Investigation of the protective effect of boric acid against hepatotoxic and nephrotoxic injury induced by acrylamide in rats / Investigación del efecto protector del ácido bórico contra lesiones hepatotóxicas y nefrotóxicas inducidas por acrilamida en ratas

SUMMARY: To investigate if the administration of boric acid (BA) would exert any protective effect against possible nephrotoxicity and hepatotoxicity induced by the exposure to acrylamide (ACR) in rats. In our study, we used a total of 28 rats that were divided into four equal groups. Group 1: the control group which was not treated with any procedure. Group 2: the ACR group that was administered ACR 50 mg/kg/day via intraperitoneal (i.p) route for 14 days. Group 3: the BA group that was administered BA 200 mg/kg/ day via gavage via peroral (p.o) route for 14 days. Group 4: the ACR+BA group that was administered BA simultaneously with ACR. Total antioxidant and oxidant (TAS/TOS) capacities were measured in all groups at the end of the experiment. In addition, the specimens obtained were evaluated with histopathological examination. Studies showed that the ACR and ACr+BA groups were not significantly different in terms of hepatic TAS level while the TOS level was higher in the ACR group than the ACR+BA group. The groups did not show any significant difference regarding renal TAS and TOS levels. In the histopathological examination of the hepatic tissue, the histopathological injury score of the ACR group was significantly higher than those of the other groups whereas it was significantly lower in the ACR+BA group than the ACR group. Our study concluded that Boric acid had a protective effect against acrylamide- induced hepatotoxicity, but not against nephrotoxicity.

El objetivo de este estudio fue investigar si la administración de ácido bórico (BA) ejercería algún efecto protector frente a la posible nefrotoxicidad y hepatotoxicidad inducida por la exposición a acrilamida (ACR) en ratas. En nuestro estudio, utilizamos un total de 28 ratas que se dividieron en cuatro grupos iguales. Grupo 1: grupo control que no fue tratado. Grupo 2: grupo ACR al que se le administró ACR 50 mg/kg/día por vía intraperitoneal (i.p) durante 14 días. Grupo 3: grupo BA al que se le administró BA 200 mg/kg/día por sonda por vía peroral (p.o) durante 14 días. Grupo 4: grupo ACR+BA al que se administró BA simultáneamente con ACR. Las capacidades antioxidantes y oxidantes totales (TAS/TOS) se midieron en todos los grupos al final del experimento. Además, los especímenes obtenidos fueron evaluados con examen histopatológico. Los estudios demostraron que los grupos ACR y ACr+BA no fueron significativamente diferentes en términos del nivel hepático de TAS, mientras que el nivel de TOS fue mayor en el grupo ACR que en el grupo ACR+BA. Los grupos no mostraron ninguna diferencia significativa con respecto a los niveles renales de TAS y TOS. En el examen histopatológico del tejido hepático, la puntuación de lesión histopatológica del grupo ACR fue significativamente mayor que la de los otros grupos, mientras que fue significativamente menor en el grupo ACR+BA que en el grupo ACR. Nuestro estudio concluyó que el ácido bórico tiene un efecto protector contra la hepatotoxicidad inducida por acrilamida, pero no contra la nefrotoxicidad.

Effects of interleukin-17A on liver and kidney injury and prognosis in septic mice / 中华危重病急救医学

OBJECTIVE@#To explore the effect of interleukin-17A (IL-17A) on liver and kidney injury and prognosis in septic mice.@*METHODS@#A total of 84 SPF male C57BL/6 mice were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis model group (CLP group), and IL-17A intervention group. IL-17A intervention group were then divided into five subgroups according to the dose of IL-17A (0.25, 0.5, 1, 2, 4 μg). Mice in the IL-17A intervention group were intraperitoneally injected with the corresponding dose of IL-17A 100 μL immediately after surgery. The other groups were intraperitoneally injected with 100 μL phosphate buffer solution (PBS). The survival rate of mice was observed at 7 days, and peripheral blood and liver, kidney and spleen tissues were collected. According to the 7-day survival, another 18 mice were randomly divided into Sham group, CLP group, and 1 μg IL-17A intervention group. Peripheral blood samples were collected at 12 hours and 24 hours after CLP, and the mice were sacrificed to obtain liver, kidney, and spleen tissues. The behavior and abdominal cavity of each group were observed. The levels of peripheral blood liver and kidney function indexes and inflammatory factors were detected. The histopathological changes of liver and kidney were observed under light microscope. The peripheral blood and spleen tissues were inoculated in the medium, the number of bacterial colonies was calculated, and the bacterial migration of each group was evaluated in vitro.@*RESULTS@#Except for the Sham group, the 7-day survival rate of mice in the 1 μg IL-17A intervention group was the highest (75.0%), so this condition was selected as the intervention condition for the subsequent study. Compared with Sham group, the liver and kidney functions of CLP group were significantly damaged at each time point after operation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr) reached the peak at 24 hours after operation, and the liver and kidney pathological scores reached the peak at 7 days after operation, the levels of inflammatory cytokines interleukin (IL-17A, IL-6, IL-10) reached the peak at 12 hours after operation, and tumor necrosis factor-α (TNF-α) reached the peak at 24 hours after operation. In addition, a large number of bacteria proliferated in the peripheral blood and spleen, which reached the peak on day 7. Compared with the CLP group, exogenous administration of 1 μg IL-17A significantly delayed the rising trend of each index in the early stage of sepsis [24-hour ALT (U/L): 166.95±5.20 vs. 271.30±6.11, 24-hour AST (U/L): 599.42±7.25 vs. 1 013.27±3.37, 24-hour BUN (mg/L): 815.4±26.3 vs. 1 191.2±39.4, 24-hour SCr (μmol/L): 29.34±0.87 vs. 60.75±3.83, 7-day liver pathological score: 2.50 (2.00, 3.00) vs. 9.00 (8.50, 9.00), 7-day kidney pathological score: 1.00 (1.00, 2.00) vs. 5.00 (4.50, 5.00), 12-hour IL-17A (ng/L): 105.21±0.31 vs. 111.28±1.37, 12-hour IL-6 (ng/L): 83.22±1.01 vs. 108.88±0.99, 12-hour IL-10 (ng/L): 731.54±3.04 vs. 790.25±2.54, 24-hour TNF-α (μg/L): 454.67±0.66 vs. 576.18±0.76, 7-day peripheral blood colony count (CFU/mL): 600 (400, 600) vs. 4 200 (4 200, 4 300), 7-day spleen tissue colony count (CFU/g): 4 600 (4 400, 4 600) vs. 23 400 (23 200, 23 500), all P < 0.05].@*CONCLUSIONS@#Appropriate dose (1 μg) of exogenous IL-17A can reduce the lethal inflammatory response induced by CLP and improve the ability of bacterial clearance, thereby alleviating liver and kidney injury and improving the 7-day survival rate of septic mice.

Effects of thymoquinone on alpha-amanitin induced hepatotoxicity in human C3A hepatocytes

Abstract Thymoquinone (TQ) has shown hepatoprotective effects in various experimental studies. We aimed to investigate the possible beneficial effects of TQ regarding its prevention of alpha-amanitin induced hepatotoxicity in human C3A hepatocytes. After administering alpha-amanitin in a concentrations of 1 and 10µg/mL on the cells in a hepatocyte cell line, TQ was administered in various concentrations (10, 5, 1, 0.5, 0.1, 0.05, 0.01, 0.005 µg/mL). The MTT test was used to determine cell viability. For the groups given only TQ at various concentrations, the cell viability rates at 48 hours post-administration were found at 82.6, 98.3, 102.1, 102.5, 99.4, 99.4, 101.9 and 106.3%, respectively. For the group with 1μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates were found at 74.6, 88.5, 87.4, 88.7, 85.7, 86.8, 88.4, and 92.9%, respectively. For the group with 10μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates for each TQ subgroup were found at 65.2, 79.2, 81.4, 81.1, 81.8, 81.8, 82.2 and 91.9%, respectively. Our study is the first in vitro study that investigates TQ's effects on alpha-amanitin induced hepatotoxicity. Although TQ had beneficial effect in low doses did not significantly increase cell viability in liver damage due to alpha-amanitin toxicity.

Hamartomatosis biliar múltiple / Multiple biliary hamartomatosis

Introducción: La hamartomatosis biliar múltiple o también llamada enfermedad de los complejos de von Meyenburg fue descrita por este autor en 1955. Tiene un origen disembriogénico con un curso evolutivo benigno y asintomático, con pruebas funcionales hepáticas normales. Por los estudios de imágenes se puede confirmar el diagnóstico, pero igualmente ante un hígado multinodular pueden diagnosticar una hepatopatía crónica sin precisar su etiología, por lo que es imprescindible el diagnóstico histológico con biopsia hepática translaparoscópica dirigida. No se necesita ningún tratamiento específico y su seguimiento es ecográfico semestral o anual. Objetivo: Presentar el valor de la biopsia hepática dirigida por laparoscopia a las lesiones por hamartomatosis biliar múltiple. Desarrollo: Se presenta un paciente de 53 años con antecedentes de ser un bebedor social con frecuencia semanal. Ingresa por fiebre asociada a una sepsis urinaria, en el que aparece un fortuito hallazgo ecográfico de un hígado multinodular, sin precisar un diagnóstico etiológico por otros estudios de imágenes. Esto motivó a realizarle una laparoscopia con toma de biopsia hepática dirigida a las lesiones observadas. Se confirma el diagnóstico histológico de esta entidad. Conclusiones: Se demostró la importancia y vigencia del valor diagnóstico de la laparoscopia, al igual que la biopsia hepática dirigida para lograr el diagnóstico histológico de certeza en esta entidad(AU)

Introduction: Multiple biliary hamartomatosis or von Meyenburg complex disease was described by this author in 1955. Its origin is dysembryogenic with a benign and asymptomatic evolutionary course, with normal liver function tests. Imaging studies can confirm the diagnosis, but likewise, when it is a multinodular liver, chronic liver disease can be diagnosed without specifying its etiology, which is why it is essential a histological diagnosis with a directed overlaparoscopic liver biopsy. No specific treatment is needed and its follow-up is semi-annual or annual ultrasound. Objective: To present the value of laparoscopically directed liver biopsy for multiple biliary hamartomatosis lesions. Case report: A 53-year-old patient with a history of being a social drinker with a weekly frequency is reported. He was admitted for fever associated with urinary sepsis, in which a fortuitous ultrasound finding of a multinodular liver appeared, without requiring an etiological diagnosis by other imaging studies. This led to a laparoscopy with a liver biopsy aimed at the observed lesions. The histological diagnosis of this entity is confirmed. Conclusions: The importance and validity of the diagnostic value of laparoscopy, as well as directed liver biopsy to achieve a certain histological diagnosis in this entity, was demonstrated(AU)

Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease / 中华胃肠外科杂志

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.

Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats

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.

Human acute Chagas disease: changes in factor VII, activated protein C and hepatic enzymes from patients of oral outbreaks in Pará State (Brazilian Amazon)

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.

Effect of dihydroartemisinin supplementation on inflammation and lipid metabolism induced by lipopolysaccharide in liver of weaned piglets / 中国中药杂志

To study the effect of dihydroartemisinin(DHA) on hepatic inflammation and lipid metabolism in weaned piglets, a liver injury model of weaned piglets was established by lipopolysaccharide(LPS)-induced method. In this study, 30 healthy weaned piglets were selected and randomly divided into control group(CON), model group(LPS) and treatment group(LD, LPS+DHA), with 10 in each group. The CON group and the LPS group were fed with a basal diet, and the LD group was fed with a basal diet+80 mg·kg~(-1) DHA. The test period was 21 days. The LPS group and the LD group were intraperitoneally injected with 100 μg·kg~(-1) LPS at 4 hours before slaughter, and the CON group was injected with the same dose of sterile physiological saline. The results showed that compared with the CON group, contents of TC, AST activity and AST/ALT ratio were significantly increased in the serum of LPS piglets(P<0.05), content of HDL-c was significantly decreased(P<0.05). In addition, in the liver, the levels of TG, NEFA, IL-1β, IL-6 and TNF-α were increased significantly(P<0.05), and activities of LPL, HL and TL were decreased significantly(P<0.05). Compared with LPS group, content of TC, activities of AST and ALT and the AST/ALT ratio were decreased significantly(P<0.05), and HDL-c content increased significantly in the serum of LD piglets(P<0.05). The contents of TG, NEFA, IL-1β, IL-6 and TNF-α and activity of FAS in the liver were decreased significantly(P<0.05), and the activities of LPL, HL and TL were increased significantly(P<0.05). Compared with the CON group, the mRNA expressions of IL-1β, IL-6, TNF-α, ACCβ and SREBP-1 c in the LPS group were significantly increased(P<0.05), the mRNA expressions of AMPKα, SIRT1, CPT-1 and SCD were decreased significantly(P<0.05). The above indicators were improved in the LD group compared with the LPS group. These results indicated that DHA had a certain effect in recovering LPS-induced liver inflammation and abnormal lipid metabolism.

Disfunção e não função primária do enxerto hepático: revisão integrativa / Primary liver graft dysfunction and non-function: integrative literature review

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.

Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model

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.

Network Meta-analysis of Chinese patent medicines in treatment of liver stagnation and spleen deficiency of depression / 中国中药杂志

To evaluate the clinical efficacy and safety of Shugan Jieyu Capsules,Jieyu Pills and Xiaoyao Pills in the treatment of liver-stagnation and spleen-deficiency depression by the network Meta-analysis( NMA),so as to provide evidence-based clinical practice. Chinese databases,including CNKI,VIP,Wan Fang Data,CBM as well as English databases including the Cochrane Library,PubMed,EMbase and Web of Science were retrieved from inception to October 30,2018,to collect randomized controlled trials( RCTs) about clinical study of the three kinds of Chinese patent medicines. The quality and bias risk of the included studies were assessed by 5. 1 standard in Cochrane Handbook,ADDIS software was applied in the statistical analysis,and the result were compared by NMA. A total of 37 studies involving 3 105 patients were included. The results of NMA showed that the adjuvant therapy with the three kinds of traditional Chinese patent medicines could improve the clinical efficacy. Jieyu Pills had the most significant effect( OR = 4. 59,95%CI[1. 94,12. 71],P<0. 05). In HAMD,Shugan Jieyu Capsules( MD = 3. 22,95%CI[2. 07,4. 39],P< 0. 05) and Xiaoyao Pills( MD= 2. 23,95%CI[0. 41,4. 03],P<0. 05) can effectively reduce the depression scale indicators. In the incidence of adverse reactions,the three kinds of Chinese patent medicines can reduce the incidence of adverse reactions. The three kinds of Chinese patent medicines can be combined with auxiliary Western medicine to treat liver-stagnation and spleen-deficiency depression,with complementary advantages in action mechanisms. In the clinical efficacy and safety,the Chinese patent medicines had good clinical manifestations. Although this study showed that Jieyu Pills may be the referred medicine for depression,this conclusion is still immature and needs to be further verified by high-quality RCTs studies,and the application shall be selective based on specific characteristics in clinic.

Topical hepatic hypothermia associated with ischemic preconditioning. Histopathological and biochemical analysis of ischemia reperfusion damage in a 24 hour model

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.

Performance during a strenuous swimming session is associated with high blood lactate: pyruvate ratio and hypoglycemia in fasted rats

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.

Avaliação de pacientes portadores de cirrose candidatos a transplante hepático pela ressonância magnética cardíaca / Cardiac magnetic resonance evaluation of patients with cirrhosis eligible to liver transplantation

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

Jatropha cake (Jatropha curcas): hepatotoxic implications / Torta de pinhão-manso (Jatropha curcas): implicações hepatotóxicas

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)

Insuficiencia suprarrenal relativa en pacientes cirróticos / Adrenal insufficiency in cirrhotic patients

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.

Alterações bioquímicas, anatômicas e histopatológicas em fígado de Gallus gallus Linnaeus, 1758 experimentalmente infectados por Borrelia anserina Sakharoff, 1891 / Biochemical, anatomical and histopathological changes in the liver of Gallus gallus Linnaeus, 1758 experimentally infected by Borrelia anserine Sakharoff, 1891

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)

Dislipidemia Diabética / Diabetic Dyslipidemia

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

Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

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.

Doppler hepático na pré-eclâmpsia e na síndrome HELLP / Doppler ultrasonography of the liver in pre-eclampsia and HELLP syndrome

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)