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Braz. j. med. biol. res ; 53(1): e8389, Jan. 2020. tab, graf
Article in English | LILACS | ID: biblio-1055479


Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

Animals , Male , Rats , Chlorophyll/analogs & derivatives , Photosensitizing Agents/administration & dosage , Oxidative Stress/drug effects , Diabetes Mellitus, Experimental/drug therapy , Glycolysis/drug effects , Liver/physiopathology , Photochemotherapy , Chlorophyll/administration & dosage , Rats, Wistar , Oxidative Stress/physiology , Diabetes Mellitus, Experimental/pathology , Drug Therapy, Combination , Energy Metabolism/drug effects , Glycolysis/physiology , Liver/pathology
Mem. Inst. Oswaldo Cruz ; 115: e190364, 2020. tab, graf
Article in English | LILACS | ID: biblio-1091242


Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.

Animals , Male , Female , Adult , Aspartate Aminotransferases/blood , Protein C/analysis , Factor VIIa/analysis , Chagas Disease/physiopathology , Alanine Transaminase/blood , Liver/physiopathology , Brazil/epidemiology , Biomarkers/blood , Case-Control Studies , Acute Disease , Prospective Studies , Chagas Disease/enzymology , Chagas Disease/blood , Chagas Disease/transmission , Parasite Load , Liver/enzymology , Middle Aged
Rev. Col. Bras. Cir ; 46(1): e2039, 2019. tab, graf
Article in Portuguese | LILACS | ID: biblio-1003080


RESUMO Evitar mortes na fila de espera por um órgão não é mais o único foco de atenção das equipes de transplantação. As pesquisas e cuidados na prática clínica têm sido cada vez mais voltados para o funcionamento do enxerto pós-implante. O objetivo desse estudo foi identificar a nomenclatura utilizada na literatura para disfunção e não função de um enxerto hepático, bem como, investigar as incidências e fatores de risco. Trata-se de uma revisão integrativa da literatura de publicações na íntegra em português, inglês e espanhol, entre 2012 e 2016, nas bases: CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE e Web of Science. Foram selecionados 14 estudos em que se identificou incidências variando entre 7% e 27% e a nomenclatura utilizada para descrever o evento foi mau funcionamento inicial, hipofunção do enxerto, função marginal ou retardo na função. Foram encontradas incidências de não função primária do enxerto hepático entre 1,4% e 8,4% dos pacientes e a nomenclatura usada para descrever o evento foi disfunção precoce ou perda do enxerto. Os fatores de risco encontrados são relacionados às variáveis do doador, receptor, enxerto e logística do transplante. Conclui-se que o conhecimento das diferentes nomenclaturas empregadas na literatura, das incidências da disfunção e não função primária e seus fatores de risco são fundamentais para qualificar as intervenções de controle dos eventos na perspectiva de melhorar a sobrevida do paciente pós-transplante hepático.

ABSTRACT Avoiding deaths in the waiting list for an organ is no longer the only focus of the transplant teams attention. Research and care in clinical practice has been increasingly focused on post transplant graft survival and functioning. In the present work, we performed an integrative literature review to identify the terminology used about liver graft dysfunction and non-function, as well as to investigate the incidence and risk factors of these clinical events. We chosen articles written in Portuguese, English and Spanish between 2012 and 2016, based on CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE and Web of Science. We selected 14 studies, in which we identified the incidence of hepatic graft dysfunction ranging from 7% to 27%. The terminology used to describe this clinical event was initial malfunction, graft hypofunction, marginal function or delay in function. The primary non-function of the liver graft was found in 1.4% to 8.4% of the patients, and the terminology used to describe the event was early dysfunction or graft loss. The risk factors found are related to donor, recipient, graft and transplant logistics variables. We conclude that knowledge of the different terminologies employed in the literature, related to dysfunction and primary non- function incidence, and of their risk factors are fundamental to qualify the control of the events, aiming to improve patients' survival after liver transplantation.

Humans , Liver Transplantation/adverse effects , Primary Graft Dysfunction/etiology , Tissue Donors , Risk Factors , Liver Transplantation/methods , Risk Assessment , Primary Graft Dysfunction/physiopathology , Transplant Recipients , Liver/physiopathology
Mem. Inst. Oswaldo Cruz ; 114: e190062, 2019. tab, graf
Article in English | LILACS | ID: biblio-1012673


BACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.

Humans , Fibrosis/diagnosis , Typhus, Endemic Flea-Borne/transmission , Liver/physiopathology , Receptors, Cannabinoid
Acta cir. bras ; 33(10): 924-934, Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-973470


Abstract Purpose: To develop a new 24 hour extended liver ischemia and reperfusion (LIR) model analyzing the late biochemical and histopathological results of the isolated and combined application of recognized hepatoprotective mechanisms. In addition, we used a new stratification with zoning to classify the histological lesion. Methods: A modified animal model of severe hepatic damage produced through 90 minutes of segmental ischemia (70% of the organ) and posterior observation for 24 hours of reperfusion, submitted to ischemic preconditioning (IPC) and topical hypothermia (TH) at 26ºC, in isolation or in combination, during the procedure. Data from intraoperative biometric parameters, besides of late biochemical markers and histopathological findings, both at 24 hours evolution time, were compared with control (C) and normothermic ischemia (NI) groups. Results: All groups were homogeneous with respect to intraoperative physiological parameters. There were no losses once the model was stablished. Animals subjected to NI and IPC had worse biochemical (gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, direct bilirubin, and total bilirubin) and histopathological scores (modified Suzuki score) compared to those of control groups and groups with isolated or associated TH (p < 0.05). Conclusion: The new extended model demonstrates liver ischemia and reperfusion at 24 hour of evolution and, in this extreme scenario, only the groups subjected to topical hypothermia, combined with ischemic preconditioning or alone, had better outcomes than those subjected to only ischemic preconditioning and normothermic ischemia, reaching similar biochemical and histopathological scores to those of the control group.

Animals , Male , Rats , Reperfusion Injury/pathology , Ischemic Preconditioning , Ischemia/pathology , Time Factors , Reperfusion Injury/etiology , Rats, Wistar , Disease Models, Animal , Hypothermia, Induced , Ischemia/etiology , Liver/physiopathology , Liver/blood supply , Liver/pathology
Braz. j. med. biol. res ; 51(5): e7057, 2018. tab, graf
Article in English | LILACS | ID: biblio-889076


The aim of this study was to investigate the effect of lactatemia elevation and glycemia reduction on strenuous swimming performance in fasted rats. Three rats were placed in a swimming tank at the same time. The first rat was removed immediately (control group) and the remaining ones were submitted to a strenuous swimming session. After the second rat was exhausted (Exh group), the third one was immediately removed from the water (Exe group). According to the period of time required for exhaustion, the rats were divided into four groups: low performance (3-7 min), low-intermediary performance (8-12 min), high-intermediary performance (13-17 min), and high performance (18-22 min). All rats were removed from the swimming tanks and immediately killed by decapitation for blood collection or anesthetized for liver perfusion experiments. Blood glucose, lactate, and pyruvate concentrations, blood lactate/pyruvate ratio, and liver lactate uptake and its conversion to glucose were evaluated. Exhaustion in low and low-intermediary performance were better associated with higher lactate/pyruvate ratio. On the other hand, exhaustion in high-intermediary and high performance was better associated with hypoglycemia. Lactate uptake and glucose production from lactate in livers from the Exe and Exh groups were maintained. We concluded that there is a time sequence in the participation of lactate/pyruvate ratio and hypoglycemia in performance during an acute strenuous swimming section in fasted rats. The liver had an important participation in preventing hyperlactatemia and hypoglycemia during swimming through lactate uptake and its conversion to glucose.

Animals , Male , Rats , Hypoglycemia/physiopathology , Lactic Acid/blood , Liver/physiopathology , Pyruvic Acid/blood , Swimming/physiology , Blood Glucose/analysis , Fasting/physiology , Hypoglycemia/blood , Hypoglycemia/metabolism , Perfusion , Physical Conditioning, Animal/physiology , Rats, Wistar , Time Factors
ABC., imagem cardiovasc ; 30(4): f:119-l:125, out.-dez. 2017. tab, graf
Article in Portuguese | LILACS | ID: biblio-876227


Fundamento: O transplante hepático (TH) é cirurgia de grande porte indicada para tratamento de portadores de cirrose avançada e está associado a diversos riscos. Por esta razão, faz-se necessário estratificar o risco no período pré- transplante através da avaliação da função miocárdica e pesquisa de doença coronariana. Objetivo: Demonstrar a aplicabilidade da ressonância miocárdica cardíaca (RMC) na avaliação morfofuncional cardíaca, bem como seu uso na avaliação da isquemia miocárdica no pré-transplante. Método: Realizou-se estudo retrospectivo e descritivo, sendo avaliados dados de pacientes cirróticos encaminhados ao ambulatório de TH no período de Janeiro/2014 a Julho/2016 que se submeteram a RMC para avaliação cardíaca e como teste provocativo de isquemia miocárdica. Resultados: Foram encaminhados 135 pacientes; destes, 39 realizaram RMC. A idade média foi de 60 anos (50 a 71). Cerca de 87% (n = 34) eram do sexo masculino. Prevaleceu etiologia etanólica 56% (n = 22). A maioria era de pacientes CHILD C, MELD ≥ 18, (n = 26). A RMC evidenciou isquemia miocárdica em 03 pacientes (7,6%). A cineangiocoronariografia foi realizada nestes pacientes e a presença de doença arterial coronariana grave (obstrução > 70%) foi confirmada em todos, com consequente revascularização miocárdica. Em um seguimento de até 2 anos e 7 meses, a sobrevida dos transplantados foi de 87%, sem intercorrências cardiológicas. Conclusões: A realização da RMC na avaliação de cirróticos no pré-transplante mostrou-se estratégia segura ao evidenciar a presença de alterações morfofuncionais da cardiomiopatia do cirrótico e a presença de isquemia miocárdica. Entretanto, novos estudos devem ser realizados para padronização de métodos e critérios para avaliação cardiovascular em cirróticos

Background: Liver transplantation (LT) is a huge surgery performed to treat patients with advanced liver cirrhosis and is associated with several risks. For this reason, is necessary to stratify the risk in the pre-transplantation period through the evaluation of myocardial function and ischemia Objective: To demonstrate the applicability of cardiac magnetic resonance (CMR) in cardiac morphologic and functional evaluation, as well use in the evaluation of myocardial ischemia in pre-transplantation. Methods: Retrospective, descriptive study. Data from patients with cirrhosis referred to the liver transplant outpatient clinic from January 2014 to July 2016 were analyzed they underwent CMR for cardiac evaluation and as provocative test of myocardial ischemia. Results: 135 patients were referred of these, 39 performed CMR. The mean age was 60 (50 to 71). About 87% (n = 34) were males. Alcoholic etiology prevailed 56% (n = 22). Most were of CHILD C patients with MELD ≥ 18, (n = 26). CMR showed myocardial ischemia in 03 patients (7,6%). Coronary angiography was performed and presence of severe coronary artery disease (obstruction > 70%) was confirmed, with consequent myocardial revascularization. At a follow-up of 2 years and 7 months, the survival of transplanted patients was 87%, without cardiologic complications. Conclusions: The realization of CMR in the evaluation of cirrhotic patients in the pre-transplantation proved to be a safe strategy by showing presence of morphologic and functional changes of the cirrhotic cardiomyopathy and the presence of myocardial ischemia. However, more studies should be performed to standardize methods and criteria for cardiovascular evaluation in cirrhotic patients before the liver transplantation

Humans , Male , Female , Middle Aged , Fibrosis/etiology , Liver Transplantation/methods , Magnetic Resonance Spectroscopy/methods , Myocardial Revascularization/methods , Patient Selection/ethics , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Coronary Artery Disease/etiology , Coronary Artery Disease/physiopathology , Diagnostic Imaging/methods , Echocardiography/methods , Heart Ventricles , Liver/physiopathology , Myocardial Ischemia/complications , Myocardial Ischemia/diagnosis , Retrospective Studies , Risk Factors
Braz. J. Vet. Res. Anim. Sci. (Online) ; 54(2): 101-108, 2017. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-875071


Jatropha has been highlighted as an oleaginous potential for the production of biofuel. The cake, produced by oil extraction, could be used in animal feed. However, some varieties of jatropha are toxic by limiting their incorporation into animal diets. The objective of this study was to evaluate the hepatotoxicity of diets added with jatropha cake ­ JC (Jatropha curcas) in rats. Thirty-five (35) male Wistar adults rats (Rattus norvegicus) with initial weight of 352.1 ± 26.8 g were used. The animals were fed for 21 days with the diets: control, 10, 25, 40 and 50% JC. In the feeding with 50% JC the animals presented themselves prostrate and with piloerection. Development and survival decreased, since the inclusion of JC in diets increased. In rats submitted to 10 and 25% JC there was an increase of 17.52% in the hepatosomatic index in relation to the control group. Increase of JC in the rat diet promoted an increase in the activity of ALT and AST enzymes. Anatomic-histopathological evaluation demonstrated that, regardless of the levels tested, JC in rat diet causes hypertrophy of the hepatocytes, with a reduction in energy reserves. This study demonstrated that the use of JC resulted in decreased food intake, associated with weight loss due to the clinical pattern of toxicity, demonstrated by biochemical and histopathological changes in the liver. It was concluded that the inclusion of jatropha cake in rat feeding presents high hepatotoxic potential leading to lesions in the liver parenchyma.(AU)

O pinhão-manso tem se destacado como oleaginosa potencial para a produção de biocombustível. A torta, coproduto da extração do óleo, poderia ser utilizada na alimentação animal. No entanto, algumas variedades de pinhão-manso são tóxicas, limitando sua incorporação em dietas animais. Objetivou-se neste estudo avaliar a hepatotoxicidade de dietas acrescidas de torta de pinhão-manso (Jatropha curcas) em ratos. Foram utilizados trinta e cinco (35) ratos Wistar (Rattus norvergicus) machos adultos com peso inicial de 352,1 ± 26,8 g. Os animais foram alimentados por 21 dias com as dietas: controle, 10, 25, 40 e 50% TPM. Na alimentação com 50% TPM os animais apresentaram-se prostrados e com piloereção. O desenvolvimento e a sobrevivência apresentaram diminuição conforme o aumento da inclusão de TPM nas dietas. Em ratos submetidos a 10 e 25% TPM houve aumento de 17,52% no índice hepatossomático em relação ao grupo controle. O aumento de TPM na dieta de ratos promoveu aumento da atividade das enzimas ALT e AST. A avaliação anatomo-histopatológica revelou que, independentemente dos níveis testados, a TPM na alimentação de ratos provoca hipertrofia dos hepatócitos, com redução das reservas energéticas. Este estudo demonstrou que a utilização de TPM resultou em diminuição do consumo de alimento associado à perda de peso devido ao quadro clínico de toxicidade demonstrado pelas alterações bioquímica e histopatológica no fígado. Conclui-se que a inclusão de torta de pinhão-manso na alimentação de ratos apresenta alto potencial hepatotóxico levando a lesões no parênquima hepático.(AU)

Animals , Rats , Animal Feed/analysis , Animal Feed/toxicity , Jatropha/toxicity , Liver/physiopathology , Rats, Wistar , Hepatocytes , Plant Poisoning/veterinary
Pesqui. vet. bras ; 36(8): 687-693, Aug. 2016. graf, ilus
Article in Portuguese | LILACS, VETINDEX | ID: lil-798004


A espiroquetose aviária é uma enfermidade septicêmica de curso agudo, cosmopolita, que acomete diversas espécies aviárias, causada por Borrelia anserina e transmitida pelo carrapato Argas miniatus. O experimento teve como objetivos avaliar as alterações bioquímicas e anátomo-histopatológicas no fígado de Gallus gallus, causadas pela infecção experimental por B. anserina. Quarenta aves da espécie G. gallus foram divididas em quatro grupos inteiramente casualizados com 10 animais cada: G1 - inoculado com soro infectado com B. anserina; G2 - inoculado com soro fisiológico a 0,9%; G3 - exposto a ninfas de terceiro ínstar de A. miniatus infectados por B. anserina; G4 - exposto a ninfas de terceiro ínstar de A. miniatus livres de B. anserina. As aves dos Grupos 1 e 3 manifestaram no 3º e 6º dias pós-inoculação (DPI) respectivamente, sintomatologia característica da doença como inapetência, perda de peso, sonolência, diarreia esverdeada, mucosas hipocoradas, penas arrepiadas e hipertermia. Os níveis de ALT do Grupo 1 mostraram-se significativamente mais elevados apenas no 12ºDPI e 24ºDPI em relação ao seu grupo controle (Grupo 2) e no Grupo 3 esses níveis se mantiveram elevados até o 20º DPI em comparação ao seu grupo controle (Grupo 4). Os níveis da enzima AST pouco oscilaram nos grupos experimentais, embora tenham sido encontradas elevações no 12ºDPI nos Grupos 1 e 3. Os fígados das aves dos Grupos 1 e 3 apresentaram à necropsia, moderada hepatomegalia, congestão, superfície irregular e coloração vermelha a cianótica; constataram-se ainda pequenos pontos esbranquiçados na superfície. A histopatologia do fígado revelou congestão, infiltrados inflamatórios mononucleares, focos de necrose fibrinoide, dilatação dos sinusoides e vacuolização de hepatócitos. A coloração de Warthin-Starry revelou, nos fígados das aves dos Grupos 1 e 3, a presença de espiroquetas compatíveis com B. anserina, frequentemente no interior de vasos sanguíneos.(AU)

Spirochetosis avian is a septicemic disease of acute course and cosmopolitan can affect various avian species, caused by Borrelia anserina and transmitted by Argas miniatus. The experiment aimed to evaluate the biochemical, anatomical and histopathological changes in the liver of Gallus gallus caused by experimental infection with B. anserina. A total of 40 fowls of the species G. gallus were divided into four randomized groups of ten fowls each: G1 - inoculated with serum infected with B. anserina; G2 - inoculated with 0.9% saline; G3 - exposed to nymphs of 3rd instar of A. miniatus infected with B. anserina; G4 - exposed to ticks nymphs of 3rd instar of A. miniatus free of B. anserina. The fowls of Groups 1 and 3 expressed at 3 and 6 days post-inoculation (DAI) respectively , symptoms characteristic of the disease as lack of appetite , weight loss , drowsiness, greenish diarrhea, pale mucous membranes , ruffled feathers and hyperthermia. ALT of group 1 levels were significantly higher only at the 12º and 24º day after inoculation (DAI) compared with its control group (group 2), and in group 3 these levels remained high until the 20º DAI as compared with its control group (group 4). AST enzyme fluctuated little in the experimental groups, although elevations at 12ºDAI has been found in group 1 and 3. The liver of fowls in groups 1 and 3, presented at necropsy moderate hepatomegaly, congestion, irregular surface and red color to cyanotic. If found even small whitish spots on the surface. The histopathology revealed congestion, mononuclear inflammatory infiltrates, fibrinoid necrotic foci, dilatation of sinusoids, and vacuolation of hepatocytes. The Warthin-Starry staining revealed in the liver of fowls in groups 1 and 3 the presence of spirochetes compatible with B. anserina, often within blood vessels.(AU)

Animals , Borrelia Infections/blood , Borrelia Infections/veterinary , Chickens/anatomy & histology , Chickens/physiology , Liver/anatomy & histology , Liver/physiopathology , Biochemical Phenomena , Spirochaetales Infections/veterinary , Tick-Borne Diseases/veterinary
Medicina (B.Aires) ; 76(4): 208-212, Aug. 2016. graf, tab
Article in Spanish | LILACS | ID: biblio-841578


La insuficiencia suprarrenal relativa (ISR) es frecuente en pacientes cirróticos con sepsis grave, asociándose a un pobre pronóstico. Se desconoce su importancia en condiciones de enfermedad estable. El objetivo del trabajo ha sido evaluar la prevalencia de la ISR en una serie de pacientes cirróticos estables y su relación con el deterioro de la función hepática. Se determinó el impacto de la ISR en la supervivencia y se correlacionaron los niveles entre el cortisol basal en plasma y saliva en sujetos controles y cirróticos. Fueron incluidos 47 pacientes ambulatorios y 16 controles. La funcionalidad del eje hipotalámico-pituitario-suprarrenal se valoró mediante la prueba de estimulación con 250 μg de ACTH sintética EV, definiendo la ISR como delta cortisol < 9 μg/dl. Respecto al grado de deterioro de la función hepática, 22 tenían un Child-Pugh ≤ 8 y 25 pacientes = 9. La prevalencia de ISR fue de un 22%, siendo significativamente más elevada en aquellos con mayor deterioro de la función hepática (8/32 vs. 3/13, p < 0.05). Se observó correlación entre el cortisol salival y el plasmático basal (r = 0.6, p < 0.0004). Por último, la supervivencia fue más elevada en los pacientes sin ISR al año (97%) y a los tres años (91%) que aquellos que desarrollaron esta complicación (79 % y 51%, p < 0.05, respectivamente). En resumen, la prevalencia de ISR es elevada en los pacientes con cirrosis estable y se relaciona con un deterioro de la función hepática y una mayor mortalidad.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 μg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh ≤ 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with ≤ 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

Humans , Male , Female , Middle Aged , Adrenal Insufficiency/epidemiology , Liver Cirrhosis/complications , Pituitary-Adrenal System/metabolism , Prognosis , Saliva/chemistry , Hydrocortisone/analysis , Hydrocortisone/blood , Case-Control Studies , Prevalence , Prospective Studies , Adrenal Insufficiency/mortality , Sepsis , Hypothalamo-Hypophyseal System/metabolism , Liver/physiopathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/mortality
Rev. Soc. Cardiol. Estado de Säo Paulo ; 26(3): 195-204, jul.-set. 2016. tab, ilus
Article in Portuguese | LILACS | ID: biblio-832613


O Diabetes mellitus é uma doença com elevada prevalência global, associada à mortalidade cardiovascular e complicações microvasculares, que conferem o caráter crônico a essa patologia. No diabetes tipo II, o processo aterosclerótico tem início antes mesmo do diagnóstico, daí a importância do reconhecimento dos fatores de risco implicados na fisiopatologia da doença vascular nessa população. A dislipidemia no diabético é caracterizada por lipoproteínas ricas em triglicérides, LDL pequenas, densas e muito aterogênicas e HDL-c baixo. As estatinas são os medicamentos de escolha para tratar a dislipidemia e reduzir de forma significativa o risco cardiovascular nesses pacientes. Apesar do controle glicêmico intensivo não reduzir eventos cardiovasculares nos estudos randomizados, alguns hipoglicemiantes apresentam efeito favorável sobre o perfil lipídico, com redução de futuros eventos

Diabetes mellitus is a disease with high global prevalence, associated with cardiovascular mortality and microvascular complications, which give this disease its chronic nature. In type II diabetes, the atherosclerotic process begins even before diagnosis, hence the importance of recognizing the risk factors involved in pathophysiology of vascular disease in this population. Dyslipidemia in the diabetic patient is characterized by triglyceride-rich lipoproteins; small-dense and very atherogenic LDLs and low HDL-c. Statins are the drugs of choice for treating dyslipidemia and significantly reducing the cardiovascular risk in these patients. Although intensive glycemic control did not reduce cardiovascular events in randomized trials, some hypoglycemic drugs have demonstrated a favorable effect on the lipid profile, and may reduce future events

Humans , Insulin Resistance , Diabetes Mellitus/diagnosis , Dyslipidemias/complications , Dyslipidemias/diagnosis , Hypertension/complications , Hypertension/physiopathology , Cardiovascular Diseases/physiopathology , Chronic Disease , Risk Factors , Lipoproteins/analysis , Lipoproteins/blood , Cholesterol, HDL/analysis , Cholesterol, HDL/blood , Cholesterol, LDL/analysis , Cholesterol, LDL/blood , Liver/physiopathology
Article in English | WPRIM | ID: wpr-54512


BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.

Aged , Antiviral Agents/therapeutic use , Bilirubin/blood , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/adverse effects , Female , Gastrointestinal Hemorrhage/etiology , Guanine/analogs & derivatives , Hepatitis B/complications , Humans , Hypoalbuminemia/etiology , Incidence , Liver/physiopathology , Liver Diseases/epidemiology , Liver Neoplasms/therapy , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Treatment Outcome
Femina ; 43(6): 245-249, nov.-dez. 2015.
Article in Portuguese | LILACS | ID: lil-771222


O fígado está entre os múltiplos órgãos que podem ser afetados na pré-eclâmpsia, e a função hepática pode ser gravemente prejudicada na síndrome HELLP. A ultrassonografia com Doppler constitui um método não invasivo que pode ser usado para o estudo da circulação hepática durante a gravidez. Com o objetivo de apresentar as evidências científicas disponíveis sobre as alterações do fluxo hepático na gravidez, foi realizada pesquisa da literatura mundial por meio das bases de dados MEDLINE/PubMed e LILACS. Em estudos de Dopplerfluxometria e Dopplervelocimetria, isoladamente ou associados ao eletrocardiograma e cardiografia por impedância, foram observadas alterações na circulação hepática durante a gravidez complicada por pré?eclâmpsia e síndrome HELLP. Entre os desafios para a pesquisa nesse campo destacamos a necessidade de aperfeiçoamento da técnica de exame, o estabelecimento de curvas de normalidade para as gestantes brasileiras, de indicadores de agravamento da pré?eclâmpsia e a aplicação potencial do método para o estudo da hipertensão crônica na gravidez.(AU)

The liver is among multiple organs that may be affected in pre-eclampsia, and liver function can be impaired in HELLP syndrome. Doppler ultrasonography of the liver provides a noninvasive method to study liver circulation during pregnancy. This paper reviews scientific evidence available in MEDLINE/ Pubmed and LILACS databases. Doppler studies on hepatic blood flow, flow velocities and vascular resistance indices, isolated or combined with Doppler?electrocardiography and impedance cardiography, observed changes in pregnancies complicated by pre?eclampsia and HELLP syndrome. Challenges to this research topic include improvements in Doppler examination techniques, establishment of normal values for Brazilian pregnant women, predictors for severe pre?eclampsia and potential use of hepatic Doppler use in chronic hypertension as well.(AU)

Humans , Female , Pregnancy , Pre-Eclampsia/diagnostic imaging , HELLP Syndrome/prevention & control , HELLP Syndrome/diagnostic imaging , Ultrasonography, Doppler/methods , Portal System/diagnostic imaging , Pregnancy Complications/diagnostic imaging , Databases, Bibliographic , Hypertension, Pregnancy-Induced/prevention & control , Hepatic Artery/diagnostic imaging , Liver/physiopathology , Liver Circulation/physiology
Femina ; 43(5): 225-234, set.-out. 2015. tab
Article in Portuguese | LILACS | ID: lil-771218


A gestação é um período de significativas modificações no organismo materno, que objetivam promover a homeostase do binômio materno-fetal. Sob o ponto de vista hepático, demais das alterações conspícuas à gravidez, deve o obstetra detectar precocemente anomalias envolvendo o fígado, que complicam até 3% das gestações e são responsáveis por elevada mortalidade materna e perinatal. Por outro lado, certas doenças hepáticas têm sua história natural modificada quando ocorrem durante a gestação, demandando cuidados especiais de uma equipe multidisciplinar que envolva o obstetra e o hepatologista. Este artigo revisa as modificações fisiológicas do sistema hepático na gravidez, assim como suas alterações hepáticas mais prevalentes no Brasil. O objetivo é auxiliar e fornecer orientações ao obstetra e guiar o melhor cuidado das pacientes a fim de prevenir e reduzir as complicações hepáticas na gravidez.(AU)

Pregnancy is a period of significant changes in the mother's organism aimed at promoting the mother-fetus homeostasis. From the hepatic standpoint, the obstetrician should detect early the abnormalities attacking the liver, which complicates up to 3% of pregnancies and are responsible for high rates of maternal and perinatal mortality. On the other hand, some liver diseases have their natural evolution changed when they occur during the pregnancy, requiring special care of a multidisciplinary team involving obstetrician and hepatologist specialists. This study presents the physiological changes of the hepatic system during pregnancy, as well as the most prevalent pregnancy hepatic disorders occurring in Brazil. It aims to help the obstetrician and guide the best patient care to prevent and reduce hepatic complications in pregnancy.(AU)

Humans , Female , Pregnancy , Pregnancy Complications/etiology , Liver/physiopathology , Liver Diseases/complications , Liver Diseases/diagnosis , Pre-Eclampsia/etiology , Pregnancy, Abdominal/physiopathology , Cholestasis, Intrahepatic/complications , Databases, Bibliographic , HELLP Syndrome/etiology , Fatty Liver/complications , Hyperemesis Gravidarum/complications
Rev. bras. plantas med ; 17(1): 9-17, Jan-Mar/2015. graf
Article in Portuguese | LILACS | ID: lil-742924


Plectranthus barbatus Andrews (Lamiaceae) é uma planta muita utilizada na medicina popular para o tratamento de doenças gastrointestinais e hepáticas. O objetivo do presente trabalho foi estudar o efeito protetor do extrato aquoso de P. barbatus (EAPB) sobre os danos hepáticos causados pela sobrecarga de ferro provocada pelo ferro-dextran em ratos. O tratamento com ferro-dextran induziu uma redução significativa na concentração de glutationa reduzida nos animais tratados em relação ao grupo controle e o tratamento prévio dos animais com o EAPB protegeu o fígado do efeito provocado pelo ferro neste parâmetro. Com relação à lipoperoxidação, houve aumento significativo na concentração de malondialdeído (MDA) nos animais tratados em relação ao controle, entretanto, quando os animais receberam o tratamento prévio com o EAPB, houve redução significativa na concentração do MDA. A análise histopatológica mostrou que o grupo tratado com ferro-dextran apresentou grânulos de ferro no citoplasma das células de Kupffer com alargamento das mesmas e algumas com os núcleos hipertróficos. O tratamento prévio com EAPB resultou no desaparecimento dos sinais de danos às células de Kupffer sem nenhum núcleo hipertrófico, mas com a presença de grânulos de ferro totalmente fagocitados, o que demonstra uma aparência morfológica normal. Portanto, o EAPB pode ser útil na prevenção de danos hepáticos induzidos por sobrecarga de ferro.

The Plectranthus barbatus Andrews (Lamiaceae) is a plant largely used in folk medicine to treat gastrointestinal and liver diseases. The objective of this work was to study the protective effect of the aqueous extract of P. barbatus (EAPB) against damage caused by iron overload induced by iron dextran in rat liver. Treatment with iron-dextran induced a significant reduction in the glutathione levels in treated animals compared to control group, and the pretreatment of animals with EAPB protected the liver from the effects caused by iron in this parameter. With respect to lipid peroxidation, a significant increase in the malondialdehyde (MDA) levels in treated animals compared to control was observed; however, when the animals were pretreated with EAPB, there was a significant reduction in the MDA levels. Histopathological analysis showed that the group treated with iron-dextran showed iron granules in the cytoplasm of the Kupffer cells and some of them presented enlarged nuclei. The group previously treated with EAPB showed the disappearance of the signs of damage to the Kupffer cells with no nucleus hypertrophy but with the presence of iron granules completely phagocytosed by these cells, which showed a normal morphological appearance. Therefore, the EAPB may be useful in the prevention of liver damage induced by iron overload.

Animals , Male , Rats , Oxidative Stress/physiology , Plectranthus/adverse effects , Toxicity , Gastrointestinal Diseases/classification , Iron/agonists , Liver/physiopathology
Article in English | WPRIM | ID: wpr-183081


Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

Cell Differentiation/physiology , Cell- and Tissue-Based Therapy/adverse effects , Hepatocytes/cytology , Humans , Liver/physiopathology , Liver Diseases/therapy , Liver Function Tests , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cells/cytology
Pakistan Journal of Medical Sciences. 2015; 31 (2): 295-299
in English | IMEMR | ID: emr-168004


This retrospective study investigated abnormal hepatic dysfunction and abdominal computed tomography [CT] findings in scrub typhus. Three hundred forty nine adult patients were diagnosed with scrub typhus. Ninety four underwent abdominal CT. The CT images were reviewed by the attending radiologist. Patient data of history, symptoms, signs, and results of laboratory tests were collected from the electronic medical records. In 349 patients with scrub typhus, elevation of aspartate aminotransferase [78.5%] and alanine aminotransferase [63.0%] were dominant compared to alkaline phosphatase [27.2%] and total bilirubin [16.1%]. Abdominal CT findings of 94 patients were, in descending order of frequency, enlarged lymph node [53.2%], inhomogeneous enhancement of liver [47.9%], splenomegaly [46.8%], ascites [28.7%], low attenuation of periportal areas [27.7%], gallbladder wall thickening [17.0%], and splenic infarct [6.4%]. Also, the level of aspartate aminotransferase tended to be elevated according to the number of CT findings [P= 0.028] We found that abdominal CT manifestations of scrub typhus with elevated aminotransferases were varied and not specific. However, knowledge of these findings may evoke the recognition of scrub typhus by clinicians in endemic areas

Humans , Male , Female , Orientia tsutsugamushi , Tomography, X-Ray Computed , Abdomen , Retrospective Studies , Liver Function Tests , Liver/physiopathology
Rev. Col. Bras. Cir ; 41(2): 112-116, Mar-Apr/2014. tab, graf
Article in English | LILACS | ID: lil-711818


OBJECTIVE: To verify whether the ileal exclusion interferes with liver and kidney functional changes secondary to extrahepatic cholestasis. METHODS: We studied 24 rats, divided into three groups with eight individuals each: Group 1 (control), Group 2 (ligation of the hepatic duct combined with internal biliary drainage), and Group 3 (bile duct ligation combined with internal biliary drainage and exclusion of the terminal ileum). Animals in Group 1 (control) underwent sham laparotomy. The animals of groups 2 and 3 underwent ligation and section of the hepatic duct and were kept in cholestasis for four weeks. Next, they underwent an internal biliary bypass. In Group 3, besides the biliary-enteric bypass, we associated the exclusion of the last ten centimeters of the terminal ileum and carried out an ileocolic anastomosis. After four weeks of monitoring, blood was collected from all animals of the three groups for liver and kidney biochemical evaluation (albumin, ALT, AST, direct and indirect bilirubin, alkaline phosphatase, cGT, creatinine and urea). RESULTS: there were increased values of ALT, AST, direct bilirubin, cGT, creatinine and urea in rats from Group 3 (p < 0.05). CONCLUSION: ileal exclusion worsened liver and kidney functions in the murine model of extrahepatic cholestasis, being disadvantageous as therapeutic procedure for cholestatic disorders. .

OBJETIVO: verificar se a exclusão ileal interfere nas alterações funcionais hepáticas e renais, secundárias à colestase extra-hepática. MÉTODOS: foram estudados 24 ratos, distribuídos em três grupos (n=8): Grupo 1 (controle), Grupo 2 (ligadura do ducto hepático combinada com drenagem biliar interna) e Grupo 3 (ligadura do ducto hepático combinada com drenagem biliar interna e exclusão do íleo terminal). Os animais do Grupo 1 (controle) foram submetidos a laparotomia e laparorrrafia. Os animais dos grupos 2 e 3 foram submetidos a ligadura e secção do ducto hepático e mantidos em colestase por oclusão biliar durante quatro semanas. A seguir, foram submetidos a derivação biliar interna. No Grupo 3, associou-se a exclusão dos últimos dez centímetros do íleo terminal e anastomose ileocólica à derivação biliodigestiva. Após outras quatro semanas de acompanhamento, foi colhido sangue de todos os animais dos três grupos, para avaliação bioquímica do fígado e dos rins (albumina, ALT, AST, bilirrubinas direta e indireta, fosfatase alcalina, cGT, creatinina e ureia). RESULTADOS: houve aumento dos valores de ALT, AST, bilirrubina direta, cGT, creatinina e ureia nos ratos do Grupo 3 (p < 0,05). CONCLUSÃO: no modelo murino de colestase extra-hepática, a exclusão ileal piorou as funções hepáticas e renais, sendo desvantajosa como proposta terapêutica para afecções colestáticas. .

Animals , Rats , Cholestasis, Extrahepatic/physiopathology , Ileum/surgery , Kidney/physiopathology , Liver/physiopathology , Rats, Wistar
Article in English | WPRIM | ID: wpr-141033


High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.

Causality , Comorbidity , Diabetes Complications/diagnosis , Elastic Modulus , Elasticity Imaging Techniques/methods , End Stage Liver Disease/epidemiology , Fatty Liver/epidemiology , Female , Humans , Image Interpretation, Computer-Assisted/methods , Incidence , Liver/physiopathology , Liver Cirrhosis/epidemiology , Male , Middle Aged , Reproducibility of Results , Republic of Korea/epidemiology , Risk Factors , Sensitivity and Specificity