RESUMO
AIMS/HYPOTHESIS: To investigate the interaction between hypertension and diabetic nephropathy, we studied the renal accumulation of fibronectin in a genetic model of hypertension with streptozotocin-induced diabetes mellitus. METHODS: Spontaneously hypertensive rats (SHR) and their genetically normotensive control Wistar Kyoto rats (WKY) were studied at 4 weeks of age. The rats were killed 20 days after the induction of diabetes mellitus. The renal accumulation of fibronectin was estimated using Western blot analysis as well as immunofluorescence technique and confocal microscopy. RESULTS: Blood glucose concentrations were similar in diabetic SHR rats (27 +/- 3.3 mmol/l) and WKY rats (25.5 +/- 2.7 mmol/l). The systolic blood pressure was higher in both groups of SHR rats than in the control rats. The abundance of renal fibronectin as detected by Western blot analysis was (p < 0.05) higher in the diabetic SHR rats (41.4 +/- 15.0 densitometric U, n = 8) than in the control rats, and no difference was observed between diabetic and control WKY rats (20.8 +/- 6.2, n = 8) and (27.8 +/- 17.2, n = 8). The mean peak intensity of fibronectin signal within the glomerulus as estimated by confocal microscopy was higher (p < 0.05) in the diabetic SHR rats (32.9 +/- 3.5) than in control SHR rats (11.9 +/- 5.7) or diabetic (7.4 +/- 2.2) and control (15.2 +/- 7.9) WKY rats. CONCLUSION/INTERPRETATION: In experimental diabetes the presence of genetic hypertension promotes earlier accumulation of renal fibronectin, a matrix protein implicated in renal glomerulosclerosis.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Fibronectinas/metabolismo , Hipertensão/genética , Rim/fisiopatologia , Animais , Glicemia/metabolismo , Pressão Sanguínea , Diabetes Mellitus Experimental/sangue , Rim/patologia , Microscopia Confocal , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
PURPOSE: To investigate whether elevated erythrocyte Na+/Li+ countertransport (Na+/Li+ CT) activity is present in patients with proliferative diabetic retinopathy (PDR). METHODS: The rate of Na+/Li+ CT activity assayed in 21 patients with type 1 diabetes mellitus (DM) presenting PDR was compared with 10 patients with nonproliferative retinopathy (NPDR) and with 11 patients with normal fundi. Twelve normal volunteers with no family history of hypertension were used as a control group. The albumin excretion rate was determined by nephelometry, and the glomerular filtration rate was measured by the plasma clearance of eidetic acid labeled with chromium-51. RESULTS: Patients with PDR showed higher diastolic blood pressure levels (mean +/- SD) compared with those with NPDR or normal fundi (95 +/- 13 versus 90 +/- 09 and 82 +/- 19 mm Hg, P = 0.02, respectively). The albumin excretion rate was higher [geometric mean (range)], and the glomerular filtration rate was lower (mean +/- SD) in patients with PDR than in those with NPDR or normal fundi [333 (2 to 5140) versus 32 (5.9 to 2200) and 6 (1.5 to 306) microg/min, P = 0.01, and 63 +/- 33 versus 99 +/- 37 and 93 +/- 43 ml/min, P = 0.02, respectively]. The mean Na+/Li+ CT in patients with PDR was significantly higher than in patients with NPDR or normal fundi and control group (0.46 +/-0.20 versus 0.32 +/- 0.12, 0.32 +/- 11, and 0.21 +/- 0.07 mM/L red blood cells (RBC)/h, respectively, P = 0.0001). In a multiple logistic regression analysis, with PDR as the dependent variable, Na+/Li+ CT (odds ratio [OR]: 4.7, confidence interval [CI]: 1.2-17.6, P = 0.02), diastolic blood pressure (OR, 3.4; CI, 1.3 to 9.6; P = 0.018), and glomerular filtration rate (OR, 5.1; CI, 1.6-17.7; P = 0.007) were the only variables that were maintained in the equation, indicating that they were the main determinants of PDR. CONCLUSIONS: Patients with type 1 DM and proliferative retinopathy have elevated erythrocyte Na+/Li+ CT.
Assuntos
Antiporters/metabolismo , Diabetes Mellitus Tipo 1/sangue , Retinopatia Diabética/sangue , Eritrócitos/metabolismo , Lítio/sangue , Sódio/sangue , Adolescente , Adulto , Pressão Sanguínea , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We have studied the molecular defect underlying band 3 deficiency in one family with hereditary spherocytosis using nonradioactive single strand conformation polymorphism of polymerase chain reaction (PCR) amplified genomic DNA of the AE1 gene. By direct sequencing, a single base substitution in the splicing donor site of intron 8 (position + 1G --> T) was identified. The study of the cDNA showed a skipping of exon 8. This exon skipping event is responsible for a frameshift leading to a premature stop codon 13 amino acids downstream. The distal urinary acidification test by furosemide was performed to verify the consequences of the band 3 deficiency in alpha intercalated cortical collecting duct cells (alphaICCDC). We found an increased basal urinary bicarbonate excretion, associated with an increased basal urinary pH and an efficient distal urinary acidification. We also tested the consequences of band 3 deficiency on the Na+/H+ exchanger, by the measurement of Na+/Li+ countertransport activity in red blood cells. The Na+/Li+ countertransport activity was increased threefold to sixfold in the patients compared with the controls. It is possible that band 3 deficiency in the kidney leads to a decrease in the reabsorption of HCO3- in alphaICCDC and anion loss, which might be associated with an increased sodium-lithium countertransport activity.
Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/genética , Antiporters/metabolismo , Bicarbonatos/metabolismo , Mutação da Fase de Leitura , Rim/metabolismo , Esferocitose Hereditária/metabolismo , Proteína 1 de Troca de Ânion do Eritrócito/deficiência , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Códon/genética , Análise Mutacional de DNA , DNA Complementar/genética , Diuréticos/farmacologia , Membrana Eritrocítica/química , Feminino , Furosemida/farmacologia , Humanos , Íntrons/genética , Transporte de Íons/efeitos dos fármacos , Túbulos Renais Coletores/efeitos dos fármacos , Túbulos Renais Coletores/metabolismo , Lítio/sangue , Masculino , Linhagem , Polimorfismo Conformacional de Fita Simples , Splicing de RNA , Sódio/sangueRESUMO
UNLABELLED: Diabetic nephropathy is a frequent cause of end-stage renal failure in patients admitted for renal replacement therapy. PURPOSE: To evaluate the prevalence of DN, as the underline disease, in patients with ESRF. METHODS: 1,303 [male (M) = 767 and female (F) = 536] patients with ESRF who were on a waiting list for cadaver kidney transplant at Nephrology Unit-University Hospital (HC-UNICAMP), from August/90 to June/93--group 1--and 193 (M = 112 and F = 81) patients admitted for renal replacement therapy in a year period (April/92 to March/93), in the city of Campinas, State of São Paulo, Brazil, were studied. RESULTS: The prevalence of DN was 10.1% in group 1 and 17.6% in group 2 (x2 = 7.15; p = 0.007), being the third cause of ESRF in both groups, and it was preceded by glomerulonephritis and arterial hypertension. In group 1 the reduction of number of patients with increase in duration of dialysis was significantly greater in patients with diabetic nephropathy (x2 = 30.9; p < 0.001). Among patients with DN 35 (26%) in group 1 and 6 (18%) in group 2 had less than 35 years when they were admitted for renal replacement therapy and are likely to be type 1 (insulin-dependent) diabetic patients. CONCLUSION: In our studied groups DN was a frequent cause of ESRF.
Assuntos
Nefropatias Diabéticas/complicações , Falência Renal Crônica/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Diálise/efeitos adversos , Feminino , Glomerulonefrite , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
A light and electronmicroscopic study in the intima of the smaller and larger curvatures of a healthy rabbit aortic arch was performed. In both curvatures there were areas of intimal thickenings of varying width, and consisting mainly of collagenous and elastic fibers and smooth muscle cells. The structure of the wider thickenings resembled the media layer. There was evidence that such intimal thickenings are media growth in thickness and physiological in nature. It is inferred that the early lipid deposition in the intimal thickenings of the smaller, but not in the larger curvature, is not related to morphological differences, since both curvatures had the same intimal pattern.
Assuntos
Aorta Torácica/anatomia & histologia , Metabolismo dos Lipídeos , Animais , Aorta Torácica/metabolismo , Aorta Torácica/ultraestrutura , Azul Evans/farmacocinética , Masculino , Microscopia Eletrônica , CoelhosRESUMO
Three hundred and twenty outpatients with diabetes mellitus (DM) were studied to evaluate the prevalence, origin (glomerular or nonglomerular), significance and possible association of glomerular hematuria (GH) with other clinical and laboratory features. In patients with 24 h proteinuria equal or superior to 500 mg, hematuria was seen in 16 out of 22 (72.7%); for those with 24 h proteinuria between 150 and 500 mg 5 out of 23 (21.7%) had hematuria, and in the general population of diabetics studied hematuria was present in 47 patients (14.7%). It was glomerular in 43 (13.4%) patients and nonglomerular in 4 (1.3%). Red blood cell casts were observed in 15 (34.9%) out of the 43 patients with GH. Ten out of 31 patients (32.3%) with GH, for whom 24 h proteinuria was available, had negative proteinuria in a 24 h urine when analyzed by routine methods. In 18 patients with GH, clinical and laboratory findings that could suggest a second form of glomerulopathy--nondiabetic--were negative. Renal biopsy in 9 of them showed only diabetic glomerulosclerosis. We have observed a significant association between GH and the male sex (p less than 0.001), high serum creatinine levels (p = 0.0002) and 24 h proteinuria greater than 150 mg (p less than 0.001). GH was more frequent among males with DM lasting more than 10 years (p less than 0.001) and among those with retinopathy (p less than 0.001). There was no association between GH and age, type of DM, insulin requirement or hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Nefropatias Diabéticas/diagnóstico , Hematúria/diagnóstico , Adulto , Biópsia , Estudos Transversais , Nefropatias Diabéticas/patologia , Feminino , Hematúria/etiologia , Humanos , Glomérulos Renais/patologia , Masculino , Proteinúria/etiologiaRESUMO
Two cases of basosquamous cell carcinoma of the skin with lymph node, lung and bone metastases are reported. Metastases occurred 4 and 7 years after identification of the primary tumour. Both the primary and metastatic lesions had areas of typical basal cell carcinoma and squamous cell carcinoma and also intermediate carcinomatous tissue. In the bone metastasis of one case there were rudimentary hair follicles and areas of matrical differentiation. These cases further support the existence of basosquamous cell carcinoma and emphasize its metastatic potential.
Assuntos
Carcinoma Basoescamoso/patologia , Neoplasias Cutâneas/patologia , Adulto , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-IdadeRESUMO
A qualitative and quantitative microscopical examination of fetal stem vessels was performed in 50 placentas of stillborn infants and 50 normal controls. The vascular changes were morphologically similar in both groups, differences being only of quantitative nature. Subendothelial edema was more frequent in control placentas suggesting that it is not pathological. Subendothelial proliferation of smooth muscle cells prevailed in control and fresh stillbirths and could be due to arterial growth. Subendothelial proliferation of undifferentiated cells or fibrous and muscular tissues was more common in stillbirths. It occurred in most placentas of macerated stillbirths, but in fresh stillbirths the frequency was lower, though significantly higher than in controls. This thickening could represent the only reaction of placental vessels to fetal or maternal disease or cessation of fetal blood flow. Occlusion of the vascular lumen by fibrous and muscular tissues and vascular lumen divided by septa were present in the majority of the placentas of macerated stillbirths and rarely in fresh stillbirths, suggesting that in the macerated ones these changes were secondary to placental retention. The progressive collagenization of the media was the alteration most closely related to time of placental retention.
Assuntos
Endotélio Vascular/patologia , Morte Fetal/patologia , Placenta/irrigação sanguínea , Constrição Patológica/complicações , Endarterite/complicações , Feminino , Humanos , Músculo Liso Vascular/patologia , Placenta/patologia , Insuficiência Placentária/etiologia , GravidezRESUMO
A case of central nervous system actinomycosis is reported. A 33-year-old male complained of headache, vomiting and blurred vision lasting for eight days prior to admission. On examination, a right hemiparesis, as well an intracranial hypertension were detected. The cerebrospinal fluid showed mild lymphomononuclear hypercytosis. Necropsy disclosed three abscess in the cerebral hemispheres, in addition to moderate cerebral edema on the left side but without purulent leptomeningitis. Actinomyces filaments and granules were demonstrated in the cerebral and lung abscessess. The Brazilian literature on actinomycosis is reviewed and six published cases with nervous system involvement were found. Relevant clinical and anatomical aspects of the cases and of the present one are discussed.