PubMed HealthSearch

Biomedical subjects

T Naicker

Publications and source records attributed to T Naicker.

14 recordsLinked to original sources

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

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

Tissue kallikrein in transplant kidney.

Literature survey, thus far, has shown a decrease in the excretion of urinary tissue kallikrein (TK) in transplant patients with a further reduction of the enzyme during episodes of acute rejection. The study aims were to compare, at cellular and subcellular levels, the localisation of tissue kallikrein in biopsies of the transplant kidney to autopsy derived normal renal tissue. Renal biopsies from eighteen transplant patients with deteriorating renal function were obtained. Immunolabelling for tissue kallikrein, using a polyclonal goat anti-TK, antibody raised against recombinant TK, was performed following routine enzymatic, immunofluorescence and electron microscopic techniques. In normal kidney tissue, TK was immunolocalised in the distal connecting tubules and collecting ducts. By comparison the renal transplant tissue showed a reduction in the intensity of label, but maintained the sites of localisation. In the sections examined by electron microscopy, although TK was confined mainly at the luminal side of the cell, some label was noted along the basolateral membranes. In the transplant kidneys, there was a reduction in the overall number of gold particles counted, which correlated with the decreased intensity observed on immunocytochemistry. In addition, there was a shift to a basolateral orientation of the immunolabel. Acute rejection is characterised by oedema, tubulitis and vasculitis. Destruction of the tubule cells and leakage of TK into the interstitial tissue space and the resultant effect of the formed kinins on renal capillary vasculature could explain the observed renal parenchymal oedema and transplant rejection.

Adult

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

Growth and cultural characteristics of Calymmatobacterium granulomatis--the aetiological agent of granuloma inguinale (Donovanosis).

Granuloma inguinale is a chronic destructive granulomatous disease of the genitalia. The clinical diagnosis is often unreliable and the definitive diagnosis is based on the visualisation of 'Donovan bodies' in tissue smears or biopsy specimens. The organism implicated in its aetiology, Calymmatobacterium granulomatis, was reported to have been cultured > 30 years ago, but little is known about the organism because of its fastidious nature and the difficulty in culturing it. Twenty-two biopsy specimens from female patients with clinical and laboratory-confirmed granuloma inguinale were treated with amikacin 10 mg/L and inoculated in a monocyte co-culture system with peripheral blood mononuclear cells (PBMC) from a single donor and autologous sera. The method was subsequently modified by pretreatment of specimens with vancomycin 5 mg/L and metronidazole 10 mg/L in addition to amikacin 10 mg/L for the purpose of decontamination, pooled blood donor PBMC and by the use of heat-inactivated fetal calf serum instead of autologous serum for culture. This modified method was used to culture additional biopsy specimens and genital ulcer scrapings from female and male patients, respectively. All monocyte co-cultures were examined by a rapid Giemsa (RapiDiff) stain and by an indirect immunofluorescence test with immune sera. Representative cultures were examined by transmission electron microscopy. C. granulomatis was successfully isolated in pure culture by the monocyte co-culture system from four biopsy specimens and 14 genital ulcer scrapings. The cultured organisms were visible both intra- and extra-cellularly and were extremely pleomorphic, with characteristic single and biopolar condensation. The numbers of the organisms increased after each passage. All positive cultures showed bright fluorescence when tested with immune sera. Transmission electron microscopy of the cultured bacteria demonstrated a typical gram-negative cell wall consisting of an outer membrane, middle electron opaque layer and an inner plasma membrane. The capsule was thick and electron dense. Numerous electron dense granules were present within the cytoplasm.

Azure Stains

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

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

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

Morphological aspects of microarterial anastomoses: a comparison of nylon with polydioxanone.

The morphological appearance of longitudinally sectioned rat femoral arteries was determined in intact arteries and from 3 to 435 days after vessel division and anastomosis with either 9/0 gauge nylon or polydioxanone (PDS) in 26 animals. The purpose of the study was to establish the mechanisms and compare the quality of healing after microarterial anastomosis and to determine whether PDS was degraded before sufficient anastomotic healing had taken place. The results revealed that there was no difference in the process of healing or quality of anastomosis with either suture material. From 3 to 21 days post anastomosis, there was a progressive separation of the ends of vessels within the developing scar. Anastomotic patency was established and maintained at first by an adventitial overgrowth of fibroblasts and undifferentiated adventitial cells and later by the growth of a smooth myocyte scar that stretched between the cut ends of the vessel and over the intima in the form of elongated circumferential plaques. The vessel was morphologically healed by the 21st day. The sutures served little or no purpose in maintaining anastomotic integrity after the 5th day, being situated in the scar forming between the separating vessel ends. PDS was present within the vessel wall up to 120 days post anastomosis and was certainly intact at the time of morphological healing, suggesting that this material is safe as a microvascular suture.

Anastomosis, Surgical

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

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

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