ovary with regard to (i) development and compartmentalization of catecholaminergic nerves, and (ii) presence of adrenoceptors on steroidogenic target cells of catecholaminergic nerve terminals. Catecholaminergic nerve fibers visualized by glyoxylic acid-induced histofluorescence first appeared at embryonic day (E) 13. From E15 through E21 the density of fluorescent aminergic nerves increased markedly in parallel with the concentration of catecholamines and numbers of nerve bundles and single axons seen at the electron-microscopic level. Catecholaminergic nerves were confined to the ovarian medulla and closely associated with interstitial cells. Nerve terminals approached interstitial cells up to a distance of 20 nm and, in their majority, exhibited uptake of the false adrenergic transmitter 5-hydroxydopamine. Although adrenaline amounted to 14% of the total catecholamine content at E21, adrenaline immunoreactivity was only detected in adrenal chromaffin cells, but not in nerve fibers or cell bodies within the ovary. Interstitial cells structurally matured between E15 and E21 as documented by an increase of smooth endoplasmic reticulum and tubular mitochondria. Monoclonal antibodies mAB 120 and BRK 2 raised against avian β 1 and mammalian β 2-adrenergic receptors revealed the presence of β 2-adrenoceptor-like immunoreactivity on the surface of interstitial cells, but not on any other cell type. The results are consistent with the notion of a dense adrenergic innervation of the embryonic chick ovarian medulla and its steroidogenic interstitial cells, and suggest the chick ovary as an excellent model for elucidating the functional role of a neural input to steroidogenic cells during development.
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  • 69
    ISSN: 1432-0878
    Keywords: Smooth muscle ; Intermediate filaments ; Dual network ; Ultrastructure ; Ascidian ; Halocynthia roretzi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An extensive network of intermediate filaments that interconnected cytoplasmic dense bodies and connected the dense bodies to the cell surface was revealed in double-fixed, tannic acid-stained preparations of ascidian smooth muscle. The filament network ran through spaces in the continuous network of myofibrils, connecting them longitudinally, obliquely and transversely to form an intimately associated, dual network. In their transverse passage, the intermediate filaments ran across myofibrils along I-zones exclusively, interconnecting successive dense bodies. The pattern of attachment of intermediate filaments to dense bodies was predominantly “one-sided.” The filaments, which themselves were not incorporated into the contractile apparatus, remained folded or unfolded between myofibrils and between sarcomere-like structures in synchrony with the contraction-relaxation cycles. These results suggest that the intermediate filaments mechanically maintain the organization and arrangement of myofibrils via an intimate association with the myofibrils in the regions of the dense bodies, in such a way that the filaments do not impede muscle function. Based on these observations, a new model for the network of intermediate filaments in smooth muscle cells is proposed.
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  • 70
    ISSN: 1432-0878
    Keywords: Tentacles ; Ultrastructure ; Adhesion ; Leptosynapta spp (Holotheorie) ; Echinodermata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The tentacles of the apodous holothurian Genus Leptosynapta have been studied by use of transmission and scanning electron microscopy. The gross anatomy, water vascular system, fibre systems and ectoneural nerve ring are described. A fuzzy coat of attenuated filaments covers the surface of the tentacle, broken only by secretory ducts. A cuticle underlies the fuzzy coat. Bacteria are common in the subcuticular space. Fixation without osmium gives poor preservation of the surface coats. The epidermis consists of a single layer of columnar cells consisting of Type-1, Type-2, support, goblet and uniciliated cells. Type-1 cells secrete electron-dense material and appear to be homologous to adhesive cells of the tentacles of other holothurians. The support cells contain large, granular vesicles not found in other holothurians. Goblet cells contain flocculent mucus and have an apical cilium. Goblet cells are not found in other holothurian tentacles and may function to lubricate and wrap adhering particles to aid their ingestion. The uniciliated cells are rare, poorly developed and the cilium does not extend past the cuticle. The ultrastructure of the tentacles is discussed in relation to those of other holothurians.
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  • 71
    ISSN: 1432-0878
    Keywords: Lung ; Ultrastructure ; Marsupial ; Newborn ; Surfactant ; Dasyurus hallucatus, Trichosurus vulpecula
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The lungs of newborn northern native cats, Dasyurus hallucatus and newborn brushtail possums, Trichosurus vulpecula were examined by both light and electron microscopy. The native cat has a birth weight of 18 mg after a gestation of about 21 days, whereas the brushtail possum weights 200 mg at birth and has a gestation period of 17.5 days. The lungs of the native cat are two large respiratory sacs, with a respiratory lining of squamous cells and surfactant-secreting cells. The capillaries are located within the connective tissue just below this respiratory epithelium. The visceral covering of the lung is formed by squamous cells. The lungs of the possum are composed of numerous large respiratory sacs which are separated by connective tissue septa in which the capillaries are located. The sacs, as in other species, are lined with squamous cells and surfactant secreting cells. It is proposed that the structure of the lung of the newborn marsupial is related more to the size of the newborn rather than to the length of the gestation period.
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  • 72
    ISSN: 1432-0878
    Keywords: Implantation ; Embryo ; Ultrastructure ; Vasculature ; Rat (Sprague-Dawley) ; Guinea pig
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    Notes: Summary Preimplantation-stage embryos were transferred to the anterior eye chamber of recipient rats and guinea-pigs. After implantation had occurred the influence of the embryo on the iris vasculature was examined ultrastructurally. In both species, the earliest effect of embryonic implantation was an increased stromal oedema. Under increasing embryonic influence the vascular endothelial cells showed an increased number of projections into the vascular lumen, while in the rat, endothelial projections were also found pushing back into the basement membrane. In the rat, the endothelium became very irregular in thickness prior to complete disintegration and loss during more advanced stages of implantation. Rat embryonic trophoblast was found invading iris vasculature, particularly in areas where the iridial endothelium was partially or completely missing. Other cells in the iris, including the stroma, appeared to be less affected. In the guinea-pig, however, trophoblast cells appeared to be capable of invading the vasculature by displacing endothelial cells that still appeared morphologically normal.
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  • 73
    ISSN: 1432-0878
    Keywords: Lateral-line sense organs ; Mechanoreceptors ; Supporting cells ; Ultrastructure ; Pleurodeles waltlii (Urodela)
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    Topics: Biology , Medicine
    Notes: Summary The ultrastructural and histochemical features of the accessory cells of the neuromast of the salamander P. waltlii have been examined. Three types of accessory cells, supporting, mantle, and basal, were found, but only the first 2 are considered in this article. Supporting cells characterized by a highly dilated endoplasmic reticulum occur among and surrounding sensory cells. Mantle cells, morphologically different from the supporting cells, surround the remainder of the neuromast. Both types of accessory cells exhibit histochemically different secretory materials. Our morphological results suggest that both accessory cells contribute to the formation of cupular material.
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  • 74
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    Cell & tissue research 254 (1988), S. 247-249 
    ISSN: 1432-0878
    Keywords: Pinealocyte ; Light exposure ; Ultrastructure ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Although it is generally known that light strongly influences N-acetyltransferase activity and melatonin production in the pineal gland, little information is available concerning morphological changes following light exposure. As exposure of rats to a short light pulse at night rapidly depresses melatonin synthesis, we decided to determine whether this experimental condition produces rapid changes in the pinealocyte organelles. A 30-min light pulse at night (six hours after lights out) provoked rapid changes in the relative volumes of some pinealocyte organelles. The volume fractions of mitochondria, Golgi apparatus and lipid droplets, and the numbers of dense-core vesicles and “synaptic” ribbons decreased, whereas the volume fraction of lysosomes increased. There were no differences in the volumes of granular endoplasmic reticulum and vacuoles containing flocculent material in those animals exposed to light compared with control animals. These results indicate that a short light pulse at night causes ultrastructural changes that can be interpreted as morphological features of diminished activity of pinealocytes.
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  • 75
    ISSN: 1432-0878
    Keywords: X-organ ; Sinus gland ; Ultrastructure ; Cyclic activity ; Siriella armata (Crustacea)
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    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the medulla interna-medulla externa X-organ (MI-ME Xo)-sinus gland (SG) complex in the eyestalk of Siriella armata is described during the normal and the experimentally inhibited molt cycle. In the normal SG, four types of neurosecretory axon terminals, each containing distinguishable neurosecretory granules, can be described. Thus, type-2 granules are synthesized by G1 neurons forming the MI-ME Xo. The cell bodies and axonal endings of these cells in the sinus gland have been examined at the following molt stages: intermolt (stage C4), premolt (D0 and D2), and postmolt (A1, A2 and B). Changes in ultrastructure of the G1 cells have been monitored and correlated to inhibitions of the molt-and reproductive cycle produced by electrocauterization of the MI-ME Xo. The results obtained suggest that the neurosecretion from the G1 cells exerts a positive influence on molt and brood preparation. The occurrence of a distal group of G1 cells whose axons terminate at a different site from the SG suggests that the neural factors of the MI-ME Xo are diverse and control different physiological activities.
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  • 76
    ISSN: 1432-0878
    Keywords: Neuropeptide Y (NPY) ; Penis erection ; Perivascular nerve fibers immunocytochemistry ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Neuropeptide Y 1–36 (IR-NPY) immunoreactive nerve-fiber processes have been observed in tunicae of veins and arteries and in smooth muscles of the human penis taken at autopsy or during surgery by use of light-and electron-microscopic immunohistochemical techniques. Numerous IR-NPY nerve fibers were mostly concentrated in the inner part of the adventitia close to the media of the arterial and venous vessels and among the intracavernous smooth muscle cells. IR-NPY nerve fibers were less abundant in veins than in arteries. Positive somata were not observed in the penises. At the ultrastructural level, IR-NPY were localized exclusively in large, dense granules of nerve terminals by means of the postembedding immunogold technique. In the deep dorsal vein, IR-NPY nerve fibers were also located in the media formed by an outer circular and an inner longitudinal layer. In the intracavernous and dorsal arteries, they showed the highest density in the inner part of the adventitia. In the corpora cavernosa and in the corpus spongiosum, IR-NPY nerve processes were intermingled between the smooth-muscle fibers around the sinusoid spaces. IR-NPY nerve fibers were present in the cavernous nerves close to the central arteries. The urethra did not show any IR-NPY-positive nerve fibers. This peculiar distribution of IR-NPY nerve fibers suggested that they could participate in regulating arterial and venous blood flow and intracavernous smooth-muscle tone. NPY may therefore be of importance in some of the mechanisms of penile erection especially during detumescence.
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  • 77
    ISSN: 1432-0878
    Keywords: Thymus ; Cultured thymic fragments ; Epithelial cells ; Microenvironment ; Ultrastructure ; Rat (nude)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cultured thymic fragments correspond to the thymic microenvironment depleted of lymphocytes and dendritic cells. When these fragments are implanted under the kidney capsule of congenitally athymic rats, lymphocytes and dendritic cells of host origin enter the graft and induce thymus-dependent immunity in the recipient. This paper describes the ultrastructure of the fragments and the changes that occur during the restoration of normal thymic architecture. At the end of the culture period of 6–9 days and in the early stages after implantation, the grafts consist of keratin-containing epithelial cells of unusual morphology that can be labelled with antibodies raised against the epithelium of the mid/deep cortex and the subcapsule/medulla. Normal thymic architecture develops, including nerves and blood vessels, as lymphocytes populate the environment, and by 4–6 weeks the epithelial cells are the same phenotypically and ultrastructurally as those found in normal rat thymus. However, some areas without lymphocytes still contain the atypical epithelial cells seen before implantation. Large multinucleated giant cells are also present with a few associated epithelial cells of subcapsular/medullary phenotype. In conclusion, the cultured thymic fragments contain a hitherto unknown precursor epithelial cell with an atypical ultrastructure and phenotype that is not seen in normal development.
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  • 78
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    Cell & tissue research 252 (1988), S. 581-587 
    ISSN: 1432-0878
    Keywords: Normal resting breast ; Ultrastructure ; Mitosis ; Cytokinesis ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The parenchyma of the normal “resting” human breast was examined by electron microscopy to characterize the cells undergoing mitosis and the mechanism by which the normal tissue architecture is maintained during this process. In this study of 112 mitotic cells, it was found that the mitotic cells were luminally positioned, polarised epithelial cells with no evidence of myoepithelial cell division. Ultrastructurally, the nuclear and cytoplasmic changes were consistent with previous reports of mitosis in other tissues. However, unlike all previous reports, two specific orientations of the nuclear spindle and thus the planes of cytokinesis were observed. In a few cases the spindle formed parallel to the lumen and division resulted in two luminally positioned daughter cells. However, in the majority of mitotic cells the spindle was approximately at right angles to the lumen and this orientation resulted in a luminally and a basally positioned daughter cell. It is proposed that the abnormally positioned basal daughter cell could develop into a myoepithelial cell or undergo deletion (apoptosis). Thus the two orientations of mitosis may explain the mechanism by which the epithelial and myoepithelial cell populations were maintained by a single progenitor cell without disrupting the integrity of the tissue architecture.
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  • 79
    ISSN: 1432-0878
    Keywords: Ovary ; Steroid-secreting cells ; Ultrastructure ; Chorionic gonadotropin ; Chicken
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural characteristics of the ovarian medulla of the newly hatched white leghorn chick were studied in control animals and compared with chicks that were treated with human chorionic gonadotropin during embryonic development. The ovarian medulla was mainly occupied by epithelial cells which formed cords or islets surrounded by a basal lamina. Within this epithelial compartment, steroidogenic cells, poorly differentiated cells and a lacunary system could be recognized. When chicks were treated with human chorionic gonadotropin, steroidogenic cells became discernible; there was an increment in the amount of cytoplasm and the area of mitochondria. Poorly differentiated cells exhibited signs of stimulation, and transitional images suggested the transformation of these cells into steroidogenic cells. The epithelial cells of the lacunar system also displayed stimulated cytoplasmic organelles. Evidence was supplied suggesting that relatively undifferentiated cells persist in the ovarian medulla until hatching and can develop into steroidogenic cells under gonadotropic stimulation.
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  • 80
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    Cell & tissue research 253 (1988), S. 137-143 
    ISSN: 1432-0878
    Keywords: Endostyle ; Ultrastructure ; Immunocytochemistry ; 5-Hydroxytryptamine ; Granules ; Ciona intestinalis ; Corella parallelogramma, (Tunicata) ; Ascidia mentula (Tunicata)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The cellular and subcellular distribution of serotonin (5-hydroxytryptamine, 5-HT) in the endostyle of three species of ascidians, Ciona intestinalis, Corella parallelogramma, Ascidia mentula, was studied by light-(immunoperoxidase) and electron-microscopic (immunogold) immunocytochemistry. At the light-microscopic level 5-HT-like immunoreactivity (5-HT-LI) was exclusively found in cells located in the lateral portion of the endostyle, between zone 7, known to have iodinating capacity, and zone 8, which consists of ciliated cells. At the electron-microscopic level, the 5-HT-immunoreactive cells were found to correspond to cells containing polymorphous, dense granules, 100–300 nm in diameter. The granules were located in the supranuclear cytoplasm facing the endostyle lumen as well as in the infranuclear cytoplasm facing the extracellular space. Quantification showed that the 5-HT-LI was considerably higher (13–67 times) in cytoplasmic areas containing granules as compared to areas devoid of granules. Most, but not all, of the 5-HT-LI was associated with the dense core of the granules. In conclusion, serotonin-containing cells are located in the peripheral portion of the endostyle, between zones 7 and 8. Serotonin is stored in cytoplasmic granules that are present both in the apical and basal cytoplasm. This suggests the possibility that the cells are bipolar and secrete serotonin both in a basal direction to the extracellular space, and in an apical direction to the pharyngeal lumen.
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  • 81
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    Cell & tissue research 251 (1988), S. 87-93 
    ISSN: 1432-0878
    Keywords: Paneth cells ; Ultrastructure ; Morphometry ; Facultative anaerobes ; Germ-free mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Germ-free mice were given live or heat-killed facultative anaerobes, and the ultrastructure of ileal Paneth cells was quantitatively examined with special reference to secretory granules showing a bipartite substructure (central core and peripheral halo). After administering live or heatkilled bacteria, there was a decrease in the area occupied by the cores of secretory granules in Paneth cells, and exocytosed core material was observed in the crypt lumen. There were no changes in the area occupied by the halo of secretory granules. None of the examined Paneth cells phagocytosed bacteria. It is concluded that certain bacteria may affect the secretion of antibacterial agents contained in the secretory granules of Paneth cells.
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  • 82
    ISSN: 1432-0878
    Keywords: Endothelium ; Swim bladder ; Capillaries ; Vesicles ; Ultrastructure ; Cryofixation ; Anguilla rostrata (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Several recent studies comparing chemically fixed and cryofixed endothelium have indicated that glutaraldehyde fixation may result in increases in the population of “vesicles” in the cytoplasm. Other reports based on ultrathin serial-section reconstruction of chemically fixed endothelium have revealed that the vesicular system is comprised of interconnected membranous compartments, which are ultimately continuous with either cell surface but do not extend across the endothelial cell. In this study, we have investigated the three-dimensional organization of the vesicular system in directly frozen, freeze-substituted capillaries of the rete mirabile from the swim bladder of the eel, specifically using the same block of embedded capillaries in which frozen capillaries had previously been found to contain less “vesicles” than chemically fixed capillaries. The results show that essentially all vesicles remain inter-connected with each other and are part of two separate sets of invaginations from the luminal and abluminal cell surface like in chemically fixed tissue. Any increase in vesicle number resulting from glutaraldehyde fixation does not affect the overall three-dimensional organization of the vesicular system in these endothelial cells.
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  • 83
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    Cell & tissue research 252 (1988), S. 123-132 
    ISSN: 1432-0878
    Keywords: Uterine epithelium ; Cell culture ; Proteins ; Ultrastructure ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Morphological and biochemical changes occurring in rabbit endometrial epithelial cells when placed in culture were investigated. Cells were examined by scanning- and transmission electron microscopy and freeze-fracture. Morphologically, cultured cells are shorter and broader than the columnar epithelial cells in vivo, but retain their polarity as indicated by the presence of apical microvilli and a well-developed junctional belt. To study changes in biochemical function, proteins synthesized by cells in primary culture were analyzed by two-dimensional gel electrophoresis. Proteins were labeled during a 24-h incubation with 35S-methionine and gels examined by fluorography. The pattern of proteins changed after cells had been in culture for 48 h. On day 3 new proteins were synthesized and several protein species labeled during days 1 or 2 of culture, including uteroglobin, no longer appeared. On days 3–8 of culture the protein patterns were similar. Addition of progesterone, estradiol, prolactin, or combinations of these hormones to the culture medium for 24–144 h failed to elicit consistent changes in the pattern of labeled proteins established after 3 days of culture. Minor differences in protein patterns among unrelated cultures appear to have been derived from the original cells of the culture. These results indicate that after 48 h in primary culture, cells grown in vitro resemble endometrial epithelial cells morphologically, but no longer reflect functionally the character of epithelial cells in the uterus.
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  • 84
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    Cell & tissue research 252 (1988), S. 157-163 
    ISSN: 1432-0878
    Keywords: Frog skin culture ; Desmogenesis ; Interdigitations ; Lamellipodia ; Ultrastructure ; Rana esculenta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Small trypsinized explants from ventral skin of frogs (Rana esculenta) were maintained in culture for 4 days during which a newly formed epithelium differentiated along the cut edges of the dermis. During the first 6 h adjacent cells produced numerous interdigitating lamellipodia. After 2 days, epithelial polarity was restored by the formation of zonulae occludentes and the epithelial cells were joined by a few small newly formed desmosomes and by numerous interdigitations. Bipartite junctional complexes consisting of a zonula occludens, followed by a series of typical desmosomes, and characteristic of adult frog epidermis were formed only after 4 days. When cultured in the presence of an inhibitor of protein synthesis (cycloheximide) the trypsinized epidermis no longer formed desmosomes. Therefore pools of one or more crucial desmosomal proteins must be very low or non-existent. However, cycloheximide did not prevent the formation of cell contact specializations, consisting of a highly developed system of complex lamellar interdigitations, between adjacent cells.
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  • 85
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    Cell & tissue research 251 (1988), S. 243-248 
    ISSN: 1432-0878
    Keywords: Thoracic duct ; Smooth muscle cell ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The three-dimensional cytoarchitecture and ultrastructure of the smooth muscle cells in the wall of the rat thoracic duct were investigated by scanning and transmission electron microscopy. The muscle layer basically consists of a single layer of circularly arranged cells. The smooth muscle cell is fusiform or ribbon-like in shape, as in veins or venules with a similar or smaller diameter. Connections by spinous processes are observed between adjacent muscle cells along their length. Spot-like membrane contacts frequently occur in areas where facing membranes are closely apposed. These are thought to be gap junctions and may be responsible for electrical coupling and mechanical attachment. Large invaginations arranged regularly in rows on the surface of the smooth muscle cells can be observed. These invaginations are closely associated with a flattened sarcoplasmic reticulum, and caveolae tend to open into the invaginations.
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  • 86
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    Cell & tissue research 253 (1988), S. 397-402 
    ISSN: 1432-0878
    Keywords: Paneth cells ; Ultrastructure ; Morphometry ; Atropine ; Germ-free/Ex-germ-free ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous studies have shown that the secretory products of Paneth cells contain antibacterial agents (lysozyme, IgA) that are affected by the bacterial milieu in the intestine. To investigate whether Paneth-cell secretion is controlled via cholinergic mechanisms, the ultrastructure of Paneth cells was studied in four animal groups: (1) germfree (GF) control mice (Jcl: ICR [GN], male, 13 weeks old), (2) GF mice injected subcutaneously with atropine sulfate (200 mg/kg body weight, dissolved in physiological saline 20 mg/ml), (3) ex-GF mice inoculated with feces from specific-pathogen-free (SPF) mice, and (4) ex-GF mice injected with atropine and inoculated with feces from SPF mice. In ex-GF mice inoculated with feces, 70–90% of the Paneth cells showed fewer secretory granules than those from GF mice (p〈0.01). Approximately 30% of the Paneth cells had a large vacuole (3–10 μm diameter) in the apical cytoplasm. Exocytosed electron-dense material from secretory granules was observed in a few crypt lumens. In ex-GF mice inoculated with feces and given atropine, about 90% of the Paneth cells contained numerous secretory granules, like those in GF control mice, but vacuolated Paneth cells and exocytotic figures were rare; thus the secretion of Paneth cells was blocked by atropine. It is therefore possible that the bacterial milieu in the intestine affects the secretory activity of Paneth cells via cholinergic mechanisms.
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  • 87
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    Cell & tissue research 251 (1988), S. 189-195 
    ISSN: 1432-0878
    Keywords: Lymphocytes ; Epithelium ; Mast cells ; Granular leukocytes ; Basophils ; Ultrastructure ; Chicken
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Examination, by light and electron microscopy, of the morphology and the staining properties of intraepithelial lymphocytes from the intestine of the chicken revealed a population of lymphoid cells, of which a proportion (up to 20%) is granulated. The majority of cells were immunoreactive with anti-T cell serum and can therefore be considered to be related to T-lymphocytes, but they did not proliferate when cultured with phytohaemagglutinin. The granulated cells were identical to those previously designated globule-containing leukocytes, but were distinct from mast cells in their morphology, staining reactions and the stability of the granules in different fixatives and buffers.
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  • 88
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    Cell & tissue research 251 (1988), S. 205-214 
    ISSN: 1432-0878
    Keywords: Kupffer cells ; Granulocytes ; Ultrastructure ; Lipopolysaccharide ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of Kupffer cells has been studied at various times after an intravenous injection of lipopolysaccharide of Salmonella abortus equii. The most prominent effects were: an increase in the number and dimensions of phagocytic vacuoles (often containing ingested LPS and neutrophilic granulocytes); mitochondrial damage, including disintegration of the matrix and cristae; an increase in the amount of dilated, lucent rough endoplasmic reticulum; presence of fat droplets in the cytoplasm. Five days after injection of lipopolysaccharide, the Kupffer cells had resumed their normal ultrastructure. Several minutes after injection of lipopolysaccharide, platelets adhered to the Kupffer and endothelial cells. Between one and six hours, neutrophilic granulocytes accumulated in the liver sinusoids. The resulting obstruction of the hepatic microcirculation most probably affected cellular ultrastructure by ischaemia. At three days, the number of Kupffer cells was doubled, and increased further at later time intervals.
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  • 89
    ISSN: 1432-0878
    Keywords: Chromatophores ; Color change ; Ultrastructure ; Melanophores ; Macrophages ; Xanthophores ; Cichlasoma citrinellum (Teleostei: Cichlidae)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We describe the histological basis of color metamorphosis in the polychromatic Midas cichlid, Cichlasoma citrinellum. Eight percent of the individuals in a natural population transform from gray with black markings to orange, simultaneously losing their ability to adjust coloration in response to background and social context. This trait is inherited. Light- and electron microscopy revealed that this transformation is a two-step process. First, the melanophores die, then macrophage-like cells remove the debris. As a result of this initial process, the underlying xanthophores become visible, producing the orange coloration. A similar process may occur in individuals that further transform to white, or go directly from gray to white.
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  • 90
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    Bulletin of experimental biology and medicine 106 (1988), S. 1246-1249 
    ISSN: 1573-8221
    Keywords: erythrocytes ; Na+/H+ exchange ; hypertension
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  • 91
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    Bulletin of experimental biology and medicine 106 (1988), S. 1337-1340 
    ISSN: 1573-8221
    Keywords: temperature ; natural conditions ; continuois light ; circadian rhythm ; segregation
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  • 92
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    Cellular and molecular life sciences 43 (1987), S. 403-405 
    ISSN: 1420-9071
    Keywords: SHR ; cyclosporin ; immune mechanisms ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In spontaneously hypertensive rats the effect of the T-cell inhibitor cyclosporin was studied at different ages. If treatment was started at the age of 2 weeks the development of hypertension was delayed, but the ultimate level of blood pressure was not affected. These results indicate the involvement of immune mechanisms in the early development of hypertension in spontaneously hypertensive rats.
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  • 93
    ISSN: 1432-1041
    Keywords: nicardipine ; propranolol ; hypertension ; concomitant administration ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A twelve-week parallel study was conducted to compare the efficacy and safety of nicardipine plus propranolol with that of propranolol alone in 67 patients with mild to moderate essential hypertension. Efficacy data was analysed for 50 patients. The regimens used were 90 mg · day−1 of nicardipine and 120 mg · day−1 of propranolol. Both treatments significantly reduced supine and standing systolic and diastolic blood pressure from baseline values at all visits. At all visits, concomitant administration of nicardipine and propranolol produced a greater reduction in systolic and diastolic pressures than did propranolol alone, although the difference between treatments did not always reach statistical significance. Few adverse events were reported, and none was clinically important. We conclude that nicardipine taken concomitantly with propranolol is more effective than propranolol alone in treating patients with hypertension and that the combined regimen is well tolerated.
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  • 94
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    European journal of clinical pharmacology 33 (1987), S. 423-426 
    ISSN: 1432-1041
    Keywords: Ketanserin ; pharmacokinetics ; hypertension ; ketanserinol ; predicted plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of ketanserin in 6 hypertensive patients after a single oral 40 mg dose and at steady-state after 4 weeks treatment with 20 mg and then 40 mg 12-hourly. Pharmacokinetic variables after a single dose were similar to those reported in healthy volunteers, with median values for Cmax 112 ng·ml−1, tmax 1 h, and t1/2 19 h. The corresponding values for the metabolite ketanserinol were Cmax 155 ng·ml−1, tmax 2 h, and t1/2 25 h. The median AUC was 3.3 times greater for ketanserinol than for the parent drug. These results were used to predict the mean steady-state plasma concentrations of ketanserin and ketanserinol. Predicted values were on average similar to those observed after four weeks treatment with 40 mg 12-hourly, although there were marked differences between the observed and predicted values in some patients. There was no evidence of time- or dose-dependent kinetics for ketanserin, but the study had insufficient power to exclude the occurrence of these phenomena entirely.
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  • 95
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    European journal of clinical pharmacology 33 (1987), S. 119-126 
    ISSN: 1432-1041
    Keywords: hypertension ; nicardipine ; propranolol ; serum lipids ; electrocardiogram ; side-effects ; ECG changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind controlled trial 22 patients with mild or moderate essential hypertension were treated with nicardipine 30 mg t.d.s. and 19 patients with propranolol 80 mg t.d.s. as monotherapy for 24 weeks. Blood pressure in both groups at the end of trial was equally and significantly reduced; systolic pressure 22.2 mmHg and diastolic pressure 15.5 mmHg in the supine position, and 24.4 mmHg and 18.4 mmHg, respectively, in the standing position in those on nicardipine, and by 23.7 and 16.2 mmHg and 28.0 and 19.2 mmHg, respectively, in the propranolol group. There was an initial increase in heart rate in the nicardipine group, but the rise was only moderate (3 beats/min supine p=0.3219, and 7 beats/min standing, p=0.0203) at the end of the 24 weeks. In the propranolol group heart rate was reduced markedly. Adverse effects occurred in 77% of patients on nicardipine and in 63% of those on propranolol, and there were no unexpected findings. The effects were mild in both groups and did not lead any patient to stop medication. One patient on propranolol was withdrawn from the trial because of poor blood pressure control and suspected angina pectoris after 5 weeks on active medication. There were no significant changes in blood chemistry, including lipoprotein classes. Overall, in comparison with propranolol, nicardipine was effective, well-tolerated and safe to use in the monotherapy of mild or moderate essential hypertension.
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  • 96
    ISSN: 1432-1041
    Keywords: muzolimine ; chlorthalidone ; hypertension ; serum electrolytes ; potassium ; ion transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous short-term studies of muzolimine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthalidone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentrations remained unchanged, while a significant fall in potassium occured with chlorthalidone. Neither drug affected the activity of sodium-potassium cotransport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial pressure and on the other metabolic variables tested.
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  • 97
    ISSN: 1432-1041
    Keywords: perindopril ; hypertension ; angiotensin converting enzyme inhibition ; renin-angiotensin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of treatment for one month with perindopril, 4 or 8 mg once daily, in seven hypertensive patients. Blood pressure was lowered from 164/93 mm Hg to 145/84 mm Hg by 4 mg of perindopril and after one month remained at 142/82 mm Hg. Neither postural hypotension nor tachycardia occurred. Inhibition of plasma angiotensin converting enzyme (ACE) lasting for over 24 h was achieved and there was a significant increase in plasma renin activity (PRA). Maximum plasma concentrations of the active metabolite of perindopril, S-9780, were detected four h after oral administration. After treatment for one month there was evidence of reduced sensitivity of plasma ACE to the action of the inhibitor. The plasma concentration of S-9780 required to produce 50% inhibition of plasma ACE rose from 2.4 ng · ml−1 following the first dose to 5.5 ng · ml−1 after one month.
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  • 98
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1987), S. 553-557 
    ISSN: 1432-1041
    Keywords: ibuprofen ; diclofenac ; sulindac ; anti-inflammatory drugs ; hypertension ; NSAIDs ; hydrochlorothiazide ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg b.i.d. Only a slight, statistically non-significant change was found, with the exception of a significant increase in systolic blood pressure after 4 weeks treatment with ibuprofen. There was considerable variation in the blood pressure response during treatment with all three NSAIDs, with slight rises in blood pressure in 13 out of 24 periods. Body weight increased significantly on treatment both with ibuprofen and diclofenac, whereas the increase on sulindac was less and was transient. No significant change was found in various biochemical parameters, including plasma electrolytes, plasma renin activity (PRA), aldosterone, albumin and creatinine, in haematocrit or in the 24-h urinary excretion of sodium and potassium. The sole exception was a decrease in PRA during ibuprofen treatment. From these observations it is concluded that ibuprofen and diclofenac differ from sulindac in their interaction with the diuretic action of hydrochlorothiazide. It appears that all three NSAIDs can safely be combined with hydrochlorothiazide in hypertensive patients, but blood pressure should be monitored carefully when an NSAID are added.
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  • 99
    ISSN: 1432-1041
    Keywords: atenolol ; amiloride ; hydrochlorothiazide ; young ; elderly ; pharmacokinetics ; pharmacodynamics ; volunteers ; patients ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six normal young and six normal elderly volunteers and six elderly hypertensive patients took part in an acute and chronic dose study of a combination capsule containing atenolol (50 mg), hydrochlorothiazide (25 mg) and amiloride (2.5 mg) designed for the treatment of hypertension. No difference in any of the drug pharmacokinetic parameters could be detected between the hypertensives and the normal elderly subjects. The bio-availability and the 24-h blood concentrations of all three drugs, half-life of atenolol and amiloride and the peak concentration of hydrochlorothiazide was significantly greater in the elderly. The 24-h blood concentrations of atenolol and hydrochlorothiazide did not alter with chronic dosing, but amiloride concentrations were significantly higher at this time in all groups. A significant fall in the blood pressure was observed in the hypertensive group. Heart rate fell more in the normal and hypertensive elderly subjects than in the young. The combination has shown to be an effective and well tolerated antihypertensive in the elderly patient with a 24-h duration of action.
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 331-334 
    ISSN: 1432-1041
    Keywords: prazosin ; clonidine ; interaction ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prazosin has been reported to reduce the hypotensive and/or bradycardic effect of clonidine in various animal models. Investigations in humans have given conflicting conclusions about the effectiveness of the combination of clonidine and prazosin. In patients with essential hypertension prazosin significantly reduced the hypotensive effect of intravenous clonidine, but it failed to affect the clonidine-induced bradycardia. This finding means that the combination of prazosin and clonidine is inappropriate in antihypertensive therapy.
    Type of Medium: Electronic Resource
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