Biomedical subjects

Maurilo Leite

Publications and source records attributed to Maurilo Leite.

6 recordsLinked to original sources

PubMed2006

Experimentally induced metabolic acidosis in rabbits modulates the interaction of aortic glycosaminoglycan with plasma low-density lipoprotein--an interesting observation about the association of acidosis and atherosclerosis.

It is well established that arterial glycosaminoglycans (GAG) undergo compositional and structural modifications during the development of atherosclerosis. On the other hand, metabolic acidosis is a common feature of chronic renal patients known to present accelerated atherogenesis. The present study was performed to determine the influence of acidosis in the modifications of aortic GAG in a model of atherosclerosis in rabbits. For this purpose, four groups of rabbits were kept for 8 weeks on a regimen of normal, hypercholesterolemic, acidemic and hypercholesterolemic plus acidemic diets. No difference was detected in the total GAG concentration among animals fed with normal, hypercholesterolemic and acidemic diets. However, we observed an increase in total GAG content when acidosis was associated with hypercholesterolemia. This increase was more pronounced in the thoracic aortic segment. The interaction between LDL and the aortic GAG was evaluated by formation of insoluble complexes. The results showed that GAG extracted from hypercholesterolemic rabbits exhibited a lower ability to interact with LDL, when compared to those fed normal diet. On the other hand, GAG extracted from rabbits submitted to hypercholesterolemic plus acidemic diet, did not show this behavior. In addition, the molecular weight of GAG from hypercholesterolemic animals, is lower than those from animals fed normal diet. Surprisingly, acidosis associated with hypercholesterolemia did not exhibit this alteration, keeping the molecular weight close to the normal range. In view of these results, we hypothesize that acidosis itself does not affect either the GAG composition or its interaction with LDL, however in an atherogenic condition, as can be seen in renal failure individuals, it may alter the GAG concentration and the size of the glycan chains.

Acidosis, Lactic↗

PubMed2006

Effects of low molecular weight heparin in obstructed kidneys: decrease of collagen, fibronectin and TGF-beta, and increase of chondroitin/dermatan sulfate proteoglycans and macrophage infiltration.

BACKGROUND: Heparin exerts beneficial effects in different experimental models of nephropathy, as observed by the preservation of the structural morphology of the kidney after heparin therapy. Here we investigate molecular and cellular events involved in the protective effects of heparin in the progression of renal disease after unilateral ureteral obstruction. METHODS: Thirty-six rats were divided into six groups: group C (control) was not subjected to any surgical manipulation; group S (sham) was subjected to surgical manipulation but without ureteral ligation; group UUO was subjected to ureteral obstruction and received no treatment; group UUO + S was subjected to ureteral obstruction and received saline subcutaneously (s.c.) once daily; group UUO + H was subjected to ureteral obstruction and received low molecular weight heparin (LMW-Hep; 4 mg/kg) s.c. once daily; and group C + H was not subjected to any surgical manipulation and received LMW-Hep (4 mg/kg) s.c. once daily. After 14 days, the content of collagen, fibronectin, total glycosaminoglycans (GAGS), chondroitin sulfate/dermatan sulfate proteoglycans (CS/DSPGs), transforming growth factor-beta (TGF-beta) and cellular infiltration were determined in the kidneys by immunohistochemical and biochemical techniques. RESULTS: Collagen, fibronectin, total GAGS, CS/DSPGs, TGF-beta and cellular infiltration increased significantly in group UUO. LMW-Hep treatment reduced collagen, fibronectin and TGF-beta, but induced an increase in the content of total GAGS, CS/DSPGs and macrophage infiltration in group UUO + H when compared with group UUO. CONCLUSIONS: LMW-Hep diminishes fibrosis in obstructed kidneys by downregulating the synthesis of collagen, fibronectin and TGF-beta. The mechanisms underlying the overproduction of CS/DSPGs and the increase in cellular infiltration upon LMW-Hep administration remain to be elucidated.

Animals↗

PubMed2004

Effects of mycophenolate mofetil and lisinopril on collagen deposition in unilateral ureteral obstruction in rats.

BACKGROUND/AIMS: Unilateral ureteral obstruction (UUO) in rats has been used as a model of renal interstitial fibrosis, in which therapeutic trials can be of important clinical relevance. In this study, we investigated the effects of mycophenolate mofetil (MMF), the angiotensin-converting enzyme (ACE) inhibitor lisinopril (L), and the combination of both drugs, given daily for 14 days to UUO rats, on the renal fibrogenic process triggered by UUO. METHODS: Rats underwent surgical UUO, followed by treatment with daily doses of either MMF, lisinopril, or both, and were then sacrificed after 14 days. Kidney fragments were fixed for histopathological examination (hematoxylin-eosin and periodic acid-Schiff reactive) and immunohistochemistry for myofibroblasts (alpha-smooth muscle actin; alpha-SMA) and macrophages (ED-1). Histomorphometrical analysis of collagen was performed with Sirius red staining, and collagen content was assessed by the amount of hydroxyproline. Cortex and medulla were analyzed separately. RESULTS: MMF, lisinopril and MMF+L reduced the density of alpha-SMA- and ED-1-positive cells (p < 0.05), interstitial volume (p < 0.05) and decreased Sirius-red-stained areas by 54.6, 35.6 and 58.0%, and hydroxyproline content by 60.1, 49.7 and 62.7%, respectively. No differences were observed among treated groups. CONCLUSION: MMF and the ACE inhibitor lisinopril attenuated the progression of the fibrogenic process of UUO in an equivalent manner. The combination of both drugs did not add any further improvement in the collagen content.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Effects of luminal flow and nucleotides on [Ca(2+)](i) in rabbit cortical collecting duct.

Nucleotide binding to purinergic P2 receptors contributes to the regulation of a variety of physiological functions in renal epithelial cells. Whereas P2 receptors have been functionally identified at the basolateral membrane of the cortical collecting duct (CCD), a final regulatory site of urinary Na(+), K(+), and acid-base excretion, controversy exists as to whether apical purinoceptors exist in this segment. Nor has the distribution of receptor subtypes present on the unique cell populations that constitute Ca(2+) the CCD been established. To examine this, we measured nucleotide-induced changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) in fura 2-loaded rabbit CCDs microperfused in vitro. Resting [Ca(2+)](i) did not differ between principal and intercalated cells, averaging approximately 120 nM. An acute increase in tubular fluid flow rate, associated with a 20% increase in tubular diameter, led to increases in [Ca(2+)](i) in both cell types. Luminal perfusion of 100 microM UTP or ATP-gamma-S, in the absence of change in flow rate, caused a rapid and transient approximately fourfold increase in [Ca(2+)](i) in both cell types (P < 0.05). Luminal suramin, a nonspecific P2 receptor antagonist, blocked the nucleotide- but not flow-induced [Ca(2+)](i) transients. Luminal perfusion with a P2X (alpha,beta-methylene-ATP), P2X(7) (benzoyl-benzoyl-ATP), P2Y(1) (2-methylthio-ATP), or P2Y(4)/P2Y(6) (UDP) receptor agonist had no effect on [Ca(2+)](i). The nucleotide-induced [Ca(2+)](i) transients were inhibited by the inositol-1,4,5-triphosphate receptor blocker 2-aminoethoxydiphenyl borate, thapsigargin, which depletes internal Ca(2+) stores, luminal perfusion with a Ca(2+)-free perfusate, or the L-type Ca(2+) channel blocker nifedipine. These results suggest that luminal nucleotides activate apical P2Y(2) receptors in the CCD via pathways that require both internal Ca(2+) mobilization and extracellular Ca(2+) entry. The flow-induced rise in [Ca(2+)](i) is apparently not mediated by apical P2 purinergic receptor signaling.

Adenosine Triphosphate↗

PubMed2002

Correction of acidosis by hemodialysis: proposal of a correlation with urea kinetics.

BACKGROUND/AIMS: We examined the effect of hemodialysis (HD) on acid-base status and its relation to urea kinetics in clinically stable renal HD patients. The purpose of this study was to design a practical approach to monitoring the correction of acidosis, as it can be assisted by routine parameters of adequacy. METHODS: Blood samples were drawn immediately before and after HD from 46 chronic renal patients to determine electrolytes, blood gases, serum albumin and blood urea nitrogen (BUN). Additional measurements of pH and serum bicarbonate were done in 35 patients in the periods before, immediately after and 4 h after HD. The normalized protein catabolic rate (nPCR) was calculated and correlated with the serum albumin and bicarbonate values before HD. Equilibrated KT/V (eKT/V) and urea reduction ratio (URR) were calculated and correlated with the degree of bicarbonate correction, defined as DeltaHCO(3)(-). RESULTS: There was no correlation between nPCR and pre-HD HCO(3)(-), while there was a significant correlation between URR and eKT/V and DeltaHCO(3)(-) (p < 0.003). CONCLUSIONS: The Deltabicarbonate was well correlated with URR and eKT/V, and the study suggests that in standard HD the correction of acidosis may be related to target URR and eKT/V levels.

Acidosis↗

PubMedDate not supplied

Ciprofloxacin and cefazolin as a combination for empirical initial therapy of peritoneal dialysis-related peritonitis: five-year follow-up.

The treatment of peritoneal dialysis (PD)-related peritonitis has been a matter of extensive investigation, frequently generating therapeutic trials. Several combinations of antibiotics have served as newer protocols and tended to be efficacious, comfortable, and cost-effective. According to the more recent recommendations from the International Society for Peritoneal Dialysis, the rationale for empirical initial therapy of clinically detected peritonitis in PD patients has been to follow the bacterial profile derived from cultured specimens of PD effluents. The current study describes 5 year's experience with the use of a new antibiotic regimen for the treatment of peritonitis. We herein analyze the outcome of 95 episodes of peritonitis in 54 patients on either automated PD or continuous ambulatory PD at the dialysis unit of the Federal University of Rio de Janeiro. Peritoneal dialysis-related peritonitis was treated with the combination of oral ciprofloxacin and intraperitoneal cefazolin. The observed cure rate was 85.2% and the sensitivity test was observed to be positive for this combination of antibiotics in 88.9% of positive cultures. Of the 14 unsuccessful episodes, 7 were due to catheter colonization and the rest did not respond to the proposed therapy within 48 hours. These 7 cases were also related to peritoneal fluid cultures that were resistant to both ciprofloxacin and cefazolin. From this study, we propose this combination of oral ciprofloxacin and intraperitoneal cefazolin as a first choice for empirical initial therapy of PD-related peritonitis, given its efficacy and low cost. However, in order to apply the most adequate cost-effective therapy, careful examination of the bacterial profile and sensitivities to antibiotics used in each unit is strongly recommended.

Anti-Infective Agents↗