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Biomedical subjects

J N Sharma

Publications and source records attributed to J N Sharma.

At least 73 records · Page 4Linked to original sources

Nature of the beta-adrenoreceptors in the tracheal smooth muscle of the adult pig.

Relaxant responses to isoprenaline (ISO), adrenaline (ADR) and noradrenaline (NA) were investigated on carbachol-contracted, isolated tracheal smooth muscle preparations of the adult pig to determine the nature of the beta-adrenoreceptors present. The order of relaxant potencies of the catecholamines on this preparation was ISO greater than ADR greater than NA. The potency ratio at 37 degrees C was 1:0.06:0.005. This suggests that beta 2-adrenoreceptors predominate in isolated tracheal smooth muscle of the adult pig. Though the order of potency for the above catecholamines did not change, at the lower temperatures of 29 degrees and 33 degrees C, the potency ratios were slightly modified to 1:0.0.98:0.004 and 1:0.07:0.004 respectively. pA2 values on pig tracheal smooth muscle were 8.65 and 9.13 respectively, for the non-selective beta-blockers propranolol and alprenolol, and 5.63, 5.20 and 6.26 respectively, for the beta 1 selective blockers practolol, atenolol and metoprolol and 6.82 for the beta 2 selective beta-blocker, H 35/25. The results suggest the existence and predominance of beta 2-adrenoreceptors in tracheal smooth muscle of the adult pig.

Adrenergic beta-Agonists↗

Separation of essential hypertensive patients based on blood pressure responses after the withdrawal of antihypertensive agents by step-wise discriminant analysis.

Thirty-five patients with uncomplicated hypertension were observed for blood pressure behaviour after prolonged antihypertensive medication withdrawal. Twenty-three patients (Group 1) remained normotensive (systolic less than 140 mmHg, diastolic less than 95 mmHg) for over 60 weeks compared to 12 patients (Group 2) who became hypertensive again during a 4-week placebo period. Discriminant analysis was performed on 31 clinical and laboratory variables measured before therapy to separate any discriminating factors for the two groups. Four variables maximized the separation of Group 1 from Group 2 patients. In descending order, these were serum sodium (p less than 0.001), mean corpuscular volume (p less than 0.01), serum albumin (p less than 0.01), and body weight (p less than 0.05). Using these four variables 73.9% of patients in Group 1 and 75% of patients in Group 2 were classified correctly into their respective groups. It is suggested that this observation may be useful in the development of new therapeutic regimens for patients with uncomplicated essential hypertension, for example by predicting those patients who may respond favourably to intermittent therapy or even to its withdrawal.

Adult↗

Effect of beta-adrenergic blockers on isolated coronary arterial strip and tracheal smooth muscle of pig.

Isolated coronary arterial strip and tracheal smooth muscle of pig, containing predominantly beta 1- and beta 2-adrenoceptors respectively, have been used for estimating the comparative potency of nine beta-adrenergic blocking agents. The order of potency of the antagonists on the isolated coronary arterial strip was propranolol greater than alprenolol greater than H 64/52 greater than H 64/55 greater than practolol greater than H 87/07 greater than atenolol greater than metoprolol greater than H 35/25, whilst the order of potency on the pig tracheal smooth muscle was alprenolol greater than propranolol greater than H 35/25 greater than H 87/07 greater than H 64/55 greater than H 64/52 greater than metoprolol greater than practolol greater than atenolol. Propranolol and alprenolol were almost equipotent in both the preparations and hence were nonspecific. Although practolol, metoprolol, H 64/55 and H 87/07 were beta 1-selective, their selectivity ratio was comparatively smaller than that of atenolol and H 64/52. The study indicates that H 64/52 and atenolol are the most specific beta-adrenergic blocking agents on isolated coronary arterial strip of pig and that their beta 1/beta 2-ratios are 126 and 120 respectively. H 64/52 like atenolol may be of therapeutic value in cardiovascular disorders.

Adrenergic beta-Antagonists↗

Detection of kallikrein-like activity in inflamed synovial tissue.

The synovial tissue kallikrein of rheumatoid patients, arthritic dogs and normal dogs has been partially characterized and estimated. Both human and dog synovial tissue kinin-forming enzyme appears to be distinct from plasmin, plasma kallikrein and pancreatic kallikrein. In three rheumatoid arthritic patients, the mean synovial tissue kallikrein level was found to be 106 +/- 13.5 ng bradykinin equivalents (BK Equiv) per g per min. In nine arthritic dogs the mean synovial tissue kallikrein level, 60.5 +/- 4.5 ng BK Equiv per g per min, was found to be greater (p less than 0.05) than that of five normal dogs (21.6 +/- 5.3 ng BK Equiv per g per min). The possible significance of this finding is discussed.

Aged↗

Pharmacological abnormality of kallikrein-kinin system in hypertension.

Until recently the possible role of vasodilator systems in the etiology of hypertension has been largely ignored, although deficiency of vasodilator influence could be more important than the presence of vasoconstriction in determining vascular tone. Lower concentrations of urinary kallikrein excretion have been widely indicated in clinical and in several experimental hypertensive situations. The reduced plasma kininogen levels may reflect either decreased synthesis compensating for a chronically reduced kinin generation or genetic abnormality leading to reduced plasma kininogen, which may be a predisposing factor in hypertension. An alternative possibly could be enhanced adrenergic control during hypertensive conditions which may cause reduction in prostaglandin and kallikrein-kinin systems. It has also been suggested that most of the pharmacological actions of the kallikrein-kinin system are mediated through prostaglandin formation. Thus, subnormal kallikrein-kininogen-kinin concentrations could be the cause of reduced vasodilating influence leading to both clinical and experimental hypertension.

Animals↗

A sensitive assay method of furosemide in plasma and urine by high-performance liquid chromotography.

A sensitive assay method of furosemide in plasma and urine by high-performance liquid chromatography (HPLC) is described. The minimum measurable concentrations of furosemide in plasma and urine were 0.2 and 5.0 microgram/ml, respectively; whereas the coefficients of variation of furosemide levels were found to be 7.8% for plasma and 2.0% for urine. These are within the acceptably low limits. Hence, the present method of furosemide is sensitive, reproducible, and accurate for therapeutic drug monitoring. The significance of this HPLC assay method is discussed.

Chromatography, High Pressure Liquid↗

Potassium conservation with amiloride/hydrochlorothiazide ("Moduret') in thiazide-induced hypokalaemia in hypertension.

A double-blind study was carried out in 24 hypertensive patients with thiazide-induced hypokalaemia (serum potassium less than 3.2 mmol/l) to compare the effects of treatment with an amiloride/hydrochlorothiazide combination or hydrochlorothiazide alone. The study was divided into three phases: (i) potassium repletion (Weeks 0 to 4) with oral potassium chloride (40 mmol/day), (ii) stabilization (Weeks 4 to 6) of normokalaemia, and (iii) active drug treatment (Weeks 6 to 14), patients being allocated at random to receive one or other of the two treatments. Dosage was 2 tablets per day of the 5 mg amiloride plus 50 mg hydrochlorothiazide combination or of 50 mg hydrochlorothiazide alone. The results showed that blood pressure control was comparable in both treatment groups but hydrochlorothiazide alone caused a statistically significant reduction in serum potassium levels compared to the drug combination. Apart from 1 patient who developed hypokalaemia on hydrochlorothiazide alone, no other side-effects of treatment were reported.

Amiloride↗

Comparison of antihypertensive efficacy: propranolol versus oxprenolol in accelerated hypertension.

An open, randomized crossover study was carried out in 8 patients with accelerated hypertension to compare the antihypertensive efficacy of oxprenolol with that of propranolol. Dosage was titrated for each patient to achieve normotensive levels and was in the range of 40 to 320 mg twice daily. The same mg dosage was maintained for the alternative drug after crossover at 32 weeks for the second treatment period. The results showed that both drugs had equivalent antihypertensive effect on the erect systolic and diastolic and supine systolic blood pressures. Oxprenolol, however, produced a significantly greater reduction in supine diastolic blood pressure than did propranolol. There were no significant changes in heart rate or any of the other clinical or laboratory parameters monitored during either treatment, and side-effects were remarkably infrequent.

Clinical Trials as Topic↗

The action of aspirin on plasma kininogen and other plasma proteins in rheumatoid patients: relationship to disease activity.

1. When six female seropositive rheumatoid patients were given placebo therapy for 48 h, their plasma kininogen level, 9.2 +/- 0.7 microgram bradykinin equivalents (bk eq) per ml, was found to be 59% greater than that of a group of eight healthy female volunteers (5.8 +/- 0.5 microgram/ml). 2. When the rheumatoid patients received aspirin therapy for 1 week, their mean plasma kininogen concentration fell by 31% to 6.3 +/- 0.8 microgram Bk eq/ml. This was accompanied by a 20.4% fall in mean plasma alpha 2-globulin level. Haematocrit and total plasma protein were not significantly altered (P > 0.05). 3. The fall in kininogen was very rapid, the main reduction occurring within the first hour. 4. Aspirin therapy greatly reduced the pain assessments but had no effect on plasma concentrations of IgG, IgA, IgM, complement component C3, nor on ESR, haemoglobin, leucocyte count, nor ring size. Left hand grip strength was increased while right hand grip strength was unchanged. 5. The action of aspirin on plasma kininogen and alpha 2-globulin was similar to that of indomethacin. Plasma kininogen has been considered to be an acute phase reactant. The possible diagnostic value of plasma kininogen estimation is discussed.

Adult↗

Some modern aspects of the mode of action of non-steroidal anti-inflammatory drugs.

The modern concepts of the mode of action of non-steroidal anti-inflammatory drugs with reference to the mediators of inflammatory processes are reviewed. It seems likely that prostaglandins (E1 and E2) and the kinin system are closely associated inflammatory mediators which are responsible for maintenance of the signs and symptoms of chronic inflammatory joint disease. It is suggested that the analgesic action of aspirin-like drugs in rheumatoid arthritis is the result not only of blocking production of prostaglandins but also of limiting the increased availability of kinin precursor (kininogen).

Animals↗

Surgical treatment of renovascular hypertension.

The evaluation of patients with inadequate control of diastolic blood pressure for surgically correctable forms of hypertension led to the detection and surgical treatment of 56 patients. Detection was facilitated by the use of hypertensive intravenous pyelography and Hippuran renal Scanning. Aortography proved the presence of renal artery disease and renal vein renin assay established its significance in the etiology of the patients' hypertension. Renal artery reconstruction was performed in 50 patients, including 5 who also had reconstruction of major aortoiliac lesions. The extent of renal artery disease precluded arterial reconstruction in six patients, who required nephrectomy. Two postoperative deaths occurred, for a mortality rate of 3.6 per cent. Improvement in mean diastolic blood pressure for the total group of patients from 118 mm Hg preoperatively to 86 mm Hg postoperatively was achieved. Forty-six patients (85 per cent) have a diastolic blood pressure of 90 mm Hg or less; in 5 patients the diastolic blood pressure is 91 to 100 mm Hg but is at least 20 mm Hg lower than the preorative level.

Adult↗

Acute renal failure in McArdle's disease.

A case of reversible acute renal failure in an adult with myophosphorylase deficiency (McArdle's disease) is described. Myoglobinuria, possibly abetted by intravenous urography, was incriminated as the cause of impairment of renal function.A muscle biopsy specimen contained necrotic fibers and no histochemically demonstrable phosphorylase activity. Ultrastructurally, nonspecific degenerative changes were observed.

Acute Kidney Injury↗