Localization of Diacylglycerol Kinase ζ in the Kidney of Adult Rats: Its Dominant Expression in Collecting Tubules and its Selective Lack in Proximal Tubules / Localización de Diacilglicerol Quinasa ζ en el Riñón de Ratas Adultas: su Expresión Dominante en Túbulos Colectores y su Carencia Selectiva en Túbulos Proximales

SUMMARY: Diacylglycerol kinase (DGK) exerts balancing the intracellular level between two-second messengers, diacylglycerol and phosphatidic acid, by its phosphorylation activity. DGK ζ is often localized in cell nuclei, suggesting its involvement in the regulation of intranuclear activities, including mitosis and apoptosis. The present immunohistochemical study of rat kidneys first revealed no detection levels of DGK ζ -immunoreactivity in nuclei of most proximal tubule epithelia in contrast to its distinct occurrence in cell nuclei of collecting and distal tubules with the former more dominant. This finding suggests that DGK ζ is a key factor regulating vulnerability to acute kidney injury in various renal tubules: its low expression represents the high vulnerability of proximal tubule cells, and its distinct expression does the resistance of collecting and distal tubule cells. In addition, this isozyme was more or less localized in nuclei of cells forming glomeruli as well as in endothelial nuclei of peritubular capillaries and other intrarenal blood vessels, and epithelial nuclei of glomerular capsules (Bowman's capsules) and renal calyces, including intrarenal interstitial cells.

La diacilglicerol quinasa (DGK) ejerce el equilibrio del nivel intracelular entre dos segundos mensajeros, diacilglicerol y ácido fosfatídico, por su actividad de fosforilación. La DGK ζ a menudo se localiza en los núcleos celulares, lo que sugiere su participación en la regulación de las actividades intranucleares, incluidas la mitosis y la apoptosis. El presente estudio inmunohistoquímico en riñones de rata no reveló niveles de detección de inmunorreactividad de DGK ζ en los núcleos de la mayoría de los epitelios de los túbulos proximales, en contraste a la detección en los núcleos celulares de los túbulos colectores y distales, siendo el primero más dominante. Este hallazgo sugiere que DGK ζ es un factor clave que regula la vulnerabilidad a la lesión renal aguda en varios túbulos renales: su baja expresión representa la alta vulnerabilidad de las células del túbulo proximal, y su expresión distinta hace a la resistencia de las células del túbulo colector y distal. Además, esta isoenzima estaba más o menos localizada en los núcleos de las células que forman los glomérulos, así como en los núcleos endoteliales de los capilares peritubulares y otros vasos sanguíneos intrarrenales, y en los núcleos epiteliales de las cápsulas glomerulares (cápsulas de Bowman) y los cálices renales, incluidas las células intersticiales intrarrenales.

Diagnóstico de infección por VIH por el hallazgo incidental de alteraciones ultraestructurales en una biopsia renal: Report of one case / Ultrastructural alterations in renal biopsy leading to the diagnosis of HIV infection

HIV infection has different clinical presentations. We report a 21-year-old male with longstanding isolated microscopic hematuria attributed to thin glomerular basement membrane disease, who after 15 years of follow-up presented with significant proteinuria. A kidney biopsy was performed, revealing the presence of tubulo-reticular inclusions in the glomerular endothelial cells. This finding led to suspect an HIV infection, which was verified. Antiretroviral therapy, angiotensin-converting enzyme and angiotensin II receptor blockers were prescribed. At 6 years of diagnosis the patient is asymptomatic and has normal kidney function. Microscopic hematuria and low level proteinuria persists.

[Ultrastructural alterations in renal biopsy leading to the diagnosis of HIV infection]. / Diagnóstico de infección por VIH por el hallazgo incidental de alteraciones ultraestructurales en una biopsia renal: Report of one case.

HIV infection has different clinical presentations. We report a 21-year-old male with longstanding isolated microscopic hematuria attributed to thin glomerular basement membrane disease, who after 15 years of follow-up presented with significant proteinuria. A kidney biopsy was performed, revealing the presence of tubulo-reticular inclusions in the glomerular endothelial cells. This finding led to suspect an HIV infection, which was verified. Antiretroviral therapy, angiotensin-converting enzyme and angiotensin II receptor blockers were prescribed. At 6 years of diagnosis the patient is asymptomatic and has normal kidney function. Microscopic hematuria and low level proteinuria persists.

Low-Intensity physical activity beneficially alters the ultrastructural renal morphology of spontaneously hypertensive rats.

INTRODUCTION AND OBJECTIVE: Kidney disorders can cause essential hypertension, which can subsequently cause renal disease. High blood pressure is also common among those with chronic kidney disease; moreover, it is a well-known risk factor for a more rapid progression to kidney failure. Because hypertension and kidney function are closely linked, the present study aimed to observe the beneficial effects of low-intensity physical activity on structural and ultrastructural renal morphology and blood pressure in normotensive and spontaneously hypertensive rats. METHOD: Male Wistar-Kyoto rats and spontaneously hypertensive rats were randomly allocated into four groups: sedentary or exercised Wistar-Kyoto and sedentary or exercised spontaneously hypertensive rats. The exercise lasted 20 weeks and consisted of treadmill training for 1 hour/day, 5 days/week. RESULTS: The exercised, spontaneously hypertensive rats showed a significant blood pressure reduction of 26%. The body masses of the Wistar-Kyoto and spontaneously hypertensive strains were significantly different. There were improvements in some of the renal structures of the animals treated with physical activity: (i) the interdigitations of the proximal and distal convoluted tubules; (ii) the basal membrane of the proximal and distal convoluted tubules; and (iii) in the basal membrane, slit diaphragm and pedicels of the glomerular filtration barrier. The spontaneously hypertensive rats also showed a decreased expression of connexin-43. CONCLUSION: Physical exercise could be a therapeutic tool for improving kidney ultrastructure and, consequently, renal function in hypertensive individuals.

Low-Intensity physical activity beneficially alters the ultrastructural renal morphology of spontaneously hypertensive rats

INTRODUCTION AND OBJECTIVE: Kidney disorders can cause essential hypertension, which can subsequently cause renal disease. High blood pressure is also common among those with chronic kidney disease; moreover, it is a well-known risk factor for a more rapid progression to kidney failure. Because hypertension and kidney function are closely linked, the present study aimed to observe the beneficial effects of low-intensity physical activity on structural and ultrastructural renal morphology and blood pressure in normotensive and spontaneously hypertensive rats. METHOD: Male Wistar-Kyoto rats and spontaneously hypertensive rats were randomly allocated into four groups: sedentary or exercised Wistar-Kyoto and sedentary or exercised spontaneously hypertensive rats. The exercise lasted 20 weeks and consisted of treadmill training for 1 hour/day, 5 days/week. RESULTS: The exercised, spontaneously hypertensive rats showed a significant blood pressure reduction of 26 percent. The body masses of the Wistar-Kyoto and spontaneously hypertensive strains were significantly different. There were improvements in some of the renal structures of the animals treated with physical activity: (i) the interdigitations of the proximal and distal convoluted tubules; (ii) the basal membrane of the proximal and distal convoluted tubules; and (iii) in the basal membrane, slit diaphragm and pedicels of the glomerular filtration barrier. The spontaneously hypertensive rats also showed a decreased expression of connexin-43. CONCLUSION: Physical exercise could be a therapeutic tool for improving kidney ultrastructure and, consequently, renal function in hypertensive individuals.

Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity.

Bites from brown spiders (Loxosceles genus) have clinical manifestations including skin necrosis with gravitational spreading, and systemic involvement that may include renal failure, hemolysis, and thrombocytopenia. Mice were exposed to recombinant wild-type phospholipase-D, or to an isoform with a mutation in the catalytic domain resulting in no phospholipasic activity. Renal biopsies from mice treated with the wild-type toxin showed glomerular edema, erythrocytes and collapse of Bowman's space, edema and deposition of proteinaceous material within the tubular lumen. Ultrastructural analyses confirmed cytotoxicity by demonstrating disorders of glomerulus at foot processes and at fenestrated endothelium. Tubule alterations include deposits of amorphous material and edema, as well as an increase of epithelial cytoplasmic multivesicular bodies and electron-dense structures. There was an absence of nephrotoxicity in mice treated with the mutated toxin. Analyses of urine and blood showed that wild type toxin induced hematuria and elevation of blood urea, while treatment with mutated toxin caused no changes. Mouse lethality experiments also showed oliguria and mortality after treatment with wild-type toxin, but not following exposure to the mutated toxin. Immunofluorescence using antibodies to phospholipase-D toxin showed deposition of both toxins along the renal tubular structures as detected by confocal microscopy. Immunoblots of urine showed a 30 kDa band in samples from animals treated with wild-type toxin, but no band from mice exposed to mutated toxin. Wild-type toxin treatment caused cytoplasmic vacuolization, impaired spreading, reduction of cellular viability, and cell-cell and cell-substratum detachment in MDCK cells, while treatment with mutated isoform had no effect. Finally, there is a direct correlation between toxin activity on cell membrane phospholipids generating choline and cytotoxicity. We have defined for the first time a molecular mechanism for Loxosceles venom nephrotoxicity that is dependent on the catalytic activity of phospholipase-D toxin.

[Adaptation of an immunohistochemistry protocol for the detection of Leptospira spp. in samples of formaldehyde-fixed tissue]. / Adaptación de un protocolo de inmunohistoquímica para la detección de Leptospira spp. en muestras de tejido fijado en formaldehído.

The immunohistochemistry technique was evaluated in tissue samples fixed in formaldehyde saline solution 10 % and included in paraffin to be used as a lab method allowing to identify leptospires in tissues. Samples obtained from the experimental inoculation of 8 guinea pigs carriers of L. interrogans Pomona isolated from a clinical case were used. The disease was reproduced in a lab model. The histologic sections of the kidneys of the animals inoculated were subjected to histopathological studies, immunofluorescence, Warthin-Starry stain, and immunohistochemistry technique using formaldehyde-fixed samples. This technique proved to be an efficient tool for the diagnosis of leptospirosis.

Ultrastructure of tubular casts.

Tubular casts are found in a variety of conditions. Ultrastructural evaluation of casts has not been critically and systematically performed to define its usefulness. A total of 157 renal biopsies routinely processed for light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM) were subjected to blind ultrastructural evaluation. The majority of the casts were in the distal nephron, and most of them (41.4%) were hyaline (HC). One-third (35%) of the cases showed admixed HC and granular casts (GC), and 25 cases (16%) had exclusively GC. In 7% of the cases, the morphology of the casts was distinctive enough to indicate specific composition. Four cases with red blood cell casts (5.6%) were associated with necrotizing glomerulopathy and IgA nephropathy. Four cases of myoglobulin casts were identified. Two cases with crystalized light-chain casts (1.3%) were associated with an underlying plasma cell dyscrasia. One case of acute pyelonephritis demonstrated polymorphonuclear cells casts (0.64%). A case of aminoglycoside toxicity revealed casts with myeloid bodies. Ultrastructural evaluation of casts may provide useful information that may be critical to establish or suggest a specific diagnosis.

Structure of the kidney of Bufo arenarum: intermediate segment, distal tubule and collecting tubule.

The ultrastructure of the intermediate segment (IS), distal tubule and collecting tubule (CT) of the south american toad Bufo arenarum, was studied by light and transmission electron microscopy. The IS is composed of cubical ciliated cells which propel the urine along the renal tubule. The distal tubule is divided into two portions: the early distal tubule (EDT) and the late distal tubule (LDT). The EDT is characterized by only one type of cells with well developed basolateral interdigitations and numerous elongated mitochondria, which are oriented normal to the basal surface. The "macula densa--like" is a specialized zone of the EDT in contact with the vascular pole, where cells are more tightly packed than in the rest of the tubule. The LDT shows two types of cells called dark and light cells according to the appearance of their cytoplasm. Dark cells have microplicae and few but long microvilli at their luminal surface, and abundant mitochondria in their cytoplasm. Light cells show basal and lateral infoldings and few mitochondria. The CT, which is composed of dark and light cells, exhibits an enlarged lumen with an undulated surface and dilated spaces between neighbouring cells. This work is a contribution to the knowledge of the kidney of B. arenarum; frequently used as an experimental model for physiological and biochemical studies.

Structure of the kidney of Bufo arenarum: intermediate segment, distal tubule and collecting tubule

The ultrastructure of the intermediate segment (IS), distal tubule and collecting tubule (CT) of the south american toad Bufo arenarum, was studied by light and transmission electron microscopy. The IS is composed of cubical ciliated cells which propel the urine along the renal tubule. The distal tubule is divided into two portions: the early distal tubule (EDT) and the late distal tubule (LDT). The EDT is characterized by only one type of cells with well developed basolateral interdigitations and numerous elongated mitochondria, which are oriented normal to the basal surface. The "macula densa--like" is a specialized zone of the EDT in contact with the vascular pole, where cells are more tightly packed than in the rest of the tubule. The LDT shows two types of cells called dark and light cells according to the appearance of their cytoplasm. Dark cells have microplicae and few but long microvilli at their luminal surface, and abundant mitochondria in their cytoplasm. Light cells show basal and lateral infoldings and few mitochondria. The CT, which is composed of dark and light cells, exhibits an enlarged lumen with an undulated surface and dilated spaces between neighbouring cells. This work is a contribution to the knowledge of the kidney of B. arenarum; frequently used as an experimental model for physiological and biochemical studies.

Structure of the kidney of Bufo arenarum: intermediate segment, distal tubule and collecting tubule

The ultrastructure of the intermediate segment (IS), distal tubule and collecting tubule (CT) of the south american toad Bufo arenarum, was studied by light and transmission electron microscopy. The IS is composed of cubical ciliated cells which propel the urine along the renal tubule. The distal tubule is divided into two portions: the early distal tubule (EDT) and the late distal tubule (LDT). The EDT is characterized by only one type of cells with well developed basolateral interdigitations and numerous elongated mitochondria, which are oriented normal to the basal surface. The "macula densa--like" is a specialized zone of the EDT in contact with the vascular pole, where cells are more tightly packed than in the rest of the tubule. The LDT shows two types of cells called dark and light cells according to the appearance of their cytoplasm. Dark cells have microplicae and few but long microvilli at their luminal surface, and abundant mitochondria in their cytoplasm. Light cells show basal and lateral infoldings and few mitochondria. The CT, which is composed of dark and light cells, exhibits an enlarged lumen with an undulated surface and dilated spaces between neighbouring cells. This work is a contribution to the knowledge of the kidney of B. arenarum; frequently used as an experimental model for physiological and biochemical studies. (AU)

Impairment of the cell-to-matrix adhesion and cytotoxicity induced by Bothrops moojeni snake venom in cultured renal tubular epithelia.

Bothrops moojeni snake venom induces acute renal failure (ARF) as a consequence of morphological and functional alterations in glomerular and tubular cells. It is still unclear whether the ARF results from a direct cytotoxic effect on renal epithelia or from a renal ischemia due to systemic hemodynamic disturbances. This work investigated the in vitro effect of B. moojeni crude venom, using cultured Madin-Darby canine kidney (MDCK) monolayers as a model. The crude venom induced a significant time- and dose-dependent decrease in transepithelial electrical resistance across MDCK monolayers. In addition, the exposure to the venom resulted in cell detachment from the substratum, as revealed by transmission electron microscopy. Immunocytochemical analysis showed no change in the distribution of some junctional proteins, such as occludin, ZO-1, and E-cadherin. Nevertheless, the staining with labeled phalloidin revealed a disarray of the cytoskeleton, specifically of the stress fibers and of the focal adhesion-associated F-actin at the cell-to-matrix contact region. The treatment with B. moojeni venom also increased the cell release of lactate dehydrogenase and decreased cellular uptake of the vital neutral red. In conclusion, B. moojeni crude venom appears to have a direct cytotoxic effect on a renal tubule-derived cell line, also inducing impairment of the cell-matrix interaction.

Kidney structural and ultrastructural pathological changes induced by uracoan rattlesnake (Crotalus vegrandis Klauber 1941) venom.

Acute renal insufficiency related to acute tubular necrosis is the most important complication caused by crotalid bite. For structural and ultrastructural studies of renal tissue, mice injected with crude venom or C. vegrandis haemorrhagic fraction, and controls were tested. Light microscopy analysis of kidneys at 24 h after injection of crude venom showed only moderate alterations such as tubular epithelia microvacuolisation. After 120 h marked glomerular and tubular capillaries congestion and interstitial oedema were observed. At 24 h after Uracoina-1 i.p. injection, intense glomerular and peritubular capillaries congestion was observed. Electron microscopic analysis of kidneys 24 h after i.p. injection of crude venom showed, capillary endothelial cell debris and pleomorphic mitochondria. Loss of interdigitations regularity, abundant dense bodies and light widening of the basal membrane were observed. Autophagic vacuoles were present as well as endothelia unfolding to the lumen and altered forms of podocytes. At 48 h, augmented endothelia without fenestrae formation with sequestration of low optical density debris inside the protrusions were noticed. At 120 h, capillary residues with loss of the endothelium were present and the basal membrane was widened. At 15 days, the number of vesicles and vacuoles in the tubules was increased and only few interdigitations were noticed. Autophagic vacuoles and mitochondrial matrix low electron density were observed. At 120 h after injection of crude venom, vascular damage with loss of capillary cell structures and collagen fibres were observed. At 24 h of haemorrhagic fraction injection, presence of autophagic vacuoles and myelinic figures were noticed.

Ultracytochemical location of Na(+)/K(+)-atpase activity and effect of high salinity acclimation in gill and renal epithelia of the freshwater shrimp Macrobrachium olfersii (Crustacea, Decapoda).

Accumulation sites of lead phosphate reaction product consequent to Na(+)/K(+)-ATPase activity in gill and renal epithelia of the freshwater shrimp Macrobrachium olfersii were located ultracytochemically by para-nitrophenyl-phosphate hydrolysis and lead precipitation, and quantified per unit membrane area and cytoplasmic volume. In shrimps in freshwater (<0.5 per thousand S, 20 mOsm/kg H(2)O, 0.7 mEq Na(+)/liter), numerous sites of electron-dense, Na(+)/K(+)-ATPase reaction product accumulation were demonstrated in the membrane invaginations of the mitochondria-rich, intralamellar septal cells (12.5 +/- 1.7 sites/microm(2) membrane, 179 +/- 22 sites/microm(3) cytoplasm, mean+/- SEM, N

Effect of allopurinol in the course of adriamycin induced nephropathy.

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, the 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 +/- 6.39 mg/24 h; NCG = 59.8 +/- 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 +/- 17.5 mg/24 h; TNG-I = 49.1 +/- 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 +/- 22.23 mg/24 h and 72.66 +/- 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48%) and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Acute renal failure in experimental envenomation with Africanized bee venom.

Human victims of multiple bee or wasp stings have been reported and develop severe clinical signs and symptoms. Acute renal failure (ARF), usually due to acute tubular necrosis (ATN) was a frequent complication. The pathogenetic mechanisms of ATN occurring in these accidents are still unclear. In the present study, female Wistar rats weighing 150-200 g were injected intravenously with Africanized bee venom at a dose of 0.4 microL/100 g body weight, and the kidney was observed under light and transmission electron microscopy and in immunohistochemical studies. The animals were divided into two groups: an Early group studied 3 to 8 hours after inoculation, and a Late group studied 24 to 30 hours after inoculation. The animals showed ATN mainly in the cortex and outer medulla with cast formation. After 24 hours, frequent mitotic figures were found in the tubular epithelium. Immunohistochemical studies revealed the presence of myoglobin and muscle actin in the tubular casts. Under electron microscopy, proximal tubule segments showed increasing intracytoplasmic vacuoles and attenuation of the brush border and of the basolateral infolding. This segment and the thick ascending limb of Henle's loop showed hydropic degeneration. Dead cells with apoptosis or necrosis due to cellular disintegration resulted in tubular basement membrane denudation. In the Late group, figures of intracytoplasmic myelin could be observed, some of them containing mitochondrial fragments. These changes are likely to be due to interactive effects of venom components, mainly mellitin and enzymes such as phospholipases, both acting on biological membranes. The ATN found was probably due to multiple causes, mainly a direct action of the venom on tubular cells, myoglobinuria, and perhaps ischemic mechanisms.

Efecto del carcinogeno dimetilnitrosamina sobre el rinon del vison / Efect of carcinogen dimethylnitrasamine on the kidney of mink

Visones de un criadero que recibian alimentos, sobre la base de restos de pescado, evidenciaron un significativo aumento en su mortalidad, presencia de canceres hepaticos y alteraciones renales revelables histologicamente. Esos efectos fueron atribuibles a presencia, en el alimento, de dimetilnitrosamina (NDMA), en concentraciones 1,8 ug/g. En este trabajo se estudia en detalle el efecto de la NDMA sobre el rinon del vison. Visones que fueron tratados ip con NDMA(7 mg/kg en sol. fis.), mostraron dano evidenciable ultraestructuralmente en la corteza renal. El dano fue mayor en los tubulos proximales, que en los distales, pero era de naturaleza similar. Las celulas epiteliales tubulares de los animales intoxicados mostraron: a)Condensacion de la cromatina nuclear y dilatacion de la membrana perinuclear. b)Marcada hinchazon mitocondrial y ruptura de sus crestas con perdida de contenida de la matriz mitocondrial. c)Despegue de ribosomas y dilatacion del reticulo endoplasmico. d)Aumento del numero y tamano de las vacuolas autofagicas. e)Aparicion de gotas lipidicas en el citiplasma. En contraste con lo previamente establecido, para el caso de cancer hepatico del vison, el mecanismo del dano renal por NDMA no se pudo correlacionar directamente con la union de metabolitos reactivos de esta a proteinas o acidos nucleicos o la biotransformacion microsomal o mitocondrial de la NDMA o formaldehido. No obstante, el rinon biotransforma la NDMA a CO2, pero lo hace 3-4 veces menos intensamente que el rinon de rata. Los resultados sugeririan la presencia, en el caso del dano renal por NDMA, de mecanismos distintos de accion, a los habitualmente aceptados como responsables del dano hepatico o el renal en otras especies. Alternativamente, el dano renal puede deberse a dano hepatico concomitante

Efecto del carcinogeno dimetilnitrosamina sobre el rinon del vison / Efect of carcinogen dimethylnitrasamine on the kidney of mink

Visones de un criadero que recibian alimentos, sobre la base de restos de pescado, evidenciaron un significativo aumento en su mortalidad, presencia de canceres hepaticos y alteraciones renales revelables histologicamente. Esos efectos fueron atribuibles a presencia, en el alimento, de dimetilnitrosamina (NDMA), en concentraciones 1,8 ug/g. En este trabajo se estudia en detalle el efecto de la NDMA sobre el rinon del vison. Visones que fueron tratados ip con NDMA(7 mg/kg en sol. fis.), mostraron dano evidenciable ultraestructuralmente en la corteza renal. El dano fue mayor en los tubulos proximales, que en los distales, pero era de naturaleza similar. Las celulas epiteliales tubulares de los animales intoxicados mostraron: a)Condensacion de la cromatina nuclear y dilatacion de la membrana perinuclear. b)Marcada hinchazon mitocondrial y ruptura de sus crestas con perdida de contenida de la matriz mitocondrial. c)Despegue de ribosomas y dilatacion del reticulo endoplasmico. d)Aumento del numero y tamano de las vacuolas autofagicas. e)Aparicion de gotas lipidicas en el citiplasma. En contraste con lo previamente establecido, para el caso de cancer hepatico del vison, el mecanismo del dano renal por NDMA no se pudo correlacionar directamente con la union de metabolitos reactivos de esta a proteinas o acidos nucleicos o la biotransformacion microsomal o mitocondrial de la NDMA o formaldehido. No obstante, el rinon biotransforma la NDMA a CO2, pero lo hace 3-4 veces menos intensamente que el rinon de rata. Los resultados sugeririan la presencia, en el caso del dano renal por NDMA, de mecanismos distintos de accion, a los habitualmente aceptados como responsables del dano hepatico o el renal en otras especies. Alternativamente, el dano renal puede deberse a dano hepatico concomitante

Sequência evolutiva dos lisossomos anormais encontrados nos túbulos renais do camundongo beige (Síndrome de Chediak-Higashi) / Evolutive sequence of abnormal lysosomes found in the kidney tubules of the beige mouse (Chediak-Higashi syndrome)

Estudamos as modificaçöes que podem ocorrer no rim do camundongo beige, em seqüência evolutiva acompanhada desde o nascimento até a idade adulta, usando a reaçäo para localizar a ß-glucoronidase e a reaçäo do ácido periódico-reativo de Schiff (PAS). Os resultados mostraram que ao nascimento ocorre um acúmulo de Schiff (PAS). Os resultados mostraram que ao nascimento ocorre um acúmulo de grânulos PAS positivos no primeiro segmento dos túbulos proximais representando glico proteínas que atravessaram os vaso glomerulares. Com o aumento da atividade enzimática as glico proteínas säo absorvidas pelas células da regiäo S3, acumulando-se sob a forma de grânulos PAS positivos nos camundongos beige. Isso seria motivado pelo fato de que apesar do aumento da atividade enzimática, os lisossomos seriam deficientes e näo conseguiriam degradar as proteínas

Specific cytochemical localization of sodium-potassium dependent adenosine-triphosphatase (Na -K -atp-ASE) activity in cortical renal tubules of rat kidney

Utilizid para-nitrophenil-phosphate as an unspecific substrate cytochemical methods have described for and electron microscopi localizarion of Na -K -ATP-ase activity (ATP-ase-A). However, when applied to renal tubules, these methods did not clearly reveal the quantitative and quantitative distribution of the enzime. In an attempt to improve this method, we evaluated shorter fixation times, using freh paraformaldehyde after immersion of the renal tissue in an isosmotic sucrose tris buffer solution and utilized ATP as the specific substrate for the ATP-ase. The results indicated good preservation of the tissue, and under these conditions ATP was able to penetrate of the cells allowing a reliable identification at the ultrastructural level, of the ATP-ase-A, associated with subcellular structures for with the enzymatic reaction was positive. The activity observed suggest that the basolateral plasma membranes of proximal and distal renal tubules are the major sites of sites of Na -K -ATP-ase localization. However, there was also significant hydrolitic activity detectived on the surface (brush border) of proximal convoluted tubules, that disappeared with the elimination of the Na and K from the incubation medium. In both cases enzymatic activities were insensitive to 10 mM Ouabain in the medium