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Biomedical subjects

I L Noronha

Publications and source records attributed to I L Noronha.

At least 19 recordsLinked to original sources
PubMed2005

Statin monotherapy attenuates renal injury in a salt-sensitive hypertension model of renal disease.

BACKGROUND: Several salutary biological effects of statins have been described. We sought to investigate more closely the anti-inflammatory and antiproliferative effects of simvastatin (SIMV) in a model of hypertension and progressive renal disease, as well as its effects on the cyclin-cdk inhibitors p21 and p27. METHODS: Munich-Wistar rats received the nitric oxide (NO) synthase inhibitor L-NAME (25 mg/kg/day p.o.) for 20 days accompanied by a high-salt diet (HS, 3% Na) and then were kept on HS for 60 days. Animals were then divided into two groups: vehicle (VH) or SIMV 2 mg/kg/day p.o. Albuminuria and tail-cuff pressure were determined at 30 and 60 days. RT-PCR was done to assess renal expression of TGF-beta1, collagen I and III, fibronectin, p27, p21 and monocyte chemoattractant protein-1 (MCP-1). Renal protein expression was assessed by Western blot (proliferating cell nuclear antigen (PCNA)) and immunostaining (macrophage, lymphocyte, PCNA). RESULTS: SIMV did not prevent the development of severe hypertension or albuminuria. SIMV-treated animals had less severe renal interstitial inflammation and cell proliferation. MCP-1 expression was significantly diminished in the SIMV-treated animals (55.4 +/- 7.3 vs. 84.4 +/- 8.2 OD, p = 0.02). mRNA renal expression for p27 and TGF-beta did not change between groups, but p21 mRNA renal expression, highly induced in this model, significantly decreased with SIMV treatment (31.6 +/- 6.6 vs. 50.2 +/- 5.8 OD, p < 0.05). The interstitial fibrosis score significantly decreased with SIMV (2.46 +/- 0.40 vs. 4.07 +/- 0.38%, p < 0.01), which was confirmed by a decrease in renal collagen I and fibronectin expression. Serum cholesterol level did not change with SIMV. CONCLUSION: SIMV attenuated interstitial fibrosis associated with this model of hypertensive renal disease. The mechanism involved MCP-1 downregulation. SIMV treatment was also associated with a p21 downregulation in the kidney, which might be involved in the protection of renal scarring.

Albuminuria↗
PubMed2004

Enteric conversion after bladder drained pancreas transplantation experience of 14 cases.

The method of exocrine diversion in pancreas allograft continues to be controversial due to the advantages versus disadvantages of bladder versus enteric techniques. Bladder drainage (BD) exposes the patient to urological and metabolic problems that may require conversion to enteric drainage (ED). The purpose of this study was to review our initial experience of conversion from BD to ED for patients who underwent pancreas transplantation originally with bladder diversion. Among 114 pancreas transplantation performed with BD, from January 1996 to April 2003, 60 were simultaneous pancreas-kidney transplantation (SPKT), 35 were pancreas transplantation alone (PA), and 19 were pancreas after kidney transplantations (PAK). Twenty-three (20.2%) cases were excluded due to early death of the patient or the graft, yielding an analyses of 91 patients. Enteric conversion (EC) was performed in 14 (15.4%) patients with a mean follow-up of 15.7 months (range, 3-51 months) after transplantation including 8 (8.8%) SPKT, 4 (4.4%) PAK, and 2 (2.2%) PA. No surgical morbidity or mortality was observed related to EC. All patients had complete resolution of the initial problem with preservation of pancreatic function. EC represents an easy, safe procedure with low morbidity and mortality rates, representing the option of choice for patients with persistent urological or metabolic disturbances.

Humans↗
PubMed2003

Immunocytochemical localization of cytokines and inducible nitric oxide synthase (iNOS) in oral mucosa and lymph nodes of patients with paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a deep mycosis caused by Paracoccidioides brasiliensis, with high incidence in Brazil. In order to examine the immune response in lesional tissue from patients with PCM, we analyzed cytokines as well as the phenotype of the cell infiltrate. Paraffin-embedded tissue from the oral mucosa of eight patients with the localized adult form (AF) of PCM and from the lymph nodes of 10 patients with the juvenile form (JF) of PCM was analyzed by immunohistochemistry to detect tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10). Most of the inflammatory cells in the lymph nodes were CD68+ (macrophages, epithelioid and giant cells), while a mixed infiltrate with macrophages, plasma cells and neutrophils was detected in the oral mucosa. TNF-alpha as well as iNOS expression was similar in lymph nodes and oral mucosa, whereas TGF-beta and IL-10 were observed in a larger number of macrophages, epithelioid and giant cells in the lymph nodes, where numerous yeast cells were visualized. The higher expression of anti-inflammatory cytokines (IL-10 and TGF-beta) in lesions of patients with the JF of PCM (lymph nodes) may represent a mechanism by which the fungus evades the host immune response, contributing to a more severe and disseminated form of the disease.

Adult↗
PubMed2003

Nephrology in Latin America, with special emphasis on Brazil.

Latin America constitutes a complex universe that shows extreme variation regarding socioeconomic and human development. Brazil is the largest and most populous Latin American country, and combines characteristics encountered in developed countries with problems typically associated with the poorest regions of the world. These disparities condition the profile of renal disease in Brazil, with glomerulonephritis still the leading cause of ESRD. Little is known about the epidemiology of renal disease in the Brazilian (or Latin American) native population, which is numerous in some Central and South American countries, but constitute a very small minority in Brazil. However, interesting information has been obtained from the Yanomamis, a tribe living in Northern Brazil and Southern Venezuela. Hypertension is virtually absent among these people, who ingest very little sodium, lending strong support to the concept that sodium retention, a "civilization" factor, plays a role in the pathogenesis of arterial hypertension. Despite Brazil's striking socioeconomic disparities, access to RRT is in principle accessible to all those in need of it. The dialysis units have been modernized in recent years, whereas the Government covers most expenses related to RRT. However, the prevalence of RRT in Brazil is currently approximately 320 per million population, less than one third as high as in the US, suggesting that ESRD may be underdiagnosed in the country. Much effort is still needed to limit the prevalence of renal disease and to improve the quality and the reach of RRT in Brazil and in Latin America.

Brazil↗
PubMed2002

Impact of parenteral n-3 fatty acids on experimental acute colitis.

The present study was undertaken to investigate the effects of parenteral lipid emulsions (LE) enriched with n-3 fatty acids (n-3 FA) in experimental acute colitis. Seventy-four adult male Wistar rats were randomized into six groups, five of which had acetic acid-induced colitis. The animals received a fat-free diet and water ad libitum in individual metabolic cages. By a central venous catheter, saline was infused (0.5 ml/h) into the control groups CS (without colitis) and CC (with colitis), while the test groups received specific LE for 7 days. The n-3/n-6 FA ratio and the lipidic compositions regarding long chain (LCT) and medium chain (MCT) triglycerides were: group L--1:7.7 (LCT, n = 12), M--1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus n-3 FA, n = 12) and MW-3--1:3.0 (MCT and LCT plus n-3 FA, n = 13). The frequency of diarrhea, oral intake/body weight ratio, intestinal alterations, macrophage cellularity were evaluated and colonic concentrations of leukotrienes (LTB4, LTC4), prostaglandins (PGE2) and thromboxanes (TXB2) were measured. Groups M, MW-3 and LW-3 had less diarrhea than the CC group (P<0.05). Average oral intake/body weight ratio in MW-3 animals was comparable to the CS and better than the CC group. n-3 FA treated rats (LW-3 and MW-3) presented less intestinal inflammatory alterations than CC rats. Mucosal ulcer formation in MW-3 group did not differ from CS rats. M and MW-3 rats had less macrophages in the colon than the CC group. Compared with CC group, lower concentrations of LTB4 in the CS, LW-3 and MW-3 groups; of PGE2 in the CS, M and MW-3 groups; and of TXB2 in the CS and MW-3 groups were found. Mean concentrations of LTC4 did not differ among the groups. Thus, a LCT-containing LE with a low n-3-n-6 ratio does not modify inflammatory colitis manifestations; LE with a high n-3-n-6 ratio reduces diarrhea, preserves oral intake-weight ratio, attenuates morphological consequences and decreases colonic concentrations of inflammatory mediators; MCT/LCT-containing LE with 1:3 n-3-n-6 ratio exerts the most profound beneficial impact on the inflammatory response.

Acute Disease↗
PubMed2002

Lamivudine therapy for hepatitis B in renal transplantation.

Antiviral therapies are associated with an increased risk of acute rejection in transplant patients. The aim of the present study was to evaluate the efficacy and safety of lamivudine therapy for hepatitis B virus (HBV) infection in renal transplant patients. Six patients were included in this study. They received 150 mg/day of lamivudine during a follow-up period of 24 months. The laboratory tests monitored were HBV DNA, HBsAg, HBeAg, ALT, gamma-GT, serum creatinine and blood cyclosporine levels. The HBV DNA became undetectable in four patients as early as in the third month of treatment. After six months, the viral load was also negative in the other two patients, and remained so until 18 months of follow-up. The medication was well tolerated with no major side effects. Lamivudine was safe and effective in blocking HBV replication in renal transplant patients without any apparent increase in the risk of graft failure for the 24-month period of study.

Adult↗
PubMed2002

Bone involvement in idiopathic hypercalciuria.

BACKGROUND: To evaluate bone involvement in idiopathic hypercalciuria, 40 lithiasic patients and 10 controls were studied. METHODS: According to urinary calcium excretion, patients were first classified as hypercalciuric (Hca, n = 22) and normocalciuric (Nca, n = 18). The Hca patients were then subclassified according to bone densitometry (BMD) as osteopenic (HcaO, n = 10) and non-osteopenic (HCaNO, n = 12). Routine biochemistry, dietary records, bone histomorphometry. and cytokines (IL-1beta, IL-6, and TNF) production by peripheral blood mononuclear cell cultures were studied. RESULTS: There were no differences in routine biochemistry between Hca and Nca groups, except for urinary calcium. Inadequate nutrition was observed in Hca group, showing high protein (80.9% of the patients), carbohydrate (76.2%) and sodium (90%) intake. Calcium intake was low in Hca (57%) and Nca (83%) groups. IL-6 and TNF were not different between the Hca and Nca groups. IL-1beta levels were significantly high in both groups when compared to controls. IL-6 and TNF were higher in HcaO than Nca. BMD in femoral neck in HcaO was lower than in HcaNO and Nca groups. Eroded surface (ES/BS) increased in 91% of the Hca group and 36% had a mineralization defect. In the HcaO group serum PTH correlated negatively with trabecular bone volume (BV/TV) and positively with ES/BS. 1,25(OH),D3 levels correlated positively with osteoblastic surface. Calcium intake correlated positively with BV/TV and inversely with ES/BS. A negative correlation was observed between IL-6 levels and Z score of the femoral neck. CONCLUSION: Bone involvement was detected in a young population with nephrolithiasis demonstrating that a strict follow-up is necessary in order to control hypercalciuria.

Absorptiometry, Photon↗
PubMed2001

Microencapsulation and tissue engineering as an alternative treatment of diabetes.

In the 70's, pancreatic islet transplantation arose as an attractive alternative to restore normoglycemia; however, the scarcity of donors and difficulties with allotransplants, even under immunosuppressive treatment, greatly hampered the use of this alternative. Several materials and devices have been developed to circumvent the problem of islet rejection by the recipient, but, so far, none has proved to be totally effective. A major barrier to transpose is the highly organized islet architecture and its physical and chemical setting in the pancreatic parenchyma. In order to tackle this problem, we assembled a multidisciplinary team that has been working towards setting up the Human Pancreatic Islets Unit at the Chemistry Institute of the University of São Paulo, to collect and process pancreas from human donors, upon consent, in order to produce purified, viable and functional islets to be used in transplants. Collaboration with the private enterprise has allowed access to the latest developed biomaterials for islet encapsulation and immunoisolation. Reasoning that the natural islet microenvironment should be mimicked for optimum viability and function, we set out to isolate extracellular matrix components from human pancreas, not only for analytical purposes, but also to be used as supplementary components of encapsulating materials. A protocol was designed to routinely culture different pancreatic tissues (islets, parenchyma and ducts) in the presence of several pancreatic extracellular matrix components and peptide growth factors to enrich the beta cell population in vitro before transplantation into patients. In addition to representing a therapeutic promise, this initiative is an example of productive partnership between the medical and scientific sectors of the university and private enterprises.

Biocompatible Materials↗
PubMed2000

[Causes and prognosis of acute renal failure in elderly patients].

UNLABELLED: The prolonged life span of populations is the obvious reason for an increasing proportion of elderly patients with acute renal failure (ARF). The role of age as a factor indicative of a poor prognosis is a matter of controversy. OBJECTIVE: To evaluate this role we have analyzed the final outcome of elderly patients with ARF treated in our Nephrology Service. MATERIAL AND METHODS: Among 361 ARF cases prospectively studied during a two-year period (January 1995 to December 1996), 130 (36%) occurred in patients over 70 years of age. Etiology, clinical course and prognosis were analyzed. The average age was 76.0 +/- 4.7 years, varying from 70 to 94 years; 84 patients (65%) were male, and surgical causes accounted for 51% of geriatric ARF. RESULTS: The most frequent causes were: ischemic (volume depletion, arterial hypotension, and/or low cardiac output) in 48 patients (38%), sepsis in 40 (312%), nephrotoxic drugs in 46 (35%) and obstructive abnormalities in 10 (7.7%); in other 14 (11%) they were diagnosed more than a causal agent. Oliguria was present in 37. 2% (81 patients), and dialysis was needed in 50 patients (39%). The mortality in the population with age below 70 years was 43% and in the elderly patients was 53.8%; total mortality was similar in both groups of patients (p=0.085). Oliguria, need for dialysis, presence of surgical causes of ARF, and ARF acquired within the intensive care unit were associated with poor prognosis in elderly group. CONCLUSION: We concluded that the percentile of elderly patients with ARF is elevated; they presented mortality about of 50%, and this is not superior to the observed in the youngest population; oliguria, dialysis need, ICU cares and surgery are factors of unfavorable prognostic in these patients.

Acute Kidney Injury↗
PubMed2000

Outcome of acute renal failure associated with cardiac surgery in infants.

OBJECTIVE: To analyze the impact of acute renal failure (ARF) on the evolution of infants undergoing cardiac surgery. METHODS: We assessed 15 infants undergoing cardiac surgery who developed (ARF). Their demographic, clinical and surgical data, and evolution were analyzed. RESULTS: Their mean age was 4.4+/-4.0 months (8 days to 24 months). Twelve infants were males, and 4 patients already had ARF at surgery. The primary cause of ARF was immediate acute cardiac dysfunction in 10 infants, cardiac dysfunction associated with sepsis in 2 infants, and isolated sepsis in 3 infants. All children depended on mechanical ventilation during their postoperative period, 14 infants used vasoactive drugs, and 11 had an infectious process associated with ARF. Thirteen infants required dialytic treatment. Eleven infants developed oluguric ARF, and all had to undergo peritoneal dialysis; of the 4 patients with non-oliguric, 2 required dialysis, the main indication being hypervolemia. Of these 13 dialyzed infants, 4 died in the first 24 hours because of the severity of the underlying cardiac disease (mean urea level of 49+/-20 mg/dl). The mortality rate for the entire group was 60%, and it was higher among the patients with oliguria ARF (73% vs 25%, p<0. 001). The cause of death was acute cardiac dysfunction in 6 infants (early type-1 ARF) and sepsis in the 3 remaining infants (late type-2 ARF). CONCLUSION: The mortality rate of ARF associated with cardiac surgery in infants was hight, being higher among children with oliguria; peritoneal dialysis was indicated due to clinically uncontrolled hypervolemia and not to the uremic hypercatabolic state.

Acute Kidney Injury↗
PubMed1999

Cyclosporine-induced interstitial fibrosis and arteriolar TGF-beta expression with preserved renal blood flow.

BACKGROUND: Cyclosporine A (CsA)-induced chronic nephrotoxicity is characterized by interstitial fibrosis and afferent arteriole hyalinosis. CsA lesion has been linked to maintained renal vasoconstriction and narrowing of the afferent arteriole lumen diameter, leading to preglomerular ischemia. We investigated the role of renal hemodynamics in CsA-induced transforming growth factor (TGF-beta) expression and interstitial fibrosis. METHODS: Groups of rats fed a low salt diet were given CsA 5 mg/kg/day (CsA) or the vehicle (olive oil, [VH]) s.c. and had the renal blood flow (RBF), glomerular filtration rate (GFR), mean arterial pressure, renal vascular resistance, renal histologic changes, and immunohistochemical features for macrophages and TGF-beta evaluated after 1, 2, and 8 weeks of treatment. RESULTS: At week 1, despite normal renal hemodynamics and MAP, there was a significant macrophage interstitial influx in CsA-treated rats (70+/-16 vs. 29+/-4 cells+/0.5 mm2, in CsA vs. VH, P=0.02) that was progressive with treatment (80+/-13 vs. 32+/-8 cells+/0.5 mm2, P=0.016 and 197+/-36 vs. 23+/-3 cells+/0.5 mm2, P=0.0002, CsA vs. VH at 2 and 8 weeks, respectively). After 2 weeks of treatment, CsA animals developed a significant interstitial fibrosis, with preserved RBF, even when it was assessed 2 hr after CsA injection. There was a significant increase in the immunostaining for TGF-beta in the juxtaglomerular arterioles in CsA-treated rats (48.6+/-3.8 vs. 35.1+/-1.1%, CsA vs. VH at 2 weeks, P<0.05 and 59.0+/-3.2 vs. 37.0+/-2.1%, CsA vs. VH at 8 weeks, P=0.0001). A significant and progressive GFR decrease followed the renal structural injury of CsA treatment. Arteriolar and glomerular anatomic injury were not found throughout the study. CONCLUSIONS: Low CsA doses might generate interstitial fibrosis without any decrease in RBF or structural arteriolar lesion evidence, possibly through early macrophage influx and increased TGF-beta expression. It clearly seems that CsA-induced ischemia and tubulointerstitial injury may occur independently, suggesting that chronic CsA nephrotoxicity may be very hard to prevent or even not be preventable at all.

Animals↗
PubMed1997

Nephrology, dialysis and transplantation in Brazil.

The European Renal Association welcomes this opportunity and feels that European nephrologists should be informed about the state of nephrology in South America, with which particularly our Latin colleagues maintain close cultural relationships. The following report on Nephrology in Brazil is a welcome addition to a series of reports designed to provide to European nephrologists a global view of nephrology. It is hoped that this is not misconstrued as a violation of nephrological Monroe doctrine.

Acute Kidney Injury↗
PubMed1995

PDGF and TGF-beta contribute to the natural course of human IgA glomerulonephritis.

PDGF and TGF-beta are known mediators of mesangial cell proliferation and matrix expansion. The presence of these regulatory factors was examined in 30 renal biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and protein level. Normal renal tissue served as control. The mRNA expression of PDGF A/B chains, PDGF-beta R and TGF-beta 1 was evaluated by means of RT/PCR with subsequent Southern blot hybridization and/or non-radioactive in situ hybridization. In addition, PDGF-AB/BB, PDGF-beta R, TGF-beta isoforms (beta 1, beta 1 + 2, beta 2 + 3), the small TGF-beta 1 latency associated peptide (TGF-beta 1 LAP) and the extracellular matrix proteins tenascin and decorin were analyzed by immunocytochemistry. The expression of growth factors was correlated with light microscopic and clinical features. Compared to normal control kidneys, an increased expression of PDGF-BB/PDGF-beta R mRNAs and the corresponding proteins was observed in all biopsies with IgA-GN. Up-regulation was related to the degree of glomerular proliferation and the extent of fibrosing interstitial lesions. In contrast, there was a discordance between TGF-beta 1 mRNA and protein expression (evaluated by immunocytochemistry). In all biopsies, irrespective of the stage of the disease, abundant TGF-beta 1 transcripts were detected, whereas TGF-beta 1 immunoreactivity was expressed to a lesser degree and disclosed a more variable staining pattern. In patients with significant proliferative glomerular lesions and minor tubulointerstitial alterations, TGF-beta 1 positivity was confined to areas of glomerular proliferation, whereas in cases with more severe histology including sclerosing lesions TGF-beta 1 immunoreactivity was less prominent. The distribution and the intensity of TGF-beta 1 LAP staining commonly exceeded the positivity noted for TGF-beta 1, indicating only limited TGF-beta 1 activation. A decreased reactivity for tenascin accompanied the morphological features of glomerular sclerosis. The staining patterns and the fact that only very few inflammatory cells, particularly CD68 positive monocytes/macrophages, were detected in glomeruli confirm that predominantly resident glomerular cells (mesangial and endothelial cells) are the major source of up-regulated growth factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the severity of proliferative glomerular changes, PDGF seems to represent a potential indicator of activity in this condition. It is suggested that an imbalance between PDGF and TGF-beta (by restricted translation and/or activation) production contribute to the progressive nature of IgA-GN.

Adult↗
PubMed1993

Expression of cytokines and growth factors in human glomerulonephritides.

Numerous experimental studies point to the potential role of cytokines and growth factors in the pathogenesis of renal disease. However, from the various autocrine and paracrine mediators identified in vitro and in animal models, so far only a few have been demonstrated in selected human glomerulopathies. We examined two types of glomerulonephritis (GN): extracapillary GN with anti-neutrophil cytoplasmic autoantibodies (ANCA), an example of an acute form of GN, and mesangial IgA GN, usually a chronic form of GN, with immunocytochemistry, in situ hybridization and the polymerase chain reaction. Normal renal tissue from tumour nephrectomies served as a control. In ANCA-positive GN with active renal lesions (crescents, glomerular and vascular necrosis), infiltrating mononuclear cells in glomeruli and in the interstitium expressed interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha, IL-2, interferon (IFN)-gamma, platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta. Cytokine expression was also observed in activated resident cells, including endothelial cells, capsular epithelial cells, smooth muscle cells of vessel walls, fibroblasts and some tubular epithelial cells. In addition, we noted an increase in the cytokine and growth factor receptors TNF-R, IL-1R type II, IL-2R, IFN-gamma R and PDGF beta-R. In contrast, in mesangial IgA-GN, IL-1 beta, TNF-alpha, IFN-gamma and IL-2 were usually absent in glomeruli. Mesangial expansion in this disorder was accompanied by an increased expression of PDGF, PDGF beta-R, TGF-beta and IL-6 in mesangial areas. In both conditions a good correlation was observed between cytokine expression at the mRNA (in situ hybridization) and protein level (immunocytochemistry).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antineutrophil Cytoplasmic↗