Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3′,4′-OH flavonoids are known inhibitors of phospholipases A2.

Goats reinfected with toxoplasma gondii: loss of viable prolificacy and gross revenue / Cabras reinfectadas com toxoplasma gondii: perdas de prolificidade viável e receita bruta

We determined the reproductive parameters and clinical disorders in pregnant goats infected and reinfected with Toxoplasma gondii, and posteriorly the loss of gross revenue due to congenital toxoplasmosis was estimated. Of the 25 non-pregnant females negative for T. gondii, 20 were orally inoculated (ME 49 strain) and of these, 15 pregnant females chronically infected were orally reinoculated (VEG strain) with T. gondii oocysts. Five groups were formed (n=5): GI, GII and GIII (reinoculations at 40, 80 and 120 days of gestation, respectively), GIV (inoculation) and GV (no inoculation). Clinical and serological exams were performed on days 0 (prior to inoculation), 3, 6 9, 15 and 21 and every 7 days post-inoculation. Exams were also performed on day 3 and every 7 days post-reinoculation. Reproductive management was performed on all females and initiated when the females infected displayed IgG titers IFAT<1,024. From the average prolificacy indexes of each experimental group were estimated: total production of kilograms of live weight (total kg LW) of goats for slaughter, gross revenue and loss of gross revenue in U.S. dollars (US$), designed for a herd of 1,000 matrices. The unviable prolificacy indexes were 0.8 (GI), 1.2 (GII) and 0.2 (GIII). Clinical disorders affected 57.1% (GI), 75.0% (GII) and 16.7% (GIII) of the offspring of goats reinfected with T. gondii. Congenital toxoplasmosis in goats reinfected resulted in the loss of 26.5% of gross revenues, being GI (US$ 10,577.60 or 57.1%) and GII (US$ 12,693.12 or 60%) holders of the highest values and percentages of economic losses. It was found that congenital toxoplasmosis reinfection cause clinical disorders in goats chronically infected with T. gondii and their offspring with birth of unviable animals and loss of gross revenue, at different stages of pregnancy (40, 80 and 120 days of gestation)...

Nós determinamos os parâmetros reprodutivos e distúrbios clínicos em cabras gestantes infectadas e reinfectados com Toxoplasma gondii, e posteriormente, foi estimada a perda de receita bruta devido à toxoplasmose congênita. Das 25 fêmeas não prenhes negativas para T. gondii, 20 foram inoculadas oralmente (cepa ME 49) e, destas, 15 fêmeas gestantes infectadas cronicamente foram reinoculadas (cepa VEG), via oral, com oocistos de T. gondii. Cinco grupos foram formados (n = 5): GI, GII e GIII (reinoculações aos 40, 80 e 120 dias de gestação, respectivamente), GIV (inoculação) e GV (não inoculação). Exames clínicos e sorológicos foram realizados nos dias 0 (antes da inoculação), 3, 6 9, 15 e 21 e a cada sete dias após a inoculação. Os exames também foram realizados nos dias 3 e a cada sete dias de pós-reinoculação. Manejo reprodutivo foi realizado em todas as fêmeas e iniciou-se quando as fêmeas infectadas exibiram títulos de anticorpos IgG<1.024. A partir dos índices médios de prolificidade de cada grupo experimental foram estimados: a produção total de kg de peso vivo (total kg PV) de cabritos para o abate, receita bruta e perda de receita bruta em dólares norte-americanos (US$), projetadas para um rebanho de 1000 matrizes. Os índices de prolificidade inviáveis foram de 0,8 (GI), 1.2 (GII) e 0,2 (GIII). Distúrbios clínicos afetaram 57,1% (GI), 75,0% (GII) e 16,7% (GIII) das crias de cabras reinfectados com T. gondii. A toxoplasmose congênita em crias das cabras reinfectadas com T. gondii resultou na perda de 26,5% da receita bruta, sendo GI (US $ 10,577.60 e 57,1%) e GII (US $ 12,693.12 e 60.0%) os detentores dos mais altos valores e porcentagens de perdas econômicas. Verificou-se que a reinfecção toxoplásmica congênita causa distúrbios clínicos em cabras cronicamente infectadas com T. gondii e sua prole com o nascimento de animais inviáveis e perda de receita bruta, em diferentes fases da gestação (40, 80 e 120 dias de gestação)...

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

Microbiological epidemiological history of meningococcal disease in Rio de Janeiro, Brazil

The main objectives of the present study were to investigate the clinical and laboratory features of meningococcal disease in the city of Rio de Janeiro, Brazil, during the overlap of 2 epidemics in the 1990s. We conducted a study of a series of cases of meningococcal disease admitted in a Meningitis Reference Hospital. All clinical isolates available were analyzed by means of microbiological epidemiological markers. In 1990, Neisseria meningitidis serogroup B:4,7:P1.19,15, 1.7,1 sulfadiazine-resistant of the ET-5 complex emerged causing epidemic disease. Despite mass vaccination campaign (VaMengoc B+C®), the ET-5 clone remained hyperendemic after the epidemic peaked. In 1993 to 1995, an epidemic of serogroup C belonged to the cluster A4 overlapped, with a significant shift in the age distribution toward older age groups and an increase of sepsis. Serogroup C epidemics are a recurrent problem in Rio de Janeiro, which can be hindered with the introduction of a conjugate vaccine. We hope the data presented here brings useful information to discuss vaccines strategies and early management of suspected cases.

Glomerulonefrite lúpica: estudo da evoluçäo a longo prazo / Lupus nephritis: a long term follow-up

OBJETIVO: Estudar a apresentação clínica e a evolução de pacientes portadores de glomerulonefrite lúpica. CASUÍSTICA E MÉTODOS: Foram estudados 37 pacientes portadores de glomerulonefrite lúpica, atendidos pela Disciplina de Nefrologia - Faculdade de Medicina de Botucatu, com seguimento médio de 52,4 + ou - 13,3 meses. Os dados foram obtidos através do levantamento retrospectivo dos prontuários. RESULTADOS: A idade média foi de 26,05 + ou - 11,12 anos, com predomínio do sexo feminino (84 por cento) sendo que a glomerulonefrite classe IV foi a mais freqüente (80 por cento). No início do seguimento a média da creatinina sérica foi de 1,74 + ou - 1,15 mg/dl, e a da proteinúria de 24h foi de 2,62 + ou - 2.89 g. Cinqüenta e um porcento dos pacientes com creatinina sérica elevada apresentaram, durante o seguimento, diminuição desses valores. Dentre diferentes variáveis estudadas, à época da biopsia renal, (idade, sexo, proteinúria, presença de hipertensão arterial e creatinina sérica) a única que se associou com pior prognóstico foi a elevação da creatinina sérica. Remissão da síndrome nefrótica ocorreu em 65 por cento das vezes. A sobrevida atuarial foi de 96 por cento, 82 por cento, 70 por cento e 70 por cento em 1, 5, 10 e 12 anos. Cinco pacientes desenvolveram insuficiência renal crônica terminal e sete morreram, sendo infecção a principal causa de óbito (57 por cento) CONCLUSÃO: Em pacientes com nefropatia lúpica, o aumento da creatinina sérica, à época da biópsia, se associou com o desenvolvimento de insuficiência renal crônica ao fim do seguimento e a principal causa de óbito foi processo infeccioso.

Insuficiência renal aguda: estudo do quadro clínico e prognóstico / Acute renal failure. Clinical statement study and prognosis

A insuficiência renal aguda orgânica (IRAo) é complicaçao freqüente em pacientes hospitalizados, associando-se a altas taxas de mortalidade. OBJETIVO. Analisar os aspectos clínicos e o quadro anatomopatológico de pacientes portadores de IRAo, bem como determinar fatores de prognóstico. MÉTODOS. Foram estudados, de forma prospectiva, 20O pacientes portadores de IRAo internados durante o período de janeiro de 1987 a julho de 1990. RESULTADOS. A freqüência de IRAo foi de 4,9/1.000 internaçoes. As causas mais comuns foram isquemia renal (50 por cento) e drogas nefrotóxicas (22 por cento). O diagnóstico anatomopatológico realizado em 43 pacientes revelou: necrose tubular aguda (53 por cento); degeneraçao) hidrópica tubular (l6 por cento), glomerulopatias (l6 por cento) e outras lesoes (l5 por cento). Tratamento dialítico foi realizado em 50,5 por cento dos pacientes; as principais indicaçoes foram: uremia (l38 vezes, 67 por cento), hipervolemia (45 vezes, 22 por cento), hiperpotassemia (19 vezes, 9 por cento). A taxa de mortalidade foi de 46,5 por cento, sendo as principais causas de óbito: septicemia (38 por cento), insuficiência respiratória (19 por cento) e falência de múltiplos órgaos (11 por cento). Somente dois pacientes (nos quais o tratamento dialítico foi suspenso) morreram por causas ligadas diretamente à insuficiência renal. Houve maior mortalidade entre pacientes oligúricos (62,9 por cento) do que em pacientes nao oligúricos (34,5 por cento) (p<0,05). Pacientes com IRAo isquêmica apresentaram maior mortalidade (56,7 por cento) do que pacientes com IRAo nefrotóxica (14,7 por cento) (p<0,05). Essas diferenças mantiveram-se quando essa comparaçao foi feita apenas entre os pacientes submetidos a tratamento dialítico. CONCLUSAO. As principais causas de óbito nao foram diretamente relacionadas à IRAo. Desta forma, os dados do presente trabalho sugerem que a IRAo é um importante marcador de gravidade de doença de base, e nao um fator determinante do óbito.

Effects of dietary protein, angiotensin I converting enzyme inhibition and mesangial overload on the progression of adriamycin-induced nephropathy

Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. We studied the effects of dietary protein and of an angiotensin I converting enzyme inhibitor on the progression of this nephropathy and the evolution of the histological lesions, as well as mesangial macromolecule flow. Adriamycin nephropathy was induced by injecting a singl iv dose of adriamycin (3 mg/kg body weight) into the tail vein of male wistar rats (weight, 180-200 g). In Experiment I animals with adriamycin-induced nephropathy were fed diets containing 6 percent (Low-Protein Diet Group = LPDG), 20 percent (Normal-Protein Diet Group = NPDG) and 40 percent (High-Protein Diet Group = HPDG) protein and were observed for 30 weeks. In Experiment II the rats with adriamycin nephropathy were divide into 2 groups: ADR, that received adriamycin alone, and ADR-ENA, that received adriamycin plus enalapril, an angiotensin I converting enzyme inhibitor. The animals were sacrificed after a 24-week observation period. Six hours before sacrifice the animals were injected with 131I-ferritin and the amount of 131I-ferritin in the glomeruli was measured. In Experiment III, renal histology was performed 4, 8 and 16 weeks after adriamycin injection. At the end of Experiment I the tubulointerstitial lesion index was 2 for LPDG, 8 for NPDG, and 7.5 for HPDG (P,0.05); the frequency of glomerulosclerosis was 19 + or - 6.1 percent in LPDG, 42.6 + or - 6 percent in NPDG, and 54 + or - 9 percent in HPDG (P,0.05); and proteinuria was 61.1 + or - 25 mg/24 h in LPDG, 218.7 + or - 27.5 mg/24 h in NPDG, and 324.5 + or - 64.8 mg/24 h in HPDG (P,0.05). In Experiment II, at sacrifice, 24-h proteinuria was 189 + or - 16.1 mg in ADR, and 216 + or - 26.1 mg in ADR-ENA (P.0.05); the tubulointerstitial lesion index was 5 for ADR, and 5 for ADR-ENA (P.0.05); the frequency of glomerulosclerosis was 40 + or - 5.2 percent in ADR and 44 + or - 6 percent in ADR-ENA (P.0.05); the amount of 131I-ferritin in the mesangium was 214.26 + or - 22.71 cpm/mg protein in ADR and 253.77 + or - 69.72 cpm/mg protein in ADR-ENA (P.0.05). In Experiment III, sequential histological analysis revealed an acute tubulointerstitial cellular infiltrate at week 4, whigh was decreased at week 8. Tubular casts and dilatation were first seen at week 8 and increased at week 16 when few glomerular lesions were found. The results suggest that the tubulointerstitial lesions may play a role in the development of glomerulosclerosis in adriamycin-induced nephropathy

Reduction of urine volume ameliorates adriamycin-induced nephropathy

1. Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. 2. The effect of urine volume on the progression of adriamycin-induced nephropathy was studied in 70 male Wistar rats (180-200 g) observed for 30 weeks and separated into 4 groups: healthy control group (HCG, N = 10) inoculated i.v. with 1 ml of saline, and nephrotic groups inoculated iv with a single dose of adriamycin of 3 mg/kg body weight. The nephrotic rats were separated into 3 groups (N = 20): nephrotic control group (NCG) receiving only adriamycin; dehydrated nephrotic group (DNG) water deprived for 36 h within each 48-h period, and furosemide nephrotic group (FNG) treated with 12 mg/dl furosemide, and 0.9 g/dl NaCl in the drinking water. 3. The 30-week survival rates of the DNG (100 per cent ) and HCG (100 per cent ) were significantly higher than those of the NCG (85 per cent ) and FNG (55 per cent ). 4. The proteinuria observed in the HCG (range, 7.38 +/- 0.7 to 13.6 +/- 1.27 mg/24 h) was significantly lower than that observed for all the nephrotic groups throughout the experiment. The DNG presented significantly less proteinuria (range, 42.71 +/- 6.83 to 140.10 +/- 19.22 mg/24 h) than the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) from week 10 on. There was no significant difference between the mean 24-h proteinuria of the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) and the FNG (range, 35.82 +/- 7.91 to 221.54 +/- 26.74). 5. The mean frequency of damaged glomeruli was 0.3 per cent +/- 0.3 for HCG, 42 per cent +/- 6 per cent for CNG, 40.8 per cent +/- 8 per cent for DNG, and 47 per cent +/- 14 per cent for FNG. The median value of the tubulointerstitial lesion, evaluated by a semiquantitative method, was 0 in HCG, 10 in CNG, 8.5 in DNG and 9.5 in FNG (P < 0.05 for all groups compared to HCG). 6. The data indicate that reduction of urine volume has a protective effect on adriamycin-induced nephropathy

Características clínicas e implicaçöes prognósticas do acometimento renal no mieloma múltiplo / Clinical characteristics and prognosis implications of renal involvement in multiple myeloma

O envolvimento renal no mieloma múltiplo tem sido associado com pior prognóstico destes pacientes. A influência da insuficiência renal no quadro clínico e no prognóstico de portadores de mieloma múltiplo foi estudada, retrospectivamente, em 45 pacientes. Pacientes com insuficiência renal, à primeira visita, apresentaram maior freqüência de perda de peso, proteinúria e hipercalcemia. Entre os pacientes com insuficiência renal, as médias de uricemia e VHS foram maiores e a média do hematócrito foi menor. Näo houve diferença com relaçäo a edema, hipertensäo arterial, fraturas e dores ósseas. A regressäo da insuficiência renal ocorreu em 47% dos casos, o que se deu mais freqüentemente no primeiro mês de seguimento. A média da creatinina foi mais baixa entre os pacientes com insuficiência renal reversível. A mediana da sobrevida foi: pacientes com insuficiência renal: 11 meses; pacientes com funçäo renal normal: 50 meses. Entre os pacientes com insuficiência renal, aqueles que apresentaram recuperaçäo da funçäo renal mostraram uma mediana de sobrevida maior (24 meses) do que aqueles com insuficiência renal irreversível (1 mês). Em conclusäo: o envolvimento renal no mieloma múltiplo é comum e freqüentemente reversível. Pacientes com insuficiência renal tiveram pior prognóstico; entre os pacientes com insuficiência renal, a normalizaçäo da funçäo renal conferiu melhor prognóstico

The long-term evolution of immune deposits in passive heymann nephritis

To study the long term course of passive Heymann nephritis (PHN), 42 adult male Wistar rats were injected with rabbit anti-FX1A serum (PHN group) and 42 rats received normal rabbit serum (control group). Two animals from each group were sacrificed 2 weeks after the inoculation and 10 animals each from the control and PHN groups were sacrificed 4, 13, 25 and 53 weeks later. The PHN group exhibited a significant elevation in 20-h proteinuria which lasted from the first week (control group, 9.19 ñ 0.87; PHN group, 25.3 ñ 2.66) to the 25th week (control group, 22.6 ñ 2.15; PHN group, 66.7 ñ 10.4) except for week 17. From week 29 to week 53 there was no statistical difference between the 2 groups. Light microscopy showed no difference between the kidneys of PHN and control rats. Immunofluorescence microscopy in PHN rats showed granular deposition of autologous and heterologous IgG on the glomerular basement m,embrane (GBM), whose intensity and pattern did not change during 53 weeks of observation. When examined by electron microscopyy the glomeruli of PHN rats showed; a) electron-dense deposits which were initial subepithelial and homogeneous and later intramembranous, granular and often surrounded by an electron-transparent halo; b) focal thickening of the GBM at the sites of intramembranous deposits; c) effacement of podocytes located close to the deposits; d) "penetration" of the podocytes into the GBM associated with the deposits; e) presence of osmiophilic granules in the cytoplasm of the podocyte located inside the GBM similar to the granules of the deposits next to them. Them. The association of the penetration of the podocytes into the GBM with the deposits and the presence of the osmiophilic granules inside the foot process have not been described previously in PHN

Mesangial overload in experimental membranous nephropathy

The distribution and amount of ferritin in the glomeruli following intravenous injection of radiolabeled ferritin (125I-ferritin) was studied in 25 normal rats with membranous nephropathy. The animals used were male Sprague-Dawley rats weighing 180-200 g at the beginning of the experiment. Membranous nephropathy was induced by repeated iv injections of 1.0 mg cationic bovine serum albumin during 28 days. At the end of the experiment the animals received 125I-ferritin iv and were sacrificed 2,6,12,24 and 36 h later, and the glomeruli were isolated. Mean (ñ SEM) levels of 125I-ferritin in the glomeruli reported as cpm/mg protein in rats injected with cationic bovine serum albumin were: 731.8 ñ 155.6 after 2 h, 946.4 ñ 268.2 after 6 h, 565.4 ñ 143.5 after 12 h, 251.8 ñ 26.5 after 24 h, and 202 ñ 29.1 after 36 h. Mean (ñ SEM) 125I-ferritin in no0rmal rats were: 2 h:256.2 ñ 44.6; 6 h: 214.2 ñ 8.78; 12 h:198.2 ñ 32.2; 24 h: 51.5 ñ 3.57: 36h: 40.6 ñ 5.48 125I-ferritin levels in the glomeruli isolated from rats injected with cationic bovine serum albumin were significantly higher than in control rats at 2, 6, 24 and 36 h. The distribution of ferritin in the glomeruli was studied by a direct immunofluorescence technique. Normal and nephrotic rats showed ferritin in the glomerular mesangium only, with similar pattern and intensity. These data show that rats with membranous glomerulonephritis induced by cationic bovine serumalbumin presented an increased macromolecule uptake by the glomerular mesangium. However, the mechanism underlying this mesangial overloading is still unknown