Nephrosis in cattle associated with consumption of Ludwigia peploides (Onagraceae).

This paper describes an outbreak of nephrosis in cattle associated with the consumption of Ludwigia peploides in Tucuman province, northwestern Argentina. Affected cows exhibited submandibular and chest edema, lethargy and ataxia, and eventually succumbed to these conditions. These animals were grazing in a floodable area severely invaded by this plant. The disease affected 7 out of a herd of 67 cows. Horses and goats grazing in the same location were not affected. The main gross and histological lesion corresponded to a severe nephrosis. The disease is similar to the poisoning by Ludwigia peruviana reported in Colombia.

Enfermedad de cambios mínimos cortico-resistente e hipotiroidismo. Reporte de caso / Steroid-resistant minimal change disease and hypothyroidism: Case report

Introducción: La enfermedad de cambios mínimos es una causa rara de síndrome nefrótico en el adulto, y su relación con el hipotiroidismo es más rara aún. Se considera que esta patología renal responde favorablemente al manejo con glucocorticoides y tiene una baja frecuencia de resistencia. Su abordaje hoy en día es objeto de investigación. Objetivo: Describir una rara etiología de síndrome nefrótico en el adulto con presentación, tratamiento y desenlace infrecuentes. Presentación del caso: Paciente femenino de 53 años quien inicia con síndrome nefrótico por enfermedad de cambios mínimos cortico-resistente y su asociación con un hipotiroidismo descontrolado, quien requiere manejo con rituximab y control de la enfermedad endocrinológica asociada, como enfermedad de base. Conclusiones: En este caso clínico se muestra como las enfermedades citadas pueden coexistir y el tratamiento en conjunto es necesario. El establecimiento de nuevas terapias en la población adulta como el rituximab podría mostrar beneficio, como en este caso. Sin embargo, aún existe la necesidad de estudios de mayor evidencia que validen firmemente la efectividad de los diferentes tratamientos en este tipo de pacientes.

Introduction: Minimal change disease is a rare cause of nephrotic syndrome in adults, and its association with hypothyroidism is even more exceptional. This renal pathology is considered to respond favorably to glucocorticoid management and has a low resistance frequency. How to approach this disease is currently under investigation. Objective: To describe a rare etiology of adult nephrotic syndrome with unusual presentation, treatment, and outcome. Case presentation: A 53 years-old female patient who initially experienced nephrotic syndrome due to steroid-resistant minimal change disease, which was also associated with uncontrolled hypothyroidism. She required management with rituximab and control of the associated endocrinological disease, which was considered as the underlying disease. Conclusions: This clinical case shows (i) how the two aforementioned diseases can coexist and (ii) that a joint treatment is necessary. Establishing new therapies may be beneficial for adult populations, such as the benefits seen in this case with the use of rituximab. However, further studies are needed to strongly validate the effectiveness of the different treatments for these types of patients.

Arsenic exposure intensifies glycogen nephrosis in diabetic rats.

It is known that either arsenic exposure or diabetes can impact renal function. However, it is unclear how these combined factors may influence kidney functions. Therefore, we evaluated morphological, functional, and oxidative parameters in the kidney of diabetic rats exposed to arsenic. Healthy male Wistar rats and streptozotocin-induced diabetic rats were exposed to 0 and 10 mg/L arsenate through drinking water for 40 days. Renal tissue was assessed using morphometry, mitosis and apoptosis markers, mineral proportion, oxidative stress markers, as well as the activity of antioxidant enzymes and membrane-bound adenosine triphosphatases. Arsenate intake altered glucose levels in healthy animals, but it did not reach hyperglycemic conditions. In diabetic animals, arsenate led to a remarkable increase of glycogen nephrosis in distal tubules. In these animals, additionally, the activity of catalase and glutathione S-transferase, besides the proportion of Fe, Cu, and K in renal tissue, was altered. Nevertheless, arsenate did not accumulate in the kidney and did not impact on other parameters previously altered by diabetes, including levels of malondialdehyde, Na, urea, creatinine, and apoptosis and mitosis markers. In conclusion, besides the intensification of glycogen nephrosis, the kidney was able to handle arsenate toxicity at this point, preventing arsenic deposition in the exposed groups and the impairment of renal function.

Poisoning by Thiloa glaucocarpa (Combretaceae) in cattle in the semiarid regions of Paraíba and Pernambuco, Brazil

The aim of this study was to describe the epidemiological, clinical and pathological aspects of spontaneous poisoning by Thiloa glaucocarpain cattle in the semiarid region of Paraíba and Pernambuco, Brazil. Eight adult cattle were examined and of those, five were necropsied. The main clinical signs consisted of dehydration, dry nose, ascites and subcutaneous edema. Renal function tests resulted in significant changes. The gross macroscopy consisted of significant fluid accumulation in the abdominal and thorax cavities, and edema of lungs, subcutaneous tissues, perirenal tissue and abomasal folds. Histologically, the main lesions consisted of epithelial coagulation necrosis of renal convoluted tubules with presence of amorphous eosinophilic material in the lumen of the tubules. The diagnosis of poisoning by T. glaucocarpawas based on epidemiological data, clinical signs, necropsy findings, histopathological evaluation, renal serum biochemistry and plant identification in the areas of cattle pastures. After the start of the rainy season in this region, T. glaucocarpais the main toxic plant responsible for significant economic losses. Since there is no effective treatment for animals with renal failure, itis recommended that the animals must be removed from the areas where the plant grows in the period immediately after the first rain.(AU)

Amprolium-induced thiamine deficiency in mice: evaluation of a practical model by oral administration

Thiamine is an essential cofactor for several cellular functions. Your deficiency results in important neurological disorders, with mechanisms and lesions not fully understood. The purpose of this work was to evaluate a thiamine deficiency through the model of oral administration of amprolium in mice. The animals, treated for 20 or 80 days, received amprolium in drinking water at doses of 10, 20, and 30 mg/mL (deficient groups A, B, and C, respectively). Deficient groups A and B showed reduction in body weight gain and performance changes in the open field (decreased distance and rearing, and increased grooming) and rotarod (reduced latency to fall) behavioural tests, when treated for 80 days. However, no histological changes were observed in the central nervous system. Moreover, group B animals exposed to amprolium developed proteinuria, with moderate tubular nephrosis, at 80 days. At the highest dose (group C) there was no interest to drink water. The data suggest that the use of oral amprolium in mice may be an interesting and viable model, when using adequate exposure times and doses. The amprolium induces thiamine deficiency progressively and moderately, which may be potentially useful for disturbed pathogenesis studies.(AU)

Spontaneous poisoning by Combretum glaucocarpum Mart. [sin.: Thiloa glaucocarpa (Mart.) Eichler] (Combretaceae) in cattle / Intoxicação espontânea por Combretum glaucocarpum Mart. [sin.: Thiloa glaucocarpa (Mart.) Eichler] (Combretaceae) em bovinos

The present study aimed to describe, for the first time in Tocantins State, the epidemiological, clinical, and pathological aspects of an outbreak of Combretum glaucocarpa poisoning in cattle. From a herd of 200 cattle that had access to the plant, 70 animals died. The signs were swelling of the posterior thigh, groin, perineum, scrotum, ventral abdomen, chest, and barb; dark and fetid stools; marked weight loss, and rough hair. The clinical course ranged from 3 to 20 days. The serum activities of alanine aminotransferase and aspartate amininotransferase and the serum concentrations of urea and creatinine were markedly elevated in all the ten animals examined. The gross lesions consisted of large amouts of transudate in the peritoneal, pleural, and pericardial cavities. Edema was also seen in the urinary bladder, perirenal tissue and gallbladder subserosa at its insertion to the liver. The liver was enlarged, congested, and bluish. Petechiae and ecchymosis were observed in the epicardium, myocardium, tracheal mucosa, omentum, ruminal serosa, urinary bladder, and testicles. Suffusions were detected in the brain. Histopathology of the liver revealed mild centrilobular degeneration. In the kidney, hemorrhagic foci in corticomedullary junction with mild tubular degeneration were observed. Additionally, some renal tubules had necrotic epithelial cells and hyaline casts. It is the first report of poisoning by C. glaucocarpum in cattle in Tocantins.(AU)

O presente trabalho tem por objetivo descrever, pela primeira vez no Estado do Tocantins, as características epidemiológicas, clínicas e patológicas de um surto de intoxicação espontânea por Combretum glaucocarpa em bovinos. De um lote de 200 bovinos acessíveis à planta, 70 animais chegaram a óbito. Os sinais observados foram edema na região posterior da coxa e inguinal, períneo, escroto e ventre do abdômen, tórax e barbela; fezes escuras e fétidas; emagrecimento e pêlos ásperos. O curso clínico variou de 3 a 20 dias. As concentrações séricas de ureia e creatinina e as atividades séricas de alanino-aminotransferase e aspartato-aminotransferase estavam elevadas nos dez animais avaliados. As lesões observadas foram grande quantidade de transudato na cavidade abdominal, tórax e saco pericárdico. Notou-se edema na bexiga, tecidos perirenais e na subserosa da vesícula biliar, junto à sua inserção com o fígado. Este estava aumentado, com bordos arredondados, congesto e azulado. Petéquias e equimoses foram observadas no epicárdio, miocárdio, mucosa da traqueia, omento, serosa do rúmen, vesícula urinária e testículos. Áreas de sufusões foram observadas no encéfalo. Na histopatologia, visualizou-se degeneração hidrópica centrolobular leve no fígado e, no rim, focos de hemorragia na junção corticomedular com degeneração tubular leve. Encontraram-se células epiteliais necróticas e cilindros hialinos em alguns túbulos renais. É a primeira descrição por C. glaucocarpum em bovinos no Tocantins.(AU)

Poisoning by Thiloa glaucocarpa (Combretaceae) in cattle in the semiarid regions of Paraíba and Pernambuco, Brazil

The aim of this study was to describe the epidemiological, clinical and pathological aspects of spontaneous poisoning by Thiloa glaucocarpain cattle in the semiarid region of Paraíba and Pernambuco, Brazil. Eight adult cattle were examined and of those, five were necropsied. The main clinical signs consisted of dehydration, dry nose, ascites and subcutaneous edema. Renal function tests resulted in significant changes. The gross macroscopy consisted of significant fluid accumulation in the abdominal and thorax cavities, and edema of lungs, subcutaneous tissues, perirenal tissue and abomasal folds. Histologically, the main lesions consisted of epithelial coagulation necrosis of renal convoluted tubules with presence of amorphous eosinophilic material in the lumen of the tubules. The diagnosis of poisoning by T. glaucocarpawas based on epidemiological data, clinical signs, necropsy findings, histopathological evaluation, renal serum biochemistry and plant identification in the areas of cattle pastures. After the start of the rainy season in this region, T. glaucocarpais the main toxic plant responsible for significant economic losses. Since there is no effective treatment for animals with renal failure, itis recommended that the animals must be removed from the areas where the plant grows in the period immediately after the first rain.

Spontaneous poisoning by Combretum glaucocarpum Mart. [sin.: Thiloa glaucocarpa (Mart.) Eichler] (Combretaceae) in cattle / Intoxicação espontânea por Combretum glaucocarpum Mart. [sin.: Thiloa glaucocarpa (Mart.) Eichler] (Combretaceae) em bovinos

The present study aimed to describe, for the first time in Tocantins State, the epidemiological, clinical, and pathological aspects of an outbreak of Combretum glaucocarpa poisoning in cattle. From a herd of 200 cattle that had access to the plant, 70 animals died. The signs were swelling of the posterior thigh, groin, perineum, scrotum, ventral abdomen, chest, and barb; dark and fetid stools; marked weight loss, and rough hair. The clinical course ranged from 3 to 20 days. The serum activities of alanine aminotransferase and aspartate amininotransferase and the serum concentrations of urea and creatinine were markedly elevated in all the ten animals examined. The gross lesions consisted of large amouts of transudate in the peritoneal, pleural, and pericardial cavities. Edema was also seen in the urinary bladder, perirenal tissue and gallbladder subserosa at its insertion to the liver. The liver was enlarged, congested, and bluish. Petechiae and ecchymosis were observed in the epicardium, myocardium, tracheal mucosa, omentum, ruminal serosa, urinary bladder, and testicles. Suffusions were detected in the brain. Histopathology of the liver revealed mild centrilobular degeneration. In the kidney, hemorrhagic foci in corticomedullary junction with mild tubular degeneration were observed. Additionally, some renal tubules had necrotic epithelial cells and hyaline casts. It is the first report of poisoning by C. glaucocarpum in cattle in Tocantins.

O presente trabalho tem por objetivo descrever, pela primeira vez no Estado do Tocantins, as características epidemiológicas, clínicas e patológicas de um surto de intoxicação espontânea por Combretum glaucocarpa em bovinos. De um lote de 200 bovinos acessíveis à planta, 70 animais chegaram a óbito. Os sinais observados foram edema na região posterior da coxa e inguinal, períneo, escroto e ventre do abdômen, tórax e barbela; fezes escuras e fétidas; emagrecimento e pêlos ásperos. O curso clínico variou de 3 a 20 dias. As concentrações séricas de ureia e creatinina e as atividades séricas de alanino-aminotransferase e aspartato-aminotransferase estavam elevadas nos dez animais avaliados. As lesões observadas foram grande quantidade de transudato na cavidade abdominal, tórax e saco pericárdico. Notou-se edema na bexiga, tecidos perirenais e na subserosa da vesícula biliar, junto à sua inserção com o fígado. Este estava aumentado, com bordos arredondados, congesto e azulado. Petéquias e equimoses foram observadas no epicárdio, miocárdio, mucosa da traqueia, omento, serosa do rúmen, vesícula urinária e testículos. Áreas de sufusões foram observadas no encéfalo. Na histopatologia, visualizou-se degeneração hidrópica centrolobular leve no fígado e, no rim, focos de hemorragia na junção corticomedular com degeneração tubular leve. Encontraram-se células epiteliais necróticas e cilindros hialinos em alguns túbulos renais. É a primeira descrição por C. glaucocarpum em bovinos no Tocantins.

Natural intoxication by Amaranthus spinosus (Amaranthaceae) in bovines in the State of Pernambuco, Brazil / Intoxicação natural por Amaranthus spinosus (Amaranthaceae) em bovinos no Agreste do estado de Pernambuco

The aim of the present study was to describe an outbreak of intoxication by Amaranthus spinosus among bovines in the northern rural region of the state of Pernambuco (northeastern Brazil). The herd was composed of 70 mixed-breed Holstein cattle. Five animals became intoxicated, two of which died and three recovered. The main clinical signs were apathy, decubitus, reduced to absent appetite, pinkish pale to pale mucous membranes, severe dehydration, accentuated enophthalmia, rumenal atony or hypomotility, submandibular swelling, hind-leg edema and fetid feces with a dark coloration. The biochemical analysis revealed high AST, GGT and creatinine levels. Necropsy reveled perirenal edema, subcapsular hematomas, paleness and multifocal petechial hemorrhaging on the cortical surface extending to the bone marrow and intensive hemorrhaging in the pelvis. The histopathological analysis revealed degeneration and necrosis of cortical region of tubular epithelial cells, especially proximal cells, and the accentuated presence of granular hyaline casts and droplets in the cortical and medullary lumen. The diagnosis of intoxication by Amaranthus spinosus  was based on the epidemiological, clinical-laboratorial, necroptic and histolopathological characteristics of intoxication by nephrotoxic plants. The scarcity of other food sources and the large quantity of the plant as the only food source for the bovines as well as the consumption of the plant in the flowering phase favored these cases of intoxication.(AU)

Descreve-se um surto de intoxicação por Amaranthus spinosus ocorrido em bovinos na região do Agreste meridional de Pernambuco. O rebanho era composto de 70 animais, mestiços de holandês, cinco animais se intoxicaram, dois morreram, três se recuperaram. Os principais sinais clínicos foram apatia, decúbito, com apetite reduzido a ausente, mucosas rosa pálidas a pálida, desidratação severa com acentuada enoftalmia, rúmen com diminuição da motilidade ou atônico, edema submandibular e edema dos membros posteriores, fezes de odor fétido e escuras. A bioquímica clínica apresentou valores aumentados para AST, GGT e Creatinina.  A necropsia revelou nos rins edema perirrenal, hematomas subcapsulares, palidez e hemorragia petequial multifocal na superfície cortical estendendo-se do parênquima até a região medular e intensa hemorragia na pelve. A histopatologia revelou degeneração e necrose na região cortical das células epiteliais tubulares, em sua maioria nos túbulos proximais e presença acentuada no lúmen de cilindros granulosos hialinos e gotículas tanto cortical como na medular. O diagnóstico da intoxicação por Amaranthus spinosus foi baseado nos achados epidemiológicos, clínico-laboratorial, de necropsia e histopatologia características da intoxicação por plantas nefrotóxicas. A escassez de alimentos associado a presença da planta em grande quantidade, como única fonte de volumoso para os bovinos, e o consumo desta no estágio de brotação, favoreceram a intoxicação.(AU)

Natural intoxication by Amaranthus spinosus (Amaranthaceae) in bovines in the State of Pernambuco, Brazil / Intoxicação natural por Amaranthus spinosus (Amaranthaceae) em bovinos no Agreste do estado de Pernambuco

The aim of the present study was to describe an outbreak of intoxication by Amaranthus spinosus among bovines in the northern rural region of the state of Pernambuco (northeastern Brazil). The herd was composed of 70 mixed-breed Holstein cattle. Five animals became intoxicated, two of which died and three recovered. The main clinical signs were apathy, decubitus, reduced to absent appetite, pinkish pale to pale mucous membranes, severe dehydration, accentuated enophthalmia, rumenal atony or hypomotility, submandibular swelling, hind-leg edema and fetid feces with a dark coloration. The biochemical analysis revealed high AST, GGT and creatinine levels. Necropsy reveled perirenal edema, subcapsular hematomas, paleness and multifocal petechial hemorrhaging on the cortical surface extending to the bone marrow and intensive hemorrhaging in the pelvis. The histopathological analysis revealed degeneration and necrosis of cortical region of tubular epithelial cells, especially proximal cells, and the accentuated presence of granular hyaline casts and droplets in the cortical and medullary lumen. The diagnosis of intoxication by Amaranthus spinosus  was based on the epidemiological, clinical-laboratorial, necroptic and histolopathological characteristics of intoxication by nephrotoxic plants. The scarcity of other food sources and the large quantity of the plant as the only food source for the bovines as well as the consumption of the plant in the flowering phase favored these cases of intoxication.

Descreve-se um surto de intoxicação por Amaranthus spinosus ocorrido em bovinos na região do Agreste meridional de Pernambuco. O rebanho era composto de 70 animais, mestiços de holandês, cinco animais se intoxicaram, dois morreram, três se recuperaram. Os principais sinais clínicos foram apatia, decúbito, com apetite reduzido a ausente, mucosas rosa pálidas a pálida, desidratação severa com acentuada enoftalmia, rúmen com diminuição da motilidade ou atônico, edema submandibular e edema dos membros posteriores, fezes de odor fétido e escuras. A bioquímica clínica apresentou valores aumentados para AST, GGT e Creatinina.  A necropsia revelou nos rins edema perirrenal, hematomas subcapsulares, palidez e hemorragia petequial multifocal na superfície cortical estendendo-se do parênquima até a região medular e intensa hemorragia na pelve. A histopatologia revelou degeneração e necrose na região cortical das células epiteliais tubulares, em sua maioria nos túbulos proximais e presença acentuada no lúmen de cilindros granulosos hialinos e gotículas tanto cortical como na medular. O diagnóstico da intoxicação por Amaranthus spinosus foi baseado nos achados epidemiológicos, clínico-laboratorial, de necropsia e histopatologia características da intoxicação por plantas nefrotóxicas. A escassez de alimentos associado a presença da planta em grande quantidade, como única fonte de volumoso para os bovinos, e o consumo desta no estágio de brotação, favoreceram a intoxicação.

Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.

Cisplatin is a commonly used chemotherapeutic agent. Its main side-effect is nephrotoxicity. It was reported that the organic anion transporter 5 (Oat5) urinary excretion is elevated, implying renal perturbation, when no modifications of traditional markers of renal damage are still observed in cisplatin-induced acute kidney injury (AKI). It was also demonstrated that Oat5 is excreted in urine by the exosomal pathway. This study was designated to demonstrate the specific response of the urinary excretion of exosomal Oat5 to kidney injury independently of other cisplatin toxic effects, in order to strengthen Oat5 urinary levels as a specific biomarker of AKI. To accomplish that aim, we evaluated if urinary excretion of exosomal Oat5 returns to its basal levels when cisplatin renal damage is prevented by the coadministration of the renoprotective compound N-acetylcysteine. Four days after cisplatin administration, AKI was induced in cisplatin-treated male Wistar rats (Cis group), as it was corroborated by increased urea and creatinine plasma levels. Tubular damage was also observed. In cotreated animals (Cis + NAC group), plasma urea and creatinine concentrations tended to return to their basal values, and tubular damage was improved. Urinary excretion of exosomal Oat5 was notably increased in the Cis group, but when renal injury was ameliorated by N-acetylcysteine coadministration, that increase was undetected. So, in this work we observed that urinary excretion of exosomal Oat5 was only increased if renal insult is produced, demonstrating its specificity as a renal injury biomarker.

Intoxicação por Metternichia princeps (Solanaceae) em caprinos no Estado da Bahia / Poisoning by Metternichia princeps (Solanaceae) in goats in the State of Bahia, Brazil

Descreve-se um surto de intoxicação por Metternichia princepsem caprinos no Estado da Bahia. De oito caprinos, três morreram, dos quais dois foram necropsiados; cinco não adoeceram. Os principais sinais clínicos caracterizaram-se por secreção nasal mucosa, emagrecimento, diarreia, apatia, debilidade leve, andar cambaleante, flexão dos membros torácicos e pélvicos, decúbito esterno-abdominal e decúbito lateral, seguidos de morte após aproximadamente dois dias de evolução clínica. Na necropsia foi observado edema pulmonar, hidrotórax, hidropericárdio, ascite, rins pálidos, edema perirrenal e hemorragias no tecido subcutâneo. Microscopicamente nos rins havia acentuada necrose de coagulação do epitélio tubular e túbulos com regeneração do epitélio. No pulmão havia acentuada congestão associada a edema interalveolar e interseptal. Na bioquímica sanguínea observou-se aumento na ureia, creatinina e creatinina fosfoquinase.(AU)

An outbreak of poisoning by Metternichia princepsis reported in goats from the State of Bahia. Out of eight goats three showed symptoms of poisoning and died; on two of them post-mortem examinations were performed. The main clinical signs were nasal mucous secretion, weight loss, diarrhea, lethargy, mild weakness, staggering gait, flexion of the fore and hind limbs, sternal recumbence, and lateral recumbence followed by death after approximately two days of clinical manifestations. The serum concentration of urea and creatinine and the serum activities of creatine phosphokinase were increased. At necropsy pulmonary edema, hydrothorax, hydropericardium, ascites, pale kidneys, perirenal edema and hemorrhages in the subcutaneous tissue were observed. Microscopically the kidneys showed accentuated coagulation necrosis of the tubular epithelium and tubules and epithelial regeneration. In the lungs there was accentuated congestion associated with interalveolar and interseptal edema.(AU)

Intoxicação por Metternichia princeps (Solanaceae) em caprinos no estado da Bahia / Poisoning by Metternichia princeps (Solanaceae) in goats in the state of Bahia, Brazil

Descreve-se um surto de intoxicação por Metternichia princepsem caprinos no Estado da Bahia. De oito caprinos, três morreram, dos quais dois foram necropsiados; cinco não adoeceram. Os principais sinais clínicos caracterizaram-se por secreção nasal mucosa, emagrecimento, diarreia, apatia, debilidade leve, andar cambaleante, flexão dos membros torácicos e pélvicos, decúbito esterno-abdominal e decúbito lateral, seguidos de morte após aproximadamente dois dias de evolução clínica. Na necropsia foi observado edema pulmonar, hidrotórax, hidropericárdio, ascite, rins pálidos, edema perirrenal e hemorragias no tecido subcutâneo. Microscopicamente nos rins havia acentuada necrose de coagulação do epitélio tubular e túbulos com regeneração do epitélio. No pulmão havia acentuada congestão associada a edema interalveolar e interseptal. Na bioquímica sanguínea observou-se aumento na ureia, creatinina e creatinina fosfoquinase.

An outbreak of poisoning by Metternichia princepsis reported in goats from the State of Bahia. Out of eight goats three showed symptoms of poisoning and died; on two of them post-mortem examinations were performed. The main clinical signs were nasal mucous secretion, weight loss, diarrhea, lethargy, mild weakness, staggering gait, flexion of the fore and hind limbs, sternal recumbence, and lateral recumbence followed by death after approximately two days of clinical manifestations. The serum concentration of urea and creatinine and the serum activities of creatine phosphokinase were increased. At necropsy pulmonary edema, hydrothorax, hydropericardium, ascites, pale kidneys, perirenal edema and hemorrhages in the subcutaneous tissue were observed. Microscopically the kidneys showed accentuated coagulation necrosis of the tubular epithelium and tubules and epithelial regeneration. In the lungs there was accentuated congestion associated with interalveolar and interseptal edema.

Two distinct WT1 mutations identified in patients and relatives with isolated nephrotic proteinuria.

Wilms' tumor type 1 gene (WT1) encodes a zinc-finger transcription factor that plays a key role during genitourinary development and in adult kidney. Mutations in exons 8 and 9 are associated with Denys-Drash Syndrome, whereas those occurring in the intron 9 donor splice site are associated with Frasier Syndrome. Familial cases of WT1 mutations are rare with only few cases described in the literature, whereas cases of WT1 mutations associated with isolated nephrotic proteinuria with or without focal segmental glomerular sclerosis (FSGS) are even rarer. Exons 8 and 9 of WT1 gene were analyzed in two non-related female patients and their parents. Patient 1, who presented with isolated nephrotic proteinuria and histologic pattern of FSGS, is heterozygous for the mutation c.1227+4C>T. This mutation was inherited from her mother, who had undergone kidney transplant due to FSGS. Patient 2 is heterozygous for the novel c.1178C>T transition inherited from her father. The putative effect of this nucleotide substitution on WT1 protein is p.Ser393Phe mutation located within the third zinc-finger domain. The patient and her father presented, respectively, isolated nephrotic proteinuria and chronic renal failure. These data highlight the importance of the inclusion of WT1 gene mutational analysis in patients with isolated nephrotic proteinuria, especially when similar conditions are referred to the family.

Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin.

INTRODUCTION: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT(1) receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. MATERIALS AND METHODS: To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O(2(-))) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. RESULTS: ADR rats showed increased expression of ICAM-1, Ang II, O(2(-)) and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. CONCLUSIONS: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT(1) receptors.

Intracellular nitric oxide assessment in whole blood leukocytes by flow cytometry: optimization and applicability to monitor patients with chronic graft nephropathy.

Flow cytometry has been proposed as an alternative method for direct determination of intracellular NO by using the 4,5-diaminofluorescein-diacetate (DAF-2DA) as a fluorescent probe. In the present study, the protocol for intracellular NO determination in peripheral blood monocytes and neutrophils of by flow cytometry was optimized and applied to monitor chronic graft nephropathy patients. The optimize method consists to incubate plasma-free whole blood samples with DAF-2DA at 2.0 microM for 180 min at 37 degrees C to determine the percentage of DAF-2T+ monocytes and neutrophils. Distinct intracellular NO profiles in monocytes and neutrophils from chronic graft nephropathy patients as compared to the healthy individuals. Although the pre-incubation with LPS was able to trigger higher percentages of DAF-2T+ monocytes and neutrophils in both groups, our data demonstrated that LPS had a greater impact on monocytes as compared to neutrophils, selectively in the group of healthy individuals. Moreover, our findings demonstrated that LPS had lower impact on monocytes from chronic graft nephropathy as compared to healthy individuals. Supplementary analysis revealed that the LPS impact tends to be resorted in those patients with longer post-transplant time, as demonstrated by a significant positive correlation index. Furthermore, our results demonstrated that AG had lower inhibitory impact on neutrophils as compared to monocytes, selectively in the group of chronic graft nephropathy patients. Taken together, this study showed a new approach to monitor the immunological status of patients with chronic graft nephropathy opening new perspectives of research regarding the monocyte and neutrophil functions in patient undergoing immunosuppressive therapy.