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Biomedical subjects

R K Goyal

Publications and source records attributed to R K Goyal.

At least 55 records · Page 3Linked to original sources
PubMed2000

Nitric oxide: a molecule of the millennium.

Recognition of Nitric oxide (NO) as the chemical entity of endothelium-derived relaxing factor (EDRF) has renewed the interest of the scientific community in the last decade. The outcome of research the world over is that the dreaded environmental pollutant is found to be a fundamental physiological mediator and effector. NO is synthesized endogenously by enzymes nitric oxide synthase (NOS) in specialized tissues from its precursor L-arginine. The L-arginine-NO biosynthetic pathway is involved in physiological processes such as vasodilation, memory, neuroprotection, peristalsis, penile erection, immune defense, various endocrine and exocrine secretions in various systems such as cardiovascular, CNS, reproductive and immune system. Small quantities of NO produced by constitutive enzymes mediate these physiological effects. The expression of inducible enzyme or overstimulation of constitutive enzymes leading to production of large quantities of NO is implicated in the cytotoxic effects observed in various disorders like AIDS, cancer, Alzheimer's, arthritis etc. In conclusion, NO is a 'double edged sword' and the challenge before the scientific community is to develop strategies for using it to our advantage.

Animals↗
PubMed2000

Antiulcer activity and the mechanism of action of magaldrate in gastric ulceration models of rat.

The present study was undertaken to investigate the mechanism of cytoprotective effects of magaldrate in aspirin plus pylorus-ligation model and ethanol-induced gastric ulcer model in rats. Magaldrate (60 mg/kg, p.o.) produced a significant reduction in the ulcer index and significant increase in mucus content in ethanol-induced gastric ulceration in rats. In aspirin plus pylorus-ligation model magaldrate produced significant decrease in ulcer index, total acidity and protein content (PR). It did not produce any significant change in volume of gastric secretion. However, it produced significant increase in total carbohydrate (TC) level but not in ratio between TC and proteins. It also produced a significant decrease in lipid peroxidation (as expressed by thiobarbituric acid reactive substance). Our data suggests the cytoprotective action of magaldrate on gastric mucosal cells which may be due to protection of gastric mucosa from lipid peroxidation.

Aluminum Hydroxide↗
PubMed2000

Insulin secretory response in healthy adult offspring of hypertensive parents.

OBJECTIVES: The present study was done to observe the insulin secretory response in healthy adult offspring of normotensive and hypertensive parents as the etiology of essential hypertension is largely treated as unknown. METHODS: The insulin secretary response was observed in 20 healthy adult offspring of normotensive parents (Group I) and 25 healthy adult offspring of hypertensive parents (Group II). The mean serum insulin levels were assessed at fasting, 30, 60, 90 and 120 minutes after 75 grams of oral glucose load in both groups. RESULTS: The mean serum insulin levels in fasting state was higher in group II (32.40 +/- 18.59) than group I (17.90 +/- 11.98) (p < 0.01). After 30 minutes mean serum insulin levels were higher in group II than group I (88.00 +/- 56.04, 40.5 +/- 15.15 respectively, p < 0.001). There was no statistically significant difference after 60, 90 and 120 minutes of oral glucose load (p > 0.05). CONCLUSIONS: Our observations suggest that the insulin secretory response in fasting and 30 minutes after oral glucose load was earliest metabolic abnormality in subjects at high risk for developing hypertension i.e. offspring of hypertensive parents.

Adult↗
PubMed2000

Tuberculous liver abscess.

Tuberculosis (TB) of liver is rare but may have a variety of presenting features similar to other more common conditions. A case of tuberculosis liver abscess with right sided pleural effusion is reported.

Aged↗
PubMed2000

Role of losartan therapy in the management of diabetic hypertension.

The management of diabetic hypertension requires meticulous selection of agents in the antihypertension armamentorium. There may be several associated factors to be considered while treating a hypertensive diabetic. These include hyperglycemia, dyslipidemia, proteinuria, left ventricular hypertrophy and heart failure to name a few. Losartan is the first of a new class of agents in the list of antihypertensive drugs. By its selective angiotension II receptor (subtype AT1) blocking action it is postulated to bring about a more complete inhibition of the renin-angiotensin system. Thus, it might produce all the benefits of angiotensin converting enzyme (ACE) inhibitor therapy with the freedom from cough so commonly seen with the use of ACE inhibitors. This review attempts to analyze the possible benefits of losartan therapy in diabetes.

Diabetes Complications↗
PubMed2000

Serum insulin assay: an important therapeutic tool in management of freshly diagnosed type 2 diabetes mellitus.

OBJECTIVES: The study was performed to see that, whether metabolic control and response to treatment in freshly diagnosed patients of type 2 diabetes mellitus is affected by primary pathology (hyperinsulinemia/inappropriate insulin secretion). METHODS: One hundred and eight freshly diagnosed patients of type 2 diabetes mellitus with age range from 30-65 years were followed for a period of three months. The blood glucose, serum triglyceride, and serum insulin levels were determined in each patient. Patients were found to have either higher or normal to low serum insulin values at fasting, and accordingly patients were distributed into two groups; group one (normal to low initial fasting serum insulin level i.e. < or = 30 microU/ml) and group two (high fasting serum insulin level i.e. > or = 30 microU/ml). Each group was further divided into two subgroups A and B. Subgroup A was treated with glipizide and B with metformin. RESULTS: Diabetic patients who had fasting hyperinsulinemia (n = 53, 100%) had blood pressure > or = 140/90 at the time of presentation. Patients who had fasting serum insulin within normal range only 30% (n = 17) had hypertension. Patients of group one had good recovery from hyperglycemia and reduction in triglyceride values when treated with sulphonylurea (subgroup A) as compared to patients treated with biguanide (subgroup B). On the contrary patients of group two showed poor glycemic control, increase in blood pressure and rise in serum triglyceride titre when treated with sulphonylurea (subgroup A) while in the same group biguanide effectively produced euglycemia with normalization of blood pressure and decrease in triglyceride levels (subgroup B). CONCLUSION: Assessment of initial serum insulin levels is helpful guide to decide about the type of oral hypoglycemic agent to be used in freshly diagnosed patients to type 2 diabetes mellitus.

Adult↗
PubMed1999

Calponin binds to the 20-kilodalton regulatory light chain of myosin.

Calponin (CaP) is a 34 kDa smooth muscle-specific protein that has been implicated in regulation of smooth muscle contractility. Two CaP binding sites on smooth muscle myosin rod have been recently described [Szymanski and Tao (1997) J.Biol.Chem. 272, 11142-11146]. We used a combination of cosedimentation, overlay, and fluorescence assays to determine the interaction between CaP and both subfragment 1 of myosin and isolated 20 kDa regulatory light chain of myosin (RLC). Subfragment 1, which was generated by cleavage of myosin with Staphylococcus aureus protease (myosin S1SA) inhibits cosedimentation of CaP with myosin filaments. Fluorescence assay showed that CaP labeled with fluorescent label (DAN-CaP) interacts with myosin S1SA in solution via a single class of binding sites. The binding constant (kaff) of this interaction at 50 mM NaCl is (2. 1 +/- 0.2) x 10(6) M-1 (n = 3). The interaction between DAN-CaP and myosin S1SA depends on ionic strength, and the EC50 of inhibition of this interaction occurs at about 130 mM NaCl. In contrast, the subfragment 1 that was generated by papain digestion (myosin S1PA), which cleaves RLC 4 kDa away from the NH2-terminal end of the molecule, does not interact with DAN-CaP. Overlay and fluorescent assay in solution showed that CaP binds to isolated RLC, suggesting that the interaction between CaP and subfragment 1 of myosin is due to a direct binding of CaP to RLC. CaP binding to myosin S1SA is stronger than to subfragment 2 in physiological salt concentrations. CaP binding to myosin head strengthened upon phosphorylation of RLC by Ca2+/calmodulin-dependent myosin light chain kinase. We suggest that CaP binds to subfragment 1 of myosin, exclusively via the NH2-terminal end of RLC, and this interaction could play a role in regulation of the actin-myosin interaction in smooth muscle contractility.

Actins↗
PubMed1999

Ajuba, a novel LIM protein, interacts with Grb2, augments mitogen-activated protein kinase activity in fibroblasts, and promotes meiotic maturation of Xenopus oocytes in a Grb2- and Ras-dependent manner.

LIM domain-containing proteins contribute to cell fate determination, the regulation of cell proliferation and differentiation, and remodeling of the cell cytoskeleton. These proteins can be found in the cell nucleus, cytoplasm, or both. Whether and how cytoplasmic LIM proteins contribute to the cellular response to extracellular stimuli is an area of active investigation. We have identified and characterized a new LIM protein, Ajuba. Although predominantly a cytosolic protein, in contrast to other like proteins, it did not localize to sites of cellular adhesion to extracellular matrix or interact with the actin cytoskeleton. Removal of the pre-LIM domain of Ajuba, including a putative nuclear export signal, led to an accumulation of the LIM domains in the cell nucleus. The pre-LIM domain contains two putative proline-rich SH3 recognition motifs. Ajuba specifically associated with Grb2 in vitro and in vivo. The interaction between these proteins was mediated by either SH3 domain of Grb2 and the N-terminal proline-rich pre-LIM domain of Ajuba. In fibroblasts expressing Ajuba mitogen-activated protein kinase activity persisted despite serum starvation and upon serum stimulation generated levels fivefold higher than that seen in control cells. Finally, when Ajuba was expressed in fully developed Xenopus oocytes, it promoted meiotic maturation in a Grb2- and Ras-dependent manner.

3T3 Cells↗
PubMed1999

Role of HERG-like K(+) currents in opossum esophageal circular smooth muscle.

An inwardly rectifying K(+) conductance closely resembling the human ether-a-go-go-related gene (HERG) current was identified in single smooth muscle cells of opossum esophageal circular muscle. When cells were voltage clamped at 0 mV, in isotonic K(+) solution (140 mM), step hyperpolarizations to -120 mV in 10-mV increments resulted in large inward currents that activated rapidly and then declined slowly (inactivated) during the test pulse in a time- and voltage- dependent fashion. The HERG K(+) channel blockers E-4031 (1 microM), cisapride (1 microM), and La(3+) (100 microM) strongly inhibited these currents as did millimolar concentrations of Ba(2+). Immunoflourescence staining with anti-HERG antibody in single cells resulted in punctate staining at the sarcolemma. At membrane potentials near the resting membrane potential (-50 to -70 mV), this K(+) conductance did not inactivate completely. In conventional microelectrode recordings, both E-4031 and cisapride depolarized tissue strips by 10 mV and also induced phasic contractions. In combination, these results provide direct experimental evidence for expression of HERG-like K(+) currents in gastrointestinal smooth muscle cells and suggest that HERG plays an important role in modulating the resting membrane potential.

Animals↗
PubMed1999

Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter.

To identify the enzymatic source of nitric oxide (NO) in the lower esophageal sphincter (LES), studies were performed in wild-type and genetically engineered endothelial nitric oxide synthase [eNOS(-)] and neuronal NOS [nNOS(-)] mice. Under nonadrenergic noncholinergic (NANC) conditions, LES ring preparations developed spontaneous tone in all animals. In the wild-type mice, electrical field stimulation produced frequency-dependent intrastimulus relaxation and a poststimulus rebound contraction. NOS inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM) abolished intrastimulus relaxation and rebound contraction. In nNOS(-) mice, both the intrastimulus relaxation and rebound contraction were absent. However, in eNOS(-) mice there was no significant difference in either the relaxation or rebound contraction from the wild-type animal. Both nNOS(-) and eNOS(-) tissues showed concentration-dependent relaxation to NO donor diethylenetriamine-NO and there was no difference in the sensitivity to the NO donor in nNOS(-), eNOS(-), or wild-type animals. These results indicate that in mouse LES, nNOS rather than eNOS is the enzymatic source of the NO that mediates NANC relaxation and rebound contraction.

Animals↗
PubMed1999

Lessons from genetically engineered animal models. IV. Nitric oxide synthase gene knockout mice.

Nitric oxide is a ubiquitous molecule implicated in a variety of biological processes. The specific action of nitric oxide depends on its enzymatic sources, namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), each having distinct tissue localization. Conventional pharmacological antagonists could not distinguish these enzymes or provide models of chronic nitric oxide depletion in whole animals. Several lines of knockout mice have been generated to distinguish the roles of nitric oxide from each enzyme: nitric oxide from nNOS is a major inhibitory neurotransmitter, nitric oxide from eNOS regulates blood flow under physiological conditions, and nitric oxide from iNOS causes hypotension during severe inflammatory conditions. Moreover, the nitric oxides from each isoform have different roles in tissue injury and inflammation. Studies of NOS-deficient animals have also identified redundant and compensatory pathways and revealed the consequences of life-long deficiency of these enzymes. The nNOS-deficient mice develop gastric dilation and stasis, the eNOS-deficient mice develop hypotension and lack vasodilatory responses to injury, and iNOS-deficient mice are more susceptible to inflammatory damage but more resistant to septic shock.

Animals↗
PubMed1999

Characterization of dopamine receptor subtypes involved in experimentally induced gastric and duodenal ulcers in rats.

There are conflicting reports about the role of dopamine in gastric and duodenal ulcers. This investigation was undertaken to characterize the specific subtypes of dopamine receptor involved in gastric and duodenal ulceration. Administration of dopamine D1 agonist fenoldopam and dopamine D2 antagonist sulpiride elicited a significant decrease in acid secretion, total acid output, pepsin output and histamine content in the gastric juice, and reduced ulcer-index values, in pylorus-ligated rats. However, dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo (d) naptho -(2,1-b) azepine) and the D2 receptor agonist quinpirole led to significant augmentation of these parameters compared with respective controls. In the restraint plus water-immersion stress model the score for intraluminal bleeding and the cumulative gastric lesion length was significantly lower for rats treated with fenoldopam and sulpiride. The opposite effects were observed after pretreatment of rats with SCH 39166 and quinpirole. In the cysteamine-induced duodenal ulcer model the mean ulcer area and the score for intensity were significantly lower for fenoldopam and sulpiride and higher for SCH 39166 and quinpirole. Our data suggest that the dopamine D1 and D2 receptors have opposite effects on gastric and duodenal ulcers. Whereas stimulation of dopamine D1 receptors inhibits the formation of gastric and duodenal ulcers, stimulation of dopamine D2 receptors has a pro-ulcerogenic effect.

Animals↗
PubMed1999

Abnormalities of cytokine receptor signalling contributing to diseases of red blood cell production.

The production of erythroid cells is a dynamic and exquisitely regulated process. The mature red cell is only the final phase of a complex but orderly series of genetic events that are initiated at the time a multipotent stem cell becomes committed to expressing the erythroid programme. Aberrations either in the intrinsic generation and/or amplification of functional erythroid cells or in the regulatory influences of microenvironment or cytokines form the basis for a number of blood diseases. In this review we focus upon abnormalities in red blood cell production and discuss how alterations in cytokine regulation of red blood cell production may contribute to these disease processes. We discuss clinical states in which blood red cell numbers are altered, including primary familial and congenital polycythaemia, the myeloproliferative disorder polycythaemia vera, erythroleukaemia, and Diamond-Blackfan anaemia. These disorders are briefly described and evidence supporting a potential role of specific cytokine receptor signalling defects as contributing to these phenotypes is discussed.

Erythropoietin↗
PubMed1999

Pharmacology of sildenafil citrate.

Erectile dysfunction is a common and multi-factorial disease that strongly impairs the quality of life in men. During the past decade, many new therapeutic strategies have become available. But the need for oral treatment was strongly felt. This need appears to have been fulfilled with the introduction of sildenafil. The drug acts by enhancing smooth muscle relaxant effect of nitric oxide. A number of clinical studies have now proved its safety and efficacy. The drug has shaken social life all over the world and to accept this "magic pill" or not remains the question of individual choice.

Clinical Trials as Topic↗
PubMed1998

An intermediate conductance K+ channel in the cell membrane of mouse intestinal smooth muscle.

Single channel currents were recorded from cell-attached and inside-out patches in smooth muscle cells of the mouse ileum in order to identify TEA-sensitive Ca2+-dependent K+ channels. Cells were bathed in high-K+ (150 mM) solution with [Ca2+] buffered to 80-150 nM with EGTA and patch pipettes were filled with low-K+ (2.5 mM) physiological solution. Two distinct TEA-sensitive unitary outward current levels were identified at a holding potential (Vh) of 0 mV, corresponding to intermediate conductance (IK, approximately 40 pS) and large conductance (BK, >200 pS) K+ channels. The open probability (Po) of IK channels increased with depolarization, the voltage for half-maximal activation averaging +12 mV in 80 nM Cabath2+. Raising the [Ca2+] in the high-K+ solution from 80 nM to 150 nM increased the Po of IK channels at Vh=0 mV from 0.078 to 0.21. Likewise, the open probability of BK channels at 0 mV was increased from 0.003 to 0.026. Unlike BK channels, IK channels inactivated with maintained depolarization with a voltage for half-maximal inactivation of -66 mV. IK channels were blocked by 2-5 mM external TEA and were sensitive to both charybdotoxin (100 nM) and apamin (500 nM). Our results suggest that IK channels contribute significantly to the Ca2+-dependent K+ conductance in visceral smooth muscle.

Animals↗