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Biomedical subjects

R K Goyal

Publications and source records attributed to R K Goyal.

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

Effect of chronic treatment with spirapril on biochemical parameters in streptozotocin-diabetic and spontaneously hypertensive rats.

Present investigation was undertaken to study the effects of 6 week treatment with spirapril (2 mg/kg po) on insulin sensitivity, and serum lipid levels in streptozotocin (STZ)-diabetic and spontaneously hypertensive (SH) rats. Treatment of rats with spirapril in diabetic and diabetic with hypertensive animals significantly prevented STZ-induced loss of body weight, hypertension, and bradycardia. It also partially but significantly prevented STZ-induced hyperglycaemia in both diabetic Wistar and SH animals. Insulin level was not altered by spirapril treatment. There was significant reduction in cholesterol levels in the diabetic rats. In conclusion, the present investigation presents a number of beneficial effects of spirapril treatment in diabetic and/or hypertensive rats. Spirapril may be considered as one of the drugs of choice in treatment of hypertension when associated with diabetes

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Neuronal constitutive nitric oxide synthase is involved in murine enteric inhibitory neurotransmission.

UNLABELLED: Mice lacking neuronal nitric oxide synthase gene (ncNOS) were used to determine the enzymatic source of nitric oxide (NO) and its relationship with other putative inhibitory neurotransmitters. Inhibitory junction potentials (IJP) of circular smooth muscle of gastric fundus were studied. The IJP in the wild-type mice consists of overlapping components, the fast and slow IJPs. NOS inhibitor L-NA or VIP receptor antagonist VIP(10-28), blocks the slow IJP but not the fast IJP. The fast UP is blocked by alpha-beta methylene ATP tachyphylaxis, by reactive blue 2, and by apamin. The IJP in the ncNOS-deficient [ncNOS(-)] mutant is of short duration and is abolished by blockers of the fast IJP, but is unaffected by blockers of the slow UP. Exogenous VIP produces membrane hyperpolarization in strips from wild-type but not ncNOS(-) mice. The hyperpolarizing action of VIP is resistant to nifedipine but is sensitive to omega-conotoxin GVIA. IN CONCLUSION: (a) NO derived from ncNOS is an inhibitory neurotransmitter rather than a postjunctional mediator; (b) VIP is a prejunctional neurotransmitter that causes release of evanescent NO; and (c) ATP acts in parallel with the VIP/NO pathway.

Adenosine Triphosphate↗
PubMed1996

Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction.

Pancreatic acinar metaplasia (PAM), defined as nodules of glandular tissue forming acini composed of cells with coarse apical eosinophilic granules, with or without mucous cells, was recently recognized in gastric mucosa, but its significance is not known. As part of a study on intestinal metaplasia at the gastroesophageal junction (GEJ), we evaluated the prevalence and clinical and histologic correlates of PAM in biopsy specimens from the gastroesophageal squamocolumnar junction. All adult patients having elective upper gastrointestinal endoscopy over a 6-month period were invited to participate. Clinical data and endoscopic findings were recorded. Biopsy specimens, obtained from both sides of the apparent squamocolumnar junction, were processed routinely and reviewed (without knowledge of the clinical data) to evaluate types of epithelium, types and degree of inflammation, and the presence of PAM. The presence or absence of PAM was then correlated with the other histologic findings and with the clinical and endoscopic data. The study comprised 155 patients (79 women, 76 men; 139 white patients, nine black patients, and seven patients of other ethnic groups). Their mean age was 52 years (range: 18-89 years). PAM was present in 37 patients (24%). PAM was not associated with any of the reported symptoms, endoscopic evidence of esophagitis or columnar epithelium in the distal esophagus, or any of the histologic features evaluated, including active esophagitis, intestinal metaplasia at the GEJ, active and chronic gastritis, intestinal metaplasia in the stomach, and Helicobacter infection. Although PAM is present in a considerable proportion (24%) of patients with mucosal biopsy specimens from the squamocolumnar junction, it appears to be an incidental finding unrelated to clinical or histologic abnormalities. We therefore suggest a congenital, rather than an acquired, origin for this entity.

Adult↗
PubMed1996

Hodgkin disease after renal transplantation in childhood.

PURPOSE: Hodgkin disease (HD) has rarely been described in organ transplant recipients. We herewith report two cases of Epstein Barr virus (EBV)-associated HD that occurred in renal transplant recipients during childhood. PATIENTS: A 19-year-old who had a renal transplant at 12 years of age developed mixed cellularity HD 1 year following diagnosis of an EBV-associated lymphoproliferative disorder. The second case is an 18-year-old man who developed nodular sclerosing HD 7 years after renal transplantation. RESULTS: EBV latent membrane protein-1 antigen was strongly expressed in the Hodgkin Reed-Sternberg cells in both cases. These patients achieved complete remission with standard chemotherapy without unusual toxicity. CONCLUSIONS: Renal transplant recipients on immunosuppressive therapy can develop Hodgkin disease. A review of literature on this subject with emphasis on recent molecular studies on EBV-associated cases and observed increase in incidence of HD in HIV seropositive individuals is presented.

Adolescent↗
PubMed1996

Tyrosine kinase-dependent modulation of calcium entry in rabbit colonic muscularis mucosae.

We studied the role of tyrosine kinase in the regulation of Ca2+ entry in single smooth muscle cells of the rabbit colonic muscularis mucosae using the whole cell patch-clamp technique. Step depolarization to +10 mV from a holding potential of -60 mV produced inward currents that were abolished by 1 microM nifedipine, consistent with the activation of L-type Ca2+ channels. The tyrosine kinase inhibitors, genistein and tyrphostin B42, dose dependently inhibited these Ca2+ currents. The inactive analogue of tyrphostins, tyrphostin A1, did not affect the currents at concentrations of up to 100 microM. Conversely, the tyrosine phosphatase inhibitor, orthovanadate, enhanced peak Ca2+ currents by 30%. Spontaneous transient outward currents (STOCs) (50-600 pA) were elicited with high K+ in the pipette and at 0-mV holding potential. STOCs were activated due to release of Ca2+ from intracellular stores, required the presence of extracellular Ca2+ concentration, and were insensitive to nifedipine. Genistein abolished STOCs; however, in its presence, outward currents activated by caffeine or carbachol were not affected. The refilling of the Ca2+ stores was studied by first depleting intracellular Ca2+ with carbachol in Ca(2+)-free media followed by reperfusing with a Ca(2+)-containing solution for 3-5 min. Under these conditions, a second application of carbachol evoked an outward current due to Ca2+ release. However, this effect was abolished when the refilling of the stores was carried out in the presence of genistein. Carbachol-evoked currents were not attenuated when the refilling was examined in the presence of orthovanadate. Epidermal growth factor (200 ng/ml) enhanced Ca2+ currents by 60% and markedly increased STOCs by over 200%. Western blot analysis, using an anti-phosphotyrosine antibody, showed a tyrosine phosphorylated protein of 60 kDa in control conditions. This was markedly increased after treatment with epidermal growth factor and carbachol. These results suggest that 1) tyrosine kinase modulates the entry of Ca2+ through L-type channels and through nifedipine-resistant pathways involved in refilling of intracellular stores and 2) stimulation of the kinase by agonists enhances Ca2+ entry in the smooth muscle cells of the rabbit colonic muscularis mucosae.

Animals↗
PubMed1996

Caffeine- and carbachol-induced Cl- and cation currents in single opossum esophageal circular muscle cells.

Cl- and cation currents may play important roles in esophageal smooth muscle membrane potential changes and contraction. We studied Ca2+ release-activated cell-shortening and membrane currents in single cells freshly dispersed from the circular muscle of the opossum esophagus using the standard patch-clamp whole cell recording method. Caffeine (10-20 microM) and carbachol (10-100 microM) shortened the single smooth muscle cells by releasing intracellular Ca2+. At a holding potential of 0 mV, spontaneous transient outward currents STOCs, representing spontaneous Ca(2+)-activated K+ currents) were recorded. Caffeine, carbachol, or ionomycin evoked large outward currents (up to 1,650 pA) and subsequently abolished STOCs. At a holding potential of -50 mV in K(+)-containing solutions, an outward current in response to the agonists was observed; in some cells, the outward current followed an inward current. In K(+)-free solutions, the agonists induced only an inward current whose reversal potential was shifted by alteration of the anion gradient but not by that of the cation. With a low-Cl- pipette solution (Cl- substituted by glucuronate or glutamate), the inward currents were dependent mainly on the external cation gradient. This cation channel was permeable to Ba2+. Inclusion of 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in the pipette solution abolished all these currents. These data suggest that in the opossum esophageal circular muscle 1) Ca2+ released from the intracellular stores by caffeine and carbachol is sufficient to induce single smooth muscle cell contraction and 2) the caffeine-, carbachol-, and ionomycin-induced membrane currents consist of Ca(2+)-activated K+, Cl-, and cation conductances.

Animals↗
PubMed1996

Effect of chronic treatment with hydralazine on various in vitro preparations of rat.

Effect of chronic treatment with hydralazine (40 mg/kg/day) on isolated heart, anococcygeus muscle and myometrial preparations from rats has been studied. The treatment for 6 weeks caused a significant increase in isoprenaline induced positive inotropic response in rat heart. However, isoprenaline induced positive chronotropic effects were not altered significantly by chronic hydralazine treatment. Chronic hydralazine treatment also failed to alter noradrenaline induced contractile effects on rat anococcygeus muscle. However, on myometrial preparations from hydralazine treated rats showed an increase in adrenaline induced relaxations. The results of the present study can be explained on the basis of the effect of hydralazine on adenylate cyclase-cyclic adenosine monophosphate (cAMP).

Animals↗
PubMed1996

Investigation into the possible mechanisms involved in altered digoxin levels in diabetic patients.

The present study was undertaken to investigate the possible factors which may contribute to the altered digoxin levels in diabetic patients. The digoxin levels were found to be significantly higher in diabetics (1.74 +/- 0.09 ng/ml) as compared to non-diabetics (0.76 +/- 0.07 ng /ml). There was a positive correlation between digoxin levels and glycosylated haemoglobin levels. All diabetic patients had serum creatinine, urea and potassium levels within normal limits. However, serum TSH levels were found to be significantly higher in diabetics as compared to controls. Serum tri-iodo-1-thyronine (T3) levels were found to be lower in diabetics as compared to non-diabetics. Our data suggests that diabetes-mellitus causes alteration of digoxin levels. One of the causes of this increase in digoxin levels may be a tendency towards mild hypothyroidism associated with diabetes mellitus.

Aged↗
PubMed1996

Effects of enalapril on lipid profile in diabetic and non-diabetic essential hypertensive patients.

Effectiveness of enalapril was studied in hypertensive patients with or without diabetes-mellitus. All the patients received enalapril, 5-20 mg per day for 9 months. Enalapril effectively controlled the blood pressure and favourably altered the lipid levels and did not affect the glucose level in diabetics as well as non-diabetics. Enalapril may be considered as a better therapeutic option for the treatment of hypertension associated with diabetes mellitus.

Aged↗
PubMed1996

Synthesis and quantitative structure-activity relationships of antihyperlipaemic 2-substituted thieno[3,2-d]pyrimidin-4(3H)-ones.

The synthesis, antihyperlipaemic evaluation and quantitative structure-activity relationships (QSAR) of two series of thieno[3,2-d]pyrimidin-4-one derivatives are reported. While most of the compounds in these series were found to exhibit antihyperlipaemic activity, the QSAR study of these two series indicated a positive influence of only the electronic nature of the 2-substitutents on the biological activity. The lipophilic and the steric parameters did not appear to be significant.

Animals↗
PubMed1996

Effect of chronic treatment with atenolol and prazosin in streptozotocin induced diabetic rats.

Diabetes-mellitus was induced in rats by single intravenous injection of (45 mg/kg) streptozotocin (STZ). STZ diabetic rats showed hypertension, decreased cardiac functions, cardiomyopathy and hypercholesterolemia observed at the end of six weeks. Chronic treatment with atenolol (10 mg/kg) for six weeks in the diabetic rats reduced the elevated blood pressure, but failed to prevent STZ induced other complications. Chronic treatment with prazosin (1 mg/kg, po) in the diabetic rats, reduced the elevated blood pressure and also partially prevented hypercholesterolemia, cardiac dysfunctions and in particular the cardiomyopathy. The results suggest that prazosin may be a better option as compared to atenolol in hypertension when it is associated with diabetes mellitus.

Adrenergic alpha-Antagonists↗
PubMed1995

Acyclovir-induced neutropenia in an infant with herpes simplex encephalitis: case report.

A newborn infant whose condition was diagnosed as herpes simplex encephalitis and who had subsequent recurrences of skin disease had repeated episodes of neutropenia while receiving therapy with intravenous (30 mg/[kg.d]) or oral (30 mg/]kg.d]) acyclovir. The neutropenia did not recur when the dosage of oral acyclovir was reduced to 10 mg/(kg.d). This case represents the first well-documented report of acyclovir-induced neutropenia.

Acyclovir↗
PubMed1995

Effects of chronic nifedipine treatment on streptozotocin-induced diabetic rats.

We studied the effects of 6-week treatment with nifedipine (35 mg/kg/day orally, p.o.) on streptozotocin (STZ)-induced diabetic rats. Injection of STZ [45 mg/kg intravenously, (i.v.) single dose] produced a significant increase in blood pressure (BP), bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism, depression in left ventricular developed pressure (LVDP), cardiomyopathy, and nephropathy. Treatment of diabetic rats with nifedipine normalized the BP and prevented bradycardia. Insulin levels were decreased after nifedipine treatment in diabetic as well as nondiabetic rats. However, serum glucose levels were also partially decreased in diabetic animals by nifedipine treatment. In control animals as well, glucose levels were in the normal range despite lower insulin levels observed after nifedipine treatment. Nifedipine treatment significantly prevented STZ-induced increase in cholesterol and triglyceride levels. Nifedipine treatment significantly prevented STZ-induced hypothyroidism and also prevented STZ-induced cardiac depression and cardiomyopathy. Our data indicate that nifedipine increases insulin sensitivity and has some beneficial effects on cardiovascular parameters. It may therefore be considered a preferred drug in the treatment of hypertension associated with diabetes mellitus.

Administration, Oral↗
PubMed1995

Gastric and duodenal anti-ulcer activity of SKF 38393, a dopamine D1-receptor agonist in rats.

The effect of SKF 38393 (1-phenyl-7,8-diol-2,3,4,5-tetrahydro-1H-3-benzazepine), a specific dopamine D1-receptor agonist, was studied on pylorus-ligation and water immersion plus restraint stress-induced gastric ulcers, and cysteamine-induced duodenal ulcers in rats. Repeated administration of SKF 38393 (5 and 10 mg kg-1, p.o.) for six days was found to be effective in the prevention of gastric ulceration induced by water immersion plus restraint stress in rats. In 19-h pylorus-ligated rats, repeated treatment with SKF 38393 showed a significant reduction in the number and severity of ulcers. SKF 38393 did not alter the total gastric-mucosal carbohydrates:protein ratio; however, the gastric content volume and the free and total acidity were significantly reduced. In cysteamine-induced duodenal ulcers, the treatment with SKF 38393 for 6 days prevented the duodenal lesions. Our data suggests the involvement of dopamine D1 receptors in the anti-ulcer activity of SKF 38393, which could be largely attributed to its anti-secretory effect. Its anti-ulcer activity against water immersion plus restraint, also points towards a central mode of action, but its failure to alter the carbohydrate:protein ratio rules out any protective effect through the strengthening of the gastric mucosal barrier.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Heartburn in patients with achalasia.

Heartburn, the main symptom of gastrooesophageal reflux disease (GORD), might be expected to occur infrequently in achalasia, a disorder characterised by a hypertensive lower oesophageal sphincter (LOS) that fails to relax. Nevertheless, it is often described by patients with achalasia. The medical records of 32 patients with untreated achalasia who complained of heartburn, and of 35 similar patients who denied the symptom, were reviewed to explore the implications of heartburn in this condition. Data on endoscopic and manometric findings, and on the onset and duration of oesophageal symptoms were collected. Three patterns of heartburn were observed: (1) in 8 patients (25%) the onset of heartburn followed the onset of dysphagia, (2) in 15 patients (47%) heartburn preceded the onset of dysphagia and persisted as dysphagia progressed, and (3) in 9 patients (28%), heartburn preceded the onset of dysphagia and stopped as dysphagia progressed. The mean (SD) basal LOS pressure in the patients with heartburn (38 (16) mm Hg) was significantly lower than that in patients without the symptom (52 (26) mm Hg); the lowest LOS pressure (29 (11) mm Hg) was observed in the subset of patients whose heartburn preceded the onset of dysphagia and then stopped. It is concluded that patients who have achalasia with heartburn have lower basal LOS pressures than patients who have achalasia without this symptom. In some patients with achalasia, the appearance of dysphagia is heralded by the disappearance of longstanding heartburn. For these patients, it is speculated that achalasia develops in the setting of underlying GORD.

Deglutition Disorders↗