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.

The renal effects and initial characterization of venom from Philodryas nattereri Steindachner, 1870.

The venom of the snake Philodryas nattereri is a mixture of proteins and toxic peptides with several important local and systemic actions, which are similar to those occurring in Bothrops snake bites. The mechanisms involved in the local and systemic actions of this venom are unknown. The aims of the work were to initial characterization of P. nattereri venom and investigate the effects of the poison in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin-Darby canine kidney). The P. nattereri venom is composed majority of proteins (86.3%) and this poison promoted changes in all the evaluated renal parameters, mainly decreasing renal perfusion pressure (PP) and renal vascular resistance (RVR) and increasing urine flow (UF) and glomerular filtration rate (GFR). The most relevant result was that this venom was highly detrimental to the renal tubules independent of the PP reduction, which was shown by a decrease in sodium (Na+), potassium (K+) and chloride (Cl-) electrolyte transport in the studied concentrations. The glomeruli and tubules contain protein bodies and blood extravasation, which were observed by histological analysis. The venom of P. nattereri reduced viability of the MDCK cells only at high concentrations (50 and 100 µg/mL) with an IC50 of 169.5 µg/mL.

Bacillary angiomatosis in HIV-positive patient from Northeastern Brazil: a case report.

It is a report of disseminated bacillary angiomatosis (BA) in a 23-year-old female patient, who is HIV-positive and with fever, weight loss, hepatomegaly, ascites, and papular-nodular skin lesions. The clinical and diagnostic aspects involved in the case were discussed. Bacillary angiomatosis must always be considered in the diagnosis of febrile cutaneous manifestations in AIDS.

The involvement of the HO-1 pathway in the anti-inflammatory action of a sulfated polysaccharide isolated from the red seaweed Gracilaria birdiae.

OBJECTIVES: The aim of this study was to investigate the involvement of the hemoxigenase-1 (HO-1) pathway in the anti-inflammatory action of a sulfated polysaccharide from the red seaweed Gracilaria birdiae (SP-Gb). METHODS: SP-Gb (5, 10 and 20 mg/kg) was administered to Wistar rats in a peritonitis model using carrageenan or a paw edema model using carrageenan or dextran. To analyze the involvement of HO-1 in the anti-inflammatory activity of SP-Gb, the animals were pretreated subcutaneously with a specific HO-1 inhibitor (ZnPP IX). To evaluate the systemic effects, SP-Gb (10 mg/kg) was administered to mice intraperitoneally before waiting for 48 h or for 14 days. RESULTS: SP-Gb (10 mg/kg) caused an anti-inflammatory effect that was evidenced by a decrease in leukocytes in the peritoneal cavity. SP-Gb also reduced the paw edema induced by carrageenan and inhibited the paw edema induced by dextran in the first half-hour. After being inhibited by ZnPP IX, the anti-inflammatory effect of SP-Gb on carrageenan-induced rat paw edema was not observed. SP-Gb did not cause mortality or significant changes in the biochemical, hematological and histopathological parameters. CONCLUSION: SP-Gb may be used as a tool for further investigations into the inflammatory processes associated with the hemoxigenase-1 pathway.

Anti-TNF therapy in renal amyloidosis in refractory rheumatoid arthritis: a new therapeutic perspective.

Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposits of a material composed of aggregates of amyloid--a poorly coupled protein--far from the site of synthesis, causing target organ dysfunction and clinical disease. Systemic amyloidosis A (AA), secondary to infections and chronic inflammation, especially rheumatoid arthritis (RA), is the most common form of amyloid deposition. Treatment of AA consists in the control or resolution of the baseline condition. The objective of the present study was to report a case of secondary renal amyloidosis in a patient with long-term refractory RA who presented sustained clinical improvement after the use of anti-TNFα (etanercept).

Castleman's disease accompanied by pleural effusion.

Castleman's 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 Castleman's 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.

Purification and renal effects of phospholipase A(2) isolated from Bothrops insularis venom.

Bothrops insularis venom contains a variety of substances presumably responsible for several pharmacological effects. We investigated the biochemical and biological effects of phospholipase A(2) protein isolated from B. insularis venom and the chromatographic profile showed 7 main fractions and the main phospholipase A(2) (PLA(2)) enzymatic activity was detected in fractions IV and V. Fraction IV was submitted to a new chromatographic procedure on ion exchange chromatography, which allowed the elution of 5 main fractions designated as IV-1 to IV-5, from which IV-4 constituted the main fraction. The molecular homogeneity of this fraction was characterized by high-performance liquid chromatography (HPLC) and demonstrated by mass spectrometry (MS), which showed a molecular mass of 13984.20 Da; its N-terminal sequence presented a high amino acid identity (up to 95%) with the PLA(2) of Bothrops jararaca and Bothrops asper. Phospholipase A(2) isolated from B. insularis (Bi PLA(2) ) venom (10 microg/mL) was also studied as to its effect on the renal function of isolated perfused kidneys of Wistar rats (n=6). Bi PLA(2) increased perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). Sodium (%TNa(+)) and chloride tubular reabsorption (%TCl(-)) decreased at 120 min, without alteration in potassium transport. In conclusion, PLA(2) isolated from B. insularis venom promoted renal alterations in the isolated perfused rat kidney.

Purification and biological effects of L-amino acid oxidase isolated from Bothrops insularis venom.

Bothrops insularis is a snake from Ilha da Queimada Grande, an island located about 20 miles away from the Southeastern coast of Brazil. Compared with other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood, and so far, no fraction from this venom with amino acid oxidase activity had been isolated or its biological activity tested. We investigated the biochemical and biological effects of one l-amino acid oxidase enzyme isolated from B. insularis snake venom (BiLAO), which was purified using HPLC and sequence grade. We also evaluated the renal effects induced by BiLAO. Chromatographic profile of B. insularis whole venom disclosed seven main fractions (I, II, III, IV, V, VI and VII) and the main LAO enzymatic activity was detected in fraction II. The group treated with BiLAO showed a decrease in perfusion pressure (C(120)=110.28+/-3.69; BiLAO(120)=82.2+/-5.6 mmHg*); renal vascular resistance (C(120)=5.48+/-0.53; BiLAO(120)=4.12+/-0.42 mmHg/mL/g/min*), urinary flow (C(120)=0.160+/-0.020; BiLAO(120)=0.064+/-0.012 mL/g/min*), glomerular filtration rate (C(120)=0.697+/-0.084; BiLAO(120)=0.176+/-0.017 mL/g/min*), sodium (C(120)=79.76+/-0.56; BiLAO(120)=65.39+/-6.19%*), potassium (C(120)=69.94+/-6.86; BiLAO(120)=60.26+/-2.24%*) and chloride tubular reabsortion (C(120)=78.53+/-2.33; BiLAO(120)=64.58+/-6.68%*). Acute tubular necrosis foci were observed in the group treated with the LAO fraction of the B. insularis snake venom. Some findings have the same morphological aspect of apoptosis, more evident cortically; otherwise, reversible degenerative phenomena represented by hydropic ballooning with extensive cytoplasmic vacuolization and discontinuity of the cell brush borders in the proximal tubular epithelium were observed; furthermore, necrotic detachment of these cells into the tubular lumina, and increased amount of protein deposits in the distal and proximal tubules were observed. In conclusion, the slowness of blood flow and of glomerular filtration resulted in more time for filtration and tubular reabsorption, with elevation of the total percentage of sodium and chlorine reabsorption. The maintenance of the decrease in glomerular filtration rate would determine the subsequent decreases, which were noticed in these parameters. The necrosis observed was the result of damage cell induced by l-amino acid oxidase isolated from B. insularis venom.

Purification and biological effects of C-type lectin isolated from Bothrops insularis venom.

Bothrops insularis is a snake from Queimada Grande Island, which is an island located about 20 miles away from the southeastern coast of Brazil. Compared to other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood. Its C-type lectin is involved in several biological processes including anticoagulant and platelet-modulating activities. We purified the C-type lectin (BiLec) from Bothrops insularis venom and investigated its effect in the isolated kidney. BiLec was purified after two chromatographic steps; firstly, the whole venom was submitted to an HPLC molecular exclusion chromatography followed by a second purification through affinity chromatography. B. insularis lectin (BiLec) was studied as to its effect on the renal function of isolated perfused rat kidneys with the use of six Wistar rats. The concentration of 10mug/mL increased perfusion pressure (PP; control(60)=108.27+/-4.9; BiLec(60)=112.9+/-5.4 mmHg; *p<0.05) and renal vascular resistance (RVR; control(60)=5.38+/-0.51; BiLec(60)=6.01+/-0.57 mmHg; *p<0.05). The urinary flow reduced significantly at 90 and 120 min of perfusion (UF; control(120)=0.160+/-0.020; BiLec(120)=0.082+/-0.008 mL g(-1) min(-1); *p<0.05). Glomerular filtration rate (GFR; control(120)=0.697+/-0.084; BiLec(120)=0.394+/-0.063 mL g(-1) min(-1); *p<0.05) diminished only at 120 min. BiLec did not change the percentage of sodium (TNa(+)), potassium (TK(+)) and chloride tubular transport (TCl(-)). The histological alterations probably reflected direct injury on glomerular and tubular renal cells, as demonstrated by the rise in permeability of glomerular endothelial cells, revealed by the presence of a proteinaceous material in the Bowman space. We postulate that the C-type lectin B. insularis promoted its effects probably through interactions with endothelial cells or through the release of other mediators by tubular, mesangial and endothelial cells.

[Histologic analysis of colonic anastomotic healing, in rats, under the action of 10% Aroeira-do-sertão (Myracrodruon urundeuva fr. all.) enema]. / Análise histológica da cicatrização da anastomose colônica, em ratos, sob ação de enema de Aroeira-do-sertão (Myracrodruon urundeuva fr. all.) a 10%.

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.

[Tensional and morphologic analysis of the colonic anastomosis on 10% acetic acid induced colitis, in Wistar rats, treated with 10% aroeira-do-sertão (Myracrodruon urundeuva fr. all.) aqueous extract]. / Análise tensional e morfológica da anastomose colônica na colite induzida por ácido acético a 10%, em ratos Wistar, tratados com extrato aquoso de aroeira-do-sertão a 10% (Myracrodruon urundeuva fr. all.).

PURPOSE: Verify, from a morphologic and tensional view point, the effect of the 10% aqueous extract of aroeira-do-sertão on the colonic anastomosis, during the occurrence of 10% acetic acid induced colitis, in Wistar rats. METHODS: There were used 48 Wistar rats, distributed in two groups. All animals were subjected to induction of colitis by aqueous solution of 10% acetic acid. Twenty-four hours later, the animals were subjected to laparotomy, transverse total colotomy and end-to-end anastomosis with 5-0 polypropylene. Group A (vehicle), animals treated with carboxymethylcellulose based vehicle. Group B (aroeira), animals treated with 10% aroeira aqueous extract. Both treatments were by means of enema. Groups A and B were distributed in subgroups A3, A7, A14 and A21; B3, B7, B 14 and B21, according to the foreseen euthanasia date (days 3, 7, 14 and 21). On these dates, the animals were relaparotomized, the colonic segment containing the anastomosis was ressected subjected to the pressure test and then to the, histological analysis. For the momphologic study, the slides were dyed with hematoxilin-eosine and the healing status was evaluated based on a score chart that ranked from 0 to 16. The higher the score, the better the healing. RESULTS: On the evaluation of the morphologic study, which quantifies the evolution and degree of healing, as a final result of the healing process, the group aroeira was superior to the group vehicle (p<0.05) on the twenty-first day, showing higher velocity on tissue repair that occurs by regeneration and not by fibrosis. With respect to the tension test, there was a statistically significant difference on day 3, with predominance of the group aroeira over the group vehicle (p<0.05). CONCLUSION: The 10% aroeira-do-sertão aqueous extract, has healing activity on the colonic anstomosis during the occurrence of 10% acetic acid induced colitis. It improves the resistance to tension on the colonic anastomosis zone on the 3rd day.