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  • Articles  (18)
  • adverse effects  (14)
  • kinetics
  • Springer  (18)
  • American Meteorological Society
  • 1995-1999
  • 1985-1989  (18)
  • 1965-1969
  • 1955-1959
  • 1950-1954
  • 1987  (18)
  • Medicine  (18)
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  • Articles  (18)
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  • Springer  (18)
  • American Meteorological Society
Years
  • 1995-1999
  • 1985-1989  (18)
  • 1965-1969
  • 1955-1959
  • 1950-1954
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 26 (1987), S. 125-137 
    ISSN: 1436-6215
    Keywords: vitamin C ; functions ; kinetics ; pool ; saturation ; requirements ; RDA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Die Bedeutung von Vitamin C für den menschlichen Organismus wird aus den wichtigen Funktionen ersichtlich, an denen das Vitamin beteiligt ist, wie zum Beispiel Kollagen- und Karnitinsynthesen. In neuerer Zeit entdeckt wurde seine Rolle bei der Noradrenalinsynthese, der Inaktivierung von freien Radikalen sowie der Verhinderung der Nitrosaminbildung. Die Vielfalt dieser Vitamin-C-abhängigen Funktionen läßt erkennen, daß die Bedarfsfestsetzung für Vitamin C nicht nur die Verhütung der Mangelkrankheit Skorbut anvisieren, sondern auch berücksichtigen sollte, daß alle diese Funktionen jederzeit genügend Vitamin C zur Verfügung haben müßten, um optimal reagieren zu können. Das Konzept der Gewebesättigung kommt diesem Ziel am nächsten. Studien mit einem kinetischen Modell haben ergeben, daß eine Sättigung mit täglicher Einnahme von 100 mg Vitamin C bei Nichtrauchern und von 140 mg bei Rauchern eintritt, Mengen, die als optimale Werte gelten können. Bei verschiedenen Krankheiten dürfte der Bedarf höher sein; die genauen Mengen müssen jedoch erst noch ermittelt werden.
    Notes: Summary The importance of vitamin C is reflected in its multifunctional roles which include participation in collagen and carnitine syntheses, promotion of iron absorption and the more recently discovered participation in noradrenaline synthesis, inactivation of free radical chain reactions, prevention of N-nitroso compound formation and more. Given the many extra-antiscorbutic functions of the vitamin, the Recommended Dietary Allowances (RDA) should not just prevent deficiency disease but should aim at providing sufficient amounts for all vitamin C-dependent functions to operate at full capacity. The concept of vitamin C tissue saturation is best able to meet this demand. The use of kinetic models has shown that the body pool is saturated with a daily intake of 100 mg vitamin C in non-smokers and 140 mg in smokers, amounts that may be regarded as optimal RDA values. Certain disease states may be accompanied by still higher vitamin C requirements but the exact amounts are not yet known.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 449-456 
    ISSN: 1432-1041
    Keywords: transcainide ; antiarrhythmic drugs ; cardiac arrhythmias ; adverse effects ; ventricular arrhythmias ; supraventricular arrhythmias
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antiarrhythmic efficacy of transcainide has been studied in 41 patients. It abolished ventricular arrhythmias in 10 out of 12 patients after i.v. administration and in 11 out of 14 after oral administration. It also reduced ventricular arrhythmias during recovery from exercise. The maximum intravenous dose prolonged the PR-interval by 43% and QRS-duration by 37%. Side-effects observed in 6 out of 41 patients included Mobitz Type I AV block, complete bundle branch block, hypotension and increased arrhythmia frequency. Transcainide is a promising new antiarrhythmic drug which should be used with caution in patients with conduction disorders and impaired cardiac function. Its value and safety in the chronic oral treatment of life-threatening arrhythmias remains to be established.
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 227-230 
    ISSN: 1432-1041
    Keywords: enoxacin ; theophylline ; drug interaction ; healthy volunteers ; adverse effects ; pharmacokinetics ; renal tubular excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The mechanism of the theophylline-enoxacin interaction has been studied in six healthy subjects. Theophylline 250 mg was administered p.o., twice daily for 11 days in a sustained release dosage form. On the 4th day of treatment, blood samples were taken every 2 h and urine was collected over 1 dose interval. From Days 5 to 11 coated tablets of enoxacin 400 mg b.i.d. were coadministered. On Day 11 blood and urine were collected as on Day 4. The mean plasma theophylline concentration rose from 4.4 to 15.1 mg/l, corresponding to a 73.6% reduction in total clearance. The urinary excretion of unchanged theophylline increased from 12.7 to 35.3%, whereas the production of metabolites was reduced (1-demethylation 81.4%; 3-demethylation 83.1%, 8-hydroxylation 74.6%). The results indicate that the theophylline-enoxacin interaction may be due to inhibition of the cytochrome P-450 isozymes responsible for theophylline metabolism. Unexpectedly, the renal clearance of theophylline metabolites was found to be drastically reduced when enoxacin was coadministered. This led to unchanged or even to elevated plasma levels of the metabolites. The mechanism of this interaction is still to be elucidated, but it may be due to competition for renal tubular secretion.
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  • 5
    Electronic Resource
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    Springer
    European journal of clinical pharmacology 33 (1987), S. 505-509 
    ISSN: 1432-1041
    Keywords: lofepramine ; amitryptyline ; anticholinergic effect ; adverse effects ; psychometric tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind five-way cross-over study, six drug free healthy elderly subjects received single oral doses of lofepramine (70 mg, 105 mg and 140 mg), amitriptyline (50 mg) and matched placebo tablets. A dose related increase in plasma drug levels and pharmacological effects of lofepramine was observed. Lofepramine (140 mg) improved psychomotor performance (choice reaction time and letter cancellation), but no such change was seen with lower dose regimes or placebo. No significant differences between lofepramine and placebo were observed in other parameters measured. Amitriptyline, as expected, reduced salivary volume, produced drowsiness and impaired psychomotor performance. These changes correlated with plasma amitriptyline levels. The incidence of subjective side-effects with amitryptyline was also higher than that of lofepramine or placebo. In the dosage used, lofepramine exhibited no deleterious effect on the peripheral cholinergic system or psychomotor performance. This drug therefore is likely to be a relatively safe antidepressant for the elderly, but further investigations during long-term medication are required to verify these observations.
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  • 6
    ISSN: 1432-1041
    Keywords: metoclopramide ; cancer chemotherapy ; high-dose ; emesis ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy. Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations. In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor. There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophospamide and doxorubicin. The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration. Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 17-22 
    ISSN: 1432-1041
    Keywords: felodipine ; calcium antagonist ; normal man ; renal function ; albumin excretion ; beta2-microglobulin excretion ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute renal effects of a single oral dose of felodipine 0.15 mg/kg were studied in 8 healthy males. Thirty minutes after administration the mean plasma concentration was 25.7 nmol/l. There was a significant reduction in diastolic blood pressure (24%) and a concomitant rise in heart rate (38%), leaving the systolic pressure unchanged. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique using the clearance of125I-iothalamate and131I-hippuran respectively. GFR was unchanged and the filtration fraction (FF) was reduced, whilst there was a decrease in renal vascular resistance (RVR). The glomerular filter characteristics were unchanged, as estimated by the unchanged excretion rate of albumin. There was a significant rise in the clearance of sodium (176%) but only a small and insignificant increase in urine volume. Clearance of potassium was decreased. An increase in the clearance of uric acid and a rise in the beta-2-microglobulin excretion rate were found, both suggesting a proximal tubular effect of felodipine. The excretion rate of calcium was increased.
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  • 8
    ISSN: 1432-1041
    Keywords: sodium valproate ; adverse effects ; anti-convulsants ; drug interaction ; hyperammonia ; metabolites ; epilepsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentrations of valproic acid (VPA) and of its metabolites 3-oxo-VPA and 4-en-VPA were measured in the plasma of 12 selected epileptic patients 1,2,3, and 4 h after administration of a loading dose of VPA. Four of the patients, all on polytherapy, had had short-term adverse effects during chronic VPA treatment, and in them there has been abnormal NH3-values after a test doese of VPA. Eight patients (4 on monotherapy and 4 on polytherapy) had been free from adverse effects. No significant difference in the VPA, 3-oxo-VPA and 4-en-VPA concentrations was found between the three groups of patients. Accumulation of 4-en-VPA is not involved in the short-term adverse effects and hyperammonaemia induced by VPA.
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  • 9
    ISSN: 1432-1041
    Keywords: cadralazine ; hypertension ; haemodynamic effects ; renal blood flow ; glomerular filtration ; renal function ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the hydralazine-related compound cadralazine (2-{3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl}ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with β-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 203-204 
    ISSN: 1432-1041
    Keywords: flosequinan ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and short term antihypertensive effect of flosequinan was determined in 16 hypertensive patients whose blood pressure was inadequately controlled despite treatment with a β-adrenoceptor blocking agent and a diuretic. Erect and supine systolic and diastolic blood pressure was significantly reduced by flosequinan over the treatment period as compared to placebo. Heart rate was unchanged by flosequinan. Adverse effects were limited to mild headache in 3 patients and taste disturbance in 1 patient, possibly due to salivary excretion of the drug. Flosequinan is a potentially useful vasodilator for the treatment of hypertension.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 381-385 
    ISSN: 1432-1041
    Keywords: WAL801 CL ; antihistamine ; skin wheals ; bronchospasm ; central effects ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The tolerability and antihistaminic activity of WAL801 CL, a new, peripherally acting H1-receptor antagonist, have been evaluated in a double-blind, placebo-controlled, within-subject cross-over study. WAL801 CL 8 mg b.d. was given to 10 healthy volunteers for 15 days. It resulted in a distinct reduction in histamine wheal size and a decreased bronchoconstrictor response to histamine inhalation. No cardiovascular side effects were observed. Transient and slight fatigue was observed in 3 subjects. Psychological tests, such as simple visual reaction time, critical flicker fusion frequency and mood self rating scale, showed that WAL801 CL had no sedative side effects and that it did not alter psychomotor performance.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1987), S. 621-623 
    ISSN: 1432-1041
    Keywords: Zopiclone ; Triazolam ; hypnotics ; insomniac patients ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind crossover therapeutic trial the hypnotic effect of Zopiclone 7.5 mg and Triazolam 0.5 mg given orally at bedtime for 7 consecutive days have been compared. 5 of the items in Spiegel's questionnaire and 12 of the 18 items in Norris' visual analogue scale were significantly more improved by Zopiclone than by Triazolam. Both drugs caused few side-effects.
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  • 13
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    Springer
    European journal of clinical pharmacology 32 (1987), S. 23-26 
    ISSN: 1432-1041
    Keywords: asthma ; enprofylline ; bronchodilatation ; combination treatment ; terbutaline ; plasma concentrations ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline is a novel xanthine derivative with negligible adenosine antagonizing ability. It is eliminated almost exclusively by renal clearance with a half-life of about 2 h. Three i.v. infusions of enprofylline (1 mg/kg body weight over 10 min) were given at hourly intervals to 16 patients with stable, reversible airway obstruction. The patients were pretreated at random with i.v. terbutaline (4 µg/kg body weight) or placebo according to a double blind cross-over design. Lung function and drug concentrations in plasma were followed. Enprofylline produced significant and concentration-dependent bronchodilatation between plasma levels of 1.24 and 3.22 mg/l. The improvement in ventilatory function was significantly enhanced by terbutaline pretreatment. At the highest plasma levels of enprofylline nausea and headache were found as subjective side effects. The results suggest that enprofylline and terbutaline might best be used in a low dose combination in the treatment of bronchial asthma.
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  • 14
    ISSN: 1432-1041
    Keywords: urapidil ; hypertension ; alpha-adrenoceptor blocker ; antihypertensive agent ; pharmacodynamics ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of infused urapidil and an infusion-capsule combination were followed to study the correlation between the serum urapidil level and the blood pressure. Prior to urapidil administration, basal blood pressure and heart rate were measured for 16 h in 12 male hypertensive patients. Six patients received infusions lasting for 4 h of urapidil 10, 2.5 and 5 mg/h. Six patients were infused with urapidil 10 mg/h for 4 h and 2 h after the end of the infusion each took a 60-mg capsule. After a 5 day washout period the procedures were crossed over. A maximum serum urapidil level of 625±232 ng/ml was achieved at the end of the 10 mg/h infusion, when the fall in blood pressure was 37/21 mmHg. During the 2.5 and 5 mg/h infusions the serum urapidil level was 330 and 420 ng/ml, respectively, and the corresponding decreases in blood pressure were 28/16 mmHg and 31/8 mmHg. Although the urapidil concentration 1 hour after beginning the infusion was only 184±89 ng/ml a near maximal blood pressure decrease had already occurred 33±9/20±8 mmHg, whereas, 1 h after the end of the infusion the reduction in blood pressure was only 10±12/3±8 mm, with a urapidil concentration of 358±120 ng/ml. During the plateau phases of both the infusion and infusion-capsule treatments the falls in blood pressure followed the serum urapidil levels. Only in the initial rising and final falling phases of the treatments were the pharmacodynamics and pharmacokinetics of urapidil not correlated.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 249-252 
    ISSN: 1432-1041
    Keywords: diclofenac ; preoperative administration ; oral surgery ; postoperative pain control ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have treated ninety-five patients undergoing surgical removal of third molar with diclofenac or placebo, administered double-blind either pre- or postoperatively. Postoperative pain was recorded hourly for the first 8 h using a 100 mm visual analogue scale. Preoperative administration of diclofenac produced more effective pain relief than either postoperative administration or placebo. Since diclofenac has an inhibitory action on prostaglandin synthesis prophylactic intramuscular administration may have reduced the inflammatory process before synthesis of prostaglandins was activated.
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  • 16
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    Springer
    Molecular and cellular biochemistry 76 (1987), S. 45-54 
    ISSN: 1573-4919
    Keywords: DNA methyltransferase ; hemimethylated DNA ; kinetics ; affinity chromatography ; (rat liver)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract DNA substrate analogs were constructed from poly(dC-dG), M13, and XP12 DNA which do not contain a mixture of types of methylation sites. These were used to distinguish different kinetic mechanisms for maintenance and de novo methylation using a highly purified rat liver DNA (cytosine-5)-methyltransferase (DMase−) preparation. De novo methylation on single (ss) and double-stranded (ds) DNA was found to obey Michaelis-Menten kinetics while methylation of hemimethylated sites showed differences depending on size of the hemimethylated region. On long stretches analogous to maintenance methylation of newly replicated DNA, saturation could not be achieved and the kinetics showed non-ideal positive cooperative kinetics, while short stretches showed non-Michaelis-Menten kinetics and rapid saturation. Two types of DMase-DNA complexes could be distinguished by means of affinity chromatography on DNA-agarose matrices and in preincubation assays. The later complex, which is engaged in methyl group turnover, exhibited enhanced stability. The competitiveness of variously configured DNAs was found to parallel the stability of complex formation, e.g., ss, hemi- and ds DNA, respectively. In studies utilizing 5-bromodeoxyuridine, the thymine analog left the basic reaction mechanisms unchanged but increased the km and S0.5 while reducing the velocity of these reactions.
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  • 17
    Electronic Resource
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    Springer
    Bulletin of experimental biology and medicine 103 (1987), S. 660-662 
    ISSN: 1573-8221
    Keywords: hydrogenated phenazepam analog ; metabolism ; kinetics ; excretion ; differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 18
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    Electronic Resource
    Springer
    Mycopathologia 98 (1987), S. 179-184 
    ISSN: 1573-0832
    Keywords: adhesion ; C. albicans ; kinetics ; concanavalin A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The early in vitro kinetics of Candida albicans attachment to human buccal epithelial cells was studied with the aid of an adhesion assay and solutions of concanavalin A (Con A), a lectin which is capable of inhibiting yeast adhesion. Various saccharides and putative receptor analogues were also tested. Solutions of each single reagent were added to tubes containing aliquots of mucosal cells and germinated yeasts at the beginning of a 1-hour incubation period (time O) or at 10 minute intervals during the assay. The number of yeasts attached to 200 mucosal cells was subsequently determined microscopically. Yeast adhesion remained constant following addition of phosphate-buffered saline (PBS) at time 0 or at any time thereafter. However, addition of Con A at 0, 10 or 20 minutes of incubation decreased adhesion significantly to 38%, 45% and 63% of control values. This inhibitory effect dwindled as time of incubation prior to lectin addition increased and Con A could not inhibit adhesion significantly after twenty minutes. Results obtained with Con A using live germinated yeasts were similar to those obtained with formalin-killed C. albicans. The other reagents tested failed to decrease adhesion significantly. These included the putative receptor analogues fibronectin, N-acetyl-d-glucosamine and d-galactose, and several non-specific saccharides such as α-d-methylglucopyranoside, d-ribose and d-xylose. It is suggested that in vitro attachment to human mucosal cells by C. albicans is inhibitable up to a defined point in time by a lectin with affinity for mannosecontaining surface moieties, but becomes non-reversible thereafter. This experimentally-observed irreversibility is independent of yeast cell viability.
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