End-stage renal disease in diabetics: dialysis or transplantation?
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Biomedical subjects
Publications and source records attributed to P Cortes.
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The mechanisms responsible for the increase in RNA per cell during the first 48h of renal compensatory growth were studied in the renal cortex. Unilaterally nephrectomized, sham-operated or non-operated rats were used. Incorporation into RNA of labelled precursors was studied in vivo and in vitro. Sham-operation produced significant changes in precursor incorporation, absolute amounts of UTP and RNA, and the rate of RNA synthesis. At 6h after surgery, the amount of RNA decreased in sham-operated controls, whereas that in growing cortex remained unchanged. Incorporation into RNA in vivo was greater in the growing cortex, although the rate of RNA synthesis was not increased. At 24h, precursor incorporation into RNA and UTP and RNA synthesis were all increased in the growing cortex. In contrast with results obtained in vivo, slices of growing cortex incorporated less labelled precursor into RNA than did cortex slices from sham-operated controls, from 3 to 48h. Maximal differences were found from 6 to 24h. An attempt was made to equalize endogenous precursor pool sizes by increasing the concentration of unlabelled uridine in the media; incorporation differences were narrowed significantly. Serum from nephrectomized animals did not increase precursor incorporation into RNA in vitro. An increase in RNA synthesis is an important factor in RNA accretion in the renal cortex beyond 12h of compensatory growth. This is accompanied by increased UTP content and preceded by expansion of other pools. The amount of labelled precursor incorporated into RNA is greatly influenced by its delivery rate to the growing kidney in vivo and by intracellular dilution of expanded precursor pools in vitro.
We determined the site of kininogenase secretion in the nephron by performing stop-flow studies in dogs. Kininogenase activity, inulin, sodium, and potassium were measured in the same fractions. The highest kininogenase concentration was found in the fractions with the lowest sodium concentration corresponding to urine samples that must have been trapped in the distal nephron. Kininogenases in these urine fractions were 5-17 times higher than in fractions from the proximal nephron or from the free-flow sample. The ratio of kininogenase increase to inulin increase was always higher than 3.0, thus indicating that the increase in kininogenase concentration was mainly due to secretion and not to water reabsorption. When a peak of potassium was present, it occurred 1-2 ml before the peak of kininogenases. We concluded that kininogenases are secreted into the urine at the level of the distal nephron by either the tubule itself or by a specialized structure located at this part of the nephron, such as the macula densa.
In diabetes mellitus abnormal quantiites of glycoprotein may be formed in the basement membrane of the glomerulus and both renal function and size may increase. It is suggested that these changes, of quite different potential significance, have a common origin an increased rate of uridine-triphosphate synthesis resulting from hyperglycemia.
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Connective tissue growth factor (CTGF), a member of the closely related CCN family of cytokines appears to be fibrotic in skin. To determine whether CTGF is implicated in diabetic glomerulosclerosis we studied cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to rhCTGF significantly increased fibronectin and collagen type I secretion. Further, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36-38 kDa). However, exposure to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in glomerulosclerosis, markedly induced the expression of CTGF transcripts. With all but mechanical strain there was a concomitant stimulation of CTGF protein secretion. TGF-beta also induced abundant quantities of a small molecular weight form of CTGF (18 kDa). The induction of CTGF protein by a high glucose concentration was mediated by TGF-beta, since a TGF-beta neutralizing antibody blocked this stimulation. In vivo studies using quantitative RT-PCR demonstrated that while CTGF transcripts were low in the glomeruli of control mice, expression was increased 27-fold after approximately 3.5 months of diabetes. These changes occurred early in diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced elevation of CTGF mRNA (2-fold) observed in whole kidney cortices indicted that the primary alteration of CTGF expression was in the glomerulus. These results suggest that CTGF upregulation is an important factor in the pathogenesis of mesangial matrix accumulation in both diabetic and non-diabetic glomerulosclerosis, acting downstream of TGF-beta.
OBJECTIVE: To present a girl with cutaneous cavernous hemangioma associated with hemangioma of the liver and neurofibromatosis type 1 (NF1). PATIENTS AND METHODS: A 3 year old girl showed cutaneous cavernous hemangioma on the right hypochondral region and numerous caf au lait spots. She was studied with abdominal echography and abdominal and thoracic magnetic resonance (MR) as well as with cerebral MR angiography. RESULTS: Both image studies, echography and MR, revealed a mass 2 x 2 cm of hemangiomatous type in the upper zone of the liver, near the external cutaneous cavernous hemangioma. Echographical follow up showed a progressive diminution of the hepatic hemangioma size. At 2 1/2 years of age a voluminous thoracic tumor extending between aorta and sternon very difficult of being removed was found. CONCLUSION: Hemangioma of the liver appears to be related with cutaneous cavernous hemangioma as a finding of the syndrome of Pascual Castroviejo II. Furthermore, the patient has NF1 which has not been previously related with the cutaneous and/or the liver pathology.
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OBJECTIVE: To evaluate the hypertension associated to different types and sub-types of cerebrovascular disease (stroke), with particular reference to the frequency of hypertension, the values of blood pressure, the risk factors and the involvement of other target organs. DEFINITION: Prospective study in 248 patients with acute stroke admitted to a Clinical Medicine Unit in three independent time periods. SETTING: Internal Medicine Clinic of University Hospital in Lisbon. METHODS: Medical, neurological and cardiologic examination were performed and all patients were also submitted to different complementary tests, including a computer tomography scan of the brain, and an echocardiogram. The values of blood pressure were measured in the admission at the urgent service and 24 h after in the the ward. We identified three sub-types of stroke: intracerebral hemorrhage (IH), ischaemic stroke (IS) and lacunes (L). For each sub-type and for those with hypertension or not, we evaluated: age, sex, duration of stay in hospital and mortality. We also compared for each sub-type the values of blood pressure, the risk factor and the repercussion on other target organs. PATIENTS: Two hundred and forty eight patients (52% were men) with mean age 68.0 +/- 10.2 years, and ages among 40 and 92 years. Thirty-seven patients (15%) died. MAIN RESULTS: In the entire population (n = 248) hypertension were more prevalent in IH 83% and L 82% than in IS 59% (p < 0.0005). Hypertension was present in 172 patients (69%) and 81 (47%) were IS, 58 (34%) L and 33 (19%) IH. Sixty six percent of the 172 patients with hypertension had at least another risk factor and the most aged ones (> 65 years old) were more frequent in IS 75% than in HI 45% or L 58% (p < 0.001). For all subtypes blood pressure measurements were higher in admission than in ward and they were also higher in IH than in IS (p < 0.05). Hypertensive cardiopathy was more prevalent in IH 76% and L 61% than in IS 49% (p < 0.05). Renal failure was more frequent in IS 37% than in IH 28% and L 17% (p < 0.05). CONCLUSIONS: Hypertension is very frequent, and like advanced age is a major risk factor of stroke. Hypertension is frequently associated with one or more risk factors. Hypertensive cardiopathy is more related with IH and L and the renal involvement with IS.