Renal pathology and HIV infection in Thailand.

The existence of a human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) as a distinct disease entity characterized by glomerulosclerosis is well established in North America and Western Europe. Although the large number of HIV-infected cases overwhelm the Asian countries, no cases of HIVAN are documented in the literature. We studied 26 cases of HIV-infected Thai patients with proteinuria greater than 1.5 g/d of protein during 1995 and 1996. None of the patients were treated with antiretroviral drugs at the time of renal biopsy. Intravenous drug addiction and sexual transmission were risk factors in 11 and 15 patients, respectively. Pathological examinations were performed by light microscopic and immunoperoxidase study. Mesangial proliferative glomerulonephritis was found in 17 cases, immunoglobulin A (IgA) nephropathy in 2 cases, and diffuse proliferative glomerulonephritis and interstitial nephritis secondary to cryptococcal infection in 2 cases each. One case each had membranous glomerulopathy, membranoproliferative glomerulonephritis, and granulomatous interstitial nephritis secondary to tuberculosis. The renal pathological findings of HIVAN with the unique features described in previous literature were not evident in these patients. Although the data in this study are limited to 26 HIV-infected Thai patients, we believe that HIVAN is uncommon in the Asian HIV-infected population.

Effects of Russell's viper venom on human erythrocytes in vitro.

The effects of Russell's viper venom (RVV) on human erythrocytes were studied in vitro with respect to packed cell volume (hematocrit), the erythrocyte morphology, and the effect of antivenom. Venom at various dosages ranging from 50 ng to 120 micrograms increased hematocrit significantly. The maximal effect was detected at 800 ng of venom. The biconcave erythrocytes shown by scanning electron microscopy became sphero-echinocytes. Such altered morphology was observed immediately at 1 minute and reached maximum at 30 minutes. The mild degree of erythrocyte deformation was observed at 60 and 120 min with 100 ng of RVV. There were no morphologic changes when ethylenediaminetetracetate (EDTA) was used as an anticoagulant or when plasma was substituted by isotonic saline, acetar, albumin added acetar solution. Phospholipase A2 at equivalent dose as compared to the venom could also produce the sphero-echinocytosis. The phospholipase A2 inhibitor, p-bromophenacyl bromide markedly reduced the degree of RVV induced sphero-echinocytosis. Verapamil, a phenylalkylamine calcium channel blocker, could not prevent the RVV induced sphero-echinocytosis. Although antivenom could not reverse the RVV induced sphero-echinocytosis, it minimized these effects. The RVV induced sphero-echinocytosis is likely caused by phospholipase A2. Calcium and some plasma factors are required for this process. Early treatment with antivenom plays some role in prevention of RVV induced sphero-echinocytosis which may reduce hypoxic cell injury.

Granulomatous interstitial nephritis in renal transplant recipient.

Tuberculosis of a transplanted kidney is a rare and serious complication. Search for renal tuberculosis as the cause of deterioration of graft function is mandatory in a renal transplant recipient with tuberculosis of other organs e.g. pulmonary tuberculosis in this patient. Renal histopathology is required for the diagnosis. Treatment with anti-tuberculosis drugs can improve renal function. Drug interactions should be considered when rifampicin is administered with cyclosporin A.

Renal and systemic hemodynamics, in falciparum malaria.

Renal and systemic hemodynamics, plasma arginine vasopressin, plasma renin activity, plasma norepinephrine, blood volume and water loading test were studied in 10 patients with falciparum malaria without renal failure. Six patients responded to water load normally, while 4 patients had a decreased response to water load. The patients with a normal water load response had normal renal and systemic hemodynamics and a normal hormonal profile. The patients with a decreased response to water load had hyponatremia, hypervolemia, high cardiac index, low systemic vascular resistance, high plasma arginine vasopressin, high plasma renin activity, high plasma norepinephrine, low creatinine and p-aminohippurate clearances, low urine sodium and high urine osmolality. They had a lower mean arterial pressure during the acute phase of the disease than during the recovery phase. The findings suggest that a decreased response to water load is due to peripheral vasodilatation which results in a decreased effective blood volume leading to the release of vasopressin and norepinephrine, increased renin activity and decreased renal hemodynamics.

Further characterization of the sorbitol permease in PAP-HT25 cells.

The sorbitol permease enables the efflux of sorbitol from cultured rabbit papillary cells (PAP-HT25) in response to a reduction in osmolality. The anion transport inhibitor 5-nitro-2-(3-phenylpropylamino)benzoate (100 microM) inhibited efflux by 92%, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.5 mM) reduced efflux by 40%. 2,4-Dinitrobenzenesulfonate and p-chloromercuriphenylsulfonic acid had no effect. The protease trypsin (0.05 mg/ml) reduced sorbitol efflux by 53%, pronase (0.01 mg/ml) by 47%, and papain (0.1 mg/ml) by 49%; chymotrypsin had no effect. Sugars and sugar alcohols at different concentrations (10-200 mM) in the bathing solution did not influence sorbitol efflux. Determination of the osmotically induced influx of sugar alcohols showed that xylitol uptake was faster than that of sorbitol; 6-deoxysorbitol was slower; L-sorbitol, arabitol, galactitol, and 2-deoxysorbitol entered at the same rate as sorbitol; and maltitol did not enter the cells. Sorbitol and 6-deoxysorbitol at 9 mM competitively inhibited [14C]sorbitol influx by 24 and 32%, respectively, whereas xylitol, taurine, betaine, and myo-inositol showed no inhibition. We conclude that 1) a specific inhibitor of the permease was not found, 2) the sorbitol permease or associated regulator is a protein, and 3) the C-6 atom of sorbitol is important in the selectivity of the permease.

Necturus gallbladder epithelial cell volume regulation and inhibitors of arachidonic acid metabolism.

Inhibition of the metabolism of arachidonic acid by the epoxygenase (cytochrome P-450) pathway with the inhibitor ketoconazole results in excessive cell swelling upon exposure to hyposmolality instead of the rapid and complete regulatory volume decrease (RVD) normally observed. NaCl entry from bathing solutions to cell interior was shown to cause this swelling, with Na influx occurring across the basolateral membrane and electrically silent Cl influx across the apical membrane. Ion substitution experiments show that the KCl efflux mediating RVD was unimpaired by ketoconazole, but was overwhelmed by the NaCl influx. Measurements of transepithelial fluid flux, Cl concentration, osmolality and pH showed that gallbladders treated with ketoconazole transiently secreted fluid rather than the normal absorption. We conclude that inhibition of arachidonic acid metabolism does not directly affect RVD by Necturus gallbladder, but that blockade of the epoxygenase pathway can have a profound influence on NaCl entry into gallbladder epithelial cells.

Effects of acute arginine loading on renal and systemic hemodynamics in dogs.

Effects of L-arginine (ARG) infusion on renal and systemic hemodynamics were studied in 12 anesthetized dogs. The experiment was performed in two groups of dogs. The dogs of group 1 (n = 6) received intravenous ARG at 2.5 mmol/kg followed by indomethacin (IND) injection (10 mg/kg) and were rechallenged with ARG at the same amount. The dogs of group 2 (n = 6) received intravenous ARG at 5 mmol/kg followed by IND injection (10 mg/kg) and were later infused with ARG at the same dose. In group 1, the first ARG infusion caused no significant changes in renal and systemic hemodynamics. During the second ARG infusion, glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly increased when compared with the IND-treated period. In group 2, the first ARG infusion increased cardiac output (CO) and decreased total peripheral resistance (TPR) without significant changes in GFR and RPF. The second ARG infusion induced acute rise of both GFR and RPF approximately twofold, compared with the IND-treated period. CO was also increased significantly. Plasma glucagon levels determined in 2 dogs showed an increase following both ARG infusions. These results indicate that an acute ARG loading induces renal and systemic vasodilatation in a dose-dependent manner despite IND effect, and would indicate that increased renal hemodynamics are not prostaglandin-mediated.