Vascular Hyperactivity in the Rat Renal Aorta Participates in the Association between Immune Complex-Mediated Glomerulonephritis and Systemic Hypertension.

Introduction: systemic hypertension (SH) involving endothelial dysfunction contributes to immune complex-mediated glomerulonephritis (ICGN). Objective, we demonstrate a relationship between ICGN and SH by analyzing vascular reactivity in renal aortic rings. Methods: 48 male Wistar rats were divided into four groups: (a) control (C); (b) injected with bovine serum albumin (BSA); (c) receiving 200 mg/L NAME (an analog of arginine that inhibits NO production) in drinking water; and (d) receiving BSA and 200 mg/L NAME. Rats were pre-immunized subcutaneously with BSA and Freund's adjuvant. After 10 days, groups (b) and (c) received 1 mg/mL of BSA in saline intravenous (IV) daily for 35 days. The urine of 24 h was measured at days 0, 15, 30 and 45. Results: vascular reactivity to norepinephrine (NE), acetylcholine (Ach) and NAME were tested. Creatinine clearance, vasodilatation, eNOS and elastic fibers were diminished (p ≤ 0.001). Blood pressure, vasoconstriction, iNOS were increased, and glomerular alterations were observed in groups (b), (c) and (d) when compared to group (a) (p ≤ 0.001). Conclusions: SH contributes to the development of progressive renal disease in ICGN. Alterations of the vascular reactivity are mediated by the endothelium in the renal aorta. Thus, the endothelium plays a determinant role in the production of vasoactive substances such as NO during this process.

Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor.

INTRODUCTION: Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients. MATERIAL AND METHODS: Patients with kidney graft biopsy were divided according to the presence or absence of CIN. We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. Histological, biochemical and clinical variables were measured. RESULTS: Calcineurin inhibitor (CI) levels were significantly higher in patients with the int 2 WW genotype than in patients with WC or CC genotypes. There was a greater degree of interstitial fibrosis in patients with int 2 CC genotype. No relationship was found between the different polymorphisms and a higher degree and/or frequency of CIN. There was also no relationship with plasma aldosterone levels. CONCLUSION: The frequency of the different polymorphisms studied was not related to plasma aldosterone levels or the development of CIN; however, the int 2 CC genotype was related to a greater degree of interstitial fibrosis, whereas the WW genotype was related to higher CI serum levels.

[Clinical baseline and post-nephrectomy characteristics of renal donors with IgA nephropathy diagnosed by time-zero renal biopsy (T0-RBx) compared with donors with normal T0-RBx]. / Características clínicas basales y post-nefrectomía de donadores renales con nefropatía por IgA diagnosticada mediante biopsia "cero" comparados con donadores con biopsia "cero" normal.

BACKGROUND: The renal manifestations of IgA nephropathy are wide, including patients with asymptomatic disease. The probability of developing advanced renal disease after 20 years of diagnosis varies. The prevalence of mesangial deposits of IgA in otherwise healthy people has been studied previously and there are only 2 reports in which the diagnosis is made by time-zero renal biopsy (TO-RBx). MATERIAL AND METHODS: We compared clinical characteristics (baseline and at followup) of renal donors with IgA nephropathy diagnosed by TO-RBx compared with 20 donors with normal TO-RBx. RESULTS: From 1999 to 2006 151 T0-RBx were analyzed. Of these 10 cases (6.62%) had IgA nephropathy. There were two patients with stage II and 8 with stage I according to HASS classification of IgA nephropathy. All donors in both groups (n=30) had normal urinary tests, however urinary protein excretion was significantly higher in the IgA nephropathy group compared with the normal group from baseline to the end of follow-up (three years). The glomerular filtration rate at three years of follow-up was significantly higher in the normal group (80 +/- 14 vs. 65 +/- 8 mL/min, p = 0.001). CONCLUSIONS: Donors with IgA nephropathy on TO-RBx had no urinary abnormalities during pre donation screening. At three years of follow-up patients with IgA nephropathy showed a greater loss of renal function as well as increased urinary protein excretion.

Ultrastructural findings in murine seminiferous tubules as a consequence of subchronic vanadium pentoxide inhalation.

Vanadium (V) is a transition metal emitted to the atmosphere during the combustion of fossil fuels. Its current status as an atmospheric pollutant increases the need for information about the effects that this element might have on the reproductive health of exposed populations. The present study investigated changes in testicular ultrastructure following inhalation exposure of male mice to V (as vanadium pentoxide). Tissue V level was constant during the 12-week time period. We observed necrosis of spermatogonium, spermatocytes and Sertoli cells, as well as pseudo-nuclear inclusion and disruption of cellular junctions. Our findings stressed the importance of the hemato-testicular barrier in supporting the function of Sertoli cells and suggest as a possible target of V, tight junction proteins. Further analysis is needed in order to identify the role that reactive oxidative species (ROS) might have on these cellular junctions, and if a specific protein is the target of its toxic effects. The relevance of this report concerns the impact that metal air pollution could have on male fertility in dense cities with vehicular traffic problems.

Inhalation of cadmium, lead or its mixture Effects on the bronchiolar structure and its relation with metal tissue concentrations.

The human population in the industrialized world is constantly exposed to chemical mixtures of pollutants such as metals; information about the consequences of the interactions of these compounds on health is scarce. The current study examines the effects of the inhalation of lead (Pb), cadmium (Cd) and Pb-Cd mixture in mice models analyzing the metal concentrations in lung, and the morphological modifications in the bronchiolar epithelium identified by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) after 4 weeks of inhalation. Our results showed that metal concentrations in lung were higher compared to controls; however, Pb concentrations drastically decrease with the mixture. This reduction was also observed in the inhalation chamber. These data correlate with the morphological alterations observed, which consisted of flattened and decreased number of nonciliated bronchiolar cells (NCBC), bald ciliated cells and bundles of NCBC. These modifications were mainly given by Cd, alone or in combination with Pb. The clusters formed by NCBC cells suggest cell proliferation which probably means that after metal inhalation, the cells enhance their proliferative capacity in order to repopulate the bronchiolar wall.

Proteinuria in rats induced by serum from patients with collapsing glomerulopathy.

BACKGROUND: Primary collapsing glomerulopathy recurs postransplant, raising the possibility of circulating factors implicated in the pathogenesis of the disease. METHODS: To determine the presence of circulating factors in collapsing glomerulopathy patients, we tested serum from those patients in an in vivo assay. Eleven groups of rats received serum from collapsing glomerulopathy patients, idiopathic focal segmental glomerulosclerosis (FSGS) or healthy subjects in its native form, isolated IgG, or serum without IgG. The presence of proteinuria and creatinine clearance were determined. Histopathologic analysis included light, immunofluorescence, and electron microscopy. RESULTS: Collapsing glomerulopathy rats developed proteinuria while rats injected with serum from FSGS and healthy subjects did not. Rats injected with serum of collapsing glomerulopathy in its native form developed marked proteinuria (99.2 +/- 42 mg/24 hours at day 5, P= 0.0001, compared to the baseline), and decreased in creatinine clearance. Rats receiving isolated IgG or serum without IgG from collapsing glomerulopathy developed mild proteinuria (46.5 +/- 8.4 mg/24 hours and 30.9 +/- 11 mg/24 hours, respectively, at day 5 (P= 0.0001). Glomerular tuft retraction and podocyte damage were seen only in collapsing glomerulapthy rats. No abnormalities were found in rats injected with serum from FSGS or healthy subjects. CONCLUSION: Circulating factors in the serum of collapsing glomerulopathy patients produce podocyte damage, whereas such factors are not present in noncollapsing FSGS. IgG eluates from collapsing glomerulopathy produce proteinuria when injected into the rat. Such factors remain in the circulation when serum of patients is adsorbed into protein A, raising the possibility that there are more than one circulating factor present in patients with collapsing glomerulopathy.

Metal mixture inhalation (Cd-Pb) and its effects on the bronchiolar epithelium. An ultrastructural approach.

The current study explores the effects of the inhalation of lead (Pb), Cd and its mixture (Pb-Cd) in a mice model, analysing metal concentrations in the lung, and the morphological modifications in the bronchiolar epithelium identified by scanning electron microscopy after eight weeks of inhalation. Our results indicate that metal concentrations in lung were higher compared to controls; however, Pb concentrations drastically decrease in the mixture. This reduction was also observed in the inhalation chamber. The main changes observed in the bronchiole were mostly in the mixture. The modifications were mainly given by Cd alone and in the mixture, with a decreased number of nonciliated bronchiolar cells and an increased number of bundles of dividing cells. The additive effect of Pb-Cd is suggested, as the extensive damage observed was more evident when mice were exposed to the mixture, and the results endured more research in the area of inhaled mixtures.

Angiotensin II-dependent increased expression of Na+-glucose cotransporter in hypertension.

Glucose uptake is increased in hypertension. Thus we investigated Na+-glucose cotransporter (SGLT2) activity and expression in proximal tubules from renovascular hypertensive rats. Sham-operated rats, aortic coarctation rats, and aortic coarctation rats treated with either ramipril (2.5 mg.kg-1.day-1 for 21 days) or losartan (10 mg.kg-1.day-1 for 21 days) were used. Na+-dependent glucose uptake was measured in brush-border membrane vesicles (BBMV). Vmax in BBMV from hypertensive rats was greater compared with those from normotensive rats (3 +/- 0.2 vs. 1.5 +/- 0.1 nmol.mg protein-1.min-1) without a change in Km. Renal immunostaining was greater, and Western blot analysis and RT-PCR showed a higher expression of SGLT2 in hypertensive rats than in normotensive rats (1,029 +/- 71 vs. 5,003 +/- 292, 199 +/- 15 vs. 95 +/- 10, and 1.4 +/- 0.2 vs. 0.3 +/- 0.1 arbitrary units, respectively). In rats treated with either ramipril or losartan, Vmax decreased to 2.1 +/- 0.3 and 1.8 +/- 0.4 nmol.mg protein-1.min-1, respectively, as well as did the intensity of immunostaining and levels of protein and mRNA. We suggest that in renovascular hypertension, angiotensin II induced SGLT2 via the AT1 receptor, which was evidenced at both the functional and expression levels, probably contributing to increased absorption of Na+ and thereby to the development or maintenance of hypertension.

Nasal cytology and genotoxic damage in nasal epithelium and leukocytes: asthmatics versus nonasthmatics.

BACKGROUND: The best example of a chronic inflammatory respiratory disease is asthma, a disease which has an increasing prevalence worldwide. This chronic inflammation is also related to the generation of oxidative stress since the cells involved in the allergic reaction are capable of producing reactive oxygen species (ROS), and this might predispose asthmatics to increased genotoxic damage. METHODS: A respiratory symptomatology questionnaire was self-applied by asthmatic and nonasthmatic students. A single cell gel electrophoresis assay in two different cell types (nasal epithelial cells and leukocytes) was performed, and the cytology of the nasal smears stained with HE was evaluated. RESULTS: Both groups reported having a runny nose. Asthmatics had greater DNA damage in the nasal epithelial cells in contrast to nonasthmatics. In leukocytes no statistical significance in DNA damage was identified. Metaplasia was evident in asthmatics that also showed eosinophils and neutrophils as well as goblet cells and mucus at a higher frequency compared with nonasthmatics. CONCLUSIONS: Nasal symptoms did not correlate with genotoxic damage, since they were reported in both groups. Nasal epithelial cells of asthmatics are more sensitive to genotoxic damage, and chronic inflammatory response. Also the activity of eosinophils might mediate the DNA damage through the generation of ROS.

Vanadium in ambient air: concentrations in lung tissue from autopsies of Mexico City residents in the 1960s and 1990s.

Vanadium concentrations in lung tissue were determined by atomic absorption spectrometry from autopsy specimens taken from residents of Mexico City during the 1960s and 1990s (20 males and 19 females, and 30 males and 18 females, respectively). Samples from the 1990s had significantly increased mean vanadium concentrations (mean +/- standard deviation: 1.36 +/- 0.08), compared with those from the 1960s (1.04 +/- 0.05). Concentrations were not correlated with gender, smoking habit, age, cause of death, or occupation. These findings suggest that vanadium in ambient air is increasing and it represents a potential health hazard for Mexico City residents. Air pollution monitoring efforts should include vanadium concentrations in suspended particles to follow-up the findings reported herein. Researchers need to acquire a better knowledge of the levels of airborne vanadium exposure at which risk to human health occurs.

Apoptosis y riñón / Apoptosis and kidney pathology

La apoptosis es uno de los dos mecanismos de muerte de las células, acontecimiento necesario para la remodelación tisular y en la renovación tisular. Se produce por isquemia, cuando ésta no es absoluta; se altera primeramente la membrana con bulas y ampollas, los organelos protoplásmicos lo hacen posteriormente, la cromatina nuclear se condensa y el DNA se fragmenta en bandas. Las células poseen factores de supervivencia (citocinas, hormonas) que evitan la apoptosis normal. Hay genes que estimulan la apoptosis y genes que la disminuyen ("genes de la muerte" y "genes de supervivencia"). El estudio de los mecanismos de regulación de la apoptosis tiene un gran potencial terapéutico: eliminación de tumores, disminución de la pérdida "normal" de neuronas, conservación de los linfocitos CD4 en el SIDA, o desaparición de las células auto-reactivas en enfermedades auto-inmunes.Este mecanismo de muerte celular es importante en la patogenia de las nefropatías tanto tubulointersticiales como glomerulares. Su comprensión y posible modificación podrá mejorar el tratamiento de trastornos inflamatorios, inmunológicos, tóxicos u obstructivos del riñón.

Kearns-Sayre syndromes and absolute indication for prophylactic implantation of definitive pacemaker?

El síndrome de Kearns-Sayre es una citopatía mitocondrial caracterizada por oftalmoplejia externa crónica progresiva, retinopatía pigmentaria y bloqueo auriculoventricular, siendo este último el determinante de la supervivencia de estos enfermos. Presentamos el caso de un hombre de 23 años con síndrome de Kearns-Sayre con trastornos de la conducción y prolapso de la válvula mitral. Se describen las características de este síndrome, así como los criterios para la implantación profiláctica de marcapaso definitivo

El sarcoma cardiaco ¿simula lupus eritematoso y vasculitis? Informe de 2 casos / Heart sarcoma mimicks systemic lupus erythematosus? Report of 2 cases

Los tumores primarios del corazón son raros. El más común es el mixoma, que es capaz de sintetizar IL-6 y con frecuencia tiene manifestaciones sistémicas, que confunden el diagnóstico. Los sarcomas cardiacos primarios, aún más raros, nunca han sido asociados a enfermedad sistémica. Informamos dos casos, en donde el diagnóstico presuntivo de lupus eritematoso sistémico fue modificado ante el hallazgo de sarcomas cardiacos primarios de estirpe muscular

Glomerulopatía colapsante: Una nueva entidad asociada a síndrome nefrótico e insuficiencia renal terminal / Collapsing glomerulopathy: a new entity associated to nephrotic syndrome and chronic renal failure

La glomerulopatía colapsante (GC) es una forma agresiva de daño glomerular definida por los datos histológicos de colapso de los capilares glomerulares, lesión de las células epiteliales viscerales y daño tubulointersticial característico. Los pacientes con glomerulopatía colapsante presentan datos clínicos que consisten en síndrome nefrótico grave, generalmente con proteinuria mayor de 10 g/24 horas, y progresión rápida a insuficiencia renal terminal o a la muerte por complicaciones del síndrome nefrótico, a pesar de cualquier forma de tratamiento. La GC, afecta a personas de cualquier sexo con ligera predominancia en el sexo masculino y en personas jóvenes. Se puede presentar como recidiva o de novo en el injerto renal. En algunos países predomina en la raza negra como sucede con las enfermedades renales en general. La GC comparte algunos datos clínicos e histológicos con la esclerosis focal y segmentaria recidivante y la nefropatía asociada al VIH, por lo que ha habido cierta controversia cerca de que se trate de una variante de estas enfermedades. Existe, sin embargo, evidencia clinicopatológica suficiente para separarla como una entidad diferente, aunque es posible que la esclerosis focal y segmentaria recidivante, la nefropatía asociada al SIDA y la glomerulopatía colapsante compartan un mecanismo fisiopatogénico común

Linfangiomiomatosis pulmonar y Linfangiomiomas: presentación de 8 casos y revisión de la literatura / Lymphangiomyomatosis and lymphangiomyomas: a study of 8 cases and review of the literature

Se presenta un estiduo clinicopatológico de 3 casos de linfangiomiomatosis pulmonar y mediastinal y de 5 linfangiomiomas de mediastino, retroperitoneo, mesenterio (2) y hombro. Seis pacientes fueron del sexo femenino y 2 del masculino, sus edades variaron de 19 meses a 47 años. Todos los pacientes presentaron grandes tumores por períodos que variaron de meses a muchos años, los cuales no afectaron su estado general. Cinco linfangiomiomas y un pulmón con linfangiomiomatosis se extirparon quirúrgicamente, a dos pacientes con linfangiomiomatosis solamente se les pudo biopsiar. Las lesiones midieron entre 12 y 32 cm de eje mayor, frecuentemente eran de aspecto multiquístico con pequeñas áreas sólidas. Microscópicamente, se observaron innumerables espacios quísticos, separados por septos tapizados con revestimiento endotelial y/o epitelial y dotados de músculo liso en haces. Un estudio inmunohistoquímico demostró que los quistes de la linfangiomiomatosis pulmonar tiene su orígen principalmente en conductos aéreos, mientras que los de los linfangiomiomas son exclusivamente de naturaleza vascular. Se informan 3 casos excepcionales en edad pediátrica (1 7/12, 9 y 11 años ) 2 localizaciones no descritas antes (mesenterio y hombro). Se presenta una revisión de las características clinicopatológicas de las dos formas de la enfermedad y su probale asociación con esclerosis tuberosa. Se discuten algunas ideas sobre la histogénesis y la etiopatogenia en estas lesiones de probable naturaleza hamartomatosa o corsistomatosa.

Linfoma de órbita y párpados. Manifestaciones clínicas, clasificación clínico-patológica y tratamiento / Lymphoma of the orbit and eyelid. Clinical manifestations, clinical-patologycal clasification and treatment

Se estudiaron nueve pacientes que presentaban linfoma de órbita y/o párpados, entre el 1o. de marzo de 1987 y el 31 de agosto de 1988, en los Servicios de Oftalmología y Hematología del Hospital General de México, S.S. En todos se llegó al diagnóstico por medio de biopsia de un ganglio comprometido o de la lesión extraganglionar; los cortes, teñidos con hematoxilina y eosina, fueron revisados por el mismo patólogo quien los describió y agrupó de acuerdo a la clasificación internacional para linfomas no Hodgkin. También se practicaron pruebas de inmunohistobioquímica para corroborar la estirpe y funcionalidad de los linfomas. A los pacientes les fué practicado examen ocular y en el Servicio de Hematología se les realizó examen físico completo y se les ordenaron estudios de extensión. Con ésto se clasificó clínico-patológicamente cada caso y se les trató de acuerdo a los esquemas seguidos en el Servicio de Hematología del Hospital General de México, S.S. Se hizo una revisión bibliográfica sobre los linfomas en general y la afección orbitaria en particular, se presenta un resumen de cada caso, luego se muestran los resultados y finalmente se hace una discusión y se establecen las conclusiones pertinentes.