Hepatic recruitment of myeloid-derived suppressor cells upon liver injury promotes both liver regeneration and fibrosis.

BACKGROUND: The liver regeneration is a highly complicated process depending on the close cooperations between the hepatocytes and non-parenchymal cells involving various inflammatory cells. Here, we explored the role of myeloid-derived suppressor cells (MDSCs) in the processes of liver regeneration and liver fibrosis after liver injury. METHODS: We established four liver injury models of mice including CCl4-induced liver injury model, bile duct ligation (BDL) model, concanavalin A (Con A)-induced hepatitis model, and lipopolysaccharide (LPS)-induced hepatitis model. The intrahepatic levels of MDSCs (CD11b+Gr-1+) after the liver injury were detected by flow cytometry. The effects of MDSCs on liver tissues were analyzed in the transwell co-culture system, in which the MDSCs cytokines including IL-10, VEGF, and TGF-ß were measured by ELISA assay and followed by being blocked with specific antibodies. RESULTS: The intrahepatic infiltrations of MDSCs with surface marker of CD11b+Gr-1+ remarkably increased after the establishment of four liver injury models. The blood served as the primary reservoir for hepatic recruitment of MDSCs during the liver injury, while the bone marrow appeared play a compensated role in increasing the number of MDSCs at the late stage of the inflammation. The recruited MDSCs in injured liver were mainly the M-MDSCs (CD11b+Ly6G-Ly6Chigh) featured by high expression levels of cytokines including IL-10, VEGF, and TGF-ß. Co-culture of the liver tissues with MDSCs significantly promoted the proliferation of both hepatocytes and hepatic stellate cells (HSCs). CONCLUSIONS: The dramatically and quickly infiltrated CD11b+Gr-1+ MDSCs in injured liver not only exerted pro-proliferative effects on hepatocytes, but also accounted for the activation of profibrotic HSCs.

Acute High-Output Heart Failure with Pulmonary Hypertension and Severe Liver Injury Caused by Amlodipine Poisoning: A Case Report.

Acute high-output heart failure (HOHF) with pulmonary hypertension and liver injury caused by amlodipine poisoning is very rare. We report a 52-year-old woman who suffered from severe shock after an overdose of amlodipine. Hemodynamic monitoring showed that while her left ventricular systolic function and cardiac output were elevated, her systemic vascular resistance decreased significantly. At the same time, the size of her right heart, her central venous pressure, and the oxygen saturation of her central venous circulation all increased abnormally. The patient's circulatory function and right ventricular dysfunction gradually improved after large doses of vasopressors and detoxification measures. However, her bilirubin and transaminase levels increased significantly on hospital day 6, with a CT scan showing patchy, low-density areas in her liver along with ascites. After liver protective treatment and plasma exchange, the patient's liver function gradually recovered. A CT scan 4 months later showed all her liver abnormalities, including ascites, had resolved. The common etiologies of HOHF were excluded in this case, and significantly reduced systemic vascular resistance caused by amlodipine overdose was thought to be the primary pathophysiological basis of HOHF. The significant increase in venous return and pulmonary blood flow is considered to be the main mechanism of right ventricular dysfunction and pulmonary hypertension. Hypoxic hepatitis caused by a combination of hepatic congestion and distributive shock may be the most important factors causing liver injury in this patient. Whether amlodipine has other mechanisms leading to HOHF and pulmonary hypertension needs to be further studied. Considering the significant increase of right heart preload, aggressive fluid resuscitation should be done very cautiously in patients with HOHF and shock secondary to amlodipine overdose.

Discomfort and unease of the subject in the interpretation movement of a Tuberculosis questionnaire / O desconforto e inquietação do sujeito em seu movimento de interpretação de um questionário sobre a tuberculose / Malestar e inquietud del sujeto en su movimiento de interpretación de un cuestionario sobre la Tuberculosis

OBJECTIVE: to propose a discussion about traces of the derivation of meanings, the subjects' discomfort and resistance when they are called upon to signify a questionnaire on the transfer of the Directly Observed Treatment of Tuberculosis policy, in order to reveal the limitations of closed questionnaires in the subject's interpretation process. METHOD: health professionals from a Primary Health Care Unit in Porto Alegre/RS were interviewed and some excerpts from the interviews were investigated in the light of French Discourse Analysis. RESULTS: resistance, discomfort, slips, silencing and the derivation of meanings were observed in the subjects' interpretation. CONCLUSION: the interpretation process has multiple meanings and varies from subject to subject. The questionnaire, as a prototype of the logically stabilized universe, fails when the purpose is to control the interpretation. Its isolated use in health research can entail inexactness or incompleteness of the collected data. Therefore, its use associated with qualitative research techniques is ideal. .

OBJETIVO: propor uma discussão a respeito de vestígios da derivação de sentidos, do desconforto e resistência dos sujeitos, quando convocados a significar um questionário referente à transferência da política do tratamento diretamente observado da tuberculose, de modo a revelar as limitações de questionários fechados, quando se trata do processo interpretativo do sujeito. MÉTODO: profissionais de saúde de uma Unidade de Atenção Primária de Saúde de Porto Alegre, RS, foram entrevistados e alguns recortes das entrevistas examinados à luz da Análise de Discurso de linha francesa. RESULTADOS: observou-se a resistência, o incômodo, o deslizamento, o silenciamento e a derivação dos sentidos no ato de interpretação dos sujeitos. CONCLUSÃO: o processo de interpretação é polissêmico e varia de sujeito para sujeito. O questionário, enquanto um protótipo do universo logicamente estabilizado, falha quando o propósito é o de controlar a interpretação. O seu uso de forma isolada, em pesquisas em saúde, pode incorrer em inexatidão ou incompletude dos dados obtidos, sendo ideal a sua utilização associada a técnicas qualitativas de pesquisa. .

OBJETIVO: proponer una discusión respecto a vestigios de la derivación de sentidos, del malestar y resistencia de los sujetos cuando convocados a significar un cuestionario respecto a la trasferencia de la política del Tratamiento Directamente Observado de la Tuberculosis, de manera a revelar las limitaciones de cuestionarios cerrados cuando se trata del proceso interpretativo del sujeto. MÉTODO: profesionales de salud de una Unidad de Atención Primaria de Salud de Porto Alegre/RS fueron entrevistados y algunos recortes de las entrevistas examinados a la luz del Análisis de Discurso de línea Francesa. RESULTADOS: fueron observados la resistencia, la molestia, el deslizamiento, el silenciamiento y la derivación de los sentidos en el acto de interpretación de los sujetos. CONCLUSIÓN: el proceso de interpretación es polisémico y varia de sujeto a sujeto. El cuestionario como un prototipo del universo lógicamente estabilizado falla cuando el objetivo es el de controlar la interpretación. Su uso de forma aislada en investigaciones en salud puede llevar a datos inexactos o incompletos, siendo ideal su utilización asociada a técnicas cualitativas de investigación. .

Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

Hepatotoxicidad por drogas: reporte de un caso y revisión de literatura / Drug-induced liver injury: a case report and literature review

La Hepatotoxicidad por drogas se define como una lesión hepática asociada a deterioro de la función de éste órgano, secundaria a exposición a una droga u otro agente no infeccioso. Es un cuadro infrecuente, pero puede determinar graves lesiones hepáticas y una mortalidad considerable si no se detecta a tiempo. Es labor del clínico mantener un alto Índice de sospecha al enfrentarse a un paciente con alteraciones hepáticas de reciente comienzo y uso concomitante de medicamentos. En el presente articulo se expone el caso clínico de un paciente masculino, 48 años de edad, con Depresión Severa en tratamiento con Sertralina, Clonazepam, Risperidona, Lamotrigna y Acido Valproico. Ingresó al Hospital de Talca con diagnostico de Síndrome Colestásico cuyo estudio demostró serología para VHB y VHC negativa y ecotomografía abdominal normal. Presentó buena respuesta clínica y de laboratorio a la suspensión de las drogas. El cuadro fue compatible con Hepatotoxicidad por drogas.

Tratamiento de intoxicaciones por compuestos hepatotóxicos: uso de la N-acetilcisteína y las carboximetilcisteína: [revisión] / Treatment of intoxications by hepatotoxic compounds: use of N-acetylcystein and S-carboxymetylcystein: [review]

La N-acetilcisteina (NAC) es un fármaco con propiedades antidóticas útiles en la intoxicación por compuestos hepatotóxicos, como paraquat, acetaminofen y fósforo inorgánico. No se encuentra fácilmente disponible en Venezuela a pesar que la frecuencia y severidad de este tipo de intoxicación son significativas. Se discuten ciertas características fármacocinéticas y fármacodinámicas de la NAC y de la S-carboximetilcisteina (SCMC), presente en el mercado farmacéutico venezolano. Además se presenta una revisión de las experiencias clínicas y experimentales con la SCMC en intoxicaciones por compuestos hepatototóxicos.

N-acetylcysteine (NAC) is a drug with antidotal properties useful in poisoning by hepatotoxic compounds such as paraquat, acetaminophen and inorganic phosphorus. Although the frequency and severity of this type of poisoning are significant, NAC is not readily available in Venezuela. Certain pharmacokinetic and pharmacodynamic characteristics of NAC and S-carboxymetylcisteine (SCMC), available in venezuelan pharmaceutical market are discussed. In addition, a review of the clinical and experimental experiences with SCMC in poisoning for hepatotoxic compounds is presented.

Hepatotoxicidad por amoxicilina/ácido clavulánico: caso clínico / Hepatotoxixity associated to the use of amoxicillin clavulanic acid

We report a 72 years old diabetic male that, after the use of combined amoxicillin-clavulanic acid, developed pruritus and jaundice. Liver function tests showed serum total bilirubin of 4.3 mg/dL aspartate aminotransferase 140 U/l (normal <35 U/L), alanine aminotransferase 470 U/L (normal <40) and alkaline phosphatases of 400 U/L (normal <100). Serology for hepatitis A, B and C viruses was negative, ERCP showed a normal biliary tree and liver biopsy disclosed a cholestatic hepatitis. Ursodeoxycholic was started to relieve pruritus. Liver function tests improved shortly thereafter, suggesting that this drug may be useful in the treatment of drug induced cholestasis

Investigacion sobre toxicidad hepatica de medicacion antituberculosa / Study of the hepatic toxicity of antituberculouis drugs treatment

El presente trabajo fue realizado en el hospital San Gabriel entre enero a marzo de 1990, con 47 pacientes que fueron estudiados durante su tratamiento en diferentes etapas, y muestra el grado de tolerancia hepatica a medicamentos que deben ser utilizados por largo tiempo y que de acuerdo a reaccion individual es imprevisible el grado de toxicidad que pueda esperarse. Los resultados son alentadores porque no se tuvieron que lamentar grados extremos de toxicidad y solo en tres casos, la suspension temporal del tratamiento