Dietary protein causes a decline in the glomerular filtration rate of the remnant kidney mediated by metabolic acidosis and endothelin receptors.

Dietary casein promotes a progressive decline in the glomerular filtration rate (GFR) of remnant kidneys associated with metabolic acidosis and an endothelin-mediated increase in renal acidification. We tested whether diets that affect the acid-base status contributes to the decline of GFR through endothelin receptors in rats with a remnant kidney. Rats on a casein diet had metabolic acidosis at baseline and developed a progressive decline in GFR after renal mass reduction. Dietary sodium bicarbonate but not sodium chloride ameliorated metabolic acidosis and prevented the decrease in GFR but only after the sodium bicarbonate-induced increase in blood pressure was treated. Dietary soy protein did not induce baseline metabolic acidosis and rats with remnant kidney on a soy diet had no decrease in their GFR. By contrast, rats with a remnant kidney on soy protein given dietary acid developed metabolic acidosis and a decreased GFR. This decline in GFR was prevented in either case by endothelin A but not endothelin A/B receptor antagonism. Our study suggests that the casein-induced decline in GFR of the remnant kidney is mediated by metabolic acidosis through endothelin A receptors.

Dietary protein induces endothelin-mediated kidney injury through enhanced intrinsic acid production.

Dietary protein as casein (CAS) augments intrinsic acid production, induces endothelin-mediated kidney acidification, and promotes kidney injury. We tested the hypothesis that dietary CAS induces endothelin-mediated kidney injury through augmented intrinsic acid production. Munich-Wistar rats ate minimum electrolyte diets from age 8 to 96 weeks with 50 or 20% protein as either acid-inducing CAS or non-acid-inducing SOY. Urine net acid excretion and distal nephron net HCO3 reabsorption by in vivo microperfusion (Net J(HCO3)) were higher in 50 than 20% CAS but not 50 and 20% SOY. At 96 weeks, 50% compared the 20% CAS had higher urine endothelin-1 excretion (U(ET-1)V) and a higher index of tubulo-interstitial injury (TII) at pathology (2.25+/-0.21 vs 1.25+/-0.13 U, P<0.03), but each parameter was similar in 50 and 20% SOY. CAS (50%) eating NaHCO3 to reduce intrinsic acid production had lower Net J(HCO3), lower U(ET-1)V, and less TII. By contrast, 50% SOY eating dietary acid as (NH4)2SO4 had higher Net J(HCO3), higher U(ET-1)V, and more TII. Endothelin A/B but not A receptor antagonism reduced Net J(HCO3) in 50% CAS and 50% SOY+(NH4)2SO4 animals. By contrast, endothelin A but not A/B receptor antagonism reduced TII in each group. The data support that increased intake of acid-inducing dietary protein induces endothelin B-receptor-mediated increased Net J(HCO3) and endothelin A-receptor-mediated TII through augmented intrinsic acid production.

Protective effect of selenium on hemoglobin mediated lipid peroxidation in vivo.

The toxicity of hemoglobin (Hb) solutions is related, at least in part, to the generation of oxygen free radicals with consequent induction of lipid peroxidation. The present study was designed to examine whether selenium (Se) may prevent the oxidative damage observed after Hb administration. Three groups of rats were compared; (I) the negative control group receiving autotransfusion; (II) the positive control group with replacement of 40% total blood volume (TBV) with modified bovine Hb solution; and (III) the experimental group which received dietary supplemented selenium (Na2SeO3) in daily doses of 5 micrograms.kg body wt-1 in drinking water, 4 days before and 3 days after administration of Hb solution in the same volume as in group II. Three days after Hb injection, all animals were sacrificed. Oxidative stress was determined by measuring conjugated dienes (CD) and thiobarbituric acid reactants (MDA) in homogenates of the perfused liver, heart, lungs, kidney, brain and plasma. Additionally, the 45k x g supernatants of the organs homogenates and plasma were assayed for the antioxidant enzymes activity: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the intracellular level of reduced glutathione (GSH). Also, a measurement of nonprotein bound intracellular free iron (Fe) and tissue Se concentrations was performed. Simultaneously, injury dysfunction of vital organs was assessed by the measurement of plasma LDH, SGPT, creatinine, blood PaO2 and by histopathological studies. Results indicate that the exchange transfusion with Hb solution introduced significant increases in CD and MDA formation, particularly in the liver and heart tissues, and in plasma. While the values of the SOD and CAT in the liver and heart tissue were generally altered, the SOD/CAT ratio was also increased. After the Hb injection, activity of GSH-Px remained unchanged and was associated with significant depletion of GSH. The plasma levels of SGPT and LDH were increased, but the creatinine and PaO2 was similar to that of the control and corresponded with histopathological findings. The liver and heart intracellular free Fe was found to be higher than that of control. Treatment with Se was very effective in the prevention of oxidative damage introduced by Hb. Full protection from MDA formation was noted in liver tissue (p < 0.001). Also, plasma levels of MDA, SGPT and LDH were significantly decreased and appeared similar to that of the control group (I). Treatment with Se increased liver (p < 0.05) and plasma (p < 0.1) level of GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of topical antiseptic in prophylaxis of catheter-related septic complications.

Pretreatment of catheters by a simple new procedure designed to reduce the incidence of septic complications was tested in both in vitro and in vivo studies. In the former experiments, the high sensitivity of gram-negative bacteria and fungi to Silastic (silicone rubber) catheters pretreated with silver nitrate solution was determined. The antimicrobrial activity remained unchanged after both sterilization and up to six weeks of storage. Furthermore, prolonged incubation of treated catheter segments in Escherichia coli inoculated plasma resulted in a significant reduction of organisms in the media and those adherent to the surface of the catheters. The in vivo experiments were performed upon two groups of rabbits. In the first group, catheters (one treated and one untreated) were implanted into contralateral jugular veins. In the second group, alternating treated and control catheter segments were threaded onto polyethylene core tubing; the resulting string of segments was positioned in the inferior vena cava. Five to 11 days after implantation of the catheter, all rabbits were intravenously injected with live E. coli (approximately 10(8) to 10(9) organisms per kilogram of weight); 18 to 24 hours later, the catheters and blood samples were removed for cultivation. Significant reductions in both incidence and magnitude of colonization in treated catheters by E. coli were observed in both rabbit groups. Additionally, histologic examination did not reveal any significant differences between contralateral jugular veins (previously in prolonged and intimate contact with the indwelling catheters), confirming the absence of any local adverse effects of silver nitrate.

Nonthrombogenic small-caliber human umbilical vein vascular prosthesis.

The present investigation demonstrates covalent binding of heparin with carbodiimide to ammonium hydroxide-treated collagenous surfaces. Human umbilical vein grafts (HUVG) outperform carotid arteries of goat, porcine, and canine origin in both heparin loading and stability of the immobilized heparin preparation. The average heparin loading on the untreated carotid arteries and HUVGs and ammonium hydroxide-treated HUVGs were 18, 27, and 31.5 micrograms/cm2, respectively. There was negligible loss of heparin activity under in vitro and in vivo conditions. In vitro studies demonstrate that heparin-bound HUVGs discourage platelet adhesion and subsequent fibrin clot formation. In vivo studies with heparin-bound HUVGs show a significant increase in thrombus-free surface compared with control grafts. Heparin-bound HUVGs also show an enhanced patency rate in the two sets of protocols tested--one lasting for 3 in vivo days (seven grafts) and the other lasting for 7 (15 grafts) in vivo days. The studies conducted so far demonstrate the promise of developing a nonthrombogenic small-caliber HUVG prosthesis.

Meckel's diverticulum: the false-negative examination.

A case of Meckel's diverticulum is presented in a 17-month-old girl following technetium pertechnetate radioisotope scan. The patient had presented 10 months earlier with the first episode of passing bloody stools. A Meckel's diverticulum was resected during surgery. Reasons for the original false-negative examination are presented.

Fibroma in a Nine-banded armadillo (Dasypus novemcinctus).

An adult male Nine-banded armadillo (Dasypus nonemcintus) had a large tumour between the first and second phalanges of the right fore-foot. The tumour was of dermal origin, consisted of dense interlacing bundles of collagen, and contained numerous fibroblasts with elongate nuclei and sparse cytoplasm. Mitotic figures were not observed, there was no evidence of lipid accumulation, and there was no metastasis to regional lymph nodes or other tissues. Electron microscopy showed that the major cells of the tumour were fibroblasts. These did not contain nuclear or cytoplasmic inclusions but had dense bodies in the nucleus and there was a conspicuous absence of lysosomes. This lesion was considered to be a benign fibroma of undetermined aetiology.

Photocarcinogenicity of 8-methoxypsoralen and aflatoxin B1 with longwave ultraviolet light.

The carcinogenicity of 8-methoxypsoralen (8-MOP) and aflatoxin B1 (AFB1) with longwave ultraviolet light (UVA) to hairless mouse skin was investigated. Skin tumors were induced efficiently by 8-MOP + UVA, and the time to 50% tumor incidence was about 24 weeks. Histopathologically, some tumors were squamous cell carcinomas. AFB1 did not show any phototoxic and photocarcinogenic effects on mouse skin in this study. Although the structure and the photoreactivity of AFB1 to DNA were similar to those of 8-MOP, the photocarcinogenic response of these compounds to mouse skin was quite different.