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Biomedical subjects

J N Sharma

Publications and source records attributed to J N Sharma.

At least 19 recordsLinked to original sources
PubMed1992

Influence of indomethacin on histamine- and acetylcholine-induced responses in the intact and denuded epithelium of guinea pig tracheal smooth muscle.

We have investigated the effect of indomethacin on histamine- and acetylcholine (ACh)-induced responses in the intact and denuded epithelium of guinea pig isolated tracheal smooth muscle. Epithelium removal resulted in increased responsiveness to ACh and histamine. Indomethacin (2.8 microM) enhanced the sensitivity of both intact and denuded preparations to histamine and ACh. These findings suggest that the tracheal epithelium of guinea pig plays a protective role against bronchoconstrictors, such as ACh and histamine. Furthermore, indomethacin-mediated hyperresponsiveness caused by these agonists in epithelium denuded preparations might be a reflection of removal of prostaglandin (PG) biosynthesis. A similar process of interaction in indomethacin-treated asthmatic patients (with damaged airway epithelium) might take place. The significance of these findings is discussed.

Acetylcholine↗
PubMed1992

Influence of a kinin antagonist on acute hypotensive responses induced by bradykinin and captopril in spontaneously hypertensive rats.

We have evaluated the effects of a B2 receptor antagonist (B5630) of kinins on BK and captopril-induced acute hypotensive responses in anaesthetized SHR. Intravenous treatment of BK (1.0 microgram) and captopril (0.3 mg/kg) caused significant (p < 0.05) fall in the SBP and DBP. Whereas BK caused greater fall in the SBP (p < 0.05), DBP (p < 0.01) and duration of hypotension (p < 0.05) when administered after captopril (Fig 1 and 2). All the hypotensive effects of BK and captopril were significantly antagonised (p < 0.05) in the presence of B5630 (2.0 mg/kg). Further, the duration of hypotensive responses of BK and captopril were blocked (p < 0.05) by B5630. The agonists and BK-antagonist did not cause significant (p > 0.05) alterations in HR during the entire investigation. These findings provide evidence to support the suggestion that B2 receptor might be involved in the regulation of the hypotensive actions of BK and captopril. Kinins should also have valuable functions in the antihypertensive property of captopril-like drugs.

Animals↗
PubMed1992

Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation.

Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.

Animals↗
PubMed1991

The role of the kallikrein-kinin system in joint inflammatory disease.

Components of kallikrein-kininogen-kinin are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B2 receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor antagonists may provide valuable new analgesic drugs. The mode of excessive kinin release in inflamed synovial joints leads to stimulation of pro-inflammatory actions of B2 kinin receptors. These properties could be antagonized by novel B2 receptor antagonists (see Fig. 4). Further, it is suggested that substances directed to reduce the activation of KKS may provide a pharmacological basis for the synthesis of novel antirheumatic or anti-inflammatory drugs.

Animals↗
PubMed1991

The role of kinin system in joint inflammatory disease.

Components of the kallikrein-kininogen-kinin are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B2 receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor antagonists may provide valuable agents as new analgesic drugs. Further, it is suggested that substances directed to reduce the activation of KKS may provide a pharmacological basis for the synthesis of novel anti-rheumatic or anti-inflammatory drugs.

Animals↗
PubMed1990

Does kinin mediate the hypotensive action of angiotensin converting enzyme (ACE) inhibitors?

The lack of kinin formation in systemic circulation and in the renal system may lead to the pathogenesis of high blood pressure (hypertension). Angiotensin converting enzyme inhibitors are able to protect the kinin inactivation by kininase II, therefore, causing an accumulation of kinin. Although the concentrations of kinin in plasma after oral administration of ACE inhibitors are conflicting this is mainly due to methodological difficulties. Kinin receptor antagonists are becoming most reliable pharmacological probes for defining the molecular actions of kinin in several physiopathological states, and in the mechanism of actions of drugs which are dependent on the kinin system. The blood pressure lowering effect of ACE inhibitors can be antagonized by the pretreatment with kinin receptor antagonists. I have therefore proposed that the hypotensive action of ACE inhibitors may reflect the activation of kinin receptor. It is suggested that the development of compounds having protective properties on the kallikrein-kinin system might be therapeutically applicable as anti-hypertensive drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

The role of chemical mediators in the pathogenesis of inflammation with emphasis on the kinin system.

In recent years, numerous agents have been recognized as inflammatory mediators. In this review, however, we discuss only those having direct relevance to human inflammatory diseases These mediators are clinically important due to their proinflammatory properties such as vasodilatation, increased vascular permeability, pain and chemotaxis. They may lead to the fifth cardinal sign, loss of function in inflammatory diseases. Agonists and non-specific antagonists are used as pharmacological tools to investigate the inflammatory role of PGs, LTs, PAF, IL-1, histamine, complement, SP, PMN-leukocytes, and kallikrein-kininogen-kinin systems. Unfortunately, no compound is known which concurrently abolishes all actions and interactions of inflammatory mediators. Therefore it would be highly useful to promote efforts in developing selective and competitive antagonists against proinflammatory actions of these chemical mediators. This may help to a better understanding of the pathogenesis of inflammatory reactions, and it may also be useful for the therapy of inflammatory diseases.

Anaphylatoxins↗
PubMed1990

Elective conversion from cyclosporine to azathioprine in sensitized patients following cadaveric renal transplantation.

The safety of conversion from cyclosporine to azathioprine following renal transplantation in patients generally considered to be at immunologic risk for allograft loss has not been established. We examined a group of 59 patients who underwent cadaveric renal transplantation and elective conversion from cyclosporine to azathioprine 8.3 +/- 3.8 months following transplantation. Forty-three of these patients received a first transplant and had panel-reactive antibodies (PRA) less than 40% (unsensitized). Sixteen patients received at least their second allograft or had PRA of 40% or more (sensitized). Average follow-up was 17.9 +/- 8.2 months. Nine patients (15%) failed conversion as manifested by the need to restart cyclosporine 1 to 10 months following conversion. All were in the unsensitized group. Of those successfully converted, there were six allograft failures, two from patient death, one from acute rejection, one from recurrent diabetic nephropathy, and two from patient noncompliance. All were in the unsensitized group, although the difference from the sensitized group was not statistically significant (P = 0.051). There were three rejection episodes, all successfully reversed, in the sensitized group and six rejection episodes in the unsensitized group, five of which were reversed. Overall renal function improved in both groups as shown by a significant decrease in serum creatinine. Neither group required increased doses of steroid to compensate for lack of cyclosporine. From these data we can recommend conversion from cyclosporine to azathioprine in patients with cytotoxic antibodies or those undergoing retransplantation.

Actuarial Analysis↗
PubMed1989

Fortified high calorie human milk for optimal growth of low birth weight babies.

This study was undertaken with the aim of providing adequate calories for optimal growth in low birth weight (LBW) by fortifying human milk with medium chain triglycerides and sugar. Twenty-one LBW babies with birth weight between 1.0 and 1.75 kg and gestational age 28-36 weeks constituted the study material. They were administered expressed human milk, initially with gavage and then by spoon. Coconut oil and sugar were added to increase the caloric density to (0.8 cal/ml). The aim was to achieve a caloric intake of 200 cal/kg. This was achieved between 6 and 11 days of birth. Additionally, vitamin C (50 mg) and vitamin E (25 IU/kg/day) were administered. Weight was recorded daily to the nearest 50 g. Head circumference was measured weekly using a non-stretch tape measure. Blood urea nitrogen was measured once the neonate started taking high calorie feeds. Stools were examined daily for the presence of fat globules and reducing substances and for the pH. All but one neonate tolerated the feeds well and there were no complications, such as vomiting, diarrhoea, abdominal distension, or necrotizing enterocolitis. The weight gain recorded was 17.29 +/- 5.30 g/day or 13.95 +/- 5.52 g/kg/day. The study demonstrates that optimal growth can be achieved within the metabolic tolerance of low birth weight infants by administering fortified high calorie breast milk.

Energy Intake↗
PubMed1989

Ratio of mid arm circumference to head circumference as a predictor of small for gestational age babies.

Birth weight (BW), mid-arm circumference (MAC), head circumference (HC) and MAC/HC ratio were evaluated in 845 term babies within 48 h of birth. MAC/HC ratio of less than 0.28 had a statistically significant sensitivity, specificity and predictive value (p less than 0.001) for identifying term small for gestational age babies. This ratio provides a simple, accurate and cheap way of screening SGA babies. This method may be employed for identification of SGA babies even by paramedical workers at community level. As with any other field index appropriate supervision and standardisation are essential for its usefulness.

Anthropometry↗
PubMed1989

Thigh circumference at birth as the best predictor of low birth weight babies.

The present study was undertaken to find out the best simple anthropometric parameter for identifying low birth weight babies (LBW). A total of 1000 newborn babies were subjected to anthropometry within 48 hours of life. Birth weight was significantly correlated (p less than 0.001) with thigh circumference (TC), mid-arm circumference (MAC), chest circumference (CC), length (L) and head circumference (HC). However, the correlation was maximum for TC (r = 0.9201). All anthropometric indicators had a statistically significant sensitivity, specificity and predictive value (p less than 0.001) for identifying less than or equal to 2500 g birth weight babies. However, thigh circumference of less than or equal to 14.5 cm and less than or equal to 13.5 cm had the best sensitivity, specificity and predictive value for identifying babies with birth weight of less than or equal to 2500 g and less than or equal to 2000 g, respectively. TC at birth is a cheap, simple, quick and reliable indicator for predicting LBW babies. It may be used whenever weighing at birth is not feasible.

Anthropometry↗
PubMed1988

Interrelationship between the kallikrein-kinin system and hypertension: a review.

The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.

Humans↗
PubMed1988

Plasma kinin-precursor levels in clinical intestinal inflammation.

Plasma kinin-precursor (kininogen) concentrations were measured in the peripheral venous blood of 7 untreated patients with inflammatory bowel diseases, 12 healthy subjects, and 5 uncomplicated fracture cases. The mean plasma kininogen levels were significantly raised (P less than 0.025) in patients with intestinal inflammation (7.0 +/- 1.0 micrograms BK Eq/ml), as compared with the value found in healthy subjects (5.7 +/- 0.7 micrograms BK Eq/ml), and in fracture cases (5.0 +/- 1.2 micrograms BK Eq/ml). The packed cell volume did not differ (P greater than 0.05) between patients and control groups. Thus, the raised plasma kininogen levels observed in patients were not the result of nonspecific changes in plasma volume. It is suggested that raised plasma kininogen might be due to increased synthesis to provide substrate for excessive kinin-formation, to a potent inflammatory agent, or to high synthesis of acute-phase reactants. The possible significance of this observation is discussed.

Acute-Phase Reaction↗