RESUMEN
AIMS: The protein alpha1-microglobulin (alpha1-microg) is filtered by the glomeruli and fully reabsorbed by the proximal tubules, and tubulointerstitial injury compromises its reabsorption. The aim of this study was to determine which functional, morphological and inflammatory renal disorders associated with tubulointerstitial damage interfere with urinary excretion of alpha1-microg in patients with glomerulopathies. PATIENTS AND METHODS: 38 patients (33.6 +/- 11.3 years) with primary or secondary glomerulopathies diagnosed by renal biopsies were studied. The urinary fractional excretion of alpha1-microg (FEalpha1-microg), the urinary monocyte chemoattractant protein-1/urinary creatinine (UMCP-1) index and 24-h proteinuria were determined. In the cortex of renal biopsies, the number of macrophages/104 microm2 of glomerular tuft (GT) and tubulointerstitial (TI) areas, the relative interstitial area (RCIA), and the relative interstitial fibrosis area (CIF) were measured. Results are reported as median and range and the Spearman non-parametric test was used to determine the correlations. RESULTS: FEalpha1-microg was 0.165% (0.008% - 14,790.0%) in patients with glomerulopathies and 0.065% (0.010% - 0.150%) in the control group (p < 0.05; Mann-Whitney U-Test). FEalpha1-microg was correlated with creatinine clearance (r = -0.4396; p = 0.0358), UMCP-1 index (r = 0.5978; p < 0.0001), number of macrophages/TI area (r = 0.5634; p = 0.0034) and RCIA (r = 0.7436; p < 0.0001). However, FEa1-microg was not correlated with proteinuria (r = 0.1465; p = 0.5153) or with CIF (r = 0.0039; p = 0.98). CONCLUSIONS: renal MCP-1 and the expansion and number of macrophages of the tubulointerstitial area participate in the increase of urinary excretion of alpha1-microg in patients with glomerulopathies. Although proteinuria and interstitial fibrosis have not been associated with this effect, the present study does not exclude some of these disorders in the pathophysiology of urinary excretion of alpha1-microg.
Asunto(s)
alfa-Globulinas/orina , Glomerulonefritis/orina , Túbulos Renales Proximales/metabolismo , Proteinuria/orina , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Biopsia , Quimiocina CCL2/orina , Creatinina/metabolismo , Progresión de la Enfermedad , Femenino , Glomerulonefritis/complicaciones , Glomerulonefritis/fisiopatología , Humanos , Inmunohistoquímica , Túbulos Renales Proximales/patología , Masculino , Nefelometría y Turbidimetría , Pronóstico , Proteinuria/etiología , Proteinuria/fisiopatologíaRESUMEN
The mechanisms involved in kidney disturbances during development, induced by vitamin D3 deficiency in female rats, that persist into adulthood were evaluated in this study. Female offspring from mothers fed normal (control group, n=8) or vitamin D-deficient (Vit.D-, n=10) diets were used. Three-month-old rats had their systolic blood pressure (SBP) measured and their blood and urine sampled to quantify vitamin D3 (Vit.D3), creatinine, Na+, Ca+2 and angiotensin II (ANGII) levels. The kidneys were then removed for nitric oxide (NO) quantification and immunohistochemical studies. Vit.D- pups showed higher SBP and plasma ANGII levels in adulthood (P<0.05) as well as decreased urine osmolality associated with increases in urinary volume (P<0.05). Decreased expression of JG12 (renal cortex and glomeruli) and synaptopodin (glomeruli) as well as reduced renal NO was also observed (P<0.05). These findings showed that renal disturbances in development in pups from Vit.D- mothers observed in adulthood may be related to the development of angiogenesis, NO and ANGII alterations.
Asunto(s)
Enfermedades Renales/etiología , Riñón/irrigación sanguínea , Deficiencia de Vitamina D/complicaciones , Animales , Femenino , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Fenómenos Fisiologicos Nutricionales Maternos , RatasRESUMEN
IgA nephropathy (IgAN) is a kidney disease with a varying renal prognosis. Recently, many studies have demonstrated that renal alpha-smooth muscle actin (alpha-SMA) and transforming growth factor (TGF-beta1) expression, as well interstitial mast cell infiltrates could represent a prognostic marker in several renal diseases. The aim of our study was to analyze the prognostic value of mast cell, TGF-beta1 and alpha-SMA expression in IgAN. A survey of the medical records and renal biopsy reports of 62 patients with a diagnosis of IgAN followed-up from 1987 to 2003 was performed. The mean follow-up time was 74.7 +/- 50.0 months. The immunohistochemical studies were performed using a monoclonal antibody anti-human mast cell tryptase, a polyclonal antibody anti-human TGF-beta1, and a monoclonal antibody anti-human alpha-SMA. An unfavorable clinical course of IgAN was related to interstitial mast cell infiltrates and alpha-SMA expression in the tubulointerstitial area. Expression of glomerular TGF-beta1 and alpha-SMA, and interstitial TGF-beta1 is not correlated with clinical course in IgAN. In conclusion, the increased number of mast cells and higher alpha-SMA expression in the tubulointerstitial area may be predictive factors for the poor prognosis of patients with IgAN.
Asunto(s)
Actinas/metabolismo , Glomerulonefritis por IGA/metabolismo , Mastocitos/citología , Factor de Crecimiento Transformador beta1/metabolismo , Adolescente , Adulto , Femenino , Glomerulonefritis por IGA/patología , Humanos , Inmunohistoquímica , MasculinoRESUMEN
To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.
Asunto(s)
Lesión Renal Aguda/fisiopatología , Factor de Crecimiento Epidérmico/uso terapéutico , Isquemia/complicaciones , Túbulos Renales/fisiopatología , Riñón/fisiopatología , Regeneración , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Animales , Autorradiografía , Nitrógeno de la Urea Sanguínea , Constricción , Creatinina/sangre , ADN/biosíntesis , Riñón/irrigación sanguínea , Ratas , Ratas Endogámicas , Arteria RenalRESUMEN
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, i.m., twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, i.m., twice a day for 9 days, and 14 with 0.15 M NaCl , i.m., twice a day for 9 days and PDTC, 50 mg kg(-1) day(-1), i.p., 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.
Asunto(s)
Antibacterianos/efectos adversos , Gentamicinas/efectos adversos , Necrosis Tubular Aguda/enzimología , FN-kappa B/metabolismo , Nefritis Intersticial/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Western Blotting , Creatinina/sangre , Femenino , Fibrosis/enzimología , Fibrosis/patología , Inmunohistoquímica , Corteza Renal/química , Corteza Renal/efectos de los fármacos , Corteza Renal/patología , Necrosis Tubular Aguda/inducido químicamente , Necrosis Tubular Aguda/patología , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/patología , Nitratos/análisis , Pirrolidinas/farmacología , Ratas , Ratas Wistar , Tiocarbamatos/farmacologíaRESUMEN
The aim of this study is to investigate the effect of sodium bicarbonate on doxorubicin-injected rats. Thirty female Wistar rats were injected with doxorubicin (3.5 mg/kg of body weight, intravenously) and 30 rats with 0.15 mol/L of sodium chloride solution (group C). Fifteen days later, we replaced the drinking water with a 0.15-mol/L sodium bicarbonate solution for 10 of the animals injected with doxorubicin (group AD-B). Three months after the beginning of treatment, urine samples were collected to quantify albumin, creatinine, and transforming growth factor-beta (TGF-beta). The rats were killed, and the kidneys were removed for histological, morphometric, immunohistochemical, and RNA studies. All doxorubicin-injected animals showed structural renal changes. However, these alterations were less intense in rats treated with doxorubicin plus sodium bicarbonate (P < 0.05). The percentage of glomerulosclerosis was 0.11% +/- 0.08% in group C, 14.7% +/- 12.8% in group AD (rats treated with doxorubicin only), and 4.38% +/- 1.9% in group AD-B, and the percentage of tubulointerstitial damage was 0. 01% +/- 0.03% in group C, 54.6% +/- 20.3% in group AD, and 16.6% +/- 10.3% in group AD-B. The immunostaining for TGF-beta in the renal cortex and glomeruli was more intense in the animals injected with doxorubicin only. A greater renal cortical TGF-beta messenger RNA content was observed in the animals injected with only doxorubicin that did not receive sodium bicarbonate (P < 0.05). These animals also presented a greater rate of urinary TGF-beta excretion reported as picograms of TGF-beta per milligram of urinary creatinine (P < 0.05), which was 202 +/- 11 pg/mg in group C, 1, 103 +/- 580 pg/mg in group AD, and 299 +/- 128 pg/mg in group AD-B. However, albuminuria was more intense in the sodium bicarbonate-treated animals (P < 0.05). The animals from group AD also showed higher immunostaining scores for vimentin and albumin in tubule cells (P < 0.05). In conclusion, treatment with sodium bicarbonate reduces structural renal damage, albumin reabsorption, and renal TGF-beta production in rats with doxorubicin-induced nephropathy.
Asunto(s)
Doxorrubicina , Enfermedades Renales/metabolismo , Riñón/patología , Bicarbonato de Sodio/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Albúminas/análisis , Albuminuria , Animales , Femenino , Fibronectinas/análisis , Inmunohistoquímica , Riñón/metabolismo , Riñón/fisiopatología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Ratas , Ratas Wistar , Albúmina Sérica/análisis , Factor de Crecimiento Transformador beta/orina , Vimentina/análisisRESUMEN
We previously showed that 3-month-old rats subjected to a 50% intrauterine food restriction had a decreased number of nephrons with increased glomerular diameter, which suggests compensatory hypertrophy. Hypertrophy could be the early event of glomerular damage. In this study, we extended our investigation and performed functional, morphological, and immunohistochemical evaluations in 3- and 18-month-old rats that underwent a 50% intrauterine food restriction (RT3 and RT18, respectively) and age-matched control rats (C3 and C18, respectively). Our findings showed that glomerular filtration rate was significant decreased in RT18 rats (2.42 +/- 0.15 mL/min/kg; n = 28; P: < 0.05) compared with C18 control rats (4.19 +/- 0.10 mL/min/kg; P: < 0.05) and the percentage of glomeruli with sclerosis was greater in RT18 rats (13.01% +/- 2.95%; n = 9; P: < 0.01) than in C18 rats (2.71% +/- 0.35%; n = 6). RT18 rats also showed more intense tubulointerstitial lesions and immunohistochemical alterations in the renal cortex. Immunohistochemical studies showed increased fibronectin and desmin expression in glomeruli and tubulointerstitium and increased vimentin and alpha-smooth muscle actin in the tubulointerstitial area from the renal cortex of RT18 rats (P: < 0.05). Desmin was also increased at the edge of glomeruli from RT18 rats, suggesting podocyte injury. Our data show that when food restriction is imposed during pregnancy, permanent damage occurs in the kidney of the offspring. Glomerular lesions were more severe than the tubulointerstitial damage in these animals.
Asunto(s)
Privación de Alimentos , Nefroesclerosis/etiología , Preñez , Efectos Tardíos de la Exposición Prenatal , Actinas/metabolismo , Animales , Peso Corporal , Desmina/metabolismo , Femenino , Fibronectinas/metabolismo , Hipertrofia , Inmunohistoquímica , Corteza Renal/metabolismo , Corteza Renal/patología , Pruebas de Función Renal , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Masculino , Nefroesclerosis/embriología , Nefroesclerosis/patología , Tamaño de los Órganos , Embarazo , Ratas , Ratas Wistar , Estadísticas no Paramétricas , Vimentina/metabolismoRESUMEN
Eight strains of a flavivirus identified as St. Louis encephalitis (SLE) virus were isolated from wild rodents, birds, and sentinel mice in three locations in the State of São Paulo, Brazil from 1967--1969. No illness attributable to SLE virus infection was detected among the local inhabitants, although about 5% of the local population had neutralizing antibodies to this virus.
Asunto(s)
Virus de la Encefalitis de San Luis/aislamiento & purificación , Virus de la Encefalitis/aislamiento & purificación , Animales , Animales Salvajes/microbiología , Anticuerpos Antivirales/análisis , Brasil , Virus de la Encefalitis de San Luis/inmunología , Encefalitis de San Luis/microbiología , Humanos , SerotipificaciónRESUMEN
From 1975 to 1978, 36 viruses were recovered from humans, bats, birds, sentinel mice and hamsters, and from mosquitoes collected in Coastal Brazil in the state of São Paulo. Identifications of 22 of these 36 viruses have been reported. Six of the remaining 14 isolates were shown to be Guama serogroup bunyaviruses. Two of these six were strains of a newly recognized virus for which the name Cananeia virus is proposed; another is a second newly recognized Guama serogroup virus for which the name Itimirim virus is proposed; a fourth is a strain of Bertioga virus and the other two are strains of Guaratuba virus. Before these studies Guaratuba virus was considered an ungrouped bunyavirus, but cross testing by complement-fixation demonstrated that this virus, and Mirim virus as well, should be considered members of the Guama serogroup. Another six viruses were shown to be strains of a single, newly recognized Group C bunyavirus for which the name Bruconha virus is proposed. Two strains of a single virus were shown by electron microscopy to belong to the family Bunyaviridae, but serologic relationships with other members of this family of viruses were not found; the name Enseada virus is proposed for this newly recognized agent.
Asunto(s)
Bunyaviridae/aislamiento & purificación , Orthobunyavirus/aislamiento & purificación , Animales , Brasil , Cebus/microbiología , Pruebas de Fijación del Complemento , Cricetinae , Culex/microbiología , Humanos , Ratones , Muridae/microbiología , SerotipificaciónRESUMEN
The venom of the Brazilian rattlesnake Crotalus durissus terrificus is know to have hemolytic and neurotoxic physiopathological activities which may cause acute renal failure with hemoglobinuria and/or methemoglobinuria. As far as we know, no report has been published on the ability of the venom of this rattlesnake species to cause rhabdomyolysis. In the present paper we demonstrate that the venom of Brazilian snakes of the genus Crotalus can induce systemic myonecrosis. Clinical, laboratory and anatomo-pathological data for two patients referred to the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, 24 hr after a rattlesnake bite, are presented. In both cases, exaggerated elevation of serum levels of the enzymes creatine phosphokinase, lactate dehydrogenase and glutamic-oxaloacetic transaminase were detected, as well as data suggesting acute hypercatabolic renal failure. Immunoelectrophoresis of the serum and urine of these patients, carried out against specific anti-myoglobin serum (Behringwerke), demonstrated myoglobinemia and myoglobinuria, confirming injury to muscle tissue. Electron microscopy of a calf muscle biopsy taken from the leg contralateral to the bite from one patient revealed foci of myonecrosis.
Asunto(s)
Lesión Renal Aguda/etiología , Venenos de Crotálidos/envenenamiento , Músculos/patología , Rabdomiólisis/etiología , Mordeduras de Serpientes/complicaciones , Niño , Humanos , Masculino , Persona de Mediana Edad , Mioglobinuria/etiología , NecrosisRESUMEN
An immunohistochemical method to detect yellow fever antigen was developed using immune sera from rabbits and hamsters and hyperimmune ascitic fluid from mice. A search for the antigen was carried out in liver, kidney and heart in three fatal cases of yellow fever. In the liver it was present in the cytoplasm of hepatocytes, Councilman bodies and Kupffer cells. Yellow fever antigen was also detected in renal tubular epithelium and in groups of myocardial fibers. These findings suggest that viral replication occurs at sites other than the liver. Since yellow fever shares many features with other haemorrhagic fevers the use of immunohistochemistry can impart a significant improvement in the accuracy of its histopathological diagnosis.
Asunto(s)
Antígenos Virales/análisis , Corazón/microbiología , Riñón/microbiología , Hígado/microbiología , Fiebre Amarilla/microbiología , Virus de la Fiebre Amarilla/aislamiento & purificación , Adulto , Humanos , Técnicas para Inmunoenzimas , MasculinoRESUMEN
The aim of the present study was to investigate the expression of alpha-smooth muscle actin (alpha-SM-actin) and proliferating cell nuclear antigen (PCNA) in renal cortex from patients with focal segmental glomerulosclerosis (FSGS) and their correlations with parameters of renal disease progression. We analyzed renal biopsies from 41 patients with idiopathic FSGS and from 14 control individuals. The alpha-SM-actin immunoreaction was evaluated using a score that reflected the changes in the extent and intensity of staining in the glomerular or cortical area. The PCNA reaction was quantified by counting the labeled cells of the glomeruli or renal cortex. The results, reported as median +/- percentile (25th; 75th), showed that the alpha-SM-actin scores in the glomeruli and tubulointerstitium from the renal cortex were 2.0 (2.0; 4.0) and 3.0 (3.0; 4.0), respectively, in patients with FSGS, and 0.5 (0.0; 1.0) and 0.0 (0.0; 0.5) in the controls. The number of PCNA-positive cells per glomerulus and graded field of tubulointerstitium from the renal cortex was 0.2 (0.0; 0.4) and 1.1 (0.3; 2.2), respectively, for patients with FSGS, and 0.0 (0.0; 0.5) and 0.0 (0.0; 0.0) for controls. The present data showed an increase of alpha-SM-actin and PCNA expression in glomeruli and renal cortex from FSGS patients. The extent of immunoreaction for alpha-SM-actin in the tubulointerstitial area was correlated with the intensity of proteinuria. However, there was no correlation between the kidney expression of these proteins and the reciprocal of plasma creatinine level or renal fibrosis. These findings suggest that the immunohistochemical alterations may be reversible.
Asunto(s)
Actinas/biosíntesis , Glomeruloesclerosis Focal y Segmentaria/patología , Músculo Liso/metabolismo , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Anticuerpos Monoclonales , Biopsia , Estudios de Casos y Controles , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Humanos , Inmunohistoquímica , Lactante , Corteza Renal/química , Glomérulos Renales/química , Masculino , Músculo Liso/patología , Antígeno Nuclear de Célula en Proliferación/análisisRESUMEN
Urinary excretion of four plasma proteins having molecular weights between 44,100 and 90,000 daltons was studied by two-dimensional immunoelectrophoresis in normal individuals and in patients with different kinds of renal pathology. The proteins studied were: alpha 1-acid glycoprotein, 44,100 molecular weight (MW) and pH 2.7 isoelectric point (IP); alpha 1-antitrypsin, 54,000 MW and 4.0 IP; albumin, 69,000 MW and 4.9 IP; and transferrin, 90,000 MW and 5.6 IP. The proteins were measured in urine with an oligospecific serum produced by the immunization of rabbits with the 4S fraction obtained from normal human plasma by gel filtration on Sephadex G-200. The increase in urinary excretion of these proteins observed both among glomerulopathic and tubulopathic patients did not correlate with MW. Mean renal albumin excretion was 2.9 mg/24 h among normal individuals, 87.38 mg/24 h among patients with tubulopathy, and 3,228 mg/24 among patients with glomerulopathy. Among patients with glomerulopathy, there was a direct correlation between the increased excretion of these proteins and their IP, except for alpha 1-acid glycoprotein.
Asunto(s)
Albuminuria , Enfermedades Renales/orina , Orosomucoide/orina , Transferrina/orina , alfa 1-Antitripsina/orina , Lesión Renal Aguda/orina , Adolescente , Adulto , Femenino , Glomerulonefritis/orina , Humanos , Inmunoelectroforesis Bidimensional , Masculino , Tasa de Depuración Metabólica , Persona de Mediana EdadRESUMEN
1. Ninety-eight adult female rats were injected with 14 micrograms/g B. jararaca venom intraperitoneally to determine functional and histopathological renal changes. 2. Glomerular filtration rate, renal plasma flow, filtration fraction, osmolar clearance, water transportation in collecting ducts, urinary sodium excretion, fractional sodium excretion, albuminuria, urinalysis, plasma creatinine, urinary output and mean arterial pressure were studied before and 24 and 48 h after venom administration. Light microscope examination of the kidneys was carried out in another group of rats before and 2, 5 and 24 h after venom administration. 3. Treated animals developed acute renal failure characterized by a decrease in glomerular filtration rate, osmolar clearance, and fractional and urinary sodium excretion, and by an increase in plasma creatinine. There was also a decrease in renal plasma flow and mean arterial pressure. Histopathological examination of the kidneys indicated mild proliferation of the mesangial matrix and degenerative changes of the tubules characterized by loss of brush border and cytoplasmic vacuolation. 4. The hemodynamic changes probably played an important role in the pathogenesis of the functional and histopathologic renal changes developed by the animals after venom injection.
Asunto(s)
Venenos de Crotálidos/farmacología , Riñón/efectos de los fármacos , Animales , Creatinina/sangre , Venenos de Crotálidos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/patología , Concentración Osmolar , Ratas , Circulación Renal/efectos de los fármacosRESUMEN
Several lines of experimental evidence have shown that transforming growth factor beta (TGF beta) may play major role in glomerular diseases, mediating the inflammatory response through glomerulosclerosis. In the present study we evaluated TGF beta activity in occasional urine samples from 7 normal individuals and from 15 patients (10 with focal glomerular sclerosis and 5 with membranous glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay. Urinary TGF beta activity (reported in relation to urine creatinine concentration, Ucr, mean +/- SD) was higher in patients with focal glomerular sclerosis (mean = 17.32 +/- 15.75/10 micrograms Ucr) and patients with membranous glomerulonephritis (mean = 17.78 +/- 11.53/10 micrograms Ucr) than in normal individuals (mean = 0.8 +/- 0.44/10 micrograms Ucr). We also observed that TGF beta activity in urine from patients with focal glomerular sclerosis correlated with their plasma creatinine levels (r = 0.85), suggesting that TGF beta activity may be correlated with other indices of disease progression. Our data suggest that measurement of urinary TGF beta activity could be a useful noninvasive procedure for the evaluation of renal TGF beta production, which may be useful to assess prognosis and to evaluate therapeutic efficacy in patients with renal disease.
Asunto(s)
Glomerulonefritis/orina , Glomeruloesclerosis Focal y Segmentaria/orina , Factor de Crecimiento Transformador beta/orina , Creatinina/sangre , Humanos , Modelos Lineales , PronósticoRESUMEN
1. To determine the effect of gentamicin on the functional properties of the glomerular barrier, 44 Wistar rats received daily doses of 80 mg/kg body weight for 6 days. Glomerular permeability to neutral dextrans and albumin was evaluated by day 6 and albuminuria was determined on the 1st, 3rd and 5th days of treatment. 2. Treatment induced an intense increase in albuminuria from 74 micrograms/24 h to 11.5 mg/24 h on the 5th day of treatment (N = 11). This increase was associated with the presence of large amounts of albumin in elements of the glomerular filter and in the apical region of the proximal tubular cells (N = 4). Fractional clearances of neutral dextrans having molecular radii in the range of 18-41 A were not significantly different in control (N = 5) and gentamicin-treated rats (N = 7). 3. These results show that gentamicin, a polycation at pH 7.4, produces an increase in the glomerular permeability to negatively charged macromolecules in rats, probably due to interaction of the polycation with negative changes in the glomerular filter.
Asunto(s)
Albúminas/metabolismo , Dextranos/metabolismo , Gentamicinas/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Albúminas/análisis , Animales , Femenino , Riñón/química , Ratas , Ratas WistarRESUMEN
Diabetic nephropathy (DN) is characterized structurally by progressive mesangial deposition of extracellular matrix (ECM). Transforming growth factor-ss (TGF-ss) is considered to be one of the major cytokines involved in the regulation of ECM synthesis and degradation. Several studies suggest that an increase in urinary TGF-ss levels may reflect an enhanced production of this polypeptide by the kidney cells. We evaluated TGF-ss in occasional urine samples from 14 normal individuals and 23 patients with type 2 diabetes (13 with persistent proteinuria >500 mg/24 h, DN, 6 with microalbuminuria, DMMA, and 4 with normal urinary albumin excretion, DMN) by enzyme immunoassay. An increase in the rate of urinary TGF-ss excretion (pg/mg U Creat.) was observed in patients with DN (296.07 +/- 330.77) (P<0.001) compared to normal individuals (17.04 +/- 18.56) (Kruskal-Wallis nonparametric analysis of variance); however, this increase was not observed in patients with DMMA (25.13 +/- 11.30) or in DMN (18.16 +/- 11.82). There was a positive correlation between the rate of urinary TGF-ss excretion and proteinuria (r = 0.70, alpha = 0.05) (Pearson's analysis), one of the parameters of disease progression.
Asunto(s)
Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/orina , Factor de Crecimiento Transformador beta/orina , Adulto , Biomarcadores/orina , Matriz Extracelular/metabolismo , Humanos , Riñón/metabolismo , Persona de Mediana Edad , Proteinuria/etiologíaRESUMEN
A total of 138 patients with the age of 4 months to 57 years were attended in different hospitals of São Paulo State with aseptic meningitis. A probable new agent was isolated from the cerebrospinal fluid of 35 of 53 specimens examined. Replication of the agent with similar characteristics was detected by CPE produced in the MDCK cell line. Virus-like particles measuring about 40 nm in diameter were observed by negative staining electron microscopy. No hemagglutinating activity was detected at pH 7.2 by using either human, guinea pig, chicken and at pH ranged 6.0-7.2 with goose red blood cells. The agent was not pathogenic to newborn or adult mice. Virus infectivity as measured by CPE was sensitive to chloroform and not inhibited by BuDR, suggesting that agent is an enveloped virus with RNA genome.
Asunto(s)
Meningitis Aséptica/líquido cefalorraquídeo , Virión/aislamiento & purificación , Adolescente , Adulto , Brasil , Niño , Preescolar , Efecto Citopatogénico Viral , Femenino , Humanos , Lactante , Masculino , Meningitis Aséptica/microbiología , Persona de Mediana Edad , Virión/fisiología , Virión/ultraestructura , Replicación ViralRESUMEN
The authors report the clinical, laboratorial and epidemiological aspects of a human case of jungle yellow fever. The patient suffered from fever, chills, sweating, headaches, backaches, myalgia, epigastric pains, nausea, vomiting, diarrhea and prostration. He was unvaccinated and had been working in areas where cases of jungle yellow fever had been confirmed. Investigations concerning the yellow fever virus were performed. Blood samples were collected on several days in the course of the illness. Three of these samples (those obtained on days 5, 7 and 10) were inoculated into suckling mice in attempt to isolate virus and to titrate the viremia level. Serological surveys were carried out by using the IgM Antibodies Capture Enzyme Linked Immunosorbent Assay (MAC-ELISA), Complement Fixation (CF), Hemagglutination Inhibition (HI) and Neutralization (N) tests. The yellow fever virus, recovered from the two first samples and the virus titration, showed high level of viremia. After that, specific antibodies appeared in all samples. The interval between the end of the viremia and the appearance of the antibodies was associated with the worsening of clinical symptoms, including bleeding of the mucous membrane. One must be aware of the risk of having a urban epidemics in areas where Aedes aegypti is found in high infestation indexes.
Asunto(s)
Fiebre Amarilla/virología , Adulto , Aedes/virología , Animales , Brasil , Humanos , Masculino , Ratones , Pruebas Serológicas , Viremia/diagnóstico , Viremia/virología , Fiebre Amarilla/diagnóstico , Fiebre Amarilla/inmunología , Fiebre Amarilla/terapia , Virus de la Fiebre Amarilla/aislamiento & purificaciónRESUMEN
OBJECTIVE: To report the first Ilheus arboviruses isolated from wild birds and analyze its public health impact. METHODS: Wild birds and mammals were captured using mist nets and Tomahawk traps, respectively. Blood samples were drawn from these animals and inoculated intracerebrally in Swiss suckling mice found in the Parque Ecológico do Tietê, Brazil. The isolates were identified by serological tests, such as hemagglutination, hemagglutination inhibition, complement fixation and neutralization. Besides virus isolation, serum samples were also tested for the presence of hemagglutination inhibition antibodies. RESULTS: Two strains of Ilheus virus were isolated from the bird species Sporophila caerulescens and Molothrus bonariensis. Specific antibodies to Ilheus virus were detected in serum samples of some birds (Columbina talpacoti, Geopelia cuneata, Sicalis flaveola and Molothrus bonariensis), marmosets (Callithrix jacchus and Callithrix penicillata) and coati (Nasua nasua). CONCLUSIONS: Virus isolation and detection of specific antibodies in serum samples of local, migratory and captive birds, captive marmosets and wild coati corroborate the circulation of Ilheus virus in the Parque Ecológico do Tietê. The migrating behavior of some species of wild birds, like Sporophila caerulescens, enables the virus spread to other regions. Taking into consideration its human pathogenicity and the presence of the virus in this area, local authorities should be aware of the risk of infecting the local community.