PubMed Health⌕ Search

Biomedical subjects

S M Khedun

Publications and source records attributed to S M Khedun.

16 recordsLinked to original sources
PubMed1997

Changes in urinary tissue kallikrein excretion in black African women with hypertensive disorders of pregnancy.

The aim of this study was firstly to establish whether tissue kallikrein (TK) was involved in the aetiology of hypertensive disorders of pregnancy. Secondly, to assess whether tissue kallikrein:creatinine ratios may differentiate normotensive pregnant women from those with hypertensive disorders of pregnancy and have a predictive value. Random untimed urine samples were collected from all women (n = 264) recruited to this study. Urine specimens were analyzed for urinary tissue kallikrein using a selective, synthetic chromogenic tripeptide substrate (H-D-Val-Leu-Arg-pNA). Urinary creatinine levels were measured using standard methods. There was a significant difference in the excretion of urinary tissue kallikrein between normotensive pregnant women (2.91 ng TK/microgram protein) and women with mild (2.52 ng TK/microgram protein; p < 0.0001) and severe (1.53 ng TK/microgram protein; p < 0.0001) hypertension in pregnancy. No statistical difference was observed with regard to urinary tissue kallikrein excretion between normotensive pregnant and normotensive non-pregnant women (2.87 ng TK/microgram protein; p = 0.16). A positive correlation was observed between the diastolic blood pressure and urinary tissue kallikrein excretion in women with hypertensive disorders of pregnancy. When compared to the normotensive pregnant group, the urinary kallikrein:creatinine ratios were significantly lower in the mild (0.6 versus 0.3; p < 0.0001) and severe (0.6 versus 0.12; p < 0.0001) hypertensive groups. The urinary creatinine excretion was significantly higher in the mild (9.55 +/- 2.6 mmol/l; p < 0.0001) and in severe (15.62 +/- 5.48 mmol/l; p < 0.0001) hypertensives when compared to normotensive pregnant values (5.65 +/- 2.6 mmol/l). The reduced urinary tissue kallikrein excretion in hypertensive disorders of pregnancy may be a significant factor in the development of the hypertension in pregnancy. Measurement of urinary tissue kallikrein: creatinine ratios may represent a simple and practical predictive test to differentiate women with hypertensive disorders of pregnancy from normotensive pregnant women.

Adult↗
PubMed1997

Localisation of tissue kallikrein in the kidney of black African women with early onset pre-eclampsia: a pilot study.

Increased renal production of vasodilator mediators like kinins would counteract the vasospasm of pre-eclampsia. This study examines the cellular localisation of tissue kallikrein (TK), the potent kinin forming enzyme within the nephron of patients with early onset pre-eclampsia. Using the peroxidase-antiperoxidase immunoenzyme complex, TK was immunolocalised in the principal cells of the distal connecting tubule and the cortical collecting duct cells of the distal nephron of control tissue. Moderate reactivity was observed in the epithelial cells lining the Bowmans capsule. In early onset pre-eclampsia, TK was additionally localised in the proximal tubule cells, however, the intensity of reactivity was reduced when compared to that of the distal tubule cells. In patients with hypertension of pregnancy, the occurrence of TK in the proximal tubule suggests either gene induction or emiocytosis of TK.

Adolescent↗
PubMed1997

Drug management of hypertensive disorders of pregnancy.

Drugs used in the acute and long-term management of hypertension in pregnancy and the preeclampsia-eclampsia syndrome have been reviewed and their therapeutic effects and maternal and fetal adverse effects have been considered. The review also focuses on recent developments in the areas of prevention and management of pre-eclampsia-eclampsia syndrome. Although a number of new drugs have emerged, as potentially useful in the management of hypertension in pregnancy and pre-eclampsia-eclampsia syndrome, some remain at the cornerstone of therapy; for example, methyldopa for long-term treatment of chronic hypertension, hydralazine or nifedipine for rapid reduction of severely elevated blood pressure, and magnesium sulphate for eclampsia. Some of these agents, especially the calcium antagonists, show promise in that their use is associated with fewer side effects. Safety for the fetus, however, has not been adequately evaluated yet. Neither aspirin nor calcium supplements appear to improve the outcome in pregnancy. Currently, the dilemma whether to treat hypertension in pregnancy and pre-eclampsia-eclampsia syndrome with old, established, cost-effective drugs or the promising newer drugs provides an interesting academic challenge.

Adrenergic Antagonists↗
PubMed1997

Correlation between histological changes and loss of anionic charge of the glomerular basement membrane in early-onset pre-eclampsia.

This study morphometrically evaluates the glomerular anionic charge and examines the renal pathology in African women with early-onset pre-eclampsia. Polyethyleneimine-labelled anionic sites were decreased within the glomerular basement membrane in the early-onset pre-eclampsia group as compared with the control group (p < or = 0.02). A strong correlation (r = -0.76) was obtained between the number of anionic sites and the severity of proteinuria. Renal biopsy specimens revealed the coexistence of decreased glomerular charge with pathology of glomerular basement membrane, endothelial cells, foot processes, and mesangial cell proliferation. The loss of glomerular charge induces structural alterations of the glomerular filtration barrier and may be the mechanism responsible for proteinuria in early-onset pre-eclampsia.

Anions↗
PubMed1996

Hexane cardiotoxicity--an experimental study.

Ventricular arrhythmia has been postulated as a possible cause of death in young black children who abuse volatile substances, primarily benzine and certain glues that contain n-hexane. A series of protocols were designed to determine the effect of n-hexane on myocardial function and morphology in male laboratory rats. In the first protocol, experiments were designed to study the effect of n-hexane in initiating ventricular fibrillation and in modifying myocardial magnesium and potassium levels. The results showed that the thresholds for ventricular fibrillation and myocardial magnesium and potassium levels were reduced compared to control values. In the second protocol, n-hexane-treated rats were supplemented with intragastric administration of magnesium and potassium salts. The outcome of the experiments indicated that although the myocardial magnesium and potassium levels were corrected, the threshold for ventricular fibrillation remained low compared to control values. In the third protocol, experiments were designed to examine myocardial morphology by electron microscopy. Cellular changes were observed in the myocardium as a result of administering n-hexane. These cellular changes were considered to be responsible for the decreased threshold for ventricular fibrillation. The present study indicates that n-hexane, a constituent of benzine and certain glues, is cardiotoxic.

Animals↗
PubMed1996

The effect of a low dose versus a conventional dose of hydrochlorothiazide on ventricular fibrillation threshold and electrolyte levels in laboratory rats.

We studied the effect of hydrochlorothiazide on metabolic and electrolyte parameters. In the first protocol, six groups of rats were studied to determine whether changes in ventricular fibrillation threshold, and serum and myocardial potassium occur after treatment with different doses of hydrochlorothiazide; three groups (N = 15) served as controls and the other three groups (N = 15) were given different doses of hydrochlorothiazide for a 3 month period. Two rats from each group were sacrificed daily. One rat heart was perfused using the Langendorff perfusion apparatus and the other used for myocardial potassium analysis. Blood was also collected for serum potassium analysis. There was no change in the threshold for ventricular fibrillation in groups treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control values. There was a nonsignificant decrease in serum and myocardial potassium levels in rats treated with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control. Seven of the 15 rats treated with 0.18 mg hydrochlorothiazide showed significantly lower ventricular fibrillation threshold levels and decreased serum potassium (P < 0.02) compared to control animals. In addition, a significant decrease in myocardial potassium was noted (P < 0.05). In the second protocol, 8 of the 15 rats treated with 0.18 mg hydrochlorothiazide showed reduced ventricular fibrillation threshold and serum potassium levels (P < 0.05). A significant decrease in myocardial potassium was also observed (P < 0.05). These variables were corrected by the intragastric administration of potassium salts. The present study indicates that 0.04 mg and 0.09 mg hydrochlorothiazide have no effect on ventricular fibrillation threshold level or on serum or myocardial potassium levels. There was a significant decrease in ventricular fibrillation threshold and serum and myocardial potassium levels in 7 of the 15 animals studied in protocol one and 8 of the 15 animals studied in protocol two, treated with 0.18 mg hydrochlorothiazide and these variables were corrected by the intragastric administration of potassium salts.

Animals↗
PubMed1995

Zinc, hydrochlorothiazide and sexual dysfunction.

This study was designed to test the hypothesis that hydrochlorothiazide a diuretic used to treat hypertension depletes body zinc and thereby cause sexual dysfunction. Serum zinc and sexual dysfunction were measured in 39 middle aged hypertensive men who had been taking hydrochlorothiazide in average daily doses of between 25 and 50 mg daily for at least six months, and a control group of 27 unmedicated middle aged normotensive men. The medicated group had a higher incidence of sexual dysfunction (56 pc) as compared to 11 pc in the control group. The use of hydrochlorothiazide did affect serum zinc levels significantly in 20 patients. Sexual dysfunction occurred more often in older and overweight patients (p < 0.004). Three of the normotensive men experienced sexual dysfunction probably related to old age. Twenty two of the 39 on hydrochlorothiazide and experiencing sexual dysfunction were divided into two groups of 11 patients. Bloods were taken from the 27 normotensive and 22 hypertensive men receiving hydrochlorothiazide for the analyses of zinc. Subsequently one group of the patients were supplemented with zinc 500 mg daily for 30 days while the other group was supplemented with magnesium chloride 1 g daily for 30 days. The normotensive men were not treated. After 30 days, bloods were again taken from the three groups of analyses for zinc and magnesium. Serum zinc was significantly decreased (p < 0.05) by hydrochlorothiazide and a non significant decrease in serum magnesium (p = ns) was observed. After supplementation with zinc, the serum zinc levels returned to normal only in eight patients. There was improvement in the symptoms of sexual dysfunction in five patients. Two patients gained weight. Hydrochlorothiazide decreased serum zinc levels (p < 0.05) and was unchanged with magnesium supplementation but the serum magnesium returned to normal values. Improvement of symptoms of sexual dysfunction was positive in one patient. This study shows that low serum zinc levels may be associated with sexual dysfunction but the definitive role of zinc in the pathogenesis of sexual dysfunction will remain controversial.

Aged↗
PubMed1994

Intravenous isradipine in the management of severe hypertension in pregnant and nonpregnant patients. A pilot study.

To determine the appropriate dosage regimen of isradipine in black patients with severe hypertension of pregnancy, 10 patients (gestational age, 30 to 38 weeks; diastolic blood pressure [DBP], 110 to 148 mm Hg; no hypertensive crises; and normal central venous pressure) were given an isradipine infusion while the fetal heart rate was continuously recorded using a cardiotocograph. The infusion rate of isradipine was adjusted at regular intervals until control (DBP < 95 mm Hg) was achieved. The optimal dosage regimen in black patients was found to be an initial dose of 0.15 micrograms/kg/min, with increments of 0.0025 micrograms/kg/min every 15 min until control is achieved. Thereafter, a maintenance infusion of 0.15 micrograms/kg/min can be commenced. This dosage regimen is associated with neither maternal hypotension nor fetal heart rate deceleration. A second group of 10 patients (9 men and 1 woman) with DBP > 115 mm Hg (range, 117 to 135 mm Hg) and no features of hypertensive crises were also studied. The optimal dosage regimen in this patient group differed from the other in two respects: dosage increments could be made more rapidly (at 10-min intervals); and the dosage that produced blood pressure control needed to be continued for 30 min before the maintenance infusion was commenced. This regimen was not associated with hypotension.

Adolescent↗
PubMed1994

Intravenous isradipine in the management of severe hypertension of pregnancy in black patients: a pilot study.

The ideal antihypertensive agent for lowering very high blood pressure levels rapidly in severe hypertension of pregnancy still eludes researchers. This pilot study was conducted to determine the appropriate dosage regimen for isradipine in black patients with severe hypertensive disorders of pregnancy. Ten black patients with gestational age > or = 30 (range 30-38) weeks and diastolic blood pressure (DBP) > or = 110 (range 110-148) mmHg following 2 h of bed rest were recruited following informed consent. None of the patients had symptoms or signs of hypertensive crisis. After correction of hypovolaemia (using central venous pressure monitoring) with Ringer's lactate, high blood pressure was lowered by an isradipine infusion. Fetal heart rate was continuously recorded using a cardiotocograph. All blood pressure measurements were made using the same mercury sphygmomanometer by a single observer. The infusion rate of isradipine was adjusted at regular intervals until blood pressure control (DBP < 95 mmHg) was achieved. The optimal dosage regimen in black patients was found to be an initial dose of 0.15 microgram kg-1 min-1 with increments of 0.0025 micrograms kg-1 min-1 every 15 min until blood pressure control is achieved. Thereafter, a maintenance infusion of 0.15 microgram kg-1 min-1 can be initiated. This dosage regimen is associated with neither maternal hypotension nor fetal heart rate deceleration.

Adolescent↗
PubMed1993

The effect of therapeutic doses of paracetamol on liver function in the rat perfused liver.

The isolated liver perfusion technique was used to study the effect of therapeutic doses of paracetamol on hepatic gluconeogenesis and bromosulphthalein clearance from the perfusate and biliary excretion of the dye in the rat. Six groups of rats were studied; those in the three experimental groups were given 0.02 g kg-1 paracetamol daily for ninety days. The livers of animals in the control group and in one of the experimental groups were perfused with a medium containing pyruvate. The animals in the second experimental and control group were perfused with a medium containing bromosulphthalein (10 mg/100 mL). The livers of the third experimental and control group were subjected to histological examination. The rate of glucose formation and glucose concentrations were decreased, while, lactate levels and lactate: pyruvate ratios were increased in paracetamol-treated rats. The mean concentration of bromosulphthalein in the perfusate and biliary excretion of the dye were decreased. Macro and micro vesicular fatty change was present in the livers of paracetamol-treated rats. This study demonstrates that chronic administration of therapeutic doses of paracetamol to rats adversely affects liver function, as evidenced by impaired gluconeogenesis and bromosulphthalein clearance from the perfusate, and excretion of the dye into the bile, and provides histological evidence of hepatic damage in rats.

Acetaminophen↗
PubMed1993

The effects of hexane on rat myocardium: a morphometric and morphological study.

Specimens from the left ventricular myocardium of 10 rats that had been exposed to subcutaneously administered hexane for 30 days were morphometrically and morphologically examined. Other than the presence of occasional necrotic fibres in hexane-treated animals, there was little difference in the histological appearance of myofibres in control or experimental specimens. There was a slight reduction in the average diameter of cardiac myofibres after exposure to hexane. Pathological ultrastructural changes of the myofibres were noted in the experimental and not in the control groups. Mitochondrial oedema and necrosis and myofilament disorganization and dissolution were significant changes noted in the experimental group. These pathological changes suggest that hexane, a constituent of glue and benzine, is cardiotoxic.

Actin Cytoskeleton↗
PubMed1992

The effect of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart.

This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals.

Animals↗
PubMed1992

Influence of ethyl alcohol when given alone or in combination with potassium and/or magnesium supplements on ventricular fibrillation threshold levels in laboratory rats.

Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of supra-therapeutic doses of rifampicin on liver function in the perfused rat liver.

The isolated liver perfusion model was used to study the effects of supra-therapeutic doses of rifampicin on hepatic gluconeogenesis and bromosulphthalein (BSP) clearance from the perfusate and biliary excretion of the dye in the rat. Three groups of rats randomly assigned to a control and two experimental groups were studied; those in the experimental groups were given 4 mg rifampicin per os daily for 90 days. The control group was untreated. The livers of the control and one experimental group were perfused with a medium containing pyruvate and subsequently these livers were perfused with a medium containing bromosulphthalein. The livers of the second experimental group were subjected to histological examination. The rate and the concentration of glucose was decreased, lactate levels and lactate: pyruvate ratios were increased in the experimental animals. The mean perfusate BSP and biliary excretion of the dye was decreased in the experimental group. Fatty change was present in the livers of rifampicin treated rats. This study demonstrates that the isolated liver model has proved to be both suitable and useful for the study of the effects of drugs and that chronic administration of supra-therapeutic doses of rifampicin to rats adversely affected liver function. It also produces histological evidence of hepatic damage in rats.

Animals↗
PubMed1991

Changes in myocardial electrolytes and ventricular fibrillation threshold induced by alcohol feeding in laboratory rats.

Three groups of rats were studied in an investigation to determine the influence of alcohol on myocardial electrolytes and the ventricular fibrillation threshold (VFT) levels. Drinking water was provided ad libitum; the control group received water while the other 2 groups drank a water-ethanol solution, constituted in a ratio of 75: 25, for periods of 3 and 9 months, respectively. Two rats from each of the experimental groups, together with a control rat were killed on each experimental day. One heart was studied on the Langendorff preparation and the other used for tissue electrolyte analysis. The mean myocardial Mg2+ levels (233 +/- 28 micrograms/g vs 148 +/- 23 micrograms/g and 233 +/- 28 micrograms/g vs 107 +/- 15 micrograms/g; p less than 0.0001), K+ levels (3260 +/- 437 micrograms/g vs 1779 +/- 312 micrograms/g and 3260 +/- 437 micrograms/g vs 1195 +/- 205 micrograms/g; p less than 0.0001) and Zn2+ levels (32.7 +/- 6.8 micrograms/g vs 14.0 +/- 4 micrograms/g and 32.7 +/- 6.8 micrograms/g vs 4.2 +/- 3.4 micrograms/g; p less than 0.0001) were significantly lower in alcohol fed rats than the controls. In addition, a significant fall in the mean VFT levels (10.1 +/- 1.94 mA vs 6.27 +/- 2.17 mA, p less than 0.001) was noted in rats given water: alcohol solution for 9 months. This study reveals that chronic exposure to alcohol induces a deficiency of myocardial Mg2+, K+ and Zn2+, and an increase in myocardial irritability in laboratory rats.

Animals↗