Biomedical subjects
Publications and source records attributed to Antonio Carlos Seguro.
We report the first case of Neisseria meningitidis-induced septic peritonitis diagnosed by PCR assay of peritoneal fluid. Concentrations of interleukin-6 were notably higher in the peritoneal fluid than in the blood. PCR diagnosis of septic meningococcal peritonitis and the pathogenesis of the disease are discussed.
Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.
BACKGROUND/AIMS: Patients severely dehydrated from diarrhea are at risk of developing hyperkalemia consequent to fluid therapy treatment. In parallel with the regulation of external potassium balance by the kidney and gastrointestinal tract, plasma potassium is rapidly regulated by redistribution of potassium between the extracellular and intracellular compartments. Erythrocytes contain ATPases that play a role in this potassium movement. In this study, erythrocyte ATPase effectiveness was evaluated in infants dehydrated from diarrhea and compared to that of healthy infants. METHODS: Blood samples were collected from dehydrated and healthy infants. The activity of Na+,K+-ATPase and of an ouabain-insensitive K+-ATPase were assessed. Serum electrolytes and blood pH were also determined. RESULTS: No hyperkalemia was found, even in dehydrated infants presenting with severe hyperchloremic metabolic acidosis. In the erythrocytes of dehydrated infants, Na+,K+-ATPase activity was increased correlating positively with the amount of sodium administered. High K+-ATPase activity in the erythrocytes correlated with low plasma potassium. The K+-ATPase activity correlated positively with the amount of potassium administered to dehydrated infants. CONCLUSION: These findings suggest that the erythrocytes Na+,K+-ATPase and K+-ATPase both protect against plasma potassium abnormalities in dehydrated infants. In such infants, the risk of hyperkalemia is probably low.
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We describe an unusual case of leptospirosis in a 54-year-old man presenting peripheral nerve palsy. The diagnosis of leptospirosis was confirmed by ELISA IgM and the microscopic agglutination test. Electrophysiological studies showed that no response could be obtained from the right fibular nerve. At 7 months after the initiation of treatment, additional electrophysiological studies and a neurological examination showed, respectively, a chronic axonal lesion of right fibular nerve with signs of re-innervation and a nearly complete clinical recovery. We feel that this case may serve to remind clinicians that peripheral nerve palsy is a potential clinical feature of leptospirosis.
BACKGROUND: Metabolic acidosis is highly prevalent in critically ill patients with acute renal failure. Little is known about the mechanisms by which renal replacement therapy intervenes in such cases. The objective of this study is to analyze the role of hemodialysis in acidosis correction in intensive care unit patients, with an emphasis on chloride levels in plasma and dialysate. METHODS: We studied 19 intermittent hemodialysis procedures in 17 acidotic patients. The patients were grouped by procedure type (conventional or sustained low-efficiency dialysis) and by predialysis plasma chloride level (higher or lower than the dialysate chloride concentration). Immediately before and after each procedure, blood samples were collected for biochemical analysis. The Stewart method was used to calculate the strong ion difference and strong ion gap. RESULTS: The patients presented acidosis related to hyperchloremia, hyperphosphatemia, and high unmeasured anions. Hypoalbuminemia had an alkalinizing effect. Hemodialysis corrected acidosis mainly by reducing phosphate and unmeasured anions. In the group as a whole, chloride levels did not change after dialysis. However, when analyzed according to predialysis plasma chloride, the high-chloride group presented a reduction in plasma chloride, resulting in better base excess improvement (Delta standard base excess) than in the low-chloride group. Among the determinants of acid-base status, the only factors correlating with Delta SBE were Delta strong ion gap and Delta chloride. CONCLUSION: The serum chloride/dialysate chloride relationship during hemodialysis has an important impact on acidosis control.
We here report the case of a previously healthy 20-y-old male with disseminated meningococcal disease and purulent pericarditis. Polymerase chain reaction was used to identify Neisseria meningitidis serogroup C as the causative agent in the pericardial fluid.
An unusual case of leptospirosis is described in a 19-month-old male child presenting with meningitis and acute renal failure without jaundice. Some aspects concerning the pathogenesis and treatment of this potentially life-threatening disease are also discussed. Leptospirosis was diagnosed on the basis of history and serological tests.
Herein, we report a case of purulent pericarditis caused by Neisseria meningitidis serogroup C in a previously healthy 5-year-old boy, which was detected in pericardial fluid by polymerase chain reaction. The concentrations of interleukin-6, interferon-gamma and interleukin-10 in pericardial fluid were notably increased compared with serum. The role of polymerase chain reaction, counterimmunoelectrophoresis and latex agglutination test in the diagnosis, as well as the participation of cytokines in the pathogenesis of meningococcal pericarditis, are discussed.
Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia+magnesium, ischemia+NAC, and ischemia+magnesium+NAC. GFR (inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone.
BACKGROUND: Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure. METHODS: Adult male Wistar rats were submitted to 5/6 nephrectomy or laparotomy (sham-operated) and received NAC (600 mg/L in drinking water, initiated on postoperative day 7 or 60), spironolactone (1.5 g/kg of diet initiated on postoperative day 7), the NAC-spironolactone combination or no treatment. Clearance studies were performed on postoperative days 21, 60, and 120. RESULTS: Mean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary potassium sodium [corrected] ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection. CONCLUSION: The NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation.
Acute renal failure (ARF) is one of the most serious complications of Bothrops snakebites. Pathogenesis of ARF in snakebite envenomation may involve hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. This study aimed at evaluating Bothrops jararaca venom direct toxicity on isolated rat renal proximal tubules (PT). PT was kept oxygenated and subjected to hypoxia (H, 15 min) and reoxygenation (R, 45 min). Bothropic antivenom effects, role of extracellular calcium and peroxide production were also evaluated. Cell injury was determined by LDH release (%) and peroxide production determined by xylenol-orange method. B. jararaca venom caused tubular injury (LDH 31.6 vs. 17.2%, P <0.05), which was prevented by simultaneous or delayed antivenom administration, but not with low extracellular calcium medium. Venom increased tubules peroxide production: 2.21 vs. 1.27 microM/mg protein (P <0.05) which was also prevented by antivenom administration. Venom toxic concentration did not enhance H/R injury. In contrast, non-toxic venom concentration afforded protection (LDH 41.3 vs. 51.5%, P <0.05). In conclusion, B. jararaca venom caused direct injury to normoxic renal tubules, but not to hypoxic/reoxygenated tubules. Tubular toxicity is independent of extracellular calcium and mediated in part by lipid peroxidation. Venom induced tubular injury was prevented by simultaneous or delayed antivenom administration.
BACKGROUND: N-Acetylcysteine has been shown to protect against contrast nephropathy, although the mechanisms underlying such an effect are unclear. Surprisingly, studies have shown that post-radiocontrast renal function actually improves in chronic renal failure patients receiving N-acetylcysteine. However, there have been no studies investigating the cause of this improvement. METHODS: In a double-blind, placebo-controlled study, 24 patients (aged 65+/-2 years) suffering from stable mild-to-moderate renal insufficiency and undergoing elective coronary angiography were randomized to receive either placebo or N-acetylcysteine. All received similar hydration. Renal function parameters were assessed 48 h before and 48 h after radiocontrast administration. Urinary 15-isoprostane F2(t), a specific marker of oxidative stress, was measured immediately before and after the procedure. Expression of urinary alpha-glutathione S-transferase protein, a specific proximal tubular injury marker, was assessed after the procedure. RESULTS: Comparing creatinine clearance values before and after angiography, a significant increase was seen in N-acetylcysteine patients (44.7+/-4.2 vs 57.2+/-6.3 ml/min/1.73 m(2); P = 0.02), whereas placebo patients presented no change (46.6+/-5.0 vs 46.9+/-4.3 ml/min/1.73 m(2); P = 0.90). After radiocontrast, urinary 15-isoprostane F2(t) levels in placebo patients increased significantly over baseline values (2.9+/-0.7 vs 10.3+/-2.1 ng/mg creatinine; P = 0.007), whereas urinary 15-isoprostane F2(t) levels in N-acetylcysteine patients remained basically unchanged (3.5+/-0.5 vs 4.1+/-0.9 ng/mg creatinine; P = 0.63). Furthermore, N-acetylcysteine treatment led to lower levels of alpha-glutathione S-transferase than did placebo treatment (0.8+/-0.2 vs 2.4+/-0.7 micro g/g; P = 0.046). CONCLUSIONS: In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury.
The aging process causes progressive deterioration in kidney structure and function. Aberrant generation of reactive oxygen species has been implicated in both age-related and ischemia-related tissue injury. Vitamin E (VE), one of the most powerful and effective exogenous antioxidants, prevents lipid peroxidation and protects against the effects of oxidative stress. The objective of this study was to determine the influence of age and VE on post-ischemic acute renal failure (ARF). Young adult, middle-aged and aged male Wistar rats were maintained on three different 30-day diets: Normal, VE absent and VE supplemented. On day 30, urinary protein and serum cholesterol and VE were measured. On day 31, rats were subjected to 60' clamping of the left renal artery plus right nephrectomy. Inulin clearance (InCl) was performed 48 h after renal ischemia. Malondialdehyde (MDA) was measured in the cortex of normal and 48-h post-ischemic kidneys. Urinary protein and serum cholesterol were higher in aged rats than in other rats. With aging, InCl decreased progressively. Vitamin E deficiency aggravated ARF. In middle-aged and aged rats, VE supplementation protected against ARF. In the absence of VE, MDA increased with age. In conclusion, our data suggest that ARF becomes more severe with age and that ischemia/reperfusion injury is exacerbated when antioxidant-scavenging ability of the kidney is impaired by VE deficiency. Supplementation with VE is essential for protecting aging kidneys against ischemic ARF.
BACKGROUND: Acyclovir (ACY) is a useful therapeutic agent for the systemic treatment of herpes virus infection. An increase in urinary phosphate excretion and polyuria has been described. The objective of this study was to analyze the exact mechanism of the urinary-concentrating dysfunction and the increase in phosphaturia associated with ACY. METHODS: We first analyzed 7 (adult and pediatric) non-AIDS cases of encephalitis receiving 15 mg/kg bw/d of intravenous ACY. Fractional phosphate and sodium excretion, urinary potassium volume, and plasma phosphate concentrations were analyzed. Additional studies in rats treated with intraperitoneal ACY (100 mg/kg bw) were also conducted. Animals were maintained in metabolic cages and 24-hour urine samples were collected to measure volume, osmolality, and sodium/potassium/phosphate excretion. Treated rats were also evaluated after 24 hours and 48 hours of water deprivation. Northern hybridization and semiquantitative immunoblotting were performed to evaluate (in both control and treated animals) expression of the cotransporters Na-Pi type IIa (Na-Pi-IIa) and Na-K-2Cl (NKCC2). Semiquantitative immunoblotting was carried out in the kidneys of ACY rats and control rats in order to analyze aquaporin 2 (AQP2) protein expression. RESULTS: Patients started on ACY developed polyuria and hyperphosphatemia after 48 hours. In rats, ACY-induced hyperphosphaturia and hypophosphatemia were accompanied by increased excretion of sodium, potassium, and magnesium, increased urine output, lower urinary osmolality, and a partial urinary concentrating defect. Concurrent downregulation of Na-Pi-IIa and NKCC2 expression was observed. There was also a decrease in medullar expression of the AQP2 collecting duct water channel. CONCLUSION: Downregulation of Na-Pi-IIa appears to play a crucial role in the downregulation of ACY-induced hyperphosphaturia. The accompanying polyuria and urinary-concentrating defect can in part be explained by the downregulation of NKCC2 and AQP2.
The effect of maternal hypercholesterolemia on the course of pregnancy and the development of offspring was investigated. Rats were fed either an enriched-cholesterol diet (HC) or a standard diet (control) from 1 week before mating until weaning of offspring. Compared with the control group, HC dams showed a fourfold increase in abortions, a twofold increase in neonatal mortality, smaller litter size, and lower birth weight of pups. At weaning, Na(+),K(+)-ATPase activity in the outer renal medulla was reduced in HC pups compared with control pups, suggesting retarded or impaired development of medullary nephron segments. At this point, to better examine the adverse effects of maternal hypercholesterolemia, the HC pups were divided into two groups: one fed a cholesterol-enriched diet (HC/hc) and the other a standard diet (HC/nc), while control pups were maintained on the standard diet. In adulthood, the HC/hc group showed growth impairment and reduced renal function, demonstrated by low creatinine clearance (0.24+/-0.04 ml/min per 100 g body weight) and high fractional excretion of sodium, potassium, and water ( P<0.05 vs. control). These effects were partially reversed in the HC/nc group. In this study, neither dams nor offspring developed hypertension. Thus, maternal hypercholesterolemia adversely affected pregnancy outcomes and the development of offspring by inducing abnormalities and thereby reducing renal function.
Indinavir (IDV) is a protease inhibitor widely used in AIDS treatment. A sustained elevation of creatinine was identified in IDV-treated patients. We have previously demonstrated that IDV causes renal vasoconstriction in rats. The objective of this study was to investigate the mechanism of IDV-induced vasoconstriction and the effect that the vasodilator agents L-arginine (LA), nifedipine (NF), as well as magnesium supplementation (Mg), have on IDV-induced nephrotoxicity. Male Wistar rats were kept on fast overnight and given free access to water. IDV (80 mg/kg BW) and NF (3 mg/kg BW) were given by gavage for 15 days. LA (1.5%) and MgCl2 x 6H2O (1%) were added to drinking water. Six groups were studied: Control (n=6): normal rats treated with vehicle, a 0.05 M citric acid solution; IDV (n=7): IDV-treated rats; IDV+LA (n=6): IDV- and LA-treated rats; IDV+NF (n=7): IDV- and NF-treated rats; IDV+Mg (n=7): IDV- and MgCl2-treated rats; IDV+Mg+L-NAME (n=9): IDV- and MgCl2-treated rats, supplemented with L-NAME (2.5 mg/l in drinking water). Clearance studies and evaluations of urinary nitrite (NO2) excretion were performed on day 16. No changes in blood pressure were observed. NO2 excretion decreased in IDV-treated rats. LA and NF protected against IDV effects, improving GFR (IDV+LA, 1.95 +/- 0.10; IDV+NF, 1.94 +/- 0.07 vs IDV, 1.15 +/- 0.07 ml/min, P<0.001) and RBF (IDV+LA, 7.83 +/- 0.09; IDV+NF, 7.63 +/- 0.14 vs IDV, 6.17 +/- 0.25 ml/min, P<0.001). These results suggest that IDV-induced vasoconstriction is mediated by NO and Ca2+ channels. Magnesium also ameliorated GFR and RBF in IDV-treated rats (GFR IDV+Mg, 1.77 +/- 0.08 ml/min, P<0.001; RBF IDV+Mg, 7.35 +/- 0.158 ml/min, P<0.001). Magnesium protection is not NO-mediated since it was not blocked by L-NAME. In conclusion, LA, NF and Mg protect against IDV-induced nephrotoxicity in rats. This study may have potential clinical implications for prevention of IDV-induced nephrotoxicity.
Toxocariasis is usually manifested as visceral larva migrans. Nervous system involvement is a rare complication. In this report, we describe one case of meningoencephalitis due to Toxocara canis and review the literature. We report a previously healthy two-year-old boy who was admitted after 24 hours of severe neurologic symptoms with marked eosinophilic pleocytosis in the cerebrospinal fluid and a single subcortical lesion detected by cerebral magnetic resonance imaging. Both serum and spinal fluid tested positive for T. canis. Initial treatment with thiabendazole was ineffective. After marked improvement in clinical and laboratory results were achieved using albendazole and corticosteroids, the child was discharged.