[FSGS collapsing variant during anabolic steroid abuse: Case Report].

Anabolic Androgenic Steroids (AAS) is an hormone family whose use has considerably increased among body-builders during the last decades. The AAS abuse, especially associated with other drugs or nutritional supplements and protein loads, may cause a variety of pathologies to several organs with a mechanism related to dosage, timing and substance. The kidney is the main metabolizer of these drugs and it can be acutely or chronically damaged with ESKD. The literature reports some cases of Focal Segmental Glomerulosclerosis (FSGS) in body-builders who abused of AAS. However, the link is not well understood and limited to some case-studies. In this paper, we report the case of a young body-builder who developed a FSGS collapsing variant with ESKD after prolonged abuse of AAS and a strongly hyperproteic diet and other dietary supplements. The patient underwent a genetic test because of the rapid and irreversibile onset of ESKD. The test showed a gene mutation of ACTN4, predisposing and causal of some genetic forms of FSGS. It was a very complex case, caused by several factors. The mutant protein of ACTN4 gene makes most vulnerable the cytoskeleton of the podocytes to external disturbances. That would explain why in those patients where the mutation has occurred, only those patients subject to "unfavorable environmental conditions", like the abuse of AAS, can develop a disease.

Huaiqihuang Granules () reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy.

OBJECTIVE: To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. METHODS: Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. RESULTS: HQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. CONCLUSION: HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Crescentic acute glomerulonephritis with isolated C3 deposition: a case report and review of literature.

An eight-year-old girl, presenting with palpebral edema, gross hematuria, and foam in urine, was admitted to our hospital. Investigations indicated increased serum antistreptolysin O (ASO) and anti-mycoplasma antibody titers. Renal biopsy showed crescentic poststreptococcal acute glomerulonephritis (CPAGN) with isolated C3 deposition in the glomeruli. Electro-microscope examination showed subepithelial deposition of electron dense material. She received the double pulse therapies of methylprednisolone and cyclophosphamide as well as the treatment of oral prednisolone, angiotensin converting enzyme-II (ACE-II) inhibitor, dipyridamole and traditional Chinese medicine. The complete clinical remission was achieved after 9 months. No serious adverse effects were observed during the follow-up. Our findings indicated that CPAGN with isolated C3 deposition might have a favorable prognosis after aggressive immunosuppressive treatment. However, the influence of isolated C3 deposition on CPAGN prognosis remains to be clarified.

Renal corpuscles were protected from dichlorvos: induced morphological alterations in rats by antioxidant vitamins / Protección de corpúsculos renales ante alteraciones morfológicas inducidas por el diclorvos en ratas mediante el uso de vitaminas antioxidantes

Dichlorvos (DDVP), an organophosphorus pesticide is a volatile compound which enters the human body through oral, dermal and inhalational routes and is excreted via the kidney. This study assessed the effects of DDVP on the histology of the kidney. Twenty five male rats (75.05 ± 5.55 g) were divided into 5 groups of 5 rats per group as follows: Unexposed group, exposure to DDVP alone for 5 weeks, and 3 other groups exposed to DDVP for 5 weeks in addition to supplement with Vitamin E, vitamin C, and red palm oil (RPO). Rats were exposed to DDVP in poorly ventilated cardboard cages for 4 hours daily. On completion of exposure, rats were euthanized and tissue processed by routine paraffin wax method and stained with H&E. Morphological alterations monitored by histological and morphometric studies using the graticule and software packages. Data were analyzed with ANOVA and p<0.05 considered as significant. DDVP caused significant reduction (10%) in the maximum glomerular diameter and 18% reduction in the maximum width of the renal corpuscle when compared with unexposed rats. However, VTE, VTC, and RPO significantly elevated the maximum glomerular diameter by 21%, 22%, 23% the respectively. Similarly, VTE, VTC, and RPO significantly elevated the maximum width of the renal corpuscle by 17%, 19%, 20% respectfully. Glomerular tuft cellularity was neither affected by DDVP treatment nor by vitamin augmentation. Inhaled DDVP caused histological alterations in the microscopic anatomy of renal corpuscles of rat which was mitigated by vitamin supplementation. Data suggest involvement of prolonged DDVP use in the aetiology of renal failure.

El diclorvos (DDVP), un pesticidas organofosforado, es un compuesto volátil que entra en el cuerpo humano a través de la vía oral, dérmica y por rutas inhalación, excretándose por vía renal. Este estudio evaluó los efectos histológicos del DDVP sobre el riñón. Veinticinco ratas machos (75,05±5,55 g) se dividieron en 5 grupos de 5 ratas cada uno: grupo no expuesto, expuesto a DDVP durante 5 semanas, y otros 3 grupos expuestos a DDVP durante 5 semanas, suplementados con vitamina E (VTE), vitamina C (VTC) y aceite de palma roja (APR). Las ratas fueron expuestas a DDVP en jaulas de cartón con poca ventilación por 4 horas diarias. Al término de la exposición, las ratas se sacrificaron y el tejido fue procesado para inclusión en parafina y tinción con H&E. Las alteraciones morfológicas se evaluaron mediante estudios histológicos y morfométricos utilizando retículas y software. Los datos se analizaron con la prueba ANOVA considerado un p<0,05 como significativo. El DDVP causó una reducción significativa (10%) en el diámetro máximo glomerular y ancho máximo del copúsculo renal (18%), en comparación con las ratas no expuestas. Sin embargo, el diámetro máximo glomerular fue significativamente elevado con VTE, VTC y APR en 21%, 22% y 23%, respectivamente, así como para el ancho máximo del corpúsculo renal por 17%, 19% y 20%, respectivamente. La celularidad de la red glomerular no fue afectada por el DDVP ni aumentó con el tratamiento de vitamina. El DDVP inhalado provocó alteraciones histológicas en la anatomía microscópica de los corpúsculos renales de rata, las que fueron mitigadas por la suplementación de vitamina. Los datos sugieren relación entre la exposición prolongada a DDVP y la etiología de la insuficiencia renal.

Injury to the endothelial surface layer induces glomerular hyperfiltration rats with early-stage diabetes.

Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

Electron microscopy of the morphological changes in rat viscera during experimental hyperthermic shock.

Hyperthermic shock is a thermoregulatory disorder that affects living organisms that are acutely or chronically exposed to high temperatures or when performing intense physical activity in a hot environment. In this paper, we will show the changes embodied in hyperthermic shock caused by multiple injuries to vital organs in Wistar rats that were suddenly exposed to high temperatures of up to 410 for about 10-15 minutes, their central temperature rising above 40.60C. This process resulted in multiple injuries of the vital organs, evidenced by electron microscopy. In addition, this suggested that most changes caused by hyperthermic shock are incompatible with life.

Vitamin D down-regulates TRPC6 expression in podocyte injury and proteinuric glomerular disease.

The transient receptor potential cation channel C6 (TRPC6) is a slit diaphragm protein expressed by podocytes. TRPC6 gain-of-function mutations cause autosomal dominant focal segmental glomerulosclerosis. In acquired proteinuric renal disease, glomerular TRPC6 expression is increased. We previously demonstrated that acquired increased TRPC6 expression is ameliorated by antiproteinuric angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. Vitamin D also has an antiproteinuric effect. We hypothesized that vitamin D reduces proteinuria by affecting TRPC6 expression in podocytes. Adriamycin-induced nephropathy increased TRPC6 mRNA and protein expression and induced proteinuria in rats. Treatment with 1,25-dihydroxyvitamin D3 (1,25-D3) normalized TRPC6 expression and reduced proteinuria. In vitro, podocyte injury induced by adriamycin exposure in cultured podocytes increased TRPC6 expression. Treatment of injured podocytes with 1,25-D3 dose dependently reduced adriamycin-induced TRPC6 expression. Chromatin immunoprecipitation analysis demonstrated that the vitamin D receptor directly binds to the TRPC6 promoter. Moreover, 1,25-D3 reduced TRPC6 promoter activity in a luciferase reporter assay. In 1,25-D3-deficient 25-hydroxy-1α-hydroxylase knockout mice, TRPC6 expression was increased, accompanied by podocyte foot process effacement and proteinuria. 1,25-D3 supplementation normalized TRPC6 expression, podocyte morphology, and proteinuria in these mice. These results demonstrate that vitamin D down-regulates the enhanced TRPC6 expression in in vivo and in vitro podocyte injury, possibly through a direct effect on TRPC6 promoter activity. This TRPC6 down-regulation could contribute to the antiproteinuric effect of vitamin D.

The Gne M712T mouse as a model for human glomerulopathy.

Pathological glomerular hyposialylation has been implicated in certain unexplained glomerulopathies, including minimal change nephrosis, membranous glomerulonephritis, and IgA nephropathy. We studied our previously established mouse model carrying a homozygous mutation in the key enzyme of sialic acid biosynthesis, N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Mutant mice died before postnatal day 3 (P3) from severe glomerulopathy with podocyte effacement and segmental glomerular basement membrane splitting due to hyposialylation. Administration of the sialic acid precursor N-acetylmannosamine (ManNAc) led to improved sialylation and survival of mutant pups beyond P3. We determined the onset of the glomerulopathy in the embryonic stage. A lectin panel, distinguishing normally sialylated from hyposialylated glycans, used WGA, SNA, PNA, Jacalin, HPA, and VVA, indicating glomerular hyposialylation of predominantly O-linked glycoproteins in mutant mice. The glomerular glycoproteins nephrin and podocalyxin were hyposialylated in this unique murine model. ManNAc treatment appeared to ameliorate the hyposialylation status of mutant mice, indicated by a lectin histochemistry pattern similar to that of wild-type mice, with improved sialylation of both nephrin and podocalyxin, as well as reduced albuminuria compared with untreated mutant mice. These findings suggest application of our lectin panel for categorizing human kidney specimens based on glomerular sialylation status. Moreover, the partial restoration of glomerular architecture in ManNAc-treated mice highlights ManNAc as a potential treatment for humans affected with disorders of glomerular hyposialylation.

[Effect of Qufengtongluo recipe on expression of nephrin mRNA in adriamycin-induced nephropathy in rats].

OBJECTIVE: To investigate the expression of nephrin mRNA in adriamycin-induced nephropathy (AN) in rats, and to explore the effect of Qufengtongluo recipe on proteinuria in AN rats and on the expression of nephrin mRNA. METHODS: Adriamycin nephropathy was induced by a single tail intravenous injection of adriamycin. We randomly divided 140 rats into a normal control group (n=32) and a nephropathy model group (n=108). Three weeks later, 90 AN rats were randomly divided into 5 groups: a model group, a qufeng group, a qufeng and prednisone group, a prednisone group, and a benazepri group (18 rats in each group). They were treated respectively, and renal tissue samples were collected at week 0, 3, 5, and 7, respectively. The distribution and expression of nephrin mRNA were examined by indirect immunofluorescence and semi-quantity RT-PCR. RESULTS: In the AN rats, the diffuse fusion and effacement of foot processes were observed at week 3. The fluorescence intensity of nephrin and the expression of nephrin mRNA significantly increased in the qufeng group and the prednisone group compared with the model group at the week 7 (P<0.01). CONCLUSION: Abnormal expression of nephrin is the important molecular mechanism that leads to the occurrence and development of proteinuria in AN rats. Qufengtongluo recipe has effect on nephrotic syndrome through altering the expression and distribution of nephrin in glomerulus.

Beneficial effect of neutrophil elastase inhibitor on anti-Thy1.1 nephritis in rats.

BACKGROUND: Neutrophil elastase, one of the proteinases released by neutrophils, plays an important role at the sites of inflammation and was reported to be involved in the pathogenesis of glomerulonephritis. Sivelestat is a selective neutrophil elastase inhibitor used for acute lung injury associated with systemic inflammatory response syndrome. There have been few reports on the effects of sivelestat on renal disease. METHODS: In male Wistar rats, anti-Thy1.1 nephritis was induced by the injection of anti-Thy1.1 antibody. The rats were divided into four groups: nephritic rats treated with low- (group A) and high-dose sivelestat (group B), those not treated with sivelestat (group C) and control rats (group D). Urine samples were obtained every day during the experiment. The rats were killed on day 6 in order to obtain the blood plasma and kidneys. Measurement of urine protein levels, blood biochemical values and histological examination of the kidneys were carried out. RESULTS: Increased levels of proteinuria were observed in the nephritic rats (groups A, B and C) compared with group D. The proteinuria level was significantly suppressed by sivelestat in groups A and B in a dose-dependent fashion compared with group C. The light microscopy revealed an increased glomerular cell count in group C, which was significantly suppressed in group B. In the electron microscopic study, sivelestat suppressed the fusion of epithelial foot process, especially in group B. CONCLUSION: Neutrophil elastase is suggested to be involved in the development of anti-Thy1.1 nephritis, and the neutrophil elastase inhibitor sivelestat reduces the tissue injury of anti-Thy1.1 nephritis in rats.

Ginkgo biloba extract protects rat kidney from diabetic and hypoxic damage.

Ginkgo biloba extract EGb 761 was studied for its nephroprotective effects in experimentally diabetic and hypoxic rats. Duration of streptozotocin-induced diabetes was 4 months, that of respiratoric hypoxia of the diabetic group 20 min. The daily dose of 100 mg EGb/kg bodyweight started 1 month after induction of the diabetes. EGb reduced diabetes-induced morphological alterations of the kidney such as increase in volume of glomeruli, capillary tufts, urinary space, and thickening of Bowman's capsule basement membrane. Diabetically increased immunostaining of interstitial collagenes of types I, III, and VI was diminished by the EGb extract. EGb reduced the relative total SOD activity from 163% in diabetic kidney to 46%. Additional hypoxia-induced ultrastructural damage was also diminished.

Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate.

We report a case of a healthy 24-year-old man who presented with acute renal failure and proteinuria while taking creatine and multiple other supplements for bodybuilding purposes. A renal biopsy showed acute interstitial nephritis. The patient recovered completely after he stopped taking the supplements. Creatine is a performance-enhancing substance that has gained widespread popularity among professional as well as amateur athletes. It is legal and considered relatively safe. Recently there have been case reports of renal dysfunction, including acute interstitial nephritis, associated with its use. Further studies are needed to evaluate the safety of creatine supplementation. It may be prudent to include a warning of this possible side effect in the product insert.

Glomerular calcification induced by bolus injection with dibasic sodium phosphate solution in Sprague-Dawley rats.

To elucidate the nephrotoxicity of phosphate, dibasic sodium phosphate solution was given to Sprague-Dawley rats by daily bolus intravenous administration at concentrations of 0, 1, 25, 250, or 360 mM (0, 1, 28, 284, or 408 mg/kg Na2HPO4) for 14 days, and the kidneys were pathologically examined. There were no remarkable changes in blood chemistry values; however, urinalysis revealed mild to moderate proteinuria in the 250 and 360 mM groups. The kidneys from the 360 mM group were macroscopically pale. Histopathology revealed panglomerular deposition of basophilic dense granules, which were positive for von Kossa's staining, accompanied by dose-dependent degeneration of the glomerular epithelium and parietal epithelium in the 250 and 360 mM groups. Electron microscopic examination showed fusion of podocytes and increased microvilli, with large amounts of debris in the Bowman's space. Low-density lamellar structures were present not only in the glomerular epithelium, basement membrane, mesangial matrix and parietal epithelium but also within the Bowman's space depending on the severity of the glomerular lesion. Phosphorus and calcium were detected by X-ray microanalysis as fine particles admixed with lamellar structures. These results suggest that high-dose phosphate used in this study transiently overloads the glomerular epithelium during filtration through glomerular capillaries and produces insoluble calcium salt and glomerular lesions, resulting in proteinuria.

Losartan ameliorates progression of glomerular structural changes in diabetic KKAy mice.

Pathological changes in glomerular structure are typically associated with the progression of diabetic nephropathy. The involvement of angiotensin II (AII) in pathogenesis of diabetic nephropathy has been extensively studied and the therapeutic advantages associated with blockade of renin-angiotensin system (RAS), primarily with angiotensin converting enzyme (ACE) inhibitors, has been well-documented. We studied the effect of RAS blockade with an AII receptor antagonist (losartan) vs. an ACE inhibitor (enalapril) on glomerular lesions in KKAy mice, a model of type 2 diabetes mellitus. Losartan was administered at 3 and 10 mg/kg/day and enalapril at 3 mg/kg/day for 14 weeks in the drinking water. The doses of losartan at 10 mg/kg/day was expected to be equivalent to 3 mg/kg/day of enalapril when considering clinical doses for lowering blood pressure. The dose of 3 mg/kg/day of losartan was selected to compare the efficacy at equivalent dose of enalapril. Histologic observation demonstrated suppression of glomerular mesangial expansion and glomerulosclerosis with exudative lesion in the 10 mg/kg/day losartan group when compared to the untreated diabetic controls. A lesser degree of glomerulosclerosis was also observed with losartan and enalapril treatment at 3 mg/kg/day. Ultrastructural examination of renal glomeruli from the high dose losartan group revealed a decreased degree of effacement and/or irregular arrangement of glomerular podocytic foot process. The beneficial effect of RAS inhibition with the AII receptor antagonist losartan on diabetic glomerular lesions was clearly demonstrated in this study. These findings, therefore, provide mechanistic explanation for the clinical utility of losartan for use in the treatment of diabetic nephropathy in man.

Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats.

The development of nephrocalcinosis in rats fed a high phosphorus diet, and the effectiveness of the Chinese traditional medicine, Wulingsan, and its components (Poria, Alismatis Rhizoma, Atractylodis Rhizoma, Cinnamomi Ramus, Polyporus) in suppressing the development of calcinosis were studied. The rats were fed a high phosphorus diet (1.5% P) supplemented with Wulingsan or its individual components (0.5 g/kg body weight) as separate experimental groups for a 2-week period. Upon histological observation by light microscopy and electron microscopy, signs of nephrocalcinosis were observed in almost all areas of the kidney. Calculi, consisting mainly of needle-shaped crystals of hydroxyapatite, were observed in the proximal tubules, in the collecting ductal lumina, and in the mitochondria of the proximal tubular cells and the interstitial cells. X-ray microanalysis revealed that the calculi were composed of hydroxyapatite (Ca and P). In the group fed the diet supplemented with Wulingsan, the severity of calcinosis in the corticomedullary junction was only slight. In all groups fed individual components of Wulingsan, the severity of calcinosis was almost the same as that in the group fed the high phosphorus diet (1.5% P). Wulingsan suppressed the development of calcinosis in rats fed the high phosphorus diet supplemented with this Chinese medicine, whereas its individual components alone had no effect. The process of calcinosis and the mechanism responsible for the activity of this Chinese medicine in the suppression of calcinosis are discussed.

[Experimental study of the protective effects of astragalus and salvia miltiorrhiza bunge on glycerol induced acute renal failure in rabbits].

The astragalus and salvia miltiorrhiza bunge alcohol extracts were used in preventive treatment of glycerol induced acute renal failure (ARF) in rabbits. The experimental rabbits were divided: astragalus group (AB), salvia miltiorrhia bunge group (SM), two extracts mixture group (ABSM), and normol saline control group (C). The extracts, mixtures and normol saline were administrated before and after the induced ARF. The counts of Na, K, creatinine in urine and blood and urinary AAP, NAG were determinated during 24-14 days periodically in all 4 groups, and the renal tissues were taken from same periods for pathomorphological studies by microscopy and transmission electromicroscopy. The damage of the glycerol induced ARF was not only in the convolute tubules but also in the glomerulus. The glomerulor filtration rate reduced abruptly, and oligouria or auria developed. The study of renal functions and renal morphogy showed that the AB and ABSM groups were damaged more lesser and promptely repaired than the SM and C groups in the early stage. No glomerular sclerosis was noted in the AB, ABSM groups in later stage, but it occurred sporadically or diffusely in the SM, C groups. Therefore, astragalus is an ideal protective drug of traditional chinese medicine for ARF.

High-dose 7-hydromethotrexate: acute toxicity and lethality in a rat model.

To elucidate mechanisms for methotrexate (MTX)-induced renal and hepatic toxicity, we investigated the acute effects of bolus plus continuous infusion of up to 0.4 g/kg 7-hydroxymethotrexate (7-OH-MTX) in the rat. We demonstrate for the first time in any species the occurrence of acute lethal toxicity within a few hours after 7-OH-MTX administration. Serum concentrations of 7-OH-MTX measured at the time of death were 1.4 mM (mean), about one-half of those achieved in some patients after infusion of high-dose MTX (HD-MTX) in the clinic. The data suggest an approximate LD50 (the dose lethal to 50% of the study population) of 0.3 g/kg and a steep dose/lethality curve for 7-OH-MTX. Moreover, acute renal and hepatic toxicity occurred as evidenced by severe morphological findings and increased serum levels of creatinine and liver transaminases. In all rats subjected to continuous infusion of 7-OH-MTX, yellow microscopic precipitations were apparent in the kidney tubules. Crystallization was also seen in bile ducts of the liver in some of the rats. These results further support that the formation of 7-OH-MTX is disadvantageous and that reported attempts to prevent its formation during MTX treatment are warranted.

[Effects of shenyan yiqiye on experimental membranous glomerulonephritis in rabbits].

The cationic bovine serum albumin (C-BSA) was used for duplicating experimental animal model of membranous glomerulonephritis with chronic renal failure. Shenyan Yiqiye (SYYQY) was adopted for treatment. The results showed that, in the therapeutic group, the urine protein and serum creatinine were reduced as compared with those in pathological group, P < 0.01. The parameter of morphometric analysis of glomeruli such as mean diameter, mean perimeter, mean surface area, mean volume, mean cross sectional area were all decreased, P < 0.01, the number of glomerular proliferative cells and thickness of glomerular capillary wall were all attenuated, P < 0.01, as compared with those in the pathological group. It suggested that SYYQY might alleviate the glomeruli lesions and benefit the renal functions.

Dietary myo-inositol supplementation does not prevent retinal and glomerular vascular structural changes in chronically diabetic rats.

To assess effects of dietary myo-inositol supplementation on diabetes-induced vascular structural lesions, diabetes was induced in Sprague-Dawley rats with streptozotocin; one-third of these rats was fed a 2% myo-inositol diet for 9 months, one-third was left untreated for 5 months then treated with myo-inositol for the last 4 months, and one-third was untreated for the entire 9 months. Controls included untreated and myo-inositol-treated groups. Weight gain was impaired and plasma glucose, glycosylated hemoglobin, food consumption, urine volume, and albuminuria were increased significantly in diabetic versus age-matched control rats. Plasma myo-inositol levels were increased approximately fivefold in controls and approximately six- to eightfold in diabetic rats treated with myo-inositol. In general, myo-inositol did not affect any of the above parameters in control or diabetic rats. Retinal capillary basement membrane width (CBMW) was increased significantly (approximately 50% versus controls) after 9 months of diabetes. In the control group myo-inositol increased CBMW to the level of untreated diabetic rats; myo-inositol had no effect on CBMW in each diabetic group. The number of retinal capillaries containing pericyte nuclei and pericyte capillary coverage were increased in untreated as well as myo-inositol-treated diabetic rats and in the myo-inositol-treated control group. Glomerular CBMW was increased after 5 and 9 months of diabetes versus age-matched controls, and was increased even more by myo-inositol. Mesangial fractional volume of the glomerulus was increased 36% by diabetes and was decreased slightly but significantly by myo-inositol. These results indicate that diets supplemented with 2% myo-inositol (1) cause capillary basement membrane (CBM) thickening and pericyte changes in retinal capillaries of normal rats, (2) are ineffective in preventing or reversing diabetes-induced retinal CBM thickening, and (3) cause further thickening of glomerular CBM in diabetic rats.

[Research on immune complex in situ type glomerulonephritis treated with mai-luo-tong in rabbits].

Applying c-BSA to duplicate immune complex in situ type glomerulonephritis in rabbits and treating it with Blood Circulation Promoting and Stasis-Removing Drugs Mai-Luo-Tong, the results showed that proteinuria in the treated group was decreased significantly, as compared to the control group (P < 0.01). Under light and electron microscope, although glomerular basement membrane was irregularly thickened and subepithelial dense electron deposits were found in both groups, but histopathologic damage in the treated group less than that of control one. In the treated group micro-thrombus, erythrocytes and platelets aggregation, leukocytes impaction were not seen within glomerular capillary. Also in the treated group mesangial cell proliferation and granulocyte infiltration were decreased significantly (P < 0.01) and there was no apparent glomerular fibrosis in former group.