ALBERT

Notes: 1 The aim of this study was to characterize the histamine receptor type mediating relaxation of the vascular bed of the nasal mucosa from the guinea-pig, and to determine the role of cyclo-oxygenase products and nitric oxide in this relaxant response to histamine. These studies were performed in isolated nasal mucosae examined in vitro to obtain potencies of histamine receptor-type selective agonists in causing vasorelaxation and to determine affinities of histamine receptor antagonists for inhibiting histamine-induced relaxation. 2 After contraction of nasal mucosae with noradrenaline, histamine caused a maximal relaxation response that was 75 ± 6% of the contraction caused by noradrenaline with a mean EC50 value of 4.3 ± 0.5 μm. Neither dimaprit (H2-receptor selective) nor R-α-methylhistamine (H3-receptor selective) caused significant relaxation of nasal mucosae. In contrast, betahistine (H1-receptor selective) caused an 81 ± 7% relaxation of noradrenaline-induced tone with an EC50 value of 15 ± 1 μm. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulated relaxation of nasal mucosae. KB values for chlorpheniramine (0.87 nm) and diphenhydramine (7.4 nm) were consistent with their interaction at the H1-receptor type. Additionally, neither 10 μm cimetidine (H2-receptor selective) nor 1 μm thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. 4 In the presence of 10 μm indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 ± 5% of the noradrenaline-induced tone with an EC50 value of 2.9 ± 0.2 μm, which was not different from control values (EC50 = 5.0 ± 0.4 μm; maximal relaxation = 71 ± 6%). In contrast, 200 μm NG-nitro-l-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal mucosae. 5 In conclusion, data from the present study suggest only the H1-receptor type mediates relaxation of nasal mucosal blood vessels to histamine, and histamine-induced relaxation of nasal mucosae is entirely dependent on nitric oxide production.

Notes: 1 This study was aimed at evaluating the effect of rutin and harmaline (1-methyl-7-methoxy-3,4-dihydro-β-carboline) on the development of the surgically induced reflux oesophagitis, on gastric secretion, lipid peroxidation, polymorphonucleocytes (PMNs) accumulation, superoxide and hydroxyl radical production in PMNs, cytokine [interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α)] production in blood and [Ca2+]i mobilization in PMNs. 2 Rutin and harmaline significantly prevented the development of reflux oesophagitis and gastric secretion. Treatments of oesophagitis rats with rutin and harmaline inhibited lipid peroxidation, and myeloperoxidase (MPO) in the oesophagus in comparison with untreated rats. 3 Superoxide anion and hydrogen peroxide production in 1 μm formylmethionylleucylphenylalanine (fMLP)- or 0.1 μg ml−1N-phorbol 12-myristate 13-acetate (PMA)-activated PMNs was inhibited by rutin and harmaline in a dose-dependent fashion. Rutin and harmaline effectively scavenged the hydroxyl radical and hydrogen peroxide. Treatments of oesophagitis rats with rutin and harmaline inhibited IL-1β production in the oesophagus in comparison with untreated rats, but TNF-α production was not affected by rutin and harmaline. The fMLP-induced elevation of [Ca2+]i was inhibited by rutin. 4 The results of this study suggest that rutin and harmaline may have beneficial protective effects against reflux oesophagitis by the inhibition of gastric acid secretion, oxidative stress, inflammatory cytokine production (i.e. IL-1β), and intracellular calcium mobilization in PMNs in rats.

Notes: 1 Although monumental efforts have been made to define the action sites of cough, the importance of neurotransmitter systems in the cough reflex has received limited attention. We studied the roles for four major neurotransmitters [acetylcholine, histamine, serotonin (5-hydroxytryptamine, 5-HT) and dopamine] in the modulation of the cough reflex. 2 Atropine (muscarinic cholinergic blocking agent), pyrilamine maleate (PM, histamine H1 blocker), cimetidine (histamine H2 blocker), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, specific 5-HT1A receptor agonist) and SCH-23390 (selective dopamine D1 receptor antagonist) were examined on the cough response to inhaled capsaicin in conscious guinea-pigs. 3 All the drugs significantly decreased the number of capsaicin-induced coughs in a dose-dependent manner. To compare the sensitivity of these drugs on cough response, we calculated the effective doses for 50% inhibition of cough (ED50) when the animals were exposed to 3 × 10−4 m capsaicin. The ED50 values were 0.03 μm kg−1 for atropine, 0.2 μm kg−1 for 8-OH-DPAT, 6.2 μm kg−1 for SCH-23390, 8.5 μm kg−1 for PM and 13.9 μm kg−1 for cimetidine. 4 These findings indicated that all these four neurotransmitters may be involved in the regulation of the cough reflex. Multiple changes of these neurotransmitters in disorders of the central nervous system might synergically affect the cough reflex.

Notes: 1 There is good evidence that β-blockers improve ventricular function, disease progression and survival in patients with left ventricular systolic dysfunction. The aim of this study was to determine the effects of atenolol therapy on the sympathetic nervous system at rest and after ergometric exercise, on left ventricular function and on baseline plasma atrial natriuretic factor (ANF) in ambulatory patients with chronic heart failure (CHF). 2 Twenty-two patients [left ventricular ejection fraction (LVEF) 〈36%; New York Heart Association II–III] were studied before atenolol treatment. Because of cardiac events (new Hospital admission or death) only 13 patients completed 1 year of treatment. Baseline noradrenaline (NE) concentrations were similar in patients and controls while ANF was higher in patients than in controls (328 ± 35 pg ml−1vs. 37 ± 3 pg ml−1; P 〈 0.01). 3 Patients with events showed higher NE (540 ± 87 pg ml−1vs. 303 ± 44 pg ml−1; P 〈 0.01) and ANF (460 ± 70 pg ml−1vs. 291 ± 44 pg ml−1; P 〈 0.03) at rest; and greater NE response to exercise (2.003 ± 525 pg ml−1vs. 694 ± 121 pg ml−1; P 〈 0.005). Atenolol treatment improved LVEF (19.5 ± 1.9%vs. 33 ± 3.9%; P 〈 0.001), increased exercise tolerance (9 ± 3.2 min vs. 17 ± 4.8 min; P 〈 0.001) and decreased plasma ANF (292 ± 42 pg ml−1vs. 133 ± 35 pg ml−1; P 〈 0.01). 4 Reduced basal dihydroxyphenylglycol (DHPG)/NE ratio (3.4 ± 0.46 vs. 4.3 ± 0.35; P 〈 0.01) was observed in patients compared with healthy volunteers. Atenolol increased DHPG plasma levels (1.398 ± 129 pg ml−1vs. 913 ± 86 pg ml−1; P 〈 0.005) but the DHPG/NE ratio during exercise was not modified after treatment, suggesting that re-uptake of released NE is not changed by β-blocker treatment. 5 In conclusion, the fact that atenolol treatment improves ventricular dysfunction and clinical status without changing plasma NE levels in CHF patients, suggests that plasma NE is a poor surrogate measurement for cardiac sympathetic activity in this pathology. In addition, decrease in plasma ANF produced by atenolol treatment may reflect the improvement of ventricular function.

Notes: 1 The aim of the study was to investigate the role of the α1D-adrenoceptor in α1-adrenoceptor-induced contraction of human prostate by means of protection experiments. 2 Responses of human prostate strips to noradrenaline were recorded, along with responses of rat aorta and vas deferens, tissues possessing predominantly α1D- and α1A-adrenoceptors respectively, for comparison. α1-adrenoceptors were then inactivated by incubation with the irreversible antagonist phenoxybenzamine. In some tissues α1A- or α1D-adrenoceptors were ‘protected’ from inactivation by incubation in the presence of the selective α1A- or 1D-adrenoceptor antagonists 5-methylurapidil and BMY 7378 before recording further responses to noradrenaline. 3 Phenoxybenzamine reduced the maximum noradrenaline-induced response and the potency of noradrenaline in all tissues. In rat vas deferens and human prostate, 5-methylurapidil protected α1A-adrenoceptors in a concentration–dependent manner. In rat aorta, 10 nm BMY 7378 almost fully protected α1D-adrenoceptors. However, concentrations of BMY 7378 up to 30-fold higher failed to protect receptors in the human prostate. 4 These results suggest that in human prostate functional α1D-adrenoceptors do not contribute to noradrenaline-induced contractile responses.

Notes: 1 A triple organ bath method allowing the synchronous recording of the motor activity of the circular muscle layer belonging to the oral and anal segments of guinea-pig small intestine adjacent to an electrically stimulated middle segment was developed to study the ascending and descending reflex motor responses. 2 Electrical field stimulation (0.8 ms, 40 V, 5 Hz, 10 s) applied to the middle part of the segments elicited tetrodotoxin (1 μm)-sensitive ascending and descending contractile responses of the nonstimulated parts, oral and anal, respectively. The ascending contraction was more pronounced as compared with the descending contraction. 3 In the presence of phentolamine (5 μm), propranolol (5 μm) and atropine (3 μm) a significant decrease in the amplitude of the ascending contraction was seen and a descending relaxation, instead of a contraction was observed. 4 Met-enkephalin applied at a single concentration (0.1 μm) or cumulatively (0.001–1 μm) inhibited both non-adrenergic non-cholinergic (NANC) descending relaxation and ascending contraction with similar efficacy but different potency, IC50 being 5.9 ± 0.3 and 39.0 ± 4 nm, respectively. Naloxone (0.5 μm) prevented the effects of Met-enkephalin. 5 L-NNA (0.5 mm), an inhibitor of nitric oxide synthesis, increased the ascending contraction and strongly reduced but not abolished the descending relaxation. l-Arginine (0.5 mm) restored the motor responses to the initial level in l-NNA-pretreated preparations, d-Arginine (0.5 nm) had no effects. 6 Met-enkephalin (0.1 μm) depressed the l-NNA-dependent increase of the ascending contraction and failed to change the l-NNA-resistant part of the descending relaxation. 7 Met-enkephalin did not alter spontaneous NANC mechanical activity. SNP (1 or 10 μm), an exogenous donor of nitric oxide, caused a concentration-dependent relaxation. The effects of SNP persisted in Met-enkephalin (0.1 μm)-pretreated preparations. 8 NANC reflex ascending contraction and descending relaxation were synchronously induced by a local nerve stimulation indicating a functional coactivation of NANC orally projected excitatory and anally directed inhibitory pathways. Acting prejunctionally, Met-enkephalin provided a negative controlling mechanism inhibiting both ascending and descending, mainly nitric oxide mediated, reflex responses. A higher sensitivity of the descending relaxation to Met-enkephalin was observed suggesting an essential role of opioid(s) in reducing the efficacy of descending motor activity.

Notes: 1 The present study was designed to investigate the secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused adrenal gland of spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKYR) at adult age. 2 The wet weight of adrenal gland in SHR was greater than that in WKYR. The CA releasing responses evoked by acetylcholine (5.32 × 10−3 m), and high potassium (5.6 × 10−2 m), a membrane depolarizer, were significantly lower in WKYR than in SHR. 3 The secretory responses of CA evoked by DMPP (10−4 m for 2 min), a selective agonist of neuronal nicotinic receptors, and McN-A-343 (10−4 m for 2 min), a selective agonist of neuronal muscarinic receptors, were also significantly lower in WKYR than in SHR. 4 The CA release evoked by Bay-K-8644 (10−5 m), a dihydropyridine-sensitive Ca2+ channel activator, and cyclopiazonic acid (10−5 m), a selective inhibitor of Ca2+-ATPase in the endoplasmic reticulum, were also significantly greater in SHR than WKYR. 5 Taken together, these experimental results demonstrate that the CA secretion evoked by stimulation of cholinergic (nicotinic and muscarinic) receptors as well as membrane depolarization is enhanced more greatly in the perfused adrenal glands of SHR than in those of WKYR. It is suggested that the augmented CA release in SHR compared with WKYR was involved in essential hypertensive pathogenesis.

Notes: 1 The contractile capacity of smooth muscle cells depends on the cytoskeletal framework of the cell. The aim of this study was to determine the functional importance of both the actin and the tubulin components of the cytoskeleton in contractile responses of the bovine isolated iris sphincter muscle. 2 In each preparation, two contractions to the muscarinic agonist carbachol were obtained. The maximum responses of the first contractions were taken as 100%. The second contractions to carbachol were elicited in the presence of either cytochalasin B (50 and 5 μm), an inhibitor of the actin cytoskeleton, or colchicine (100 μm), an inhibitor of the tubulin cytoskeleton (30 min incubation). 3 Cytochalasin B, at a concentration of 50 μm, significantly decreased the contractions induced by carbachol, with the maximum response reduced to 21.8 ± 6.6% (n = 12) of the initial maximum. The maximal contractions to carbachol in the presence of colchicine reached 96.2 ± 7.9% (n = 9) of the initial contraction, which was not significantly different from control second responses to carbachol with neither drug present, which reached 113.3 ± 7.6% (n = 7). 4 The effect of cytochalasin B was dose-dependent, since at a lower concentration of 5 μm, the drug decreased the maximum contraction to carbachol to 60.3 ± 8.8% (n = 6). The effect of cytochalasin B was at least partially reversible, since after the use of the higher concentration of 50 μm, contractions to carbachol increased to 62.3 ± 15.5% (n = 4) of the maximal response, after 1 h repeated washing of the preparations. 5 Cytochalasin D, at a concentration of 50 μm, completely abolished the contractions induced by carbachol (n = 4). 6 These findings suggest that in bovine iris sphincter muscle, contractions to carbachol are highly dependent, from a functional point of view, on actin polymerization, and not, to any important degree, on the polymerization of tubulin.

Notes: 1 The parasympathetic nervous system is responsible for maintaining normal bladder function, contracting the bladder smooth muscle (detrusor) and relaxing the bladder outlet during micturition. 2 Contraction of the bladder involves direct contraction via M3 receptors and an indirect ‘re-contraction’ via M2-receptors whereby a reduction in adenylate cyclase activity reverses the relaxation induced by β-adrenoceptor stimulation. 3 Muscarinic receptors are also located on the epithelial lining of the bladder (urothelium) where they induce the release of a diffusible factor responsible for inhibiting contraction of the underlying detrusor smooth muscle. The factor remains unidentified but is not nitric oxide, a cyclooxygenase product or adenosine triphosphate. 4 Finally, muscarinic receptors are also located prejunctionally in the bladder on cholinergic and adrenergic nerve terminals, where M1-receptors facilitate transmitter release and M2 or M4-receptors inhibit transmitter release. 5 In pathological states, changes may occur in these receptor systems resulting in bladder dysfunction. Muscarinic receptor antagonists are the main therapeutic agents available for treatment of the overactive bladder, but whether their therapeutic effect involves actions at all three locations (detrusor, prejunctional, urothelial) has yet to be established.

Notes: 1 In this study, we have investigated the vasodilator response to acetylcholine under diabetes conditions in isolated renal arteries of rabbits. We have also examined the contribution of endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) to the endothelium-dependent relaxation caused by acetylcholine in the renal arteries of alloxan-induced diabetic rabbits. 2 Acetylcholine (10−10−10−4 m) produced cumulative concentration–response curve in the renal arteries of both control and diabetic rabbits. The EC50 values and maximal responses to acetylcholine were not significantly different relative to diabetic conditions. In order to isolate the EDHF component of acetylcholine-induced vasodilator response, l-nitro-methyl arginine ester (l-NAME, 10−4 m) and indomethacin (10−6 m) were added to the Krebs' solution throughout the experiment. Under these conditions, acetylcholine induced vasodilatation in the isolated renal arteries from both control and diabetic rabbits. The vasodilator response to acetylcholine was not affected under diabetic conditions. 3 Sodium nitroprusside (SNP)-induced relaxation was increased in the diabetic rabbits compared with the control animals. 4 Tetrabutyl ammonium (TBA, 0.5 mm) produced a significant reduction in acetylcholine-induced vasodilatation in both preparations from control and diabetic animals, consistent with involvement of K+ channels in mediating this response. Glibenclamide (1 μm) attenuated acetylcholine-induced vasodilatation in preparations from control animals only, while iberiotoxin (0.05 μm) significantly reduced the vasodilator response to acetylcholine in preparations from both control and diabetic animals. 5 The role of EDNO in mediating acetylcholine-induced vasodilatation was examined. The vascular preparations were incubated with 20 mm K+-Krebs' solution to inhibit the EDHF contribution to acetylcholine-induced vasodilatation. Under this condition, acetylcholine induced a vasodilator response in both preparations from control and diabetic rats. Pretreatment with l-NAME (10−4 m) attenuated acetylcholine-induced vasodilatation in both preparations, indicating an nitric oxide-mediated vasodilator response. 6 Our results indicated that acetylcholine-induced vasodilatation in the isolated renal arteries of alloxan-induced diabetic rabbits was not affected under diabetic conditions. Acetylcholine-induced vasodilatation is mediated by two vasodilator components; namely, EDHF and EDNO. The contribution of EDHF and EDNO to acetylcholine-induced vasodilatation was not affected under diabetic conditions and there was no indication of endothelial dysfunction associated with diabetes. EDHF component was found to act mainly through high conductance Ca2+-activated K+ channels under normal and diabetic conditions, while the adenosine triphosphate-dependent K+ channels were involved in mediating acetylcholine vasodilator response in the control preparations only.

Notes: Summary 1 It was shown recently that stimulation of cardiac muscarinic M2-receptors revealed an enhanced negative inotropic response in isolated rat left atria after exposure to hypochlorite-induced oxidative stress. This phenomenon was not observed after stimulation of the cardiac A1-receptor, which like the M2-receptor is coupled to Gi-proteins. Since even the contractile response to M3-receptor stimulation was not amplified in the rat portal vein, we hypothesized a M2-receptor specificity of this hypochlorite-induced enhancement. 2 The present study was performed in order to investigate whether the sympathoinhibitory response to presynaptically located M2-receptor stimulation would also be modified after exposure to hypochlorite in the rat tail artery. We applied electrical field stimulation (EFS) in order to mimic sympathetic neurotransmission. 3 EFS increased the vascular tone frequency-dependently (0.3–4 Hz). EFS-induced vasoconstriction could be attenuated by acetylcholine (30 nm−1 μm) in a concentration-dependent manner. Hypochlorite (10 and 100 μm) did not affect the sympathoinhibitory effect of acetylcholine (100 nm). 4 In conclusion, in contrast to cardiac M2-receptors, hypochlorite did not amplify the sympathoinhibitory effects of presynaptic M2-receptors. The different responsiveness between neuronal and cardiac M2-receptors to hypochlorite may be explained by the different G-protein subunits involved in the activation of the underlying signalling cascade.

Notes: 1 The effects of intraperitoneal (i.p.) lipopolysaccharide on vascular reactivity to noradrenaline in rat aorta under different conditions of passive tension, as well as on mortality in normotensive and hypertensive rats, were studied. 2 Concentration–response curves to noradrenaline were obtained in aorta rings, at two levels of passive tension: 3 and 0.5 g, from control and lipopolysaccharide-treated Wistar rats. Contractile responses were expressed as percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a resting tension of 2 g. The maxima were significantly larger (P 〈 0.05) at 3 g than at 0.5 g in both groups of rats: 117.8 vs. 62.3%, respectively, for control animals; 85.8 vs. 32.5%, respectively, for lipopolysaccharide-treated rats. 3 The 24-h mortality after the i.p. administration of lipopolysaccharide was lower in spontaneously hypertensive rats (1/12; 8%), when compared with control Wistar–Kyoto rats (5/11; 45%). However, mortality was higher in Wistar–Kyoto made hypertensive by 8-day administration of corticosterone (6/6; 100%). 4 We conclude that a differential sensitivity to noradrenaline of aortic smooth muscle at two different levels of passive tension is still present in lipopolysaccharide-treated animals. Chronic hypertension in SHR rats is associated with resistance to the lethal effects of lipopolysaccharide, whereas abrupt-onset hypertension induced by corticosterone leads to an increased mortality. 5 These results are compatible with the myofibrillary hypothesis, which explains vascular hyper-reactivity in chronic arterial hypertension, by postulating that a more favourable relative position (and/or proportion) for actin and myosin occurs, whereas in states of vascular hypo-reactivity, such as vasodilatory shock, the opposite phenomenon may exist.

Notes: 1 The present study aimed to evaluate the role of κ-opioid receptors at two peripheral sites, the vas deferens and the proximal colon, in κ-opioid receptor knockout mice. We investigated the role of the κ-opioid receptor in the vas deferens twitch response and in the colonic ‘off-contraction’, a rebound contractile response which follows the inhibitory response to low frequencies stimulation (10, 20, 30 Hz) and which has been suggested to ‘locally’ reproduce the contractile component of the peristaltic reflex. 2 Transmural stimulation of the vas deferens at lower frequencies (10 Hz, 10 V, 1 ms pulse trains lasting 0.5 s) evoked a contractile response that was significantly higher in the preparations from knockout mice because of lack of κ-opioid receptors than in wild type mice. A selective κ-opioid receptor agonist, U-50,488H, induced a dose-dependent inhibition of the electrically stimulated contraction in vas deferens. The percentages of reduction of the twitch response were significantly lower in knockout mice than in wild type mice after treatment with U-50,488H. The reduction of twitch response caused by U-50,488H was not reversed by administration of nor-binaltorphimine (nor-BNI) (5 × 10−6 m), a selective κ-opioid receptor antagonist, in preparations from both knockout mice and wild type mice. U-50,488H has no effect on postsynaptic adrenergic receptors, as its administration did not affect the direct contractile response to noradrenaline. 3 Transmural stimulation (5 Hz, 20 V, 2 ms pulse trains lasting 30 s) induced inhibition of spontaneous activity of colonic strips during the period of stimulation, followed by an ‘off-contraction’ after the cessation of stimulation. The statistical evaluation of the ‘off-contraction’ responses between the two strains showed no significant difference. The off-contraction, measured in specimens from knockout mice, was inhibited concentration-dependently by U-50,488H (P 〈 0.01) and significantly less than from wild type mice. 4 The effect of U-50,488H was not reversed by administration of nor-BNI (5 × 10−6 m), either in preparations from knockout mice or from wild type mice. 5 Our data may suggest that κ-opioid receptors are involved in some peripheral responses to the nerve stimulation, as indicated by the effect of U-50,488H, a selective κ-opioid receptor agonist. However, the involvement of κ-opioid receptor was also present, although less apparent, in κ -opioid receptor knockout mice, suggesting either that this drug acts not only on κ-opioid receptors but also on other receptor sites, such as κ-like receptors. An alternative interpretation can be related to a sodium channel blocking action of U-50,488H, which could explain the inhibitory effects of twitch response still present but less evident in knockout strain and the lack of effect of the antagonist nor-BNI.

Notes: 1 The effects of neuropeptide Y (NPY) upon the isolated vasculature are reviewed. 2 The vasconstrictor responses to periarterial nerve stimulation (PNS) and neurotransmission by noradrenaline (NA) and ATP are discussed and illustrated using canine isolated perfused splenic artery. 3 Modulation of the vascular responses to PNS by NPY via pre- and post-junctional NPY Y2 and Y1 receptors is discussed. 4 Evidence is presented for different α1-adrenoceptor subtypes mediating vasoconstriction to exogenous and endogenously released NA and their different locations in the neurovascular junction and extrajunctional regions. 5 Activation of NPY Y1-receptors potentiates sympathetic nerve activated α1-adrenoceptor vasoconstriction. The proposal that the postjunctional α1B adrenoceptor may be linked to the NPY Y1-receptor and is responsible for co-operation between sympathetic and NPYergic interactions in the vasculature is discussed.

Notes: Summary 1 GABAB1 receptor subunit knockout mice were generated and the effects of the GABAB receptor agonist, baclofen, were evaluated within the peripheral nervous system (PNS) of wildtype (+/+), heterozygote (+/–) and knockout (–/–) animals. For this purpose, neuronally-mediated responses were evoked in both the isolated ileum and urinary bladder, using selective electrical field stimulation (EFS). 2 In ileum resected from 4–8-week-old-mice, low frequencies of EFS (0.5 Hz) evoked irregular muscle contractions which were prevented by atropine 1 μM and reduced by baclofen (33.4 ± 5.6%, 100 μm). The latter effect was antagonized by the GABAB receptor antagonist CGP54626 0.2 μm. Baclofen 100 μm did not affect contractions of similar amplitude induced by carbachol, indicating that the ability of baclofen to inhibit cholinergic function in mouse ileum may be due to an action at prejunctional GABAB receptors. 3 To avoid the development of grand mal seizure by GABAB1 (–/–) mice, a behaviour observed when the mice were greater than 3 weeks old, it was necessary to study the effects of this knockout in 1–3-week-old-animals. However, at this age, EFS at 0.5 Hz did not evoke robust muscle contractions. Consequently we used EFS at 5 Hz, which did evoke cholinergically mediated contractions, found to be of similar amplitude in (+/+) and (+/–) mice, of both 1–3 weeks and 4–8 weeks of age. At this frequency of EFS, baclofen reduced the amplitude of the evoked contractions [n=6 (+/+) and n=5 (+/–), IC50 19.2 ± 4.8 μm) and this effect was greatly reduced in the presence of CGP54626 0.2 μm. 4 In urinary bladder from 1–3-week-old-mice, using higher frequencies of EFS to evoke clear, nerve-mediated contractions (10 Hz), baclofen 10–300 μm concentration-dependently inhibited contractions in (+/+) mice (IC50 9.6 ± 3.8 μm). This effect was inhibited by CGP54626 (0.2 μm, 46.2 ± 13.6% inhibition, 300 μm baclofen n=7) a concentration which, by itself, had no effect on the EFS-evoked contractions. 5 The effects of baclofen in both ileum and urinary bladder were absent in the GABAB1 receptor subunit (–/–) mice; however, responses to EFS were unaffected in (–/–) when compared to the (+/+) mice. 6 Our data suggest that, as in the central nervous system (CNS), the GABAB1 receptor subunit is an essential requirement for GABAB receptor function in the enteric and PNS. As such, these data do not provide a structural explanation for the existence of putative subtypes of GABAB receptor, suggested by studies such as those in which different rank-orders of GABAB agonist affinity have been reported in different tissues.

Notes: 1 Type 2 diabetes is associated with diverse oral pathologies in which salivary flow reduction is one of the causes of these oral abnormalities. Scarce literature exists regarding noradrenergic transmission and adrenergic-induced salivary flow in submaxillary and parotid glands of type 2 diabetic rats. 2 We studied noradrenergic transmission as well as the secretory response to α1- and β-adrenoceptor stimulation in the parotid and submaxillary glands of type 2 diabetic rats. 3 Diabetic rats exhibited diminished neuronal uptake, release and endogenous content of noradrenaline (NE) in both salivary glands. Further, NE synthesis was also diminished accompanied by decreased tyrosine hydroxylase activity. Salivary flow responses to α1-(methoxamine) and β-(isoprenaline) adrenoceptor stimulation were reduced in the submaxillary as well as the parotid glands of diabetic rats. 4 Our results suggest that the reduction of noradrenergic transmission in the salivary glands of type 2 diabetic rats is in part responsible for the diminished salivary flow evoked by α1- and β-adrenergic stimulation. Reduced noradrenergic activity may contribute to the pathophysiology of oral abnormalities in diabetic patients.

Notes: 1 We investigated the effects of exogenously applied steroids and endogenously released cortisol on catecholamine (CA) secretion induced by cholinergic agonists in perfused guinea-pig adrenal glands. 2 Acetylcholine (ACh) and electrical stimulation induced CA secretion, which was reversibly inhibited by cortisol. Adrenocorticotropic hormone (ACTH) increased the concentration of cortisol in the perfusion effluent and partly inhibited the secretory response to ACh. 3 Cortisol or aldosterone dose-dependently inhibited secretory responses to nicotine and muscarine. These inhibitory effects were not antagonized by mifepristone and spironolactone, respective cortisol and aldosterone receptor blockers. 4 Dexamethasone, cortisone, corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, prednisolone and cholesterol inhibited nicotine-evoked CA secretion. The secretory response to muscarine was inhibited by these compounds except for dexamethasone and prednisolone. 5 Dexamethasone, cortisol and aldosterone had no effect on CA secretion induced by high KCl. 6 These results suggest that steroids affect nicotinic and muscarinic ACh receptor-mediated responses through distinct mechanisms, and that cortisol released from the adrenal cortex inhibits CA secretion from the adrenal medulla.

Notes: 1 The aim of this study was to characterize the adenosine receptor mediating vasodilation in the microvasculature of the hamster cheek pouch in vivo. A range of adenosine agonists was used including N6-cyclopentyladenosine (CPA) (A1 agonist), 5′-N-ethylcarboxamidoadenosine (NECA) (non-selective), 2-chloroadenosine (2CADO) (non-selective), 2-p-(2-carboxyethyl)-phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS 21680) (A2A agonist), N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IBMECA) (A3 agonist) and adenosine, as well as the adenosine antagonists 8-sulphophenyltheophylline (8-SPT) (A1/A2 antagonist), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (A1 antagonist) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) (A2A antagonist). 2 All the adenosine analogues used induced vasodilation at concentrations between 10 nm and 1 μm, and the potency order was NECA 〉 CGS 21680 〉 2CADO 〉 CPA=IBMECA 〉〉 adenosine, indicating an action at A2A receptors. 8-SPT (50 μm) antagonized vasodilator responses to NECA with an apparent pKB of 5.4, consistent with an action at A1 or A2 receptors and confirming that A3 receptors are not involved in this response. 3 DPCPX (10 nm) had no effect on vasodilation evoked by NECA, suggesting that this response was not mediated via A1 receptors, while ZM 241385 (10 nm) antagonized dilator responses to NECA with an apparent pKB of 8.9 consistent with an action via A2A receptors. 4 Overall these results suggest that adenosine A2A receptors mediate vasodilation in the hamster cheek pouch in vivo.

Notes: 1 The hypothesis that the non-adrenergic, non-cholinergic excitatory (NANC-e) innervation is involved in the induction of asthma and that antagonists of NANC-e neurotransmitter could reduce bronchoconstriction during asthma was tested. 2 The first objective was to identify the neurotransmitter(s) of NANC-e innervation from a group of selected putative neurotransmitters. The second objective was to use the antagonist of the identified neurotransmitter(s) to determine its effectiveness against bronchoconstriction to ovalbumin (OVA) in sensitized guinea-pigs. 3 Neurotransmitter identification was performed using the ‘tracheal pouch’, a surgical preparation established for demonstrating NANC innervation, in anaesthetized guinea-pig airways. A segment of trachea was cannulated and clamped at one end and the other end was connected to a pressure transducer. The stump of the trachea was connected to a ventilator to keep the blood gas values within the normal range. The vagus nerve and the sympathetic nerves were isolated bilaterally and cut. The left carotid artery was cannulated to monitor blood pressure and for sampling blood for blood gas analysis. The jugular vein was cannulated for administration of test agents. 4 Both NANC-e and NANC-i (inhibitory) control responses of airways were obtained by bilateral vagal stimulation after complete autonomic blockade with atropine, propranolol and prazosin. The relaxation of the tracheal pouch was indicative of the NANC-i response and the increase in insufflation pressure of the ventilated peripheral airways was due to NANC-e stimulation. 5 The involvement of the putative neurotransmitters such as neurokinin-A (NK-A), histamine, serotonin and endothelin (ET) was investigated by using the respective antagonists, MEN-10376, pyrilamine maleate, cyproheptadine hydrochloride, and two ET receptor antagonists (BQ-123 and IRL-1038), respectively. The antagonists were administered at the dose rate of 4 mg kg−1 i.v. which was determined from preliminary studies by testing against the respective agonists. 6 MEN-10376 (neurokinin-2 receptor antagonist) significantly inhibited the insufflation pressure (peripheral airway pressure) increase caused by NANC-e stimulation. MEN-10376 also inhibited the fall in blood pressure caused by bilateral vagal stimulation. The 5-HT antagonist, cyproheptadine, significantly enhanced the NANC-e response. 7 After identifying the NANC-e neurotransmitter as NK-A, the effectiveness of its antagonist, MEN-10376, was evaluated for its ability to attenuate the increase in insufflation pressure (bronchoconstriction) induced in guinea-pigs sensitized by OVA. Guinea-pigs were sensitized to OVA (200 mg i.p.) and 10 days later prepared for the determination of tracheal pouch and insufflation responses to 100 μg of OVA administered i.v. (challenge dose). This caused an increase in insufflation pressure in the presence of adrenergic and cholinergic blockade, which was significantly attenuated by MEN-10376. 8 These studies indicated that neurokinin-2 receptors were involved in the vagally mediated efferent neurotransmission of NANC-e and that NANC-e plays a role in allergen-induced bronchoconstriction.

Notes: 1 The effect of WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), a 5-HT1A receptor antagonist, on cardiovascular function was studied. 2 The i.v. injection of WAY100635 dose-dependently decreased blood pressure in anaesthetized rats; while in pithed rats WAY100635 (1 mg  kg−1) displaced the phenylephrine pressor effect. 3 WAY100635 antagonized phenylephrine-induced contraction in rabbit and rat aorta (pA2 of 6.88 and 7.93 and Schild slopes of −0.83 and −1.21, respectively); while in rat caudal artery pKB was 7.45 and the Schild slope of −0.56, suggesting a complex interaction in this vessel. 4 The results show that WAY100635 induced hypotension in the anaesthetized rat and suggest that this effect could be partially explained by antagonism of vascular α1-adrenoceptors.

Notes: 1 Purinergic transmission from sympathetic nerves in the guinea-pig vas deferens was monitored using intracellular recording techniques. Stimulation of the hypogastric nerve with trains of 15 pulses at 1 Hz evoked excitatory junction potentials (EJPs) which increased in amplitude from the first pulse and reached a maximum after 6–8 pulses. 2 Caffeine (3 and 10 mm), depolarized cells by 5–10 mV and increased the amplitude of the first few EJPs in each train but reduced the maximum amplitude of EJPs late in the train. 3 The adenosine receptor antagonist 8-p-sulphophenyl-theophylline (8-SPT; 30 μm) had no effect on either the resting membrane potential or the EJP amplitude; however, at 100 μm it reduced the amplitude of all EJPs by 5–10%. 4 Adenosine (10 and 30 μm) reduced the amplitude of EJPs in a concentration-dependent manner. The inhibitory effect of adenosine on EJP amplitude was prevented by pretreatment with either caffeine (3 mm) or 8-SPT (30 μm). 5 Ryanodine (30 μm) did not alter EJP amplitude and did not inhibit the enhancement of the first EJP by caffeine (3 mm). Incubation of the tissue with the cell permeable calcium chelator 1-2-bis(o-aminophenoxy)ethane-N,N-N′,N′-tetraacetic acid (BAPT-AM) resulted in a depression of EJP amplitude and a longer time to reach maximum amplitude. In cells that had been exposed to BAPT-AM, caffeine 3 mm still increased amplitude of EJP early in the train. 6 The phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX; 500 μm), hyperpolarized cells and increased the amplitude of EJP throughout the train of stimulation. In the presence of IBMX, caffeine 3 mm still depolarized the cells and enhanced the EJP early in the train of stimulation. 7 The findings in this study confirm that caffeine and 8-SPT are effective inhibitors of the actions of adenosine. However, caffeine has an additional action to enhance EJP early during a train of stimulation, which cannot be attributed to blockade of adenosine receptors, but which may be related to inhibition of phosphodiesterase.

Notes: 1 The β3-adrenoceptor agonist ZD 7114, like the non-selective β-adrenoceptor agonist isoprenaline, but unlike the β1-adrenoceptor agonist dobutamine and the β2-adrenoceptor agonist salbutamol, produced an increment on mouse embryonic fibroblast proliferation. The half-maximal stimulation of cell growth occurred at substantially lower concentrations with the β3-adrenoceptor agonist (EC50: 5.5 × 10−8 m) than with isoprenaline (EC50: 1.25 × 10−6 m). 2 The selective β3-adrenoceptor antagonist SR 5923 OA prevented the β3-stimulated fibroblast proliferation. Conversely, practolol and butoxamine did not prevent fibroblast growth. 3 Additionally, a decrease of cAMP was obtained in fibroblasts cells upon stimulation with isoprenaline and ZD 7114. 4 The expression of β-adrenoreceptors on fibroblast cells was also studied by radioligand binding. The Ki values in the presence of β1- and β2-adrenoceptor antagonist was two-fold higher than the Ki values for β3 adrenoceptor antagonist indicating the presence of A3-receptor subtype. 5 Inhibitors of different intracellular coupling pathways including phospholipase C (U 73122), protein kinase C (staurosporine), calcium/calmodulin (trifluoroperazine) and calcium channel (verapamil), prevented the stimulatory actions of the selective β3-adrenoceptor agonist ZD 7114. 6 The presence of β3-adrenoceptors on embryonic mouse fibroblast cells may play a role in the modulation of cell growth and biologic activity. The mechanism by which ZD 7114 triggers cell proliferation and function, involves the activation of phospholipase C, PKC, calcium/calmodulin and the influx of calcium.

Notes: 1 Cytokines may parallel or regulate the beneficial effects of β-adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in β-blocker-treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional β1-blocker metoprolol (CHFmet). Interleukin-(IL)-1α, IL-1β, IL-1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF), soluble TNF receptor type 1 (sTNF-R1), sTNF-R2, and sCD14 were measured by ELISA. 3 IL-1α and IL-1β were not detectable in any of the tested groups. IL-2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL-1ra, IL-6, IL-8, IL-10, sTNF-R1 and sTNF-R2. In CHFmet patients IL-1ra, IL-6 and IL-8 remained at the same level. In contrast, sTNF-R1 levels were significantly reduced, although not to control, whereas the sTNF-R2 and IL-10 were reduced to control levels. 4 The cAMP levels of mononuclear cells – recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]– correlated inversely with the sTNF-R2 data (Pearson, r=−0.46; P=0.041; Spearman, r=−0.64, P=0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF-R2 and cAMP may provide a tool useful during investigation of β-blocker therapy.

Notes: 1 The effects of BIIE 0246, a novel and non-peptide neuropeptide Y (NPY) Y2 receptor antagonist on sympathetic vasoconstriction of the canine splenic artery were investigated. 2 The vasoconstrictor response to periarterial electrical nerve stimulation was described to be a double peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor-mediated constriction followed by a prolonged, mainly α1 adrenoceptor-induced response. 3 BIIE 0246 at a concentration of 0.1–1 μm dose-dependently potentiated double peaked constrictions at low frequencies (1 and 4 Hz), whereas at high frequency (10 Hz), it failed to affect these responses. BIIE 0246 (1 μm) also enhanced double peaked responses even in the presence of rauwolscine (0.1 μm). NPY (13–36) (1–100 nm), a selective Y2 receptor agonist reduced these two peaked responses in a dose-related manner. The vasoconstriction to noradrenaline (0.1–10 nmol) or adenosine triphosphate (0.01–1 μmol) was not significantly influenced by either 1 μm BIIE 0246 or 100 nm NPY (13–36). Exposure of tissues to 1 μm BIIE 0246 almost completely prevented the suppression of double peaked constrictions by NPY (13–36) (10 nm) or by NPY (10 nm). 4 We conclude that NPY inhibits sympathetic purinergic and adrenergic vasoconstrictions through an activation of prejunctional Y2 receptor subtype in the neurovascular junction of the canine splenic artery.

Notes: Summary 1 The agonistic and antagonistic effects of labetalol, the α1- and β-adrenoceptor antagonist, were studied on β3-adrenoceptors in the guinea-pig gastric fundus. 2 Labetalol caused a concentration-dependent relaxation with a pD2 value of 5.58 ± 0.09 and an intrinsic activity of 0.64 ± 0.06, which was not affected by pretreatment with both the selective β1-adrenoceptor antagonist, (±)-atenolol (100 μM), and the selective β2-adrenoceptor antagonist, (±)-butoxamine (100 μM). 3 However, the non-selective β1-, β2- and β3-adrenoceptor antagonist, (±)-bupranolol (3–30 μM), shifted the concentration–response curve of labetalol to the right (pA2 value=5.97 ± 0.08). 4 In the presence of (±)-atenolol (100 μM) and (±)-butoxamine (100 μM), relaxations to catecholamines [(−)-isoprenaline, (−)-noradrenaline and (−)-adrenaline], to the selective β3-adrenoceptor agonist, BRL37344, and to the non-conventional partial β3-adrenoceptor agonist, (±)-CGP12177A, were weakly antagonized by labetalol (10 μM). 5 These results indicate that labetalol, the arylethanolamine, acts as a partial agonist on β3-adrenoceptors in the guinea-pig gastric fundus.

Notes: 1 This study examined the potentiating effects of competitive antagonists of the adrenergic alpha2 receptors and of phenoxybenzamine (POB) an irreversible antagonist, on the stimulation-induced efflux of [3H]-noradrenaline in arterial tissue of rabbit. This was done to determine if the lack of concordance of efflux potentiation by antagonists with the expectations of presynaptic negative feedback theory can be attributed to increasingly successful competition from rising perineuronal transmitter concentrations, when stimulation parameters are increased, in the presence of a fixed concentration of competitive antagonist. 2 Tissues were stimulated with a fixed pulse number and frequency, to rule out confounding factors, and major alterations in the concentration of released transmitter were achieved through variations in the pulse duration. 3 Rauwolscine potentiated transmitter release less at the longest, rather than at the shortest pulse duration, and showed a potentiation of release that was indifferent to the quantities of released transmitter. This was also seen with POB although it binds covalently to the presynaptic receptor. 4 Noradrenaline inhibited stimulation-induced transmitter release confirming the presence of presynaptic alpha inhibitory sites. 5 Yohimbine potentiated transmitter release the same as did rauwolscine and POB, and protected the relevant sites against POB potentiation, confirming site identity. The combination of POB and rauwolscine had no greater effect than did either alone certifying that they acted similarly and that maximally effective concentrations of each were used. 6 Consequently, noradrenaline breakthrough of presynaptic receptor blockade does not explain the non-conforming observations made with competitive antagonists in tests of presynaptic theory.

Notes: 1 The present study attempted to pharmacologically characterize the subtypes of α-adrenoceptors mediating the vasoconstriction in the isolated and perfused canine vesical artery. 2 Noradrenaline (NA) and phenylephrine (PE, an α1-adrenoceptor agonist) induced a dose-dependent vasoconstriction, whereas xylazine (an α2-agonist) did not induce any clear vascular constrictor response. 3 Prazosin at 0.01 μm and rauwolscine at 0.1 μm failed to affect the NA-induced vasoconstriction. Prazosin at 0.1 μm antagonized the vasoconstrictor responses to NA, with pKB value of 7.8. 4 WB 4101 at 0.01–0.1 μm dose-dependently inhibited the responses to NA, with a pKB value of 8.9. The vasoconstrictor responses to NA were not significantly affected by chloroethylclonidine (10–30 μm) or BMY 7378 (0.1 μm). 5 The present results indicate that the canine vesical arteries dominantly contain α1-adrenoceptors but have no α2-adrenoceptors, and the functional subtype of α1-adrenoceptor is characterized as an α1A-adrenoceptor subtype.

Notes: 1 The aim of this study was to examine whether sodium nitroprusside (SNP)-induced relaxation of rat fundus longitudinal smooth muscle involves ryanodine-sensitive Ca2+ release. 2 SNP (300 nm–30 μm) elicited concentration-dependent relaxation of precontracted (1 μm carbachol) rat fundus, an effect almost abolished by the selective guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 μm). 3 SNP-mediated relaxations were almost abolished by 10 μm ryanodine. 4 SNP-mediated relaxations were also reduced by either 1 μm apamin (a selective small conductance Ca2+-sensitive K+ channel, SKCa, inhibitor) or the selective L-type Ca2+ channel inhibitor, nicardipine (3 μm). 5 SNP-induced relaxations were insensitive to 1 mm tetraethylammonium chloride (an inhibitor of large-conductance Ca2+-sensitive K+ channels) and 1 μm glibenclamide (an ATP-sensitive K+ channel inhibitor). 6 These data suggest that SNP-mediated fundus relaxation occurs via a cGMP-mediated and ryanodine-sensitive mechanism which requires, at least in part, SKCa and L-type Ca2+ channel activity.

Notes: 1 The aim of this work was to investigate the effect of acute and chronic exposure of rat pheochromocytoma (PC12) cells to elevated cAMP, using forskolin, dibutyryl-cAMP (db-cAMP) or isobutylmethylxanthine (IBMX), on endogenous dopamine content and release and on [3H]-1-methyl-4-phenylpyridinium ([3H]-MPP+) uptake and release, under basal conditions and under KCl-stimulation. 2 Cultured PC12 cells synthetized and accumulated large amounts of dopamine, but not noradrenaline or adrenaline. The release of dopamine by the cells was markedly increased in response to 50 mm KCl. 3 Acute and chronic treatment of the cells with forskolin (30 μm), but not IBMX (100 μm), slightly increased the spontaneous release of dopamine and significantly decreased the release induced by 50 mm KCl. 4 Chronic treatment of the cells with forskolin (30 μm), but not IBMX (100 μm), markedly decreased the cellular content of dopamine. 5 Cultured PC12 cells removed and accumulated [3H]-MPP+, which, similarly to dopamine, was released by KCl. 6 Acute treatment of the cells with forskolin (30 μm) or db-cAMP (2.5 mm), but not IBMX (100 μm), slightly increased the spontaneous release, but did not affect KCl-induced release of [3H]-MPP+. On the other hand, chronic treatment of the cells with forskolin produced, on [3H]-MPP+, similar effects to those obtained for dopamine. 7 Acute and chronic treatment of the cells with reserpine (50 nm) produced similar results to those obtained with forskolin on either dopamine or [3H]-MPP+ handling. 8 In conclusion, cAMP, similarly to reserpine, increases the spontaneous release and decreases the KCl-induced release of [3H]-MPP+ and dopamine. This suggests that cAMP impairs the vesicular monoamine transporter.

Notes: 1 The aim of this study was to determine if stimulation of duodenal motility by duodenal fluid distension or by administration of carbachol, activates the sphincter of Oddi-duodenal reflex, in an in vitro preparation from the Australian possum. 2 Duodenal distension was achieved by infusion of Krebs solution (0–8 cm H2O). In separate experiments, the sphincter of Oddi (SO) was partitioned from the duodenum and carbachol (10−7−5 × 10−6 m) added to the duodenal compartment. 3 Fluid distension increased duodenal motility to 120–600% of control activity. These treatments induced increased SO motility (to 120–390% of control) in six preparations, reduced activity (to 60% of control) in one and no response in another. 4 Addition of carbachol to the duodenal compartment resulted in increased duodenal motility. SO motility was increased in seven preparations, reduced in another two and no response were evoked in two others. All SO responses were blocked by tetrodotoxin pretreatment. 5 These data suggest that the SO receives inputs from duodenal mechano and/or stretch receptors resulting in excitatory or inhibitory responses, with the excitatory response dominating. These findings support the role for the SO-duodenal reflex in preventing duodeno-biliary/pancreatic reflux during periods of elevated duodenal activity.

Notes: 1 It has been suggested that opioids may play an indirect role in the regulation of the peripheral circulation through the control of nitric oxide (NO) release in vascular tissue. The current study was undertaken to investigate the effect of nitric oxide synthase (NOS) blockade on responses to morphine in phenylephrine (PE)- or KCl-precontracted rat aortic rings. 2 Morphine (3 × 10−8−3 × 10−5 m) administration did not cause any significant effect on basal tonus of endothelium-intact or endothelium-denuded preparations. Morphine produced concentration-dependent relaxation responses in endothelium-intact as well as in endothelium-denuded rat aortic rings precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. 3 The relaxant responses to morphine were significantly and partially inhibited by pretreatment of tissues with naloxone (NAL, 3 × 10−5 m) for 5 min. The inhibitory effect of NAL on relaxant responses to morphine in PE- or KCl-precontracted rings did not differ significantly between endothelium-intact and endothelium-denuded preparations. 4 Incubation of endothelium-intact or endothelium-denuded rat aortic rings with NOS inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME, 10−4 m) for 20 min did not cause a significant inhibition on relaxation responses to morphine. 5 These findings confirmed the presence of opiate receptors in rat thoracic aorta, but suggested that mechanisms other than NO release play a role in the relaxant effect of morphine on rat aortic rings.

Notes: Summary 1 Bradykinin (BK) is a nine amino acid peptide (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) formed from the plasma precursor kininogen during inflammation and tissue injury. The actions of BK are mediated by G protein-coupled cell surface receptors, designated B1 and B2. 2 BK has a plethora of effects in the airways including bronchoconstriction, bronchodilation, stimulation of cholinergic and sensory nerves, mucus secretion, cough and oedema resulting from promotion of microvascular leakage. These airway effects are mediated in the main by the B2 receptor subtype. 3 BK acts mainly indirectly, primarily through airway nerve activation, but also by the release of prostanoids, thromboxanes and nitric oxide (NO). 4 Airway responses to BK have been studied in detail in guinea-pigs, mice, sheep and rats. This review describes the effects of BK in these species and draws comparison with its effects in normal humans and patients with respiratory diseases. 5 Despite its many and varied effects in the airways of animals and man, the exact contribution of BK to airways disease remains unclear.

Notes: 1 The purpose of this study was to demonstrate that the adrenergic nervous system regulates the in vivo choline levels in the mouse major salivary glands. 2 Methoxamine (α1-adrenoceptor agonist, 2.5–20 mg kg−1, s.c.) elevated choline levels dose-dependently and the effect of methoxamine (10 mg kg−1) was completely inhibited by the α-adrenoceptor antagonist phentolamine (5 mg kg−1, i.p.) but not by the β-adrenoceptor antagonist propranolol (3 mg kg−1, i.p.). 3 In contrast, isoprenaline (β-adrenoceptor agonist 0.25–20 mg kg−1, s.c.) lowered choline levels and the effect of isoprenaline (2 mg kg−1) was inhibited by propranolol, but not by phentolamine. 4 Noradrenaline (1–4 mg kg−1, s.c.) manifested both the α- and β-adrenergic actions depending on its dose. Noradrenaline at 1–2 mg kg−1, lowered choline levels and the effect of noradrenaline (1 mg kg−1) was inhibited by propranolol, but not by phentolamine. On the other hand, noradrenaline (4 mg kg−1) elevated choline levels and the effect was blocked by phentolamine, but not by propranolol. 5 Tyramine (5–80 mg kg−1, s.c.) elicited the release of noradrenaline from sympathetic nerve terminals and induced essentially the same effects on the choline levels as noradrenaline. Tyramine (10 mg kg−1) lowered choline levels and the effect was inhibited by propranolol, but not by phentolamine. However, tyramine (80 mg kg−1) elevated choline levels and the effect was inhibited by phentolamine, but not by propranolol. 6 These results suggest that choline levels in the salivary glands may be under separate α- and β-adrenergic control and suggest a possibility that the neurotransmitter noradrenaline released for sympathetic nerve terminals can manage the dual control of choline levels in some autonomic organs in a characteristic dose-dependent manner.

Notes: 1 The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia–reperfusion injury to the liver using a rat model. 2 Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte–endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3 Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4 A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5 We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.

Notes: The usefulness of ‘user centred design’ as a concept in the design of software systems is considered. It is concluded that the concept is frequently used in a way so vacuous as to be devoid of meaning, and would be better discarded. Some suggestions are made for further research in this area; some modest suggestions are also offered to those who wish to develop systems of a type better suited to the needs of civilized society.

Notes: Increasing evidence over the past decade indicates that financial markets exhibit nonlinear dynamics in the form of chaotic behavior. Traditionally, the prediction of stock markets has relied on statistical methods including multivariate statistical methods, autoregressive integrated moving average models and autoregressive conditional heteroskedasticity models. In recent years, neural networks and other knowledge techniques have been applied extensively to the task of predicting financial variables.This paper examines the relationship between chaotic models and learning techniques. In particular, chaotic analysis indicates the upper limits of predictability for a time series. The learning techniques involve neural networks and case–based reasoning. The chaotic models take the form of R/S analysis to measure persistence in a time series, the correlation dimension to encapsulate system complexity, and Lyapunov exponents to indicate predictive horizons. The concepts are illustrated in the context of a major emerging market, namely the Polish stock market.

Notes: This paper concerns the study of destination choice modelling, more specifically identifying within some area (e.g. a city) the region where a particular store is the most favourable to be visited by individuals. An influence measure is constructed for each individual, which incorporates the modern technique known as Dempster–Shafer theory. Based on the evidence of the shopping destinations of individuals, geographical regions are found for levels of largest belief and plausibility (within Dempster–Shafer theory) for specific stores being the most favourable to visit. Additionally, this method may be used to identify the possible position of new stores, based on regions of most uncertainty or conflict in store choice. A prototype choice modelling system is introduced to enable the series of associated results to be easily visualized and analysed.

Notes: Fuzzy logic principles and neural networks, both being computational intelligence technologies, can be combined to produce synergetic effects through the formation of a unified approach which takes advantage of the benefits and at the same time counterbalances the flaws of the two technologies. In this paper, a fuzzy neural approach, which is characterized by its ability to suggest the appropriate adjustment of product quantity from various suppliers with different quality standards in a supply chain network, is presented. This approach is particularly useful in situations where multiple supply chain partners are involved to achieve the common objective of producing products to the best satisfaction of customer demands at the lowest possible cost. To validate the feasibility of this approach, a test has been conducted based on the proposed fuzzy neural approach with the objective of suggesting the appropriate selection of suppliers and the optimal quantity allocated to them to meet the required quality standards. This paper describes the methodology for the deployment of this proposed hybrid approach to enhance the machine intelligence of a supply chain network with the description of a case study to exemplify its underlying principles.

Notes: The paper investigates the impact of trust on market efficiency and bilateral contracts. We prove that a market in which agents are trusted to the degree they deserve to be trusted is as efficient as a market with complete trustworthiness. In other words, complete trustworthiness is not a necessary condition for market efficiency. We prove that distrust could significantly reduce market efficiency, and we show how to solve the problem by using appropriately designed multiagent contracts. The problem of trust is studied in the context of a bilateral negotiation game between a buyer and a seller. It is shown that if the seller’s trust equals the buyer’s trustworthiness, then the social welfare, the amount of trade, and the agents’ utility functions are maximized. The paper also studies the efficiency of advance payment contracts as a tool for improving trustworthiness. It is proved that advance payment contracts maximize the social welfare and the amount of trade. Finally, the paper studies the problem of how to make agents truthfully reveal their level of trustworthiness. An incentive–compatible contract is defined, in which agents do not benefit from lying about their trustworthiness. The analysis and the solutions proposed in this paper could help agent designers avoid many market failures and produce efficient interaction mechanisms.

Notes: This paper uses the notion of control from programming languages to look at the organization of mental code. Data for the analysis comes principally from language breakdown. The paper first outlines the well known distinction between logic and control in algorithms and argues that the same distinction holds in mental code. Discussion then focuses mainly on control—the management of data flow—and shows that a variety of language disorders affect either the logic component of the mental algorithms for language (e.g., Specific Language Impairment) or the control component (e.g., Williams syndrome and Turner syndrome). A comparative study of the loss of morphology in Williams syndrome and Specific Language Impairment reinforces the logic/control split as an accurate guide to the explanation of linguistic behavior in these disorders. The data, moreover, are not accountable to sheer performance factors, but to the way the disorders disrupt the structure of mental algorithms. The paper closes with a discussion of how control and the management of cross-domain computation fit into recent theories of modular mental architecture and proposals about the explicitness of representations and their availability to working memory.

Notes: Expert systems constitute a branch of artificial intelligence, and their unique characteristics enable computer systems to perform at the level of a human expert by the use of algorithms that can capture domain-specific knowledge. Through an extensive survey of research about ship-design expert systems, we conclude that although development and implementation of expert systems for ship design offer substantial barriers, the shipbuilding industry needs them nonetheless. We examine the major reasons that use of expert systems in this industry has lagged behind. These include the problems of integration with existing computer-aided design systems, problems of knowledge representation and sizable development costs. We discuss in detail some key factors that can lead to the solution of these problems.

Notes: A methodology based on case-based reasoning is proposed to build a topological-level influence diagram. It is then applied to a project proposal review process. The formulation of decision problems requires much time and effort, and the resulting model, such as an influence diagram, is applicable only to one specific problem. However, some prior knowledge from the experience in modeling influence diagrams can be utilized to resolve other similar decision problems. The basic idea of case-based reasoning is that humans reuse the problem-solving experience to solve new problems.In this paper, we suggest case-based decision class analysis (CB-DCA), a methodology based on case-based reasoning, to build an influence diagram. CB-DCA is composed of a case retrieval procedure and an adaptation procedure. Two measures are suggested for the retrieval procedure, one a fitting ratio and the other a garbage ratio. The adaptation procedure is based on decision-analytic knowledge and decision participants' domain-specific knowledge. Our proposed methodology has been applied to an environmental review process in which decision-makers need decision models to decide whether a project proposal is accepted or not. Experimental results show that our methodology for decision class analysis provides decision-makers with robust knowledge-based support.

Notes: We report on work concerning the use of object-oriented analysis and design (OAD) methods in the development of artificial intelligence (AI) software applications, in which we compare such techniques to software development methods more commonly used in AI, in particular CommonKADS. As a contribution to clarifying the role of OAD methods in AI, in this paper we compare the analysis models of the object-oriented methods and the CommonKADS high-level expertise model. In particular, we study the correspondences between generic tasks, methods and ontologies in methodologies such as CommonKADS and analysis patterns in object-oriented analysis. Our aim in carrying out this study is to explore to what extent, in areas of AI where the object-oriented paradigm may be the most adequate way of conceiving applications, an analysis level ‘pattern language’ could play the role of the libraries of generic knowledge models in the more commonly used AI software development methods. As a case study we use the decision task — its importance arising from its status as the basic task of the intelligent agent — and the associated heuristic multi-attribute decision method, for which we derive a corresponding decision pattern described in the unified modelling language, a de facto standard in OAD.

Notes: Maintenance issues comprise an important, though frequently overlooked, area of manufacturing operations. In smaller companies in particular, expertise for effective maintenance project planning may be lacking. In this paper we discuss the development of an object-oriented expert system to support such project planning. The system was developed to meet the needs of an automotive components manufacturer, and focuses solely on its material-handling-oriented projects. The microcomputer-based expert system considers issues of schedule, inventory availability and cost.

Notes: This paper describes the development and implementation of a real-time knowledge-based system (RTKBS) carried out in collaboration with Eli Lilly in the UK. The RTKBS was developed in order to provide consistent advice to the operators of a large-scale antibiotic production plant in real time. The ultimate objective was to reduce variability and improve the process yield. A wealth of process information exists in the experience of the process operators, engineers and scientists, and it was capitalized upon in this application. However, this information tends primarily to be qualitative in nature and its elicitation traditionally represents a bottleneck in developing an RTKBS. The paper demonstrates that this type of process knowledge can be effectively and rapidly captured and then coded within an RTKBS. The project was undertaken in two stages. During the knowledge elicitation stage the specific application area was identified in consultation with the industrial partner and qualitative knowledge in the selected area was extracted from experts/operators using KAT™ (a structured technique for knowledge elicitation). Subsequently this knowledge was converted into a rule base and implemented within G2, which then acted as an advisory/decision support system.

Notes: Search is a fundamental problem-solving method in artificial intelligence. Traditional off-line search algorithms attempt to find an optimal solution whereas real-time search algorithms try to find a suboptimal solution more quickly than traditional algorithms to meet real-time constraints. In this work, a new multi-agent real-time search algorithm is developed and its effectiveness is illustrated on a sample domain, namely maze problems. Searching agents can see their environment with a specified visual depth and hence can partially observe their environment. An agent makes use of its partial observation to select a next move, instead of using only one-move-ahead information. Furthermore agents cooperate through a marking mechanism to be able to search different parts of the search space. When an agent selects its next move, it marks its direction of move before executing the move. When another agent comes to this position, it sees this mark and, if possible, moves in a different direction than the previously selected direction. In this way, marking helps agents coordinate their moves with other agents. Although coordination brings an overhead, from experiments we observe that this mechanism is effective in both search time and solution length in maze problems.

Notes: Sequential decision models are an important component of expert systems since, in general, the cost of acquiring information is significant and there is a trade-off between the cost and the value of information. Many expert systems in various domains (business, engineering, medicine etc.), needing costly inputs that are not known until the system operates, have to face this problem. In the last decade the field of sequential decision models based on decision theory (sequential decision-theoretic models) have become more and more important due to both the continuous progress made by research in Bayesian networks and the availability of modern powerful tools for building Bayesian networks and for probability propagation. This paper provides readers (especially knowledge engineers and expert system designers) with a unified and integrated presentation of the disparate literature in the field of sequential decision-making based on decision theory, in order to improve comprehensibility and accessibility. Besides the presentation of the general theory, a view of sequential diagnosis as an instance of the general concept of sequential decision-theoretic models is also shown.

Notes: The present work describes an operational knowledge-based system able to reason with uncertain knowledge, by using methodologies and formalisms that provide for representation of facts and rules with various degrees of certainty and precision. The user interface is windows based, and its design allows high flexibility both in describing the facts in the knowledge base and in adapting the reasoning mechanism. It can therefore be used to evaluate user-generated hypotheses on plant disorders and diagnostic scenarios, as well as provide an environment for education and training in phytopathology.

Notes: Book reviewed:Nils J. Nilsson, Artificial Intelligence: A New Synthesis

Notes: A fuzzy torque distribution controller for energy management (and emission control) of a parallel hybrid electric vehicle is proposed. The proposed controller is implemented in terms of a hierarchical architecture which incorporates the mode of operation of the vehicle as well as empirical knowledge of energy flow in each mode. Moreover, the rule set for each mode of operation of the vehicle is designed in view of an overall energy management strategy that ranges from maximal emphasis on battery charge sustenance to complete reliance on the electrical power source. The proposed control system is evaluated via computational simulations under the FTP75 urban drive cycle. Simulation results reveal that the proposed fuzzy torque distribution strategy is effective over the entire operating range of the vehicle in terms of performance, fuel economy and emissions.

Notes: This paper presents the design, tuning and performance analysis of a new predictive fuzzy controller structure for higher order plants with large time delays. The designed controller consists of a fuzzy proportional-integral (PI) part and a fuzzy predictor. The fuzzy predictive PI controller combines the advantages of fuzzy control while maintaining the simplicity and robustness of a conventional PI controller. The dynamics of the prediction term are adaptive to the system’s time delay. The prediction term has two parts: a fuzzy predictor that uses the system time delay as an input for calculating the prediction horizon and an exponential term that uses the prediction horizon as its positive power. The prediction term also introduces phase lead into the system which compensates for the phase lag due to the time delay in the plant, thereby stabilizing the closed-loop configuration. The performance of the proposed controller is compared with the responses of the conventional predictive PI controller, showing many advantages of the new design over its conventional counterpart.

Notes: The development of online drug administration strategies in operating theatres represents a highly safety-critical situation. The usefulness of different levels of simulation prior to clinical trials has been shown in previous studies in muscle relaxant anaesthesia. Thus, in earlier work on predictive self-tuning control for muscle relaxation a dual computer real-time simulation was undertaken, subsequent to algorithm validation via off-line simulation. In the present approach a supervised rule-based control algorithm is used. The control software was implemented on the actual machine to be used in theatre, while another computer acted as a real-time patient simulator. This set-up has further advantages of providing accurate timing and also finite data accuracy via the ADC/DAC interface, or the equivalent digital lines. Also, it provides for controller design fast simulation studies compared to the real-time application. In this paper, a new architecture which combines several hierarchical levels for control (a Mamdani-type fuzzy controller), adaptation (self-organizing fuzzy logic control) and performance monitoring (fault detection, isolation and accommodation) is developed and applied to a computer real-time simulation platform for muscle relaxant anaesthesia. Experimental results showed that the proposed algorithm fulfilled successfully the requirements for autonomy, i.e. automatic control, adaptation and supervision, and proved effective in dealing with the faults and disturbances which are normally encountered in operating theatres during surgery.

Notes: Fuzzy controller design includes both linear and non-linear dynamic analysis. The knowledge base parameters associated within the fuzzy rule base influence the non-linear control dynamics while the linear parameters associated within the fuzzy output signal influence the overall control dynamics. For distinct identification of tuning levels, an equivalent linear controller output and a normalized non-linear controller output are defined. A linear proportional-integral-derivative (PID) controller analogy is used for determining the linear tuning parameters. Non-linear tuning is derived from the locally defined control properties in the non-linear fuzzy output. The non-linearity in the fuzzy output is then represented in a graphical form for achieving the necessary non-linear tuning. Three different tuning strategies are evaluated. The first strategy uses a genetic algorithm to simultaneously tune both linear and non-linear parameters. In the second strategy the non-linear parameters are initially selected on the basis of some desired non-linear control characteristics and the linear tuning is then performed using a trial and error approach. In the third method the linear tuning is initially performed off-line using an existing linear PID law and an adaptive non-linear tuning is then performed online in a hierarchical fashion. The control performance of each design is compared against its corresponding linear PID system. The controllers based on the first two design methods show superior performance when they are implemented on the estimated process system. However, in the presence of process uncertainties and external disturbances these controllers fail to perform any better than linear controllers. In the hierarchical control architecture, the non-linear fuzzy control method adapts to process uncertainties and disturbances to produce superior performance.

Notes: The sensory data from three different methods, multidimensional sorting, similarity scaling, and free-choice profiling were compared using ten commercial grape jellies as a model system. Without any prior training, the overall similarities/dissimilarities between stimuli were judged using both multidimensional sorting and pair-wise scaling and the sensory attributes were rated using free-choice profiling by different panels. A two-dimensional stimulus configuration best represented the data from each of the three methods. The underlying dimensions of stimulus space were identified from free-choice profiling data and also explained some background variables. The texture, sweetness, sourness, grape flavor and color contributed to both dimensions. All three methods were very similar in describing the most important differences among stimuli as suggested by the highly significant correlation between their first dimensions. The Procrustes analysis coupled with permutation tests, as well as RV coefficient, indicated that similarity scaling and free-choice profiling reached maximum consensus, whereas multidimensional sorting shared slightly lesser consensus with the other two methods.

Notes: This study aimed to check the hypothesis that aroma concentration in the aqueous phase of an oil-in-water emulsion controlled the odor intensity of single aroma compounds. A set of flavored oil-in-water emulsions, prepared according to a 22 experimental design (aroma concentration, oil volume fraction) with two central points, was assessed for odor intensity by a 24-member panel during four sessions. In each session, three of the four-studied aroma molecules (benzaldehyde, ethyl butyrate, linalool and acetophenone) were investigated. Whatever the aroma, the experimental data showed that the oil volume fraction of the emulsion (from 0.12 to 0.48) did not influence the odor intensity. For each emulsion composition, aroma concentrations at equilibrium in both phases were calculated using the oil-water partition coefficient of the compound. Odor intensities, estimated from aroma concentration in the aqueous phase using previously reported modeling of odor intensity above water solutions, were then compared to experimental data. It is confirmed that the perceived odor intensity is governed by the aroma concentration in the aqueous phase at the time of the trial and not by the averaged apparent concentration in the emulsion.

Notes: Many researchers have compared results from experiments using paper ballots and computer ballots, yet few have studied the interchangeability of the two data collection methods. If computers fail between sessions of an experiment, one would like to be able to use paper ballots for that session with some confidence that the experimental results will not be affected. The objective of this study was to determine if ballot type had a significant influence on descriptive analysis results. Multivariate analysis of variance indicated no significant differences (P〈0.05) between ballot types. No significant sample * ballot interactions were found from the univariate analysis of variance. Mann Whitney nonparamatric tests found that substituting paper ballots for computer ballots in a single session did not significantly alter experimental results. One can conclude from this experiment that if a situation occurs forcing panelists to use an alternative ballot, the results probably will not be significantly affected.

Notes: Sensory profiling laboratories rate products for sets of attributes. Order of tasting and carry-over effects from sample to sample are widely recognized. However, within samples, work investigating the possibility of effects due to the order of rating attributes and attribute to attribute carry-over has not been reported. Individual attributes were classified according to whether their presence in a product was perceived to be desirable or not. For both yoghurt and cheese, sample ratings for each attribute were compared when attributes perceived as desirable preceded those perceived as undesirable and vice-versa. In both stimuli, there was evidence that desirable attributes were biased to a lower value when preceded by undesirable ones. Similarly, negative attributes were biased downwards when preceded by desirable ones. For absolute scores, these effects, albeit small, make randomizing attribute ordering desirable. However, lack of evidence of interactions between samples and attribute ordering suggests comparative differences between samples are unaffected.

Notes: Pork patties from M. longissimus dorsi and M. psoas major were used by a sensory panel to develop a descriptive vocabulary to describe warmed-over flavor development. The patties were made from meat from animals supplemented with one of four dietary treatments, (I) control diet, (II) supplemental iron (7 g iron (II) sulfate/kg feed), (III) supplemental vitamin E (200 mg dl-α-tocopherol acetate/kg of feed) and (IV) supplemental vitamin E + supplemental iron. The sample set used for training reflected the variation in muscle type and degree of warmed-over flavor development (day 1 and 5). The sensory terms selected had to be relevant to the samples, discriminate between the samples, have cognitive clarity and be nonredundant. Based on these selection criteria an initial training list of 36 sensory terms consisting of odors, flavors, basic tastes and aftertastes was developed in a pretrial using experts with product knowledge. This list constituted the start of training the panel. Principle Component Analysis (PCA) and assessor suggestions were used for reducing the number of terms and after 5 days of training this list was reduced to 21 sensory terms. The discriminative ability of the sensory panel improved over the course of sensory training and was quantified by using the mean assessor signal to noise ratios (S/N) for the sensory terms for each training session. This signal to noise ratio is essentially the total initial variance divided by the residual cross-validated variance. Subsequent detailed multivariate analysis found that the bilinear descriptor leverage was a particularly efficient method for term reduction.

Notes: The objective of this study was to investigate the effect beverages have on subsequently perceived basic tastes. Two types of milk, Cola and water were used to rinse the mouth prior to conducting a Time Intensity study with basic taste solutions. From this some effects of the prior beverage onto the TI parameters was found. Especially Cola showed an effect on the intensity of the subsequently tasted sweet taste, and whole milk showed a stronger effect than skim milk. The effects showed both in size and timing of the basic taste intensities.

Notes: The objective of this study was to determine the effect fat has on the intensity of sweet, salty, sour, bitter and umami tastes in oil-in-water emulsions. The first experiment used two levels of fat (9% and 17% in oil-in-water emulsions) and two intensities of each taste (high and low). We compared the taste intensities of these emulsions to the intensities of oil-free samples with equal total volume, and to oil free samples of the same aqueous taste compound concentrations. Because of potential confusion between taste intensity and viscosity, we repeated the experiment, having panelists rate both thickness and taste intensity. Diluting with oil, compared to diluting with water, decreased bitterness, but increased the intensity of salty, sweet, sour and umami tastes. When compared to samples with equal aqueous taste compound concentrations, fat suppressed bitterness, but had no effect on the other tastes.

Notes: This study was undertaken to establish category and product descriptive characteristics of commercial creamy style peanut butters for use in subsequent modeling of consumer response. An established descriptive lexicon for peanut flavor was modified with additional appearance and texture terminology to describe these samples. To determine the full category space for the appearance, flavor and texture characteristics for commercial creamy style peanut butters, a highly trained descriptive panel screened 42 brands. A subset of 22 peanut butters was identified which represented the available range of appearance, flavor and texture variations and determined the product category. These 22 commercial creamy style peanut butters were subsequently evaluated and quantitatively described using 4 appearance, 19 flavor and 12 texture descriptors. Using both hierarchical clustering and principal component analysis, 4 logical associative groupings of products were identified: store and name brands, natural brands, reduced fat brands, and some store or name brands with unique or unusual appearance, flavor or texture characteristics. Omission of products with redundant characteristics within a factor grouping enabled further reduction to 15 products for subsequent quantitative consumer testing to establish a model for descriptive analysis as a predictor of consumer research responses.

Notes: Roncal cheese is made from raw ovine milk and is regulated by an Appellation of Origin. This cheese variety is quite popular with consumers because of its special properties, which are unlike those of other ewe's-milk cheeses. To date there have been no studies aimed at characterizing the flavor and odor attributes of Roncal cheese. To remedy this situation, sensory analysis has been performed using Roncal cheese samples collected from artisanal and industrial cheese-making establishments. The cheeses were made at three different times of year (winter, spring, and summer) and were ripened for four or eight months. Sensory descriptors were generated, and after discussion suitable descriptors for describing and discriminating among Roncal cheese samples were selected by multivariate analysis. In all, 19 descriptors were employed, namely:odor: cream, meat broth, olive, toffee, liquid caramel, toasted, acetic acid, sweat, acidified milk, ammonia, leather, stable straw, wool, and odor intensity.flavor: characteristic flavor, acetic acid, sweat, butyric acid, and flavor intensity.

Notes: Two independent, highly trained panels separately conducted descriptive analysis of orange juices using different descriptive analysis methods and sets of samples. Lexicons were developed independently. One panel evaluated 23 orange juice products and identified and referenced 24 attributes. The other panel evaluated 17 products and identified 17 attributes for testing. Though not identical, the lexicons developed by both panels were similar overall. To compare the sensory space of the product category, Principal Component Analysis (PCA) and sensory maps were developed separately for each panel. The comparison showed that the underlying sample spaces obtained from both panels were comparable in many ways. Key flavor characteristics for the same types of orange juice products were described similarly by both panels. These data indicate that the process of using highly trained panels that define attributes and use reference standards for descriptive sensory analysis can give objective and comparable information for a product category across different panels.

Notes: Can labels suggestively influence sensory perceptions and taste? Using a “ Phantom Ingredient” taste test, we show that the presence or absence of a labeled ingredient (soy) and the presence or absence of a health claim negatively bias taste perceptions toward a food erroneously thought to contain soy. We found a label highlighting soy content made health claims believable but negatively influenced perceptions of taste for certain segments of consumers. Our results and discussion provide better direction for researchers who work with ingredient labeling as well as for those who work with soybean products.

Notes: Using an intensity rating with no external calibration, experiments were designed to measure the sensory oil-water partition coefficients of four aroma molecules (benzaldehyde, ethyl butyrate, linalool and acetophenone) as the ratios of concentration producing stimuli of equivalent intensities. Flavored water and oil phases were successively assessed for odor intensity by 24 panelists who were given total freedom regarding scaling strategy. Each session combined five concentration levels of three out of the four studied aromas in a solvent (water or oil). A predominant concentration effect was found for each aroma in both solvents and concentration dependencies of perceived intensity above water and oil were similar. Experimental data were modeled with Fechner, Stevens and Hill equations. Combining results above water and oil solutions to feed a common model led to the evaluation of an overall sensory oil-water partition coefficient for each aroma compound. All three models produced similar partition coefficient values for each aroma that were lower than the related instrumental partition coefficients. Biases previously detected when external calibration had been used were reduced in a large proportion while suggested enhancement of odor intensity by water vapor could not be excluded.

Notes: Variability is a fundamental characteristic of sensory profile data. Ignoring the variability may result in biased solutions that cannot be improved by the collection of additional data. Probabilistic multidimensional scaling (PMDS) models provide a means of accounting for the variability inherent in sensory data by using distributions, instead of points, to portray sensory objects. For profile data with high levels of variability, the probabilistic model recovers latent structure parameters very well — traditional deterministic MDS models and principal components analyses (PCA) do not. Advantages of the PMDS models include their parsimony, testability and extensibility. Two particularly attractive PMDS attributes are their ability to relate consumers’ expressions of liking to product profiles and their ability to estimate a product's “ perceptual share” from liking and profile data. Used as a criterion with what-if modeling, perceptual share estimates enable the evaluation of alternative product development strategies.

Notes: Judges on anti-nausea medication, used hedonic scales to assess a set of foods and beverages on two occasions, initially on beginning a treatment with anti-nausea medication and then four weeks later. To detect the possibility that changes in hedonic scores for the foods and beverages may be caused not by changes in liking but by ‘scaling drift’: changes in the use of the scale, control stimuli were also assessed. These control stimuli were sets of stimuli to be assessed for intensity and a set to be assessed for liking. These latter stimuli were a class of stimuli that were unlikely to be liked to a different extent on the two testing occasions. The lack of change in the control stimuli and the change in the hedonic scores for the foods and beverages suggested that the latter was due to changes in liking for the foods and beverages rather than ‘scaling drift’.

Notes: The objectives of the present study were to measure the sensory profile and acceptability of 8 commercial samples of mayonnaise (4 whole fat and 4 low fat) and then to apply preference mapping to address the relationship between the descriptive and acceptability data. A total of 240 consumers were recruited in 3 Argentine cities. In each city 40 young adults and 40 older adults were recruited. Samples differed in their sensory profiles and average acceptabilities. Cluster analysis of consumers showed clear segmentation in appearance, texture, flavor and overall acceptance. Sensory acceptability segmentation was far more pronounced than age or city segmentation. Extended preference mapping showed the sensory descriptors of mayonnaise which drove the acceptability of some of the consumer clusters.

Notes: This paper deals with the design and optimization of lemon juice, a common ingredient in different foods. Lemon juice is usually added for flavoring purposes to different foods, consumed under different conditions. Through experimental design and evaluation in multiple carriers, the product developer can identify the combination of ingredients in lemon juice which, in concert, generate an acceptable product. Through optimization, taking into account these different end-uses, the developer can create a product that will perform well in different types of carriers.

Notes: We tested the hypothesis that exposure to an aroma through a food or beverage in the first part of a meal (preload) would reduce the consumption of a food with the same aroma in the second portion of the meal, because of olfactory-specific satiety. In a first experiment, 35 young, normal-weight adults participated in 2 lunch sessions during which they consumed a fixed preload of either ranch-flavored or plain potato chips and sparkling water, followed by ad libitum consumption of a pasta salad with ranch dressing and sparkling water. In the second experiment, 33 subjects consumed a fixed preload of either lemon-flavored or plain sparkling water and pasta salad with ranch dressing, followed by ad libitum consumption of lemon-flavored yogurt and plain sparkling water. No difference was observed in the amount of food consumed (corrected for session order effects) as a function of prior exposure to ranch flavor in the chips or lemon flavor in the water. We conclude that exposure to a preload aroma may not have a significant effect on subsequent intake of a food with the same aroma.

Notes: The tenderness of carcasses of ten bulls of Norwegian Red breed was analyzed by sensory and mechanical analyses. Four samples representing the range of tenderness in the material were served to 118 consumers in an in-house test. The consumers rated the samples for the degree of tenderness. High correlation was found between sensory analyses and the consumer ratings of tenderness, r = 0.96 (P〈0.0005), and between Warner Bratzler Shear force values and the consumer ratings, r =− 0.87 (P〈0.005).The consumers found it easier to evaluate the very tender and very tough samples, while the moderately tough samples were more difficult to evaluate, and were mixed up in both the sensory and consumer analyses.A lower percent of women than men considered each sample as acceptably tender and women in general used a lower grade to describe the degree of tenderness of the samples. Indications of high variety of consumer acceptability at different levels of tenderness, suggests a need for a larger study of tenderness levels in the areas where large changes in acceptability are found, and of responses from different consumer groups.

Notes: Mapping is a popularly accepted statistical method, currently used in many applications in order to reveal and perhaps understand relations between stimuli. This paper discusses some of the shortcomings of mapping as a procedure, specifically those having to do with the ‘actionability’ of the data. The paper recommends that mapping be used to embed the stimuli in a geometric space, but then the coordinates of that space be used as independent variables in a model. In this way the geometrical representation does not stop at being a ‘pretty picture’ without further utility, but instead incorporates within it the necessary tools to allow researchers to go from any location in the space to any other location.

Notes: The objective of this study was to demonstrate that the dimensions of a sensory booth modified to comply with the Americans with Disabilities Act of 1990 (ADA) guidelines have no impact on consumer evaluations of chocolate pudding. One set of booths each were constructed per ASTM and ADA guidelines. Control pudding was prepared according to package directions with 2% fat milk; other treatments were modified with red food coloring, sugar or nonfat milk. Twenty-four panelists evaluated instant chocolate puddings in directional difference and hedonic tests in each type of booth. Booth type and test date had no effect on judgments.

Notes: Communication and replication of sensory data from different sites are important to track progress on fundamental research issues and to ensure that research efforts are not duplicated. A uniform anchored Cheddar cheese sensory language has previously been identified and refined. The objective of this study was to demonstrate application of the defined sensory language for Cheddar cheese for communication between sensory panels at three different sites. The defined and referenced sensory language for Cheddar cheese was disseminated to panel leaders at the three sites and sensory panels (n ≤ 8) were trained for 40 to 80 h at each site. Ten forty-pound blocks of Cheddar cheese representing different ages were collected and evaluated by the panels. Cheeses were differentiated by the three panels by univariate and multivariate analysis (P〈0.05). Cheeses were differentiated by the three panels in a similar manner. Results indicate that it is possible to calibrate panels using a standardized defined sensory language.

Notes: Clothing movement was evaluated on a video screen by a descriptive analysis sensory technique and correlated to tactile attributes and fabric mechanical properties. Six fabrics were tailored into identical wide-leg trousers and dresses, animated by a professional model, filmed and edited for sensory evaluation. Tactile attributes were assessed sensorially and fabric mechanical properties were characterized by F.A.S.T. (Fabric Assurance by Simple Testing) and drape measurements. The following bipolar attribute pairs dominate movement language and perception: flowing to stiff and heavyweight to lightweight. Perceptual space of clothing movement is essentially two dimensional and high correlation coefficients between visual and tactile attributes were found. The fabric drape coefficient correlates highly with visual and tactile attributes and is a simple screening method for clothing movement prediction.

Notes: This study aimed to identify a scaling technique, which would offer the greatest degree of discrimination and accuracy in an evaluation of soup samples, varying in salt concentration (0.3, 0.8 and 1.3% salt). A Seven Point Category Scale, a 100 mm Line scale and non-modulus Magnitude Estimation were used to evaluate samples by consumers (n = 36).A Friedman Two-Way ANOVA and a Wilcoxon Signed Ranks test were applied to the data to compare discriminatory ability and accuracy of the scaling techniques. Results revealed that each of the techniques could be used to discriminate between samples (P〈0.001). However, none of the three techniques were significantly more accurate than one another. In view of the results and consumer preference/comments for using the Seven Point Category Scale, this technique is proposed as an effective method for consumer rating of salt intensity.

Notes: Sherry wine vinegar is a highly appreciated product due to its sensory properties which are acquired thanks to its aging in wood. Despite its relevance, studies involving aging of vinegars are scarce. In this paper, sensorial characteristics of Sherry wine vinegar had been studied during aging. Samples were obtained by acetifying Sherry wine in the laboratory and aging them in oak wood casks for two years. By means of triangle tests, significative differences have been found among vinegars aged 0, 6, 12, 18 and 24 months. In order to obtain more information descriptive analysis was performed. Sherry wine vinegars were described on the basis of the attributes previously selected and from these results their spider charts were drawn. The remaining alcoholic degree of vinegars plays an important role in the ethyl acetate and woody aroma components. Overall impression, aroma intensity and quality clearly increase with aging.

Notes: Defatted soybean flour mixed with a combination of 0.03% Red No. 40 and 0.01% annatto (Bixa orellana) colorants was extruded into textured soy protein (TSP) in a counter-rotating twin extruder to produce a red-meat like product suitable for hamburger patties. Ground beef patties were processed replacing the meat (15 and 30%) with resulting hydrated textured soybean protein (TSP) prepared with and without the colorants. The resulting cooked patties were evaluated by eight trained judges for tenderness, juiciness, number of chews, beef flavor and overall flavor quality using a nine point nonstructured horizontal scale. Other patty characteristics examined included cooking losses (weight loss and diameter reduction) and color, by tristimulus colorimetric measurement. The results from sensory analysis revealed that ground beef patties with high TSP level were more tender than control, and they had less beef flavor and overall flavor quality. Weight loss was not significantly (P 〉 0.05) affected by TSP level but the patties with 30% TSP showed less shrinkage than the others. Results of the study suggested that while patties with 15% TSP had sensory attributes similar to the control, adding 30% TSP with coloring significantly (P 〈 0.05) increased the redness of the patties.

Notes: The present study considers the influence of reducing the fat content of ovine milk on the sensory and instrumental texture characteristics of the resulting cheeses. Three manufacturing runs were performed. In each run three cheese batches were manufactured using milks with differing percentage fat contents (8%, 4%, and 2% fat). Analysis of cheese samples was performed at 60, 90, and 120 days of ripening.The instrumental method used to evaluate cheese texture was uniaxial compression at constant speed, taking readings of stress, strain, and modulus of elasticity (E). Statisticalanalysis revealed differences forboth the differentfat contents and the ripening times considered. Instrumental parameter values increased with lower cheese fat contents; with a 20% reduction in the fat to dry matter content from full-fat to reduced-fat cheeses, resulting in a 35% increase in maximum stress and in the slope of the stress-strain curve at the end of ripening. The greatest sensory differences between samples were recorded for firmness.