Delayed redo pyeloplasty fails to recover lost renal function after failed pyeloplasty: Early sonographic changes that correlate with a loss of differential renal function

PURPOSE: To evaluate changes in differential renal function (DRF), as a functional outcome, in children who underwent redo pyeloplasty for management of failed pyeloplasty and to examine the factors that affect functional outcomes. MATERIALS AND METHODS: Between January 2002 and November 2010, a total of 18 patients who underwent redo pyeloplasty for persistent ureteropelvic junction obstruction after failed pyeloplasty were enrolled in this study. We assessed perioperative factors and evaluated changes in renal cortical thickness (RCT), renal function, and hydronephrosis by use of serial ultrasound and diuretic renography. RESULTS: The mean follow-up period was 44.83+/-28.86 months. After redo pyeloplasty, prevention of further functional deterioration was observed in only 12 of the 18 patients. After dividing the patients according to this observation, we discovered significant differences in both change in DRF (dDRF) and change in RCT (dRCT) (difference between before and after initial pyeloplasty) between the two groups (p<0.001). Additionally, we noted a significant positive correlation between dRCT and dDRF. All patients showed improvements in hydronephrosis grade and relief of symptoms compared with before redo pyeloplasty. CONCLUSIONS: Redo pyeloplasty should be considered in cases of failed pyeloplasty to preserve renal function and obtain relief from symptoms. If patients show severe deterioration of DRF or a decrease in RCT after initial pyeloplasty, preservation of DRF in these patients after redo pyeloplasty could be difficult. Therefore, redo pyeloplasty should be performed before severe deterioration of DRF or decrease in RCT.

Papel de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal / Mitochondria and oxidative stress participation in renal inflammatory process

La muerte celular programada y la fibrosis renal son procesos inherentes a la enfermedad renal crónica y, en tal sentido, ha sido recientemente descripta una clara desregulación de la maquinaria respiratoria mitocondrial en pacientes con enfermedad renal crónica asociada con un aumento del estrés oxidativo. Las células tubulares lesionadas vinculadas a los macrófagos intersticiales y miofibroblastos producen citoquinas y factores de crecimiento que promueven un estado inflamatorio, inducen la apoptosis de las células tubulares y facilitan la acumulación de matriz extracelular. La angiotensina II desempeña un papel central en la fibrogénesis renal y conduce a una rápida progresión de la enfermedad renal crónica. Los niveles crecientes de la angiotensina II inducen citoquinas pro-inflamatorias, la activación de NF-kB, moléculas de adhesión, quimiocinas, factores de crecimiento y estrés oxidativo. Toda la evidencia actual sugiere que la angiotensina II aumenta el estrés oxidativo mitocondrial, regula la inducción de apoptosis y condiciona al estado inflamatorio. Por lo tanto, existiría un papel determinante de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal. Finalmente, esta revisión resume nuestro actual conocimiento acerca de los posibles mecanismos que contribuirían con la apoptosis modulada por la inflamación y/o el estrés oxidativo durante la enfermedad renal crónica. Además, se propone un nuevo concepto de herramientas anti-inflamatorias que regulan el estrés oxidativo mitocondrial lo cual afectaría directamente al proceso inflamatorio y la apoptosis. Esta idea podría tener consecuencias atractivas sobre el tratamiento de patologías inflamatorias renales y de otras afines.

The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.

Histological and biochemical study on the protective effect of losartan on rat renal cortex in experimentally induced liver failure

Hepatic ischemia/reperfusion [I/R] injury is an unavoidable problem during liver surgery that often results in acute liver failure, with its complications. Losartan may be beneficial in such conditions. This study was designed to investigate the histological and biochemical alterations that could occur in the renal cortex in case of liver cell failure and to assess the possible protective role of losartan. Thirty male albino rats were equally divided into three groups: group I [control] was equally subdivided into sham operated-untreated [Ca] and sham-operated, losartan-treated [Cb] subgroups. In group II [operated], rats were subjected to experimentally induced I/R. In group III [losartan treated], rats were subjected to a surgical procedure and treated with losartan [5 mg/kg body weight]. At the end of the experiment, blood samples were obtained for the biochemical assay. The liver was processed for assessment of antioxidant markers and for light microscope examination. Both kidneys were processed for light and electron microscope examinations. The results were morphometrically and statistically analyzed. Light microscope examination of the operated group indicated shrunken glomeruli with wide Bowman's space. Some tubules were distorted with cytoplasmic vacuoles and cellular casts, whereas others were dilated. The interstitium contained an acidophilic material, increased collagen fibers, cellular infiltration, and congested blood vessels. Ultrastructurally, podocytes had small electron-dense nuclei and fused foot processes. Some renal tubules had small heterochromatic nuclei, mitochondria with disrupted cristae, and small electron-dense bodies. The biochemical results of the same group showed the occurrence of oxidative stress and deterioration in liver and kidney functions. The treated group showed preserved structure of the renal corpuscles and tubules. Liver I/R adversely affected the renal cortex histologically and biochemically. Losartan could be promising as an adjuvant therapy before hepatic surgery for rescuing the kidney from hepatic I/R injury

Hazards of nanotechnology: effect of titanium dioxide nanoparticles on the liver and renal cortex of albino rats. An electron microscopic study

Exposure to titanium dioxide nanoparticles [TiO[2] NPs] results from its wide use in the fields of medicine, industry, engineering, and environmental technology. To investigate the effect of administration of TiO[2] NPs on the ultrastructure of the rat liver and renal cortex. Rats were subdivided into two groups: group A [served as control] and group B [TiO[2] group]. TiO[2] was suspended in PBS and administered by an oral gavage to the rats of group B daily for 90 days at a dose of 5 mg/kg body weight. Thereafter, group B was subdivided into group B1 and sacrificed 24 h after the last dose of titanium. Group B2 was left untreated for 12 months and then sacrificed. Specimens from the liver and renal cortex were obtained and processed for examination by transmission electron microscopy. Histopathological changes were detected in the hepatocytes of group B1 in the form of dilated rough endoplasmic reticulum, numerous lysosomes, and abnormal mitochondria. Moreover, accumulation of large lipid droplets and wide cytoplasmic vacuoles was observed. The renal cortex was also affected. Numerous lysosomes were observed in the lining cells of the proximal tubules and the glomerulus showed an apparent increase in the number of mesangial cells. The interstitium was the site of excessive collagen bundles. These hepatic and renal cortical changes were partially ameliorated 12 months after the last dose of TiO[2]. Small doses of TiO[2] NPs for a long duration resulted in a variety of degenerative changes in the rat liver and renal cortex. Therefore, further studies are required to investigate the underlying mechanisms of this toxicity and to search for possible protective measures

Immunoexpression of gelatinase and apolipoprotein E in induced glomerulosclerosis in adult male albino rat

Introduction: The abnormal expressions of gelatinase are implicated in the pathogenesis of extracellular matrix accumulation in glomerulosclerosis [GS]. Apolipoprotein E [apoE] is an important plasma protein in cholesterol that plays a key role in the progression of GS

Aim: The aim of this work was to study the immunoexpression of gelatinases and apoE in experimentally induced GS

Materials and methods: Twenty male rats were divided into two equal groups: a control group and a GS model group [each n=10]. The GS was induced by an injection of adriamycin [5 mg/kg]. At the end of 4 weeks, the 10 rats in each group were killed and kidney specimens were processed for [histological and immunohistochemical study] biochemical studies

Results: Serum total protein and serum albumin in the GS group were reduced compared with those of the control group [P<0.01]. Compared with the control group, the values of 24-h urine total protein, 24-h urine excretion for albumin, blood urea nitrogen, serum creatinine, and GS index in the GS group were significantly increased [P<0.01]. In the GS group, there was glomerular hypercellularity and hypertrophy with focal obliteration of some capillaries. Interstitial fibrosis and inflammation were detected. The immunostaining for gelatinase was decreased, whereas apoE, transforming growth factor-beta1, and alpha-smooth muscle actin were increased

Conclusion: In induced GS, an increased expression of apoE was associated with decreased expression of gelatinase and this led to accumulation of extracellular material in glomeruli

Antithyroid drug or hypothyroidism causes cellular damage in the renal cortex of adult male albino rats: a histological and immunohistochemical study

Introduction: Thyroid and kidney functions interact with each other in the respective organ's diseased states. Drugs used to treat the respective diseases may have adverse effects on the other organ's functions. Antithyroid drugs cause hypothyroidism as well as renal dysfunction through immune mechanisms. The extrathyroidal effects of antithyroid drugs could contribute to oxidative stress and nitrosative stress and to cellular damage in the kidney

Aim: This study aimed to determine whether antithyroid drugs [e.g. methimazole] or hypothyroidism itself causes cellular damage in the rat renal cortex

Materials and methods: Twenty-five male albino rats were randomly divided into four groups. Group I [the control group] was subdivided into the euthyroid group and the false thyroidectomy group. Group II included rats with thyroidectomy-caused hypothyroidism. Group III included rats with methimazole-induced hypothyroidism, which received 60 mg/kg/day of methimazole in drinking water. Rats in group IV received methimazole [60 mg/kg/day] and l-thyroxine [T[4]] injection [20 microg/kg/day, subcutaneous]. At the end of treatment [4 weeks for the pharmacological groups and 8 weeks for the surgical groups], the animals were anesthetized and samples of kidney and sera were obtained. Renal cortex changes were evaluated by biochemical, histological, and immunohistochemical study

Results: The histological study revealed that only the methimazole-treated group showed cellular damage in the renal cortex. This damage was associated with an increase in oxidative and nitrosative stress, which was not compensated for by the decrease in the renal antioxidant enzymes and led to H[2]O[2]-caused cellular damage. The renal cortex in thyroidectomized rats did not show any histological alteration. Animals treated with methimazole with a T[4] supplement showed less damage in the renal cortex

Conclusion: Methimazole induces hypothyroidism and causes cellular damage in the renal cortex, and these effects are not caused only by hypothyroidism induced by surgical thyroidectomy. l-Thyroxine [T[4]] can improve the renal cortex changes

Effect of Nigella sativa oil on paracetamol-induced renal cortical damage in rats: light and electron microscopic study

Paracetamol or acetaminophen [IV-acetyl-p-aminophenol; APAP] is a widely used analgesic and antipyretic drug. Unfortunately, it is now reported as the most common cause of toxic ingestion in the world. Nigella sativa oil [NSO] is an extract of N. sativa having antioxidant properties. This study aimed to assess the possible role of NSO in ameliorating the toxic effect of APAP overdose on the rat renal cortical structure. Thirty male albino rats were divided into three equal groups. Group I was the control group. Group II comprised rats treated with APAP [750 mg/kg/day] orally for 7 days. Group III received NSO [2 ml/kg/day orally] 30 min before oral administration of APAP at the same dose as that of group II for 7 days. Kidney specimens were processed for light and electron microscopic study of the renal cortex. Plasma renin activity and arterial blood pressure were estimated. APAP-treated rats showed marked structural changes in the proximal convoluted tubules with dense nuclear staining, cytoplasmic vacuolization, increased peroxisomes, and partial loss of apical brush border and basal striations. Renal corpuscles revealed focal fusion of podocyte foot processes and irregular thickening of glomerular basement membranes. Juxtaglomerular cells contained few renin granules, reflecting an increase in renin exocytosis that coincided with increased plasma renin activity and increased arterial blood pressure. Concomitant administration of NSO with APAP revealed a noticeable amelioration of these histological and physiological changes. NSO exerted a protective effect against APAP-induced renal cortical damage

Renal cortex copper concentration in acute copper poisoning in calves / Concentração de cobre no córtex renal na intoxicação aguda de cobre em bezerros

The aim of this study was to estimate the diagnostic value of renal cortex copper (Cu) concentration in clinical cases of acute copper poisoning (ACP). A total of 97 calves that died due to subcutaneous copper administration were compiled in eleven farms. At least, one necropsy was conducted on each farm and samples for complementary analysis were taken. The degree of autolysis in each necropsy was evaluated. The cases appeared on extensive grazing calf breeding and intensive feedlot farms, in calves of 60 to 200 kg body weight. Mortality varied from 0.86 to 6.96 percent, on the farms studied. The first succumbed calf was found on the farms between 6 and 72 hours after the susbcutaneous Cu administration. As discrepancies regarding the reference value arose, the local value (19.9 parts per million) was used, confirming the diagnosis of acute copper poisoning in 93 percent of the analyzed kidney samples. These results confirm the value of analysis of the cortical kidney Cu concentration for the diagnosis of acute copper poisoning.

O objetivo deste trabalho foi estimar o valor diagnóstico de concentração de cobre (Cu) no córtex do rim em casos clínicos da intoxicação cobre aguda (ACP). Um total de 97 bezerros foi compilado em onze fazendas. Pelo menos, uma necropsia foi realizada em cada caso e foram colhidas amostras para análise complementar. O grau de autólise em cada necropsia foi avaliado. Os casos aparecem em criação extensiva e também em fazendas de confinamento intensivo. Os pesos dos animais variavam de 60 até 200 kg. Mortalidade variou entre 0,86 e 6,96 por cento, em todas as fazendas estudadas, o primeiro animal morto foi observado entre 6 e 72 horas após à administração parenteral de Cu. Surgirem discrepâncias em relação ao valor de referência a ser usado. O valor local (19. 9 partes por milhão) foi usado, confirmando o diagnóstico de intoxicação aguda de cobre em 93 por cento das amostras analisadas nos rins. Estes resultados confirmam o valor diagnóstico da concentração de Cu no rim córtex para o diagnóstico de ACP.

Influence of Gibberellic Acid [GA3] on Renal Cortex of Adult Male albino Rats [Histological, Immunohistochemical and Biochemical Study]

Plant growth regulators [PGRs] especially gibberellic acids [GA3] are widely used in Egypt to increase plant size, production and to increase plant availability all the year. Little is known about the biochemical or physiological effects of GA3 in mammalian tissues. This study aimed to evaluate the histological, immunohistochemical and biochemical changes in the rat renal cortex with subacute and subchronic exposure to GA3 and to detect the possible mechanism of such toxicities. Fifty adult male albino rats were classified into control group [I], experimental group [IIa and IIb] received GA3 in a dose of 75ppm [part per million]. Seventy five parts per million of GA3 as drinking water for 2weeks in subgroup IIa [subacute exposure] and for 8 weeks in subgroup IIb [subchronic exposure]. Group III [recovery group]: Rats received GA3 for 8weeks and stopped for other 6weeks. Renal cortex was stained with H and E, Masson's trichrome, immunohistochemically for Bcl-2 protein and electron microscopic examination. Oxidative biomarker [MDA] was detected in kidney tissue and antioxidant enzymes were detected in erythrocyte pellets prepared from blood sample. GA3 administration in group [II], led to degeneration, necrosis, apoptosis of the epithelial cells lining some of the tubules of the renal cortex with subacute toxicity and in most of the tubules with subchronic toxicity, fibrosis is significantly apparent in the subchronic subgroup. Interstitial cellular infiltration and hemorhage were seen. Hyaline casts in the lumen of renal tubules were apparent in the subchronic subgroup. Area percentage of antiapoptotic protein Bcl-2 immunoreactivity was decreased in the subchronic subgroup. Picture of cystic glomerular atrophy, acute tubular necrosis, degenerated podocytes and thickened blood renal barrier became prominent in the subchronic subgroup. The histological changes were associated with biochemical markers of oxidative stress. These changes were reduced in the recovery group but not retained to normal and the picture of oxidative stress was still present. The findings implied that gibberellic acid [GA3] induced nephrotoxic effect associated with oxidative stress with some sort of self recovery after stoppage of exposure. So, gibberellic acid should be used cautionary. Also, producers and consumers should be in conscious on the probable toxic effects of these chemicals

Doença parenquimatosa renal: correlação histológico-sonográfica / Renal parenchymal disease: histopathologic-sonographic correlation

OBJETIVO: Este estudo foi planejado para avaliar a correlação da ecografia do rim com as lesões histológicas e com os achados clínico-laboratoriais na doença parenquimatosa renal, por análise de regressão logística multivariada. MÉTODOS: Os dados clínicos, laboratoriais, ecográficos e as biópsias foram avaliados em 154 pacientes. A ecogenicidade cortical foi graduada como menor que grau zero, igual a grau um ou maior que grau dois a do parênquima hepático ou esplênico. As lesões histológicas - proliferação mesangial (PM), permeação leucocitária (PL), crescente e necrose fibrinóide (CNF), infiltrado inflamatório intersticial (II), esclerose glomerular segmentar (ES), obsolescência glomerular (OG), atrofia tubular (AT), fibrose intersticial (FI) e edema intersticial (EI) - foram graduadas de acordo com a extensão, em normal (0 por cento), leve (<25 por cento), moderada (>25 por cento <50 por cento), e grave (>50 por cento). RESULTADOS: a) II, FI, ES, EI e creatinina elevada ocorreram menos no grau 0 de ecogenicidade cortical; b) PM, hipertensão arterial e espessura normal do parênquima foram preditores do grau 1 de ecogenicidade cortical; c) FI, EI, creatinina elevada e parênquima fino foram preditores do grau 2 de ecogenicidade cortical; d) Excluindos os obesos, em jovens com hematócrito baixo, a pirâmide proeminente foi mais comum; e) Creatinina elevada e OG foram preditores de rins pequenos. CONCLUSÃO: A ecogenicidade cortical foi um sensível marcador de doença parenquimatosa renal. Lesões distintas mais do que o grau de severidade da lesão contribuiram para o aumento da ecogenicidade cortical. O EI aumenta exponencialmente o efeito da FI na ecogenicidade cortical.

PURPOSE: This study was designed to address the correlation between sonography of a kidney with histological lesions and clinical findings in patients with renal parenchymal disease based on a multivariate logistic regression analysis. METHODS: Clinical and laboratory data, sonograms and renal biopsies were evaluated in 154 patients. Cortical echogenicity was graded as less than (0), equal to (1) or greater than (2) liver/spleen parenchyma. Histological lesions - mesangial proliferation (MP), leukocyte permeation (LP), fibrinoid necrosis and crescents (FNC), interstitial infiltrate (II), segmental glomerular sclerosis (SGS), glomerular obsolescence (GO), tubular atrophy (TA) interstitial fibrosis (IF) and interstitial edema (IE) - were graded according to extension and severity as normal (0 percent), mild (<25 percent), moderate (>25 percent <50 percent), and severe (>50 percent). RESULTS: a) II, IF, SGS, IE and increased creatinine occurred less in cortical echogenicity grade 0; b) MP, arterial hypertension and normal parenchymal thickness predict cortical echogenicity grade 1; c) IF, IE, increased creatinine and thin parenchyma predict occurrence of echogenicity grade 2; d) Excluding obese patients, both youth and hematocrit accounted for pyramid prominence; e) increased creatinine and GO was probable in patients with small kidneys. CONCLUSIONS: Increased cortical echogenicity was a very sensitive marker of renal parenchymal disease. Different lesions rather than degree of lesion severity accounted for progressive increase of cortical echogenicity. IE exponentially increased the effect of IF on cortical echogenicity.

The repeated extracorporeal shock waves and the renal parenchyma injury on normal and diabetic rats

PURPOSE: To assess the effect of repeated extracorporeal shock waves (ESW) on renal parenchyma of normal and diabetic rats. METHODS: 40 normal rats (A) and 40 diabetic rats (B) were assigned for ESW (Direx Tripter X1® - 14 KVA) as follow: A1/B1 and A3/B3 no ESW; A2/B2 one ESW (2,000 SW); A4/B4 two ESW (4,000 SW) in an elapsed 14 days. All the animals were sacrificed 3 days after the ESW and samples of renal parenchyma were histological prepared, stained by H&E. For each animal the frequency of hemorrhage focus (HF) in the subcapasular, interstitial and glomerulus area was calculated (porcentage) on 20 randomly histological sections. RESULTS: No one HF was identified in all normal or diabetic animals without ESW (A1, A3 and B1, B3). In the normal rats the HF frequency was similar to one ESW (subcapsular =15 percent; interstitial =20 percent and glomerular =10 percent) or repetead ESW (subcapsular =25 percent; interstitial =20 percent; glomerular=10 percent). In diabetic rats the occurence of HF with repetead ESW was more frequent (subcapsular =40 percent; interstitial =30 percent and glomerular =10 percent) than with a single ESW (subcapsular =25 percent; interstitial =15 percent and glomerular =15 percent). CONCLUSION: A single ESW or a repeated ESW caused a mild and similar damage on renal cortex of normal rats. In diabetic rats the repetead ESW may result in an accumulated damage, especially with focus of hemorrhage in subcapsular and interstitial tissue and glomerulus edema.

RESUMO OBJETIVO: Avaliar o efeito de repetidas ondas de choque extracorpóreas (OCE) sobre o parênquima renal de ratos normais e diabéticos. MÉTODOS: 40 ratos normais e 40 ratos diabéticos foram distribuídos para aplicação de OCE (Direx Tripter X1® - 14 KVA) como segue: A1/B1 e A3/B3 sem OCE; A2/B2 uma sessão de OCE (2000 OC); A4/B4 duas sessões de OC (4000 OC) num intervalo de 14 dias. Todos os animais foram sacrificados no 3°. dia após a aplicação da OCE e amostras de parênquima renal foram histologicamente preparados e corados em H&E. Para cada animal foi calculado, em 20 campos aleatórios, a freqüência (em porcentagem) de focos hemorrágicos (FH) nas áreas subcapsular, intersticial e glomerular. RESULTADOS: Nenhum foco hemorrágico foi identificado nos animais normais ou diabéticos que não receberam nenhuma OCE (A1, A3 e B1, B3). Nos ratos normais a freqüência de FH foi similar com uma sessão de OCE (subcapsular =15 por cento; intersticial =20 por cento e glomerular =10 por cento) ou duas sessões de OCE (subcapsular =25 por cento; intersticial =20 por cento; glomerular =10 por cento). Nos ratos diabéticos a ocorrência de FH com duas sessões de OCE foi mais freqüente (subcapsular =40 por cento; intersticial =30 por cento e glomerular =10 por cento) do que com uma simples sessão de OCE (subcapsular =25 por cento; intersticial =15 por cento e glomerular =15 por cento). CONCLUSÃO: Uma única ou duas sessões de OCE causa um discreto e semelhante dano no parênquima renal de ratos normais. Nos ratos diabéticos a repetição da OCE pode resultar em acúmulo de danos, especialmente com FH nas áreas subcapsular e intersticial e no edema do glomérulo.

Protection against cephalosporin-induced lipid peroxidation and nephrotoxicity by (+)-cyanidanol-3 and vitamin E

The ability of the clinically used cephalosporins: cephalothin, cefotaxime and cefotiam to induce lipid peroxidation (LPO) and renal damage was compared to that of nephrotoxic cephaloridine under in vivo conditions. Glutathione was measured in rat liver or in renal cortex as non-protein sulfhydryls. LPO was measured in plasma, renal cortex and liver by the generation of malondialdehyde or as the increase in renal cortical concentration of conjugated dienes. Impairment of renal function was measured as the decrease in renal cortical accumulation of the organic anion p-aminohippurate (PAH). Administration of cephalosporins to rats as a single dose (2000 mg/kg, ip) induced a significant glutathione-depletion in the renal cortex with cephaloridine, and in the liver with cephaloridine, cephalothin and cefotiam. Treatment of rats with cephaloridine, cephalothin and cefotiam (200, 500, or 1000 mg kg-1 day-1, ip) for 5 days resulted in a dose-dependent increase of LPO in the renal cortex. While cephaloridine induced the highest concentration of conjugated diene, cefotaxime had no effect. Measurements of PAH accumulation in renal cortical slices from cephalosporin-treated rats showed a dose-dependent decrease in the renal cortical accumulation of PAH. Pretreatment with the antioxidants vitamin E or cyanidanol (400 mg kg-1 day-1, ip) 1 h before treatment with cephaloridine, cephalothin or cefotiam (1000 mg kg-1 day-1, ip) for 3 days inhibited cephalosporin-induced LPO and significantly reduced the impairment of renal cortical accumulation of PAH. The potential of different cephalosporins for inducing LPO and reducing PAH accumulation was ranked as follows: cephaloridine > cephalothin > cefotiam > cefotaxime.

Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin

Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, im, twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, im, twice a day for 9 days, and 14 with 0.15 M NaCl , im, twice a day for 9 days and PDTC, 50 mg kg-1 day-1, ip, twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm². Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

Isquemia e reperfusão hepática total em condicões de normalidade e sob estado de choque hemorrágico controlado: efeitos no sequestro de neutrófilos no rim do rato / Total hepatic ischemia and reperfusion under normal conditions and submitted to controlled hemorrhagic shock state: effects of neutrophil sequestration in kidney of rats

OBJETIVO: Avaliar os efeitos da isquemia e reperfusão hepática total em condicões de normalidade e estado de choque hemorrágico controlado no acúmulo de neutrófilos no interstício do rim do rato. MÉTODOS: Foram utilizados 32 ratos adultos da raca Wistar, machos, divididos em quatro grupos: Grupo Controle (GC), condicões de normalidade, submetidos às cateterizacões e laparotomia, seguido de um período de 60 minutos de observacão; Grupo Choque (GCh): estado de choque hemorrágico controlado (CHC) por 20 minutos (20') em pressão arterial média (PAM) de 40 mmHg, seguido de reanimacão volêmica e de 60 minutos de reperfusão (RP60); Grupo Pringle (GP): Manobra de Pringle (MP) por 15 minutos (15'), seguido de RP60; Grupo Choque-Pringle (GCP): estado de CHC por 20" em PAM de 40 mmHg, seguido de laparotomia e MP por 15', seguido de RP60. Para caracterizacão da má perfusão tecidual foram medidos o lactato sangüíneo (LS) e a reserva de base (RB), no início do período de reperfusão (RP0), aos trinta minutos de reperfusão (RP30) e no RP60. RESULTADOS: No RP0 o valor médio do LS e RB apenas o GC apresentou níveis dentro das normalidades. Nos RP30 e RP60 o valores médios do LS e RB do GC demonstrou-se estatisticamente diferente dos demais grupos (p<0,0001). Os valores médios de neutrófilos encontrado foram: GC = 0,24 (n0,28); GCh = 1,06 (n0,61); GP = 0,18 (n0,16); GCP = 0,24(n0,19). O GC apresentou diferenca estatística quando comparado aos demais, os quais não diferiam entre si. CONCLUSAO: O presente modelo experimental demonstrou que o estado de CHC por 20' seguido de RP60 foram os principais responsáveis pelo maior seqüestro de neutrófilo no córtex renal.

Estudio bioquímico-histológico de los efectos de litio en algunos organos de vizcacha (Lagostomus maximus maximus) / Biochemical-histological study of the effects of lithium in some organs of vizcacha (Lagostomus maximus maximus)

Considerando que la vizcacha (lagostomus maximus maximus) es un roedor muy sensible al Litio (Li), planificamos un estudio bioquímico-histológico inyectando cloruro de Li 1 mEq/Kg/día vía intraperitoneal durante un mes a vizcachas adultas de ambos sexos agrupadas en tres lotes. En el lote I se comprobó por técnicas de microscopía óptica un evidente dano renal, gonodal, hipofisario y adrenal; por métodos bioquímicos se comprobó que el Li disminuyó significativamente los niveles séricos de LH en hembra, el contenido de testosterona y estradiol no fue modificado. En machos el Li sérico resultó significativamente mayor (p<0.01, Prueba de t) que en hembras. El dano fue mayor en machos. en el Lote II se estudió a 30 días de la última administración el grado de recuperación tisular del dano comprobado en el Lote I. Se verificó una recuperación total en hipófisis, parcial en testículo, nula en rinón y se incrementó el dano en adrenal y ovario. Con respecto al efecto seletivo sobre la zona glomerulosa adrenal del Li sería producido via hipófisis. En conclusión el efecto selectivo de Li en adrenal y gónadas en este roedor es una contribución para alertar sobre la posible producción de estos efectos en humanos

Renal subcapsular islet cell transplantation in the dog: a preliminary report

During the last two decades, islet cell transplantation has been pursued both experimentally and clinically in an effort to ameliorate diabetes mellitus. At present, however, islet cell transplantation still remains at the experimental stages as far as the treatment of diabetes is concerned. Also, culture of islet cells has proved to be rather frustrating and difficult. No consistent techniques have been developed, and simplified methods for islet cell preparation and adequate sites for islet cell placement would allow for further progress in this area. Ultimately, rejection remains the greatest obstacle to success. We report a simplified technique for enriching dog pancreatic islet cells. This preparation was injected into the renal subcapsular space in both homograft (3 experiments) and heterograft (3 experiments) situations. After six weeks, nephrectomy was performed, and histochemical techniques demonstrated many groups of live islets in between the tubules in the renal cortex. No acinar cells were observed. Blood samples from the renal artery and renal vein at the time of nephrectomy revealed an average 36.9% increase in insulin concentraction on the renal veins, supporting an active secretory role of these transplanted islet cells. This technique points to (i) the possible role of a "renal factor" in promoting growth of islet cells and (ii) the feasibility of successful transplantarion of enriched islet cells as a potential approach to the curative treatment of diabetes mellitus