The effect of Cratylia floribunda lectin on renal hemodynamics and ion transport

As lectinas são descritas como (glico)proteínas que se ligam, especificamente e reversivelmente, a carboidratos. Lectinas de leguminosas isoladas da subtribo Diocleinae (Canavalia, Dioclea eCratylia) são estruturalmente homólogas em relação às suas estruturas primárias. Demonstrou-se que as lectinas de DiocleinaeCanavalia brasiliensis, Dioclea guianensis eCanavalia ensiformis alteram diferentemente parâmetros fisiológicos em rins isolados de ratos. Dessa maneira, o objetivo deste estudo foi investigar o papel da lectina de Cratylia floribunda (CFL) na hemodinâmica renal e no transporte de íons em ratos. Em rins isolados perfundidos, CFL (10 mg/mL, n=5) aumentou a pressão de perfusão renal, a resistência vascular renal e reduziu o percentual do transporte tubular de K+, mas não alterou o fluxo urinário, a taxa de filtração glomerular e o percentual de transporte tubular dos íons sódio e cloreto. No leito mesentérico isolado perfundido, CFL (3 e 10 mg/mL/min, n=4) não alterou o tônus basal ou a contração do tecido induzida por fenilefrina (1 mM/mL/min). Em conclusão, a lectina de sementes de Cratylia floribunda altera parâmetros hemodinâmicos renais, provavelmente de origem tubular, e não por alterações hemodinâmicas.Lectins have been described as glycoproteins that reversibly and specifically bind to carbohydrates. Legume lectins isolated from the subtribe Diocleinae (Canavalia, Dioclea andCratylia) are structurally homologous with respect to their primary structures. The Diocleinae lectins of Canavalia brasiliensis, Dioclea guianensis andCanavalia ensiformis have been shown to distinctly alter physiological parameters in isolated rat kidneys. Thus, the aim of this study was to investigate the effect of Cratylia floribunda lectin (CFL) on renal hemodynamics and ion transport in rats. In isolated perfused kidneys, CFL (10 mg/mL, n=5) increased RPP, RVR and decreased %TK+, but did not change urinary flow, glomerular filtration rate, sodium or chloride tubular transport. In isolated perfused mesenteric bed, CFL (3 and 10 mg/mL/min; n=4) did not alter tissue basal tonus or tissue contraction by phenylephrine (1 mM/mL/min). In conclusion, the seed lectin of Cratylia floribunda increased renal hemodynamic parameters showing a kaliuretic effect. This effect could be of tubular origin, rather than a result from haemodynamic alterations

Effects of a sulfated polysaccharide isolated from the red seaweed Solieria filiformis on models of nociception and inflammation

AbstractThis work reports the effects of a sulfated polysaccharide (SP-Sf), isolated from the seaweed Solieria filiformis and characterized by Fourier transformed infrared (FT-IR), on nociception and inflammation. Male Swiss mice were pretreated with SP-Sf 30min before receiving an injection of 0.8% acetic acid, 1% formalin or 30min prior to a thermal stimulus. We observed that SP-Sf (1, 3 or 9mg/kg) significantly reduced the number of writhes. SP-Sf also reduced the second phase of the formalin test and did not cause a significant antinociceptive effect in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. SP-Sf (1, 3 or 9mg/kg) did not show a significant anti-inflammatory effect in Wistar rats when administrated by the systemic route 1h before testing using carrageenan or dextran. Finally, SP-Sf (9mg/kg) did not show significant signs of toxicity when administrated in mice

Efeitos nefrotoxicos do veneno de Bothrops jararaca e estudo da ação de antagonistas do PAF e da cicloxigenase no rim perfundido de rato

Orientador : Manasses Claudino FontelesTese (doutorado) - Universidade Estadualde Campinas, Faculdade de Ciencias MedicasResumo: Este trabalho objetivou avaliar os efeitos nefrotóxicos do veneno de Bothrops jararaca cuja importância se deve a alta frequência dos acidentes ofídicos,que constituem mn sério problema de saúde pública em nossopaís. Omodeloexperimental utilizado foio sistema de perfusão de rim isolado de rato para evitar a interferência de outros fatores sistêmicos. A análise dos parâmetros funcionais renais foi realizada em perfusões com solução de Krebs-Henseleit modificada, sendo escolhida a concentração de 6g% de albumina, por apresentar melhores parâmetros quando comparados a outras preparações com 2 e 4g%.Os parâmetros estudados foram: pressão de perfusão (PP), resistência vascular renal (RVR),fluxo urinário (FU), ribno de filtração gromerular (RFG), transporte de sódio (TNa+), transporte de potássio (TJ<:f'), clearance de água livre (CH2Ü),transporte proximal de sódio (pTNa+) , transporte distal de sódio(dTNa+). Os grupos controle se mantiveram constantes durante todo o experimento e apresentaram os seguintes parâmetros: PP=149,17:t 4,03 mmHg, RVR-6,38 :t 0,68 'mmHgImrl.g-l.min -I; FU-O,26:t:0,005ml-l.g-l.min -I; Rro-l,13 :t 0,21mr l.g-l.min -I; TNa+-136,13:t 28,681J.Eq.g-l.min 1;%TNa+-78,53:t1,91. Nos grupos tratados pelo veneno lOJ1glml)obselVamos,aos 30 minutos de perfusão, a diminuição acentuada destes parâmetros em decoITênciado efeito nefrotóxico, com os seguintes dados: PP=I00,50 :t 10,81 mmHg.ml-l.g-l.min-l (45%);RVR-3,92 :t 0,47 mmHglml-l.g-l.min -I (31,10%);FU-0,02 :t 0,05 ml-l.gl. min -1 85%),RFG=O,06:!:0,02 rnl-l.g-l.min -1 (90%);TNa+=5,30:!:2,73 JiEq.g'" l.min -1(90%).Os dados estatísticos expressama média e o erro padrão da média. Na tentativa de bloquearestes efeitos tóxicos,utilizamoso BN52021e WEB2086,duas drogas antagonistas do PAF (fator ativador de plaquetas). O BN 52021não apresentou proteção aos efeitos t6xicosdoveneno,exceto o fato de evitar a diminuição de sódio e potássio tissulares, obselV8dacom o uso isolado da peçonha.OWEB 2086além de impedir a diminuiçãodo fluxo urinário e do ribno de filtração glomerular causados pelo veneno, elevou estes parâmetros em relação ao controle, embora a pressão d~ perfusão continuasse baixa. Os outros parâmetros CH~, dTNa+ e %dTNa+ se apresentaram negativos quando comparados ao controle e ao uso isolado do veneno. A outra substância utilizada foi a indometacina que promoveu antagonismototal aos efeitos tóxicos do veneno no fluxo urinârio, ritmo de -vifiltração glomerular, resistência vascular renal e bloqueio parcial da pressão de perfusão. A peçonha produziu diminuição de s6dio e potássio teciduais, sendo estes efeitosbloqueadospeloBN52021, WEB2086e Indometacina. Comesta técnica empregada dispomos de um modelo para o estudo de efeitos tóxicos direto de drogas sobre o rim. Podemos concluir que o veneno de Bothrops jllraraca produz alterações de FU, RFG, RVR, PP, TNa+, TK+ e %TK+, com diminuiçãode sódio e potássio no tecido renal, levando a um quadro compatível à insuficiência renal aguda. No estudo histopatológicodos rins, obselvamos que os grupos controle e tratado comoveneno, apresentaram moderada dilatação e tumefação de túbulos provavelmente decon-ente da técnica utilizada de perfusão com presença de albumina no líquido perfusor. Nos grupos tratados com o veneno detectamos maior intensidade de material proteico nos lúmens tubulares e nos espaços uriníferos dos glomérulos. Outro achado foi a necrose de células tubulares em dois dos rins perfundidoscom o veneno.Abstract: This work evaluates nephrotoxic efTects of the venom of Botluvps jarll/'8ca , a snake responsible formany snake bite accidents in the Northeast or This work evaluates nephrotoxic efTects of the venom of Botluvps jarll/'8ca , a snake responsible formany snake bite accidents in the Northeast or Brazil and thus is an important public health problem in our counhy. The model used was the isolated perfused rat kidney. Weused a modified Krebs-Henseleit solution with added albmnin at 6g% whichproducedmore reliable than albumin concentrations or 2 and 4g%. The parameters studied were: perfusion pressure (PP), renal vascular resistance (RVR), urinary fiow (UF), glomerular filtration rate (GFR), sodium transport (TNa+), potassium transport (TK+), free water clearance (CH20), proximal transport of sodi':ffil(pTNa+)and distal transport of sodium(dTNa+). The results for the control group were: PP=149,17 :I: 4,03 mmHg, RVIt-6,38 :t: 0,68 nUl1Hg/ml-1.g-1.min -1; UFaO,26 :t: 0,005 mt1.g-1.min -I; GFIV=I,13 :I: 0,21 mtl.g-l.min -1; TNa+= 136,13 :I: 28,68 ~Eq.g'"I.min-1; %TNa+a78,53:t:1,91. In the kidneys treated by the venom (lOmg/ml)we observed, at 30 min or perfusion,a markeddecreasein these arameters:PP=100,50:I:10,81mmHg.mt 1.g-1.min-1 (45%); RV1V=3,92t 0,47 mmHglmrl.g-1.min-1(31,10%);UF=0,02:t: 0,05 mr1.g-1.min -1 (85%),GF1t-0,06t 0,02 mr1.g-1.min -1 (90%);TNa+.5,30 t 2,73 ~Eq.g'"I.min-1 (90%). In an attempt to block these toxicefTectswehave used BN52021andWEB 2086,two drugs which are platelet activating faetor (PAF) antagunists. BN 52021 did not proteet against the toxic efTectsor the venom, except in block.ingthe decrease in sodimn and potassium in the tissues. WEB2086blocked the urinaIJ' fiow and GFR changes by the venom and even elevated these parameters in relation to the controls. The perfusionpressure was not reversed. CH20, dTNa+ and %dTNa+ alI presented negative values when compared to controls. We also found that indomethacin antagonized the toxic efTectsof the venom foundin UF,GFR,RVR,and partially blocked PP. The venom also produced a decn:ase in tissue Na+ and K+,which in tum blockedbyBN52021,WEB2086and indometbacin. Histopathological study revealed that in both groups, treated and untreated by the venom, there was a tubular dilatation and tumefaction. These efTeetscould be the result of the perfusion itself. However,in the groups treated -with the venom we fOWldgreater amoWlts of protein inside the tubules and in the glomendar spaces. We also fOWlda tubular necrosis in two kidneys. With this technique we now have a model to study nephrotoxic drugs. We conclude that the venom produces significant alterations of UF, GFR, RVR, PP, TNa+, %TNa+ and %TK+,with a decrease in levels of tissue Na+ and K+. Brazil and thus is an important public health problem in our counhy. The model used was the isolated perfused rat kidney. Weused a modified Krebs-Henseleit solution with added albmnin at 6g% whichproducedmore reliable than albumin concentrations or 2 and 4g%. The parameters studied were: perfusion pressure (PP), renal vascular resistance (RVR), urinary fiow (UF), glomerular filtration rate (GFR), sodium transport (TNa+), potassium transport (TK+), free water clearance (CH20), proximal transport of sodi':ffil(pTNa+)and distal transport of sodium(dTNa+). The results for the control group were: PP=149,17 :I: 4,03 mmHg, RVIt-6,38 :t: 0,68 nUl1Hg/ml-1.g-1.min -1; UFaO,26 :t: 0,005 mt1.g-1.min -I; GFIV=I,13 :I: 0,21 mtl.g-l.min -1; TNa+= 136,13 :I: 28,68 ~Eq.g'"I.min-1; %TNa+a78,53:t:1,91. In the kidneys treated by the venom (lOmg/ml)we observed, at 30 min or perfusion,a markeddecreasein these arameters:PP=100,50:I:10,81mmHg.mt 1.g-1.min-1 (45%); RV1V=3,92t 0,47 mmHglmrl.g-1.min-1(31,10%);UF=0,02:t: 0,05 mr1.g-1.min -1 (85%),GF1t-0,06t 0,02 mr1.g-1.min -1 (90%);TNa+.5,30 t 2,73 ~Eq.g'"I.min-1 (90%). In an attempt to block these toxicefTectswehave used BN52021andWEB 2086,two drugs which are platelet activating faetor (PAF) antagunists. BN 52021 did not proteet against the toxic efTectsor the venom, except in block.ingthe decrease in sodimn and potassium in the tissues. WEB2086blocked the urinaIJ' fiow and GFR changes by the venom and even elevated these parameters in relation to the controls. The perfusionpressure was not reversed. CH20, dTNa+ and %dTNa+ alI presented negative values when compared to controls. We also found that indomethacin antagonized the toxic efTectsof the venom foundin UF,GFR,RVR,and partially blocked PP. The venom also produced a decn:ase in tissue Na+ and K+,which in tum wasblockedbyBN52021,WEB2086and indometbacin. Histopathological study revealed that in both groups, treated and untreated by the venom, there was a tubular dilatation and tumefaction. These efTeetscould be the result of the perfusion itself. However,in the groups treated -viiiwith the venom we fOWldgreater amoWlts of protein inside the tubules and in the glomendar spaces. We also fOWlda tubular necrosis in two kidneys. With this technique we now have a model to study nephrotoxic drugs. We conclude that the venom produces significant alterations of UF, GFR, RVR, PP, TNa+, %TNa+ and %TK+,with a decrease in levels of tissue Na+ and K+.DoutoradoDoutor em Medicin

Epidemiologia dos acidentes por serpentes peçonhentas no Estado do Ceará - Brasil

Foram notificados à Secretaria de Saúde do Estado do Ceará, no período de 1992 a 1995, 688 acidentes causados por serpentes peçonhentas (média anual de 172 casos), com coeficiente de incidência variando entre 0,9 e 5,8 por 100.000 habitantes. Dentre 473 casos em que houve referência ao gênero da serpente 88,3% foram por Bothrops, 10,6% por Crotalus, 0,8% por Micrurus e 0,2% por Lachesis. Os meses de abril a setembro apresentaram maior incidência. Houve predominância de pacientes do sexo masculino (75,6%) e com idades entre 10 a 49 anos (72,3%). As regiões anatômicas mais freqüentemente picadas foram os membros inferiores (81,9%) e superiores (14,7%). O atendimento na unidade de saúde que notificou o acidente ocorreu dentro de seis horas em 66,9% dos casos. A letalidade foi de 0,7%. Os acidentados foram sobretudo agricultores (62,7%), a maioria dos casos ocorreu no próprio local de trabalho. Os autores reforçam que os acidentes ofídicos no Estado do Ceará podem ser considerados acidentes de trabalho, acometem principalmente os trabalhadores rurais e constituem causa de óbito

Renal and cardiovascular effects of Bothrops marajoensis venom and phospholipase A(2)

Bothrops marajoensis is found in the savannah of Marajo Island in the State of Par S and regions of Amapa State, Brazil. The aim of the work was to study the renal and cardiovascular effects of the B. marajoensis venom and phospholipase A(2) (PLA(2)). The venom was fractionated by Protein Pack 5PW. N-terminal amino acid sequencing of sPLA(2) showed amino acid identity with other lysine K49sPLA(2)s of snake venom. B. marajoensis venom (30 mu g/mL) decreased the perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and sodium tubular transport. PLA(2) did not change the renal parameters. The perfusion pressure of the mesenteric bed did not change after infusion of venom. In isolated heart, the venom decreased the force of contraction and increased PP but did not change coronary flow. In the arterial pressure, the venom and PLA(2) decreased mean arterial pressure and cardiac frequency. The presence of atrial flutter and late hyperpolarisation reversed, indicating QRS complex arrhythmia and dysfunction in atrial conduction. In conclusion, B. marajoensis venom and PLA(2) induce hypotension and bradycardia while simultaneously blocking electrical conduction in the heart. Moreover, the decrease in glomerular filtration rate, urinary flow and electrolyte transport demonstrates physiological changes to the renal system. (C) 2009 Elsevier Ltd. All rights reserved

Antiophidic Solanidane Steroidal Alkaloids from Solanum campaniforme

Three new solanidane alkaloids bearing a 22,23-epoxy ring (1-3) and four known compounds were isolated from leaves of Solanum campaniforme. The structures were determined using spectroscopic techniques, including ID and 2D NMR, and HRESIMS experiments. The antiophidic activity of the alkaloids was tested against Bothrops pauloensis venom. Compounds 1-3 completely inhibited myotoxicity without inhibiting phospholipase A(2) activity of the venom, while hemorrhage and skin necrosis were significantly reduced in the presence of alkaloids 1 and 2.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Diagnóstico e tratamento da tuberculose latente em pacientes com doenças inflamatórias crônicas e uso de imunobiológicos inibidores do TNF-&#945; Diagnosis and treatment of latent tuberculosis in patients with chronic inflammatory diseases: use of TNF-alpha-targeting biological products

OBJETIVO: Traçar o perfil clínico-epidemiológico de pacientes candidatos ao uso de fármacos anti-TNF-&#945; diagnosticados como portadores de tuberculose latente (TBL) e avaliar os desfechos do tratamento profilático com isoniazida. MÉTODOS: Análise descritiva prospectiva seguida de um estudo analítico observacional transversal dos desfechos do tratamento profilático em um grupo de 45 candidatos ao uso de fármacos anti-TNF-&#945;. A avaliação dos pacientes constou de anamnese, exame clínico, radiografia de tórax e teste tuberculínico (TT) por Mantoux. RESULTADOS: A idade média dos pacientes foi 45 anos, e 56,0% dos pacientes eram mulheres. Doenças reumatológicas crônicas, doenças dermatológicas crônicas e doença de Crohn estavam presentes em 46,7%, 40,0% e 13,3% dos pacientes, respectivamente. A média de enduração do TT foi 14,6 mm (variação: 5-30 mm). A maioria dos pacientes (n = 30; 66,7%) apresentou enduração > 10 mm. Dos 16 pacientes com cicatriz vacinal BCG, a média de enduração foi de 15,7 mm, sendo que 14 tiveram enduração > 10 mm. Os resultados de radiografia de tórax foram considerados normais e com alterações mínimas em 64,4% e em 35,6%, respectivamente. Apenas 1 paciente (2,2%) abandonou o tratamento com isoniazida, 41 (91,2%) completaram o tratamento, 2 (4,4%) tiveram de interromper o tratamento por hepatite medicamentosa, e 1 (2,2%) foi transferido para outro hospital. Dos que completaram o tratamento, 5 apresentaram efeitos colaterais leves. CONCLUSÕES: A determinação do perfil dos candidatos ao uso de inibidores do TNF-&#945; é importante para o manejo do tratamento da TBL, bem como para estabelecer protocolos clínicos de uso e acompanhamento do uso desses fármacosOBJECTIVE: To determine the clinical and epidemiological profile of patients who are candidates for TNF-&#945; inhibitor use and are classified as having latent tuberculosis (LTB), as well as to evaluate the outcomes of prophylactic treatment with isoniazid. METHODS: A prospective descriptive analysis followed by an analytical, observational, cross-sectional study of the outcomes of prophylactic treatment in a group of 45 candidates for TNF-&#945; inhibitor use. We evaluated the patients through anamnesis, clinical examination, chest X-ray, and tuberculin skin test (TST) using the Mantoux method. RESULTS: The mean age was 45 years, and 56.0% of the patients were female. Chronic rheumatic diseases, chronic dermatological diseases, and Crohn's disease were present in 46.7%, 40.0%, and 13.3% of the patients, respectively. The mean TST induration was 14.6 mm (range: 5-30 mm). The majority (n = 30) of the 45 patients (66.7%) had an induration > 10 mm. In the 16 patients with BCG vaccination scars, the mean induration was 15.7 mm, and 14 of those patients had an induration > 10 mm. Chest X-ray results were considered normal, with minimal alterations, in 64.4% and 35.6% of the patients, respectively. The treatment with isoniazid was abandoned by 1 patient (2.2%) and completed by 41 (91.2%), whereas it was interrupted because of drug-induced hepatitis in 2 (4.4%), and 1 patient (2.2%) was transferred to another hospital. Of those who completed the treatment, 5 experienced mild side effects. CONCLUSIONS: Determining the profile of candidates for TNF-&#945; inhibitor use is important for the management of LTB treatment and for the establishment of clinical protocols for the use and monitoring of the use of these medication

K-ATP(+) Channels-Independent Analgesic Action of Crotalus durissus cumanensis venom

The effect was investigated of the K+ channel blocker, glibenclamide, on the ability of Crotalus durissus cumanensis venom (CDCM) to promote peripheral antinociception. This was measured by formalin-induced nociception in male Swiss mice. CDCM (200 and 300 mu g/kg) produced an antinociceptive effect during phase 2 in the formalin test. The effect of CDCM (200 mu g/kg) was unaffected by the ATP-sensitive K+ channel blocker glibenclamide (2 mg/kg). These results suggest that CDCM is effective against acute pain. However, the ATP-sensitive K+ channels pathway is not contributable to the antinoeiceptive mechanism of CDCM