RESUMO
BACKGROUND: Glyphosate is a pesticide considered of low toxicity, but scientific evidences show it can be harmful to health. This study aimed to evaluate the toxicity in mice offspring exposed to glyphosate-based herbicide (GBH) during the intrauterine period. METHODS: Female matrices received glyphosate 0.3 mg/kg daily per oral throughout the gestational period, which was variable between 18 and 22 days. From the 25th until the 28th days post-birth, mice offspring were subjected to behavioral tests, and the prefrontal cortex was processed for immunohistochemical analysis. RESULTS: Two significant behavioral changes were observed: anxiety in the GLIF0.3 group, increase in the behavior burying marbles in the marble-burying test and hyperactivity, expressed by the significant increase of the crossing number in the open field test. The increased microglia, TNF-alpha, and astrocyte expression were also observed in the prefrontal cortex of offspring treated with GLIF0.3. CONCLUSION: Exposure to GBH during mice intrauterine development induces hyperactive and anxious behavior, evidencing neuroinflammation.
Assuntos
Herbicidas , Animais , Camundongos , Feminino , Herbicidas/toxicidade , Doenças Neuroinflamatórias , Glicina/toxicidade , Comportamento Animal , GlifosatoRESUMO
PURPOSE: Antineoplastic treatments, mainly chemotherapy, affect the kidneys, causing toxicity, and can trigger acute and chronic kidney injuries. This study aimed to analyze the prevalence of renal disorders in patients with oncohematological neoplasms receiving antineoplastic treatment. METHODS: This retrospective cohort study included 75 patients with hematological cancer who underwent chemotherapy between 2012 and 2018 in the Hematology Sector of the Walter Cantídeo University Hospital of the Federal University of Ceará. Sociodemographic and clinical data, blood biochemical assessment findings, and glomerular filtration rate (GFR) were analyzed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The data were tabulated; transferred to the Statistical Package for the Social Sciences software, version 20.0; and analyzed using Pearson's chi-square test or Fisher's exact test for categorical variables followed by a multinomial logistic regression model (p < 0.05). RESULTS: The prevalence of renal disorders was 52.4% according to the CKD-EPI equation for GFR events. There was a significant association between the decrease in GFRs and the following variables: female sex (p = 0.002), diagnosis of multiple myeloma (p = 0.008), start of treatment within 40 days (p = 0.005), and the following antineoplastic treatments: cyclophosphamide, vincristine, and prednisone (p = 0.026); irarubicin (p = 0.032); azacytidine, dexamethasone, and cyclophosphamide (p < 0.001); zoledronic acid (p < 0.001); and pamidronate (p = 0.012). CALGB 8811 (p < 0.001) was inversely associated with a reduction in the GFR. CONCLUSIONS: The prevalence of renal disorders was high in patients with oncohematological neoplasms receiving antineoplastic treatment. This requires periodic monitoring of the evaluation of renal function since reductions in GFRs were significantly associated with different treatment protocols used.
Assuntos
Antineoplásicos , Neoplasias Hematológicas , Insuficiência Renal Crônica , Antineoplásicos/efeitos adversos , Creatinina , Ciclofosfamida , Feminino , Taxa de Filtração Glomerular , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Humanos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
FUNDAMENTO: A doença renal crônica representa hoje um grande desafio para a saúde pública no sentido de se obterem conhecimentos para subsidiar intervenções que possam alterar a velocidade de perda da função renal. OBJETIVO: Avaliar a magnitude do déficit da função renal em hipertensos adultos e sua relação com marcadores inflamatórios: proteína C reativa ultrassensível, velocidade de hemossedimentação e relação neutrófilos/linfócitos. MÉTODOS: Estudo transversal envolvendo 1.273 adultos hipertensos, de ambos os sexos, sendo 1.052 com déficit da função renal e 221 sem déficit, diagnosticados pela equação Modification of Diet in the Renal Disease. A razão de chances (OR) e a razão de prevalência (RP) foram utilizadas para determinar a probabilidade de ocorrência de atividade inflamatória na doença renal. RESULTADOS: O déficit de função renal foi diagnosticado em 82,6% dos avaliados, sendo que a maioria da amostra (70,8%) estava inserida no estágio 2 da doença renal crônica. No modelo de regressão permaneceram independentemente associadas ao déficit da função renal a síndrome metabólica (RPajustada = 1,09 [IC95%: 1,04-1,14]), a proteína C reativa ultrassensível (RPajustada = 1,54 [IC95%: 1,40-1,69]) e a velocidade de hemossedimentação (RPajustada = 1,20 [IC95%: 1,12-1,28]). No entanto, considerando os indivíduos classificados no estágio 2 do déficit da função renal, a chance de alteração dos marcadores inflamatórios foram de OR = 10,25 (IC95%: 7,00-15,05) para a proteína C reativa ultrassensível, OR = 8,50 (IC95%: 5.70-12.71) para a relação neutrófilos/linfócitos e OR = 7,18 (IC95%: 4,87-10,61) para a velocidade de hemossedimentação. CONCLUSÃO: Os resultados mostram associação da atividade inflamatória e da síndrome metabólica com o déficit da função renal.
BACKGROUND: Today, chronic kidney diseases represent a great challenge to public health as regards the acquisition of knowledge to support interventions that can slow the progression of renal function loss. OBJECTIVE: To analyze the magnitude of the renal function deficit in hypertensive adult patients and its relationship with the following inflammatory markers: high-sensitivity C reactive protein, erythrocyte sedimentation rate, and neutrophil/lymphocyte ratio. METHODS: Cross-sectional study including 1,273 adult hypertensive patients of both genders, of whom 1,052 had renal function deficit, and 221 had no deficit, as diagnosed by the Modification of Diet in Renal Disease equation. The odds ratio (OR) and the prevalence ratio (PR) were used to determine the probability of the occurrence of inflammatory activity in renal disease. RESULTS: Renal function deficit was diagnosed in 82.6% of the patients assessed, and most of the sample (70.8%) was classified as in stage 2 of chronic kidney disease. In the regression model, metabolic syndrome (PRadjusted = 1.09 [95%CI: 1.04-1.14]), high-sensitivity C reactive protein (PRadjusted = 1.54 [95%CI: 1.40-1.69]) and erythrocyte sedimentation rate (PRadjusted = 1.20 [95%CI: 1.12-1.28]) remained independently associated with the renal function deficit. However, considering the individuals classified as in stage 2 of renal function deficit, the chance of abnormalities in inflammatory markers were OR = 10.25 (95%CI: 7.00-15.05) for high-sensitivity C reactive protein, OR = 8.50 (95%CI: 5.70-12.71) for neutrophil/lymphocyte ratio, and OR = 7.18 (95%CI: 4.87-10.61) for erythrocyte sedimentation rate. CONCLUSION: The results show an association of inflammatory activity and metabolic syndrome with renal function deficit.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão/sangue , Insuficiência Renal Crônica/sangue , Sedimentação Sanguínea , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos Transversais , Taxa de Filtração Glomerular , Hospitais Universitários , Hipertensão/fisiopatologia , Inflamação/sangue , Linfócitos , Síndrome Metabólica/fisiopatologia , Neutrófilos , Fatores de Risco , Insuficiência Renal Crônica/fisiopatologia , Estatísticas não ParamétricasRESUMO
BACKGROUND: Today, chronic kidney diseases represent a great challenge to public health as regards the acquisition of knowledge to support interventions that can slow the progression of renal function loss. OBJECTIVE: To analyze the magnitude of the renal function deficit in hypertensive adult patients and its relationship with the following inflammatory markers: high-sensitivity C reactive protein, erythrocyte sedimentation rate, and neutrophil/lymphocyte ratio. METHODS: Cross-sectional study including 1,273 adult hypertensive patients of both genders, of whom 1,052 had renal function deficit, and 221 had no deficit, as diagnosed by the Modification of Diet in Renal Disease equation. The odds ratio (OR) and the prevalence ratio (PR) were used to determine the probability of the occurrence of inflammatory activity in renal disease. RESULTS: Renal function deficit was diagnosed in 82.6% of the patients assessed, and most of the sample (70.8%) was classified as in stage 2 of chronic kidney disease. In the regression model, metabolic syndrome (PR adjusted = 1.09 [95%CI: 1.04-1.14]), high-sensitivity C reactive protein (PR adjusted = 1.54 [95%CI: 1.40-1.69]) and erythrocyte sedimentation rate (PR adjusted = 1.20 [95%CI: 1.12-1.28]) remained independently associated with the renal function deficit. However, considering the individuals classified as in stage 2 of renal function deficit, the chance of abnormalities in inflammatory markers were OR = 10.25 (95%CI: 7.00-15.05) for high-sensitivity C reactive protein, OR = 8.50 (95%CI: 5.70-12.71) for neutrophil/lymphocyte ratio, and OR = 7.18 (95%CI: 4.87-10.61) for erythrocyte sedimentation rate. CONCLUSION: The results show an association of inflammatory activity and metabolic syndrome with renal function deficit.
Assuntos
Hipertensão/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Hospitais Universitários , Humanos , Hipertensão/fisiopatologia , Inflamação/sangue , Linfócitos , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Neutrófilos , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Estatísticas não ParamétricasRESUMO
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.
Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Túbulos Renais/efeitos dos fármacos , Oxirredutases/toxicidade , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Venenos de Crotalídeos/química , Túbulos Renais/fisiopatologia , Masculino , Dados de Sequência Molecular , Oxirredutases/química , Ratos , Ratos Wistar , Circulação Renal/efeitos dos fármacosRESUMO
The venom of Bothrops insularis snake, known in Brazil as jararaca ilhoa, contains a variety of proteolytic enzymes such as a thrombin-like substance that is responsible for various pharmacological effects. B. insularis venom chromatography profile showed an elution of seven main fractions. The thrombin-like activity was detected in fractions I and III, the latter being subjected to two other chromatographic procedures, so to say DEAE and Hi Trap Benzamidine. The purity degree of this fraction was confirmed by analytical reverse phase HPLC, which displayed only one main fraction confirmed by SDS-PAGE constituting fraction III. About 5 microg of fraction III protein potentiated the secretion of insulin induced by 2.8 mM of glucose in rats isolated pancreatic beta-cells treated; the increase being around 3-fold higher than its respective control. B. insularis lectin (BiLec; 10 microg/mL) was also studied as to its effect on the renal function of isolated perfused rat kidneys with the use of six Wistar rats. BiLec 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, the thrombin-like substance isolated from B. insularis venom induced an increase in insulin secretion, in vitro, and transiently altered vascular, glomerular and tubular parameters in the isolated rat kidney.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Bothrops , Venenos de Crotalídeos/isolamento & purificação , Hemostáticos/isolamento & purificação , Animais , Células Cultivadas , Cloretos/metabolismo , Cromatografia Líquida de Alta Pressão , Venenos de Crotalídeos/química , Venenos de Crotalídeos/farmacologia , Eletroforese em Gel de Poliacrilamida , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Lectinas/farmacologia , Masculino , Perfusão , Ratos , Ratos Wistar , Micção/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosRESUMO
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.
Assuntos
Bothrops , Venenos de Crotalídeos/química , Lectinas Tipo C/isolamento & purificação , Sequência de Aminoácidos , Animais , Rim/irrigação sanguínea , Rim/citologia , Rim/efeitos dos fármacos , Lectinas Tipo C/química , Masculino , Dados de Sequência Molecular , Ratos , Ratos Wistar , Resistência Vascular/efeitos dos fármacosRESUMO
Foram investigados os efeitos do veneno da serpente Bothrops insularis e de suas frações, lectina, L-aminoácido oxidase, trombina símile e fosfolipase A2, no rim isolado e sistema vascular de rato. As frações foram purificadas a partir de uma combinação de procedimentos cromatográficos, usando colunas de HPLC de exclusão molecular, troca iônica, fase reversa e colunas de baixa pressão de afinidade. Foi utilizada a perfusão de rim isolado de rato e a solução de Krebs-Henseleit modificada (Bowman, 1970; Fonteles et al. 1998). Parâmetros selecionados da função renal foram avaliados durante as condições experimentais, com a infusão do veneno e suas frações, aos 60, 90 e 120 minutos. Os primeiros 30 minutos serviram de controle interno. No leito arterial sistêmico de rato (Ferreira, 1965) a pressão arterial foi avaliada por manômetro conectado por cânula à artéria carótida comum, e o veneno injetado na veia jugular. Os registros foram realizados a cada 10 minutos após a administração de doses crescentes do veneno, até a infusão da dose de 300μg, aos 60 minutos. Na Perfusão do leito arterial mesentérico isolado de rato (McGregor, 1965), utilizou-se a solução de Krebs-Henseleit em fluxo constante de 4mL/minuto. A pressão de perfusão foi registrada manometricamente. A avaliação estatística foi determinada por análise de variância (ANOVA) e teste de Bonferroni, com nível de significância menor de 5%. No rim, o grupo tratado com o veneno apresentou redução em todos os parâmetros avaliados, com exceção da absorção de potássio. Com a lectina a pressão de perfusão aumentou inicialmente e caiu em seguida, juntamente com o fluxo urinário e o ritmo de filtração glomerular...
Assuntos
Humanos , Bothrops , Rim , Lectinas , Venenos de SerpentesRESUMO
An autopsied case is reported concerning fulminant sepsis with predominantly pulmonary lesions, caused by Burkholderia pseudomallei, etiologic agent of melioidosis, originating from interior of Ceará State, Northeastern Brazil where there had been no previous cases reported. Autopsy findings and differential diagnosis are discussed.
Assuntos
Burkholderia pseudomallei/isolamento & purificação , Melioidose/patologia , Sepse/microbiologia , Adolescente , Autopsia , Brasil , Evolução Fatal , Feminino , Humanos , Masculino , Sepse/patologiaRESUMO
Relata-se um caso autopsiado de paciente acometida por sepse fulminante com lesões predominantemente pulmonares, causada pela Burkholderia pseudomallei, agente etiológico da melioidose, proveniente de município do interior do Ceará, estado do nordeste do Brasil onde ainda não tinham sido descritos casos da doença. São discutidos os achados da autópsia e os diagnósticos diferenciais.
Assuntos
Adolescente , Feminino , Humanos , Masculino , Burkholderia pseudomallei/isolamento & purificação , Melioidose/patologia , Sepse/microbiologia , Autopsia , Brasil , Evolução Fatal , Sepse/patologiaRESUMO
Starting from a case of cerebral malaria in Ceará, the authors get the attention for that possibility of this occurrence in no-endemic zone, due to the retard of the diagnosis. Besides the serious implications of the disease, uncommon for this determined species, Plasmodium vivax, it is observed the probable existence of mixed infection and the potential dissemination with the presence of the sand fly transmitter.
Assuntos
Malária Cerebral/diagnóstico , Plasmodium vivax , Adulto , Animais , Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Humanos , Malária Cerebral/tratamento farmacológico , Mefloquina/uso terapêutico , Primaquina/uso terapêuticoRESUMO
A partir de um caso de malária cerebral no Ceará observa-se a possibilidade dessa ocorrência em zona näo endêmica, secundária a retardo diagnóstico. Além da gravidade da doença, incomum para a espécie determinada, Plasmodium vivax, verifica-se a possível existência de infecçäo mista e sua potencial disseminaçäo na presença do vetor.