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Effects of microcystin-LR in isolated perfused rat kidney

Microcystin is a hepatotoxic peptide which inhibits protein phosphatase types 1 and 2A. The objective of the present study was to evaluate the physiopathologic effects of microcystin-LR in isolated perfused rat kidney. Adult Wistar rats (N = 5) of both sexes (240-280 g) were utilized. Microcystin-LR (1 microg/ml) was perfused over a period of 120 min, during which samples of urine and perfusate were collected at 10-min intervals to determine the levels of inulin, sodium, potassium and osmolality. We observed a significant increase in urinary flow with a peak effect at 90 min (control (C) = 0.20 +/- 0.01 and treated (T) = 0.32 +/- 0.01 ml g-1 min-1, P<0.05). At 90 min there was a significant increase in perfusate pressure (C = 129.7 +/- 4.81 and T = 175.0 +/- 1.15 mmHg) and glomerular filtration rate (C = 0.66 +/- 0.07 and T = 1.10 +/- 0. 04 ml g-1 min-1) and there was a significant reduction in fractional sodium tubular transport at 120 min (C = 78.6 +/- 0.98 and T = 73.9 +/- 0.95%). Histopathologic analysis of the perfused kidneys showed protein material in the urinary space, suggestive of renal toxicity. These data demonstrate renal vascular, glomerular and urinary effects of microcystin-LR, indicating that microcystin acts directly on the kidney by probable inhibition of protein phosphatases.

Effects of Crotalus durissus cascavella venom in the isolated rat kidney

Crotalus durissus cascavella (C.d.c) is a snake usually found in scrubland of Brazilian Northeast and its bite constitutes an important public health problem. Isolated kidneys from wistar rats, weighing 240 to 280 g, were perfused with Krebs Henseleit solution containing 6 g% of previously dialysed bovine serum albumin. The effects of C.d.c venom were studied on the perfusion pressure (PP), urinary flow (UF), glomerular filtration rate (GFR), percent of sodium tubular transport (%TNa+) and percent of proximal tubule sodium transport (%pTNa+). All experiments were preceded by a 30 min internal control period and an external control group. The infusion of C.d.c (10 microg ml(-1)) increased the PP, UF at 60 and 90min of perfusion, and decreased the GFR, %TNa+ and %pTNa+ at 120 min of perfusion. The proximal renal tubule was the major site for this toxic effect. In the group treated with the venom we found hyalin cylinders inside all tubules and proteinaceous material, alternating from moderate to intense presence in urinary space. Dexamethasone (Dexa 20 microg ml(-1)) protected against the increase in PP, UF, and against the decrease in GFR, it produced the reversion of the effect also in %TNa+ and %pTNa+. Indomethacin (Indo 10 microg ml(-1)) antagonized the effect observed in PP and UF, but was not able to reverse the changes in GFR, %TNa+ and %pTNa+. Nifedipine (Nif 10 microg ml(-1)) promoted a reversion of almost all functional changes, except the %pTNa+ was not reversed. We conclude that these alterations may be caused by a direct action of the venom on the kidneys and indirectly by the release of mediators from endothelial cells. Dexa protected against renal lesions caused by the venom, perhaps by inhibiting phospholipase A2 a toxic component of the venom. The reversion partially induced by indo may be due to cyclooxygenase inhibition that will inhibit the formation of prostaglandins. Nif blocked the renal alterations that may involve cell calcium influx that resulted from the venom aggression.

The role of phospholipase A2 and cyclooxygenase in renal toxicity induced by microcystin-LR

We have shown previously that exposure to microcystin-LR (MCLR) causes renal toxic effects in isolated perfused rat kidney. That study was extended further to approach the perspective of pharmacological blockade of renal toxic effects by MCLR through the use of experimental therapeutic agents. An isolated kidney perfusion system was utilized and samples of urine and perfusate were collected at 10min intervals to determine the levels of inulin, sodium, potassium and osmolality. Dexamethasone (20microg ml(-1)) and indomethacin (10microg ml(-1)) were administered in the beginning of the perfusion and MCLR was employed in a dose of 1microg ml(-1) after an internal control of 30min to evaluate the perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR) and urinary flow (UF). Dexamethasone and indomethacin antagonized the toxic effects of MCLR on PP, RVR, GFR and UF. Histologic analysis of dexamethasone and indomethacin treated groups did not show any vascular or interstitial alterations. MCLR potentially impairs the renal function, probably causing vascular and glomerular lesions and, promoting renal alterations through direct or indirect actions. These data seem to indicate that the renal alterations promoted by MCLR involves also phospholipase A(2) and arachidonic acid-derived mediators.

Effects of Thalassophryne nattereri fish venom in isolated perfused rat kidney.

Thalassophryne nattereri, popularly known as Niquim, is a venomous fish responsible for many accidents in fishermen in the Northeast of Brazil. The effects of T. nattereri venom on renal physiology has not been tested. Isolated kidneys from Wistar rats of 240-280 g weight were perfused with Krebs-Henseleit solution containing 6g% of previously dialyzed bovine serum albumin. The effects of Niquim venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), percent of sodium tubular transport (%TNa(+)), percent of potassium tubular transport (%TK(+)) and percent of chloride tubular transport (%TCl(-)). The venom of T. nattereri (0.3, 1.0, and 3.0 microg/ml) was always added to the system 30 minutes after the beginning of each experiment (n=6). All experiments were preceded by 30 minutes internal control period and an external control group, where kidneys were perfused with only Krebs-Henseleit solution. All three doses tested promoted increases in PP and RVR. The first two doses also increased GFR and UF. The higher dose promoted decreases in GFR, UF, %TNa(+), %TK(+), %TCl(-). In the treated groups we observed hyalin casts inside all tubules and proteinaceous material in the urinary space. We conclude that the effects resulted from niquim venom agents that promoted a direct effect in kidney cells causing the release of vasoactive factors.

Histologic analysis of colonic anastomotic healing, in rats, under the action of 10% Aroeira-do-sertão (Myracrodruon urundeuva fr. all.) enema

PURPOSE Evaluate, from a histologic view point, the action of the aqueous extract of aroeira-do-sertão on the healing of colonic anastomosis, in Wistar rats. METHODS There were used 48 Wistar rats, males, with average weight of 320g, distributed in two groups, with 24 animals, each. All animals were subjected to a complete transverse section of the descending colon, followed by colonic anastomosis. The rats on group A received daily post-operative enemas of carboxymethylcellulose (CMC) based vehicle. The animals on group B received post-operative enemas of 10% aqueous extract of aroeira-do-sertão in CMC based vehicle, until the date of euthanasia. On days 3, 7, 14 and 21 of the experiment, six rats in each group were subjected to removal of a colonic segment, including the anastomosis, destined to histological evaluation and qualitative analysis of inflammatory and healing cell response. RESULTS The morphologic analysis reveals a significant difference between groups, on day 7 (ñ < 0.05), when the group studied showed lower score than the control group. The collagen deposition on the aroeira group was lower, on days 3, 7 and 14 (ñ < 0.05), compared to the control group. CONCLUSION The aqueous extract of aroeira-do-sertão has anti-inflammatory action. It also has inhibitory effect on collagen deposition during the phases of inflammation and fibroplasia of the healing process of colonic anastomoses, in Wistar rats, but in advanced phases (day 21) the healing process is similar to that in the animals of the control group.

Rare nasosinusal tumors: case series and literature review

Tumors of the nasal cavity and paranasal sinuses are unusual pathologies found in clinical practice. Approximately 0.8% of all human cancers are located in this area. Despite being rare, nasosinusal neoplasms usually manifest through nonspecific symptoms that are common to numerous inflammatory pathologies. The aim of this study is to describe a series of rare nasosinusal tumors, including esthesioneuroblastomas, central giant cell granulomas, extramedullary plasmocytomas, nasosinusal hemangiopericytomas, neurofibromas and cemento-ossifying fibromas, diagnosed at the Fortaleza General Hospital. We, hereby, briefly review each of the aforementioned pathologies, stressing the need for a precise histological diagnosis for proper treatment in each case.

Tumores nasossinusais raros: série de casos e revisão de literatura

Tumors of the nasal cavity and paranasal sinuses are unusual pathologies found in clinical practice. Approximately 0.8% of all human cancers are located in this area. Despite being rare, nasosinusal neoplasms usually manifest through nonspecific symptoms that are common to numerous inflammatory pathologies. The aim of this study is to describe a series of rare nasosinusal tumors, including esthesioneuroblastomas, central giant cell granulomas, extramedullary plasmocytomas, nasosinusal hemangiopericytomas, neurofibromas and cemento-ossifying fibromas, diagnosed at the Fortaleza General Hospital. We, hereby, briefly review each of the aforementioned pathologies, stressing the need for a precise histological diagnosis for proper treatment in each case.

Towards a better understanding of Ipomoea asarifolia toxicity: evidence of the involvement of a leaf lectin.

Natural intoxication of livestock by ingestion of Ipomoea asarifolia leaves has been reported to occur widely in Brazil. Previous studies carried out by our research group provided strong evidence that a lectin could be involved with the toxic properties of I. asarifolia. To reinforce this hypothesis, a lectin-enriched fraction (LEF) was isolated from I. asarifolia leaves and its toxic effects were assessed. Leaves of I. asarifolia were excised from plants growing widely in the field, mechanically wounded and maintained in a chamber at 25 ± 3 °C for 72h in the dark, under near 100% relative humidity. The leaf proteins were extracted, ammonium sulfate precipitated, chromatographed on DEAE-cellulose and Phenyl-Sepharose to produce LEF that under SDS-PAGE showed a molecular mass of 44.0 kDa and after N-terminal amino acid analysis a primary sequence composed of AGYTPVLDIGAEVLAAGEPY. The in vivo toxicity of LEF assessed by intraorbital injection in mice showed induced severe uncoordinated movements without death. LEF reduced the muscular contraction in a dose depend way and at 29.8 μg/mL (CE(50)) it produces 50% inhibition of contraction, suggesting that LEF blunts autonomic neurotransmission. Isolated rat kidneys were perfused with LEF and no effects on the perfusion pressure or renal vascular resistance were observed, but urinary flow and glomerular filtration rate increased. Moreover, the percentage of tubular transport of Na(+), K(+) and Cl(-) decreased. Histological examination of the kidneys perfused with LEF exhibited little alterations. These toxic effects observed above were concomitant with the increase of LEF hemagglutination activity, which strongly suggest that one of the toxic principles of I. asarifolia is a lectin present in its leaves.

Castleman's disease accompanied by pleural effusion

Castlemans disease is a rare disorder of the lymphoid tissue. We report the case of a female patient with bilateral otosclerosis, no respiratory symptoms, and pleural effusion discovered as an incidental finding on a chest X-ray. Computed tomography of the chest revealed a mediastinal mass. The biopsy findings demonstrated that it was a plasmacytic variant of Castlemans disease. The patient underwent mediastinal mass resection. This resulted in near-total resolution of the effusion, which remained as a small loculation within the left pleural space.

Metabolic acidosis aggravates experimental acute kidney injury

AIMS Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury. MAIN METHODS Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9). KEY FINDINGS Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury. SIGNIFICANCE Acute ischemic kidney injury is exacerbated by acidic conditions.