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Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 91 records · Page 5Linked to original sources
PubMed1997

Actions of S-nitrosocysteine in the nucleus tractus solitarii are unrelated to release of nitric oxide.

Cardiovascular effects elicited by microinjection of L-S-nitrosocysteine in the nucleus tractus solitarii (NTS) were compared and contrasted with those produced by the dextroisomer, other nitric oxide donors and nitric oxide itself. L-S-nitrosocysteine produced dose-related decreases of arterial pressure and heart rate. In contrast, D-S-nitrosocysteine, S-nitrosoglutathione, glyceryl trinitrate, and sodium nitroprusside produced minimal responses that were not dose-related. Likewise, injection of cystine and nitric oxide, two products of S-nitrosocysteine breakdown, produced no significant response. Headspace analysis using chemiluminescence revealed that L- and D-S-nitrosocysteine released identical amounts of nitric oxide when exposed to homogenates of whole rat brain. Responses to L-S-nitrosocysteine were not affected by local injection of oxyhemoglobin or the nitric oxide synthase inhibitor L-nitroarginine methylester. Although injection of L-cysteine into the NTS produced responses similar to those seen with injection of L-S-nitrosocysteine, blockade of excitatory amino acid receptors with kynurenic acid inhibited responses to cysteine but not those to the nitrosothiol. The study demonstrates that S-nitrosocysteine is biologically active in the NTS. Its action is independent of release of nitric oxide from the nitrosothiol but may be mediated through stereoselective sites on target neurons.

Animals↗
PubMed1997

Improvement in specificity of [14C]d-xylose breath test for bacterial overgrowth.

The aim of the study was to determine whether the specificity of the [14C]d-xylose breath test could be improved, by excluding false-positive tests due to premature colonic metabolism of the [14C]d-xylose caused by rapid colonic transit. Forty-seven patients with suspected small bowel bacterial overgrowth were investigated by (1) aspiration and culture of duodenal fluid and (2) a [14C]d-xylose breath test. Those with either a positive duodenal culture or breath test had a repeat [14C]d-xylose breath test given with one of three transit markers (barium, Gastrografin or 99mTc-labeled tin colloid) to determine if the site of metabolism was in the small bowel or colon. Fourteen patients had positive duodenal cultures, four of whom had a negative [14C]d-xylose breath test, 15 patients had a positive [14C]d-xylose breath test, three of which were due to colonic metabolism of the xylose. Where transit markers were used, 14C was detectable in the breath and serum before barium had entered the small bowel, thus the barium did not comigrate with the xylose. Gastrografin accelerated small bowel transit, leading to malabsorption of the xylose in the small intestine and subsequent colonic metabolism of the xylose. 99mTc-labeled tin colloid had no obvious disadvantages and appeared to be the marker of choice. The use of a transit marker increased the specificity of the [14C]d-xylose breath test from 85% to 94%. The specificity of the [14C]d-xylose breath test for the detection of small bowel bacterial overgrowth is improved to greater than 90% by the use of an appropriate transit marker.

Bacteria↗
PubMed1997

Lower serum oestrogen concentrations associated with faster intestinal transit.

Increased fibre intake has been shown to reduce serum oestrogen concentrations. We hypothesized that fibre exerts this effect by decreasing the time available for reabsorption of oestrogens in the colon. We tested this in volunteers by measuring changes in serum oestrogen levels in response to manipulation of intestinal transit times with senna and loperamide, then comparing the results with changes caused by wheat bran. Forty healthy premenopausal volunteers were placed at random into one of three groups. The first group took senna for two menstrual cycles then, after a washout period, took wheat bran, again for two menstrual cycles. The second group did the reverse. The third group took loperamide for two menstrual cycles. At the beginning and end of each intervention a 4-day dietary record was kept and whole-gut transit time was measured; stools were taken for measurement of pH and beta-glucuronidase activity and blood for measurement of oestrone and oestradiol and their non-protein-bound fractions and of oestrone sulphate. Senna and loperamide caused the intended alterations in intestinal transit, whereas on wheat bran supplements there was a trend towards faster transit. Serum oestrone sulphate fell with wheat bran (mean intake 19.8 g day(-1)) and with senna; total- and non-protein-bound oestrone fell with senna. No significant changes in serum oestrogens were seen with loperamide. No significant changes were seen in faecal beta-glucuronidase activity. Stool pH changed only with senna, in which case it fell. In conclusion, speeding up intestinal transit can lower serum oestrogen concentrations.

Adult↗
PubMed1997

Extensive tyrosine nitration in human myocardial inflammation: evidence for the presence of peroxynitrite.

OBJECTIVES: Production of nitric oxide via the cytokine-mediated activation of myocardial inducible nitric oxide synthase decreases myocardial contractility. Whether myocardial dysfunction is mediated directly by nitric oxide or indirectly through the formation of secondary reaction products, such as peroxynitrite, has not been established. Peroxynitrite, but not nitric oxide, reacts with the phenolic ring of tyrosine to form the stable product 3-nitro-L-tyrosine. Demonstration of tissue nitrotyrosine residues, therefore, infers the presence of peroxynitrite or related nitrogen-centered oxidants. DESIGN: Retrospective analysis of human autopsy specimens. SETTING: University pathology and basic science laboratories. PATIENTS: Formalin-fixed, paraffin-embedded myocardial tissue samples were obtained from 11 patients with a diagnosis of sepsis, seven patients with a diagnosis of viral myocarditis, and five control patients without clinical or pathologic cardiac disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Specific antibodies to nitrotyrosine were utilized to detect nitrotyrosine residues in human autopsy specimens. Cardiac tissue obtained from patients with myocarditis or sepsis demonstrated intense nitrotyrosine immunoreactivity in the endocardium, myocardium, and coronary vascular endothelium and smooth muscle. In contrast, connective tissue elements were without appreciable immunohistochemical staining. Nitrotyrosine antibody binding was blocked by coincubation with nitrotyrosine or nitrated bovine serum albumin, but not by aminotyrosine, phosphotyrosine, or bovine serum albumin. In situ reduction of tissue nitrotyrosine to aminotyrosine by sodium hydrosulfite also blocked antibody binding. Densitometric analysis of nitrotyrosine immunoreactivity demonstrated significantly higher values for specimens from myocarditis and sepsis patients when compared with control tissue specimens. CONCLUSION: These results demonstrate the formation of peroxynitrite within the myocardium during inflammatory disease states, suggesting a role for peroxynitrite in inflammation-associated myocardial dysfunction.

Adolescent↗
PubMed1997

The intestinal effects of bran-like plastic particles: is the concept of 'roughage' valid after all?

OBJECTIVE: The mechanisms by which dietary fibre exerts is laxative action are not fully understood. Studies using sliced plastic tubing as a fibre substitute showed a decrease in both small and large bowel transit time. The significance of these studies is hard to interpret. We set out to compare the effects on intestinal function of wheat bran with plastic flakes similar in size and flaky shape to wheat bran (and devoid of plasticizers). DESIGN AND METHODS: Volunteers consumed coarse wheat bran then, after a washout period, plastic flakes of the same size and shape as the bran. Before and after each intervention whole-gut transit time (WGTT), defecation frequency, stool form, stool water content, stool beta-glucuronidase activity and dietary intake were assessed. RESULTS: Twenty-nine volunteers consumed a mean of 27.1 g of raw wheat bran and 24 g of plastic flakes a day. Baseline WGTT, interdefecatory intervals (IDI), stool form, weight, output, water content, and beta-glucuronidase were similar before both interventions. Both led to a decrease in mean faecal beta-glucuronidase activity, median WGTT (bran 25.8%, plastic 28.6%) and IDI (bran 23.3% plastic 25.0%). Both also increased stool form score (bran 28.6%, plastic 21.2%) and stool output (bran 67.1%, plastic 79.0%). Stool water content only rose with wheat bran (72%-75%, P = 0.014). CONCLUSION: Overall, plastic 'pseudobran' was as effective at altering colonic function as wheat bran at a similar dosage but with fewer particles. The mechanism is not by increased faecal water. Reduction in enzyme activity with plastic flakes suggests that the plastic led to qualitative and, probably, beneficial changes in the bacterial flora or their metabolic processes. The concept of roughage deserves to be revived.

Adult↗
PubMed1997

Prevalence of Helicobacter pylori in respiratory physicians performing bronchoscopy: a comparison with gastroenterologists using the carbon 13 urea breath test.

BACKGROUND: The mode of transmission of Helicobacter pylori is unclear, but it has been shown that gastroenterologists are at a greater risk of acquiring the infection when performing endoscopy. The current study was designed to assess the risk H. pylori infection in respiratory physicians performing bronchoscopy compared to an at-risk group of gastroenterologists. We were interested in identifying whether the oral cavity is important in the transmission of H. pylori. MATERIALS AND METHODS: Respiratory physicians and gastroenterologists in southern England and Wales were invited to participate in the study. Medical, personal, and professional details were recorded, and H. pylori status was established using a carbon 13 urea breath test. RESULTS: The study included 30 gastroenterologists and 30 respiratory physicians. The groups were similar for age (mean age, 46.2 years [SD 8.7] and 43.9 years [SD 8.5], respectively), number of years in practice (mean, 16.1 [6.8] and 13.2 [5.5], respectively), amount of Third-World travel, and glove and drug use (antacids, H2 antagonists, proton pump inhibitors, promotility agents, and bismuth). The prevalence of upper gastrointestinal symptoms (indigestion, heartburn, abdominal pain) and history of previous peptic ulcer or hiatus hernia were similar for both groups. Fifteen of thirty gastroenterologists and three of thirty respiratory physicians had positive breath tests (chi square, p < .001, 1 df). There was no relation between age and H. pylori status. Within the group of gastroenterologists, performance of endoscopy without gloves for longer than 7 years was associated with an increased prevalence of infection (> 7 years, 11 of 15 breath-test-positive; < 7 years, 4 of 15 breath-test-positive [chi square, p = .01, 1 df]). CONCLUSIONS: Gastroenterologists in this study appeared to be at risk of infection, whereas respiratory physicians are not. Gastroenterologists who wear gloves during endoscopy appear to be at lower risk of H. pylori infection.

Adult↗
PubMed1997

Increasing butyrate concentration in the distal colon by accelerating intestinal transit.

BACKGROUND: Populations at low risk of colonic cancer consume large amounts of fibre and starch and pass acid, bulky stools. One short chain fatty acid (SCFA), butyrate, is the colon's main energy source and inhibits malignant transformation in vitro. AIM: To test the hypothesis that altering colonic transit rate alters colonic pH and the SCFA content of the stools. PATIENTS: Thirteen healthy adults recruited by advertisement. METHODS: Volunteers consumed, in turn, wheat bran, senna and loperamide, each for nine days with a two week washout period between study periods, dietary intake being unchanged. Before, and in the last four days of each intervention, whole gut transit time (WGTT), defaecation frequency, stool form, stool beta-glucuronidase activity, stool pH, stool SCFA concentrations and intracolonic pH (using a radiotelemetry capsule for continuous monitoring) were assessed. RESULTS: WGTT decreased, stool, output and frequency increased with wheat bran and senna, vice versa with loperamide. The pH was similar in the distal colon and stool. Distal colonic pH fell with wheat bran and senna and tended to increase with loperamide. Faecal SCFA concentrations, including butyrate, increased with senna and fell with loperamide. With wheat bran the changes were non-significant, possibly because of the short duration of the study. Baseline WGTT correlated with faecal SCFA concentration (r = -0.511, p = 0.001), with faecal butyrate (r = -0.577, p < 0.001) and with distal colonic pH (r = 0.359, p = 0.029). CONCLUSION: Bowel transit rate is a determinant of stool SCFA concentration including butyrate and distal colonic pH. This may explain the inter-relations between colonic cancer, dietary fibre intake, stool output, and stool pH.

Adult↗
PubMed1997

Retrospective estimation of exposure to benzene in a leukaemia case-control study of petroleum marketing and distribution workers in the United Kingdom.

OBJECTIVE: To provide quantitative estimates of exposure to benzene for cases and controls in an epidemiology study to investigate the risk of leukaemia in petroleum distribution workers. METHODS: Work histories were obtained for cases and controls together with detailed information on the distribution sites. For each job in the work history, an estimate of exposure (parts per million (ppm)) was obtained by multiplying a measure derived from exposure data by modifying factors to reflect the differences between the conditions that existed at the time of measurement and those at the time of interest. The modifying factors used related to job activity, the number of road tankers loaded, the benzene content of the gasoline, the mixture of products handled, temperature, and loading technology. Cumulative exposures for each case and control were obtained by multiplying the exposure estimates for each job by the duration of time in the respective jobs, and summing these over all jobs in the work history. Peak exposure and exposure through dermal contact were quantitatively classified for each job. RESULTS: Measured exposures were obtained for 30 job categories, and ranged from 0.003 to 8.20 ppm. 40% of work histories were assigned background exposures, with a further 34% assigned the exposure estimate for a driver carrying out top submerged loading of motor fuel into road tankers. Cumulative exposures ranged from < 1 to > 200 ppm-years, although 81% were < 5 ppm-years. Comparison of the exposure estimates for selected jobs with data from sources not used in the study showed similar results. CONCLUSION: The estimates of exposure to benzene in this study provide a sound basis for the epidemiological analyses.

Benzene↗
PubMed1997

Stereoselective actions of S-nitrosocysteine in central nervous system of conscious rats.

This study examined whether the stereoselective actions of S-nitrosocysteine (SNC) in the central nervous system involves the activation of stereoselective SNC recognition sites. We examined the effects produced by intracerebroventricular injection of the L- and D-isomers of SNC (L- and D-SNC) on mean arterial blood pressure, heart rate, and vascular resistances in conscious rats. We also examined the hemodynamic effects produced by intracerebroventricular injections of 1) L-cystine, the major non-nitric oxide (NO) decomposition product of L-SNC, 2) the parent thiols L- and D-cysteine, and 3) the bulky S-nitrosothiol L-S-nitroso-gamma-glutamylcysteinylglycine [L-S-nitrosoglutathione, (L-SNOG)]. Finally, we examined the decomposition of L- and D-SNC and L-SNOG to NO on their addition to brain homogenates. The intracerebroventricular injection of L-SNC (250-1,000 nmol) produced falls in mean arterial pressure, increases in heart rate, and a dose-dependent pattern of changes in hindquarter, renal, and mesenteric vascular resistances. The intracerebroventricular injections of D-SNC, L-cystine, and L-SNOG produced only minor effects. The intracerebroventricular injection of L-cysteine produced pressor responses and tachycardia, whereas D-cysteine was inactive. L- and D-SNC decomposed equally to NO on addition to brain homogenates. L-SNOG decomposed to similar amounts of NO as L- and D-SNC. These results suggest that SNC may activate stereoselective SNC recognition sites on brain neurons and that S-nitrosothiols of substantially different structure do not stimulate these sites. These recognition sites may be stereoselective membrane-bound receptors for which L-SNC is the unique ligand.

Animals↗
PubMed1997

Neurogenically derived nitrosyl factors mediate sympathetic vasodilation in the hindlimb of the rat.

Skeletal muscle vasculature of the hindlimb is innervated by a sympathetic noncholinergic vasodilator system. The aim of this study was to determine whether this vasodilator system may represent postganglionic lumbar sympathetic neurons that synthesize and release nitric oxide (NO) or related NO-containing factors. We examined whether NO synthase (NOS)-positive postganglionic lumbar nerves innervate the hindlimb vasculature of the rat and whether the hindlimb vasodilation produced by electrical stimulation of the lumbar sympathetic chain of anesthetized rats is reduced after the systemic administration of the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI). Subpopulations of lumbar sympathetic cell bodies stained intensely for NOS. Postganglionic fibers and varicosities within the iliac and femoral arteries also stained for NOS. Double ligation of the lumbar chain demonstrated that NOS was transported from the cell bodies toward the peripheral terminals. Low-intensity electrical stimulation of the lumbar chain produced a pronounced hindlimb vasodilation that was markedly diminished by pretreatment with 7-NI (45 mg/kg i.v.). In contrast, the vasodilator potency of acetylcholine and S-nitrosocysteine were augmented by 7-NI. These results suggest that postganglionic lumbar sympathetic neurons may synthesize and release NO-containing factors.

Acetylcholine↗
PubMed1997

NO-containing factors mediate hindlimb vasodilation produced by superior laryngeal nerve stimulation.

The electrical stimulation (ES) of the superior laryngeal nerve (SLN) produces reflex vasodilation in the rat hindlimb. This study determined whether this vasodilation is mediated by the release of nitric oxide (NO)-containing factors (NOF) from NO synthase (NOS)-positive postganglionic lumbar sympathetic fibers that innervate the rat hindlimb vasculature. ES of the SLN (1-10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and hindlimb and mesenteric (MR) vascular resistances. The hindlimb vasodilation was not observed in rats in which the lumbar sympathetic trunk was transected 7-10 days previously. The falls in hindquarter vascular resistance (HQR) produced by lower intensity ES of the SLN were virtually abolished by the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI, 45 mg/kg i.v.). The fall in HQR produced by 10 Hz ES of the SLN was not affected by 7-NI. The falls in MR produced by 1-10 Hz ES of the SLN were unaffected by 7-NI. Four consecutive episodes of ES at 10 Hz produced pronounced and equivalent reductions in MAP, HQR, and MR. After administration of 7-NI, the first ES produced similar hemodynamic responses to those observed before injection. However, each subsequent ES produced progressively and markedly smaller falls in HQR, whereas each episode of ES produced similar falls in MR. These results suggest that the reflex vasodilation in the rat hindlimb produced by ES of the SLN involves the release of newly synthesized and performed stores of NOF from NOS-positive postganglionic lumbar sympathetic nerves.

Animals↗
PubMed1997

Hemodynamic effects of L- and D-S-nitroso-beta,beta-dimethylcysteine in rats.

This study examined whether S-nitroso-beta,beta-dimethylcysteine (S-nitrosopenicillamine; SNPEN) may activate stereoselective S-nitrosothiol receptors within the vasculature. We examined 1) the hemodynamic effects produced by the L- and D-isomers of SNPEN (12.5-400 nmol/kg iv), the L- and D-isomers of the parent thiols [L- and D-penicillamine (PEN); 12.5-400 nmol/kg iv], and the nitric oxide (NO) donor sodium nitroprusside (SNP; 1-10 micrograms/kg iv) in conscious rats; 2) the hemodynamic effects produced by these compounds in urethan-anesthetized rats; and 3) the relative decomposition of L- and D-SNPEN to NO on addition to rat blood or cultured porcine aortic smooth muscle (PASM) cells. We found that 1) L-SNPEN was a more potent hypotensive and vasodilator agent within the mesenteric bed and within sympathetically intact and sympathetically denervated hindlimb beds of conscious rats than was D-SNPEN; 2) the hypotension and vasodilation produced by L-SNPEN was similar in conscious and anesthetized rats, whereas the effects of D-SNPEN and SNP were augmented by urethan-anesthesia; 3) L- and D-PEN did not affect hemodynamic parameters in conscious or anesthetized rats; and 4) L- and D-SNPEN decomposed equally to NO on addition to rat blood or PASM cells. These results suggest that the vasodilator effects of SNPEN involve the interaction of this S-nitrosothiol with stereoselective recognition sites within the vasculature and that urethan alters the mechanisms by which L- and D-SNPEN relax vascular smooth muscle.

Analysis of Variance↗
PubMed1997

Role of nitrosyl factors in the hemodynamic adjustments to heat stress in the rat.

The present study examined the mechanisms responsible for the hindlimb vasodilation produced by elevating core body (colonic) temperature (Tco) of alpha-chloralose-anesthetized rats from 37 to 39 degrees C. Elevating Tco to 39 degrees C produced equivalent decreases in hindlimb vascular resistance in sham-operated (-48 +/- 2%) and sinoaortic baroreceptor-denervated rats (-44 +/- 3%) rats. There were no changes in mean arterial blood pressure, heart rate, or lumbar sympathetic nerve activity in either group. The prior administration of the alpha 1-adrenoceptor antagonist prazosin (100 micrograms/kg i.v.) did not prevent the heat-induced decrease in hindlimb resistance in sham-operated rats (-52 +/- 7% vs. baseline). In contrast, the fall in hindlimb resistance was markedly attenuated (-20 +/- 5% vs. baseline) in sham-operated rats that had received a prior injection of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (100 mumol/kg i.v.). Dexamethasone (1 mg/kg i.v.), administered to prevent the possible induction of inducible NOS, did not modify the heat-induced hindlimb vasodilation in sham-operated rats (-41 +/- 5%). These results demonstrate that the elevation of Tco to 39 degrees C in alpha-chloralose-anesthetized rats produces a relative vasodilation in the hindlimb that is not obviously linked to an alteration in lumbar sympathetic nerve activity. Because the vasodilation occurred in the presence of prazosin, it is unlikely that the decline in resistance is due to the loss of the vasoconstrictor potency of neurally derived catecholamines. The findings that NG-nitro-L-arginine methyl ester, but not dexamethasone, diminished the heat-induced hindlimb vasodilation suggests that the fall in resistance is due in part to constitutive NOS and supports a role for NOS as a mediator of thermoregulatory active vasodilation.

Acclimatization↗
PubMed1997

Stool form scale as a useful guide to intestinal transit time.

BACKGROUND: Stool form scales are a simple method of assessing intestinal transit rate but are not widely used in clinical practice or research, possibly because of the lack of evidence that they are responsive to changes in transit time. We set out to assess the responsiveness of the Bristol stool form scale to change in transit time. METHODS: Sixty-six volunteers had their whole-gut transit time (WGTT) measured with radiopaque marker pellets and their stools weighed, and they kept a diary of their stool form on a 7-point scale and of their defecatory frequency. WGTT was then altered with senna and loperamide, and the measurements were repeated. RESULTS: The base-line WGTT measurements correlated with defecatory frequency (r = 0.35, P = 0.005) and with stool output (r = -0.41, P = 0.001) but best with stool form (r = -0.54, P < 0.001). When the volunteers took senna (n = 44), the WGTT decreased, whereas defecatory frequency, stool form score, and stool output increased (all, P < 0.001). With loperamide (n = 43) all measurements changed in the opposite direction. Change in WGTT from base line correlated with change in defecatory frequency (r = 0.41, P < 0.001) and with change in stool output (n = -0.54, P < 0.001) but best with change in stool form (r = -0.65, P < 0.001). CONCLUSIONS: This study has shown that a stool form scale can be used to monitor change in intestinal function. Such scales have utility in both clinical practice and research.

Adult↗
PubMed1997

Military family adaptation to United Nations Operations in Somalia.

In this first known investigation of family responses to the absence of the active duty sponsor deployed to Somalia, 16 adults and 12 children repeatedly completed self-report measures of psychopathology and parenting attitudes. Stay-home parents registered more distress than their deployed spouses. Levels of parental intimacy varied significantly over time, reaching its lowest point near the end of the mission. Future humanitarian mission deployment support programs may need to more effectively address issues of parenting and spousal stress if future research confirms our findings.

Adaptation, Psychological↗
PubMed1997

Regulation of neuronal and recombinant GABA(A) receptor ion channels by xenovulene A, a natural product isolated from Acremonium strictum.

Xenovulene A (XR368) is a natural product exhibiting little structural resemblance with classical benzodiazepines yet is able to displace high-affinity ligand binding to the benzodiazepine site of the gamma-aminobutyric acid (GABA)A receptor. We have characterized this compound and an associated congener (XR7009) by use of radioligand binding and electrophysiological methodologies with native neurons and the Xenopus oocyte expression system. Xenovulene A, and the more potent XR7009, inhibited [3H]flunitrazepam binding to rat forebrain with Ki values of 7 and 192 nM, and 1.7 and 42 nM, respectively, each site accounting for approximately 50% of the total specific binding. In cerebellar and spinal cord membranes, these ligands identified only single binding sites. These ligands demonstrated no intrinsic agonist activity at recombinant GABA(A) receptors comprising alpha1beta1gamma2S subunits expressed in Xenopus oocytes, yet at 1 microM both significantly potentiated the GABA-induced response and reduced the GABA EC50 from 10.9 (control) to 5.1 (Xenovulene A) or 2.7 microM (XR7009). The rank potency order for enhancement of the 10 microM GABA response is: XR7009 (EC50, 0.02 microM) > diazepam (0.03) > Xenovulene A (0.05) > flurazepam (0.17). The activity of XR368 and XR7009 was reduced by the benzodiazepine antagonist, flumazenil, and absent in receptors devoid of the gamma2 subunit. These agents exhibited receptor subtype selectivity because alpha3beta1gamma2S receptors were less sensitive to these compounds relative to alpha1 subunit-containing receptors, whereas alpha6beta1gamma2S receptors were completely insensitive. Potentiation of the response to GABA on native GABA(A) receptors in cortical neurons substantiates the profile of the novel structures of Xenovulene A and XR7009 as specific benzodiazepine agonists.

Acremonium↗
PubMed1996

L- and D-S-nitroso-beta,beta-dimethylcysteine differentially increase cGMP in cultured vascular smooth muscle cells.

We examined the effects of the L- and D-isomers of S-nitroso-beta,beta-dimethylcysteine (L- and D-S-nitrosopenicillamine, 10(-7)-10(-5) M) on the guanosine 3',5'-cyclic monophosphate (cGMP) content of cultured porcine aortic smooth muscle cells and the decomposition of these stereoisomers to nitric oxide (NO). L-S-nitrosopenicillamine was a more potent generator of cGMP than D-S-nitrosopenicillamine although both stereoisomers equally decomposed to NO. The 10(-7) M concentration of L- or D-S-nitrosopenicillamine did not generate detectable amounts of NO although 10(-7) M L-S-nitrosopenicillamine but not D-S-nitrosopenicillamine generated significant amounts of cGMP. This study shows that the stereoisomeric configuration of S-nitrosopenicillamine is an important factor in its biological potency. The data suggest that the extracellular or intracellular generation of NO is not the only mechanism by which this S-nitrosothiol generates cGMP in vascular smooth muscle.

Analysis of Variance↗