Alteración de la microbiota intestinal y su relación con enfermedades gastrointestinales y hepatobiliares / Disruption of the intestinal microbiota and its relationship with gastrointestinal and hepatobiliary diseases

La interrupción de la simbiosis que existe entre el cuerpo humano y su microbioma puede resultar en una disbiosis, un desequilibrio en la interacción huésped-microbiota, que puede asociarse al desarrollo de diversas enfermedades como el síndrome de intestino irritable, hígado graso no alco-hólico, enfermedad hepática alcohólica y cirrosis, entre otras. En ciertas condiciones patológicas y por múltiples factores de riesgo, la capacidad de autorregulación del intestino se puede alterar, contribuyendo al incremento de la permeabilidad con inflamación intestinal crónica. El diagnóstico y el tratamiento, así como la relación entre la permeabilidad intestinal, la disbiosis y las patologías gastrointestinales y hepatobiliares, todavía no tienen estudios clínicos validados o con el soporte científico adecuado, por lo que se realiza una revisión de la literatura con la finalidad de aportar conceptos que puedan orientar con respecto a la importancia del estudio del microbioma humano en estas enfermedades.

Disruption of the symbiosis that exists between the human body and its microbiome can result in dys-biosis, an imbalance in the host-microbiota interaction, which may be associated with the develop-ment of various diseases such as irritable bowel syndrome, non-alcoholic fatty liver disease, alcoholic liver disease and cirrhosis, among others. In certain pathological conditions and due to multiple risk factors, the self-regulating capacity of the intestine may be lost, contributing to increased permeability with chronic intestinal inflammation. Its diagnosis and treatment as well as the relationship between intestinal permeability, dysbiosis and gastrointestinal and hepatobiliary pathologies have not been validated in clinical studies or have adequate scientific support, so a review of the literature is carried out in order to provide concepts that can guide with respect to the importance of the study of the human microbiome in these diseases

Comorbilidades en pacientes con enfermedad hepática alcohólica / Comorbidities in patients with alcoholic hepatic disease

Introducción: El consumo excesivo y prolongado de alcohol se asocia a una morbilidad elevada por afecciones hepáticas y de otros órganos. Objetivo: Precisar las lesiones hepáticas y su relación con otras enfermedades asociadas al alcohol y el estado nutricional en pacientes con enfermedad hepática alcohólica. Métodos: Se efectuó un estudio observacional, descriptivo y transversal de 270 pacientes con enfermedad hepática alcohólica, atendidos en el Servicio de Medicina Interna y la consulta especializada de Hepatología del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora de Santiago de Cuba, quienes fueron examinados clínicamente para detectar síntomas y signos de enfermedades hepática y asociadas al alcohol en diferentes sistemas, durante el decenio 2010-2019. Resultados: Predominaron los hombres (234), de los cuales 117 estuvieron en el grupo de 25 - 44 años de edad. La forma clínica preponderante fue la cirrosis hepática en 109 pacie2ntes, de ellos una proporción importante eran bebedores con más de 20 años de exposición al hábito. La enfermedad por reflujo gastroesofágico junto a las formas de gastropatía y la polineuropatía en 89 y 96 afectados, respectivamente, fueron las comorbilidades más asociadas a la lesión hepática. Se observaron diferentes grados de desnutrición en 167 afectados (61,8 %), de los cuales primaron aquellos con cirrosis hepática, de estos 51 (49,0 %) presentaron desnutrición moderada y 31 (49,2 %) grave. Conclusiones: Resulta elevada la presencia de comorbilidades en pacientes con enfermedad hepática alcohólica, lo cual se asocia al deterioro nutricional y a una exposición prolongada al hábito nocivo.

Introduction: The excessive and prolonged consumption of alcohol is associated with a high morbidity due to hepatic disorders and affections of other organs. Objective: To specify the hepatic lesions and their relationship with other diseases associated with alcohol and the nutritional state in patients with alcoholic hepatic disease. Methods: An observational, descriptive and cross-sectional study of 270 patients with alcoholic hepatic disease was carried out. They were assisted in the Internal Medicine Service and in the specialized visit of Hepatology from Saturnino Lora Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba who were clinically examined to detect symptoms and signs of hepatic disease and those associated with alcohol in different systems, during the decade 2010-2019. Results: There was a prevalence of men (234), of which 117 were in the group of 25 - 44 years of age. The preponderant clinical form was the hepatic cirrhosis in 109 patients, an important proportion of them were drinkers with more than 20 years of exhibition to the habit. The disease due to gastroesophagic reflux along with the forms of gastropathy and polyneuropathy in 89 and 96 affected patients, respectively, were the comorbidities more associated with the hepatic lesion. Different degrees of malnutrition were observed in 167 affected patients (61.8 %), of which those with hepatic cirrhosis prevailed, of these 51 (49.0 %) presented moderate malnutrition and 31 (49.2 %) a serious one. Conclusions: The presence of comorbidities in patients with alcoholic hepatic disease is high, which is associated to the nutritional deterioration and a prolong exposure to the harmful habit.

Dilema terapéutico: síndrome de abstinencia alcohólica y encefalopatía hepática concurrentes. A propósito de un caso / Therapeutic dilemma: alcohol withdrawal syndrome and concurrent hepatic encephalopathy. A case report

RESUMEN El trastorno por consumo de alcohol es una de las principales causas de morbimortalidad en el mundo. La enfermedad hepática alcohólica es una complicación común de este trastorno y la encefalopatía hepática es una seria comorbilidad de la cirrosis alcohólica. Los factores precipitantes pueden relacionarse con infección, sangrado gastrointestinal, deshidratación o efectos de psicofármacos (p. ej., benzodiacepinas e hipnóticos no benzodiacepínicos). Se expone un caso del manejo hospitalario de un paciente con un trastorno severo por consumo de alcohol, cirrosis y encefalopatía hepática, quien desarrolla síntomas de abstinencia alcohólica durante su hospitalización y la complejidad del manejo antagónico de un delirium gabaérgico propio de la encefalopatía hepática en el contexto de un delirium glutamatérgico-noradrenérgico por abstinencia alcohólica.

ABSTRACT Alcohol use disorder is one of the main causes of morbidity and mortality in the world. Alcoholic liver disease is a common complication of this disorder, and hepatic encephalopathy is a serious complication of alcoholic cirrhosis. Precipitating factors may be related to infection, gastrointestinal bleeding, dehydration or the effects of psychotropic drugs (e.g. benzodiazepines and non-benzodiazepine hypnotics). We present a case of the hospital management of a patient with a severe alcohol use disorder, cirrhosis and hepatic encephalopathy who developed alcohol withdrawal symptoms while in hospital, and discuss the complexity of the antagonistic management of a GABAergic delirium characteristic of hepatic encephalopathy in the context of a glutamatergic-noradrenergic delirium due to alcohol withdrawal.

Comparison of tru-cut biopsy and fine-needle aspiration cytology in an experimental alcoholic liver disease model

SUMMARY INTRODUCTION Liver biopsies such as tru-cut (sharp needle) and fine-needle aspiration cytology (FNAC) are the most commonly preferred techniques to detect the grade and stage of certain liver diseases. In this study, we aimed to compare the efficiency of USG-guided tru-cut biopsy and fine-needle aspiration cytology in an experimental alcoholic liver disease model. METHODS Thirty-six female Wistar albino rats, 4-6 months old, and weighing from 190 to 250 g, were used in this study. The animals were randomly divided into six equal groups: G1 (control), G2 (tru-cut control), G3 (FNAC control), G4 (Alcoholic liver disease model), G5 (Alcoholic liver disease model + FNAC), and G6 (Alcoholic liver disease model + tru-cut biopsy). After a histopathological evaluation by light microscopy, the sensitivity, specificity, positive and negative predictive values of FNAC and tru-cut biopsy for the diagnosis of liver lesions were calculated. RESULTS No pathology was detected in G1 except for mild congestion. On the other hand, hepatocyte damage, periportal inflammation, congestion, and fatty changes were detected in all liver tissues of the alcoholic liver disease groups. The sensitivity of hepatocyte damage, inflammation, congestion, and fatty change parameters for FNAC were 33.3%, 80%, 0%, and 0%, respectively, while the sensitivity of the same variables for tru-cut were 66.7%, 40%, 100%, and 20%, respectively. DISCUSSION Both techniques were superior in some aspects. FNAC can be an attractive alternative to tru-cutbiopsy and applied in routine practice in the diagnosis of non-tumoral liver diseases.

RESUMO INTRODUÇÃO Biópsias hepáticas tais como por agulha tru-cut e por citologia aspirativa por agulha fina (CAAF) são as técnicas frequentemente preferidas para detectar o grau e o estágio de certas doenças hepáticas. Neste estudo, nosso objetivo foi comparar a eficiência da biopsia com agulha tru-cut guiada por ultrassom e a citologia aspirativa por agulha fina em um modelo experimental de doença hepática alcoólica. MÉTODOS Trinta e seis ratos Wistar albinos fêmeas, de 4 a 6 meses de idade e pesando entre 190 e 250g, foram utilizados neste estudo. Os animais foram divididos aleatoriamente em seis grupos: G1 (controle), G2 (controle tru-cut), G3 (CAAF), G4 (modelo de doença hepática alcoólica), G5 (modelo de doença hepática alcoólica + CAAF) e G6 (modelo de doença hepática alcoólica + biópsia tru-cut). Após uma avaliação histopatológica por microscopia de luz, foram calculados a sensibilidade, especificidade e os valores preditivos positivos e negativos da CAAF e biópsia por tru-cut para o diagnóstico de lesões hepáticas. RESULTADOS Nenhuma patologia foi detectada no G1, apenas leve congestão. Por outro lado, detectamos danos nos hepatócitos, inflamação periportal, congestão e alterações nos ácidos graxos nos tecidos hepáticos de todos os grupos de doença hepática alcoólica. As sensibilidades encontradas para os danos nos hepatócitos, inflamação, congestão e alterações nos parâmetros de ácidos graxos para a CAAF foram 33,3%, 80%, 0% e 0%, respectivamente, enquanto que as sensibilidades das mesmas variáveis para o método tru-cut foram 66,7%, 40%, 100% e 20%, respectivamente. DISCUSSÃO Ambas as técnicas foram superiores em alguns aspectos. A CAAF pode ser uma alternativa atraente à biópsia por tru-cut e aplicada como prática de rotina no diagnóstico de doenças hepáticas não tumorais.

Diagnóstico de un caso inusual de micetoma por Aspergillus / Diagnosis of an unusual case of Mycetoma due to Aspergillus

Introducción: Las aspergilosis comprenden un amplio y heterogéneo grupo de enfermedades oportunistas causadas por hongos del género Aspergillus, considerados como una causa inusual de infección. Es la causa más frecuente de muerte por neumonía infecciosa e infección diseminada o respiratoria oportunista, en pacientes inmunocomprometidos. Objetivos: Describir las características clínicas de un caso inusual de aspergilosis pulmonar. Caso clínico: Paciente de 56 años de edad con antecedentes personales de hepatopatía alcohólica, ingresado por episodios de expectoración con sangre y tos seca. Se realizaron estudios de laboratorio, imagenológicos y anatomopatológicos que condujeron al diagnóstico de micetoma por Aspergillus fumigatus, lo cual posibilitó indicar el tratamiento adecuado y realizar el seguimiento clínico. Conclusiones: La infección por Aspergillus fumigatus debe ser considerada por el médico de cabecera, debido a que su reporte constituye una herramienta para que pueda establecer una terapéutica temprana y adecuada, dada sus implicaciones pronósticas, su morbilidad y mortalidad en pacientes inmunodeprimidos(AU)

Introduction: Aspergillosis comprises a wide and heterogeneous group of opportunistic diseases caused by fungi of the Aspergillus genus, considered as an unusual cause of infection. It is the most frequent cause of death from infectious pneumonia and disseminated or opportunistic respiratory infection in immunocompromised patients. Objectives: Describe the clinical characteristics of an unusual case of pulmonary aspergillosis. Case report: 56-year-old patient with a personal history of alcoholic liver disease, admitted due to episodes of expectoration with blood and dry cough. Laboratory, imaging, and pathological studies were conducted that led to the diagnosis of mytoma by Aspergillus fumigatus, which made it possible to indicate the appropriate treatment and perform clinical follow-up. Conclusions: Aspergillus fumigatus infection should be considered by the attending physician, because his report constitutes a tool for him to establish an early and adequate therapy, given its prognostic implications and for its morbidity and mortality in immunocompromised patients(AU)

Linderae radix ethanol extract attenuates alcoholic liver injury via attenuating inflammation and regulating gut microbiota in rats

This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.

Hepatoprotective effect of Alhagi sparsifolia against Alcoholic Liver injury in mice

Overconsumption of alcohol leads to alcoholic liver disease (ALD). Natural compounds have been investigated previously for their hepatoprotective activities against liver injury. This study investigated the protective effect of Alhagi sparsifolia on ALD. Alcohol was administered to mice for three consecutive days; either alone or in combination with Alhagi sparsifolia extract (150, 300, 600 mg/kg). Serum aspartate aminotransferase and alanine transaminase as biomarkers of liver injury, the content of malonaldehyde, hydrogen peroxide (H2O2) and glutathione which indicated the redox status of liver and the antioxidant enzyme activity of super oxide dismutase were detected, respectively. Moreover, the expression of protein cytochrome P450 2E1 (CYP2E1) the key enzyme of alcohol metabolism, and also tested by western blot experiment. Subsequently, the mRNA levels of inflammatory factors including TNF- α and TLR4 was determined real-time PCR. Results showed that Alhagi sparsifolia significantly alleviated alcohol-induced liver injury by reducing serum ALT and AST, inhibiting MDA and H2O2 content, increasing SOD, and GSH level in the liver (P< 0.05). In addition, the Alhagi sparsifolia treatment inhibited the expression of CYP2E1 (P< 0.05). The results suggest that Alhagi sparsifolia could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury

Alcohol, cirrosis y predisposición genética / Alcohol, Cirrhosis, and Genetic Predisposition

La cirrosis hepática es la tercera causa de muerte alrededor del mundo que es atribuible al consumo de alcohol. Más del 80% de los consumidores crónicos de alcohol desarrollan esteatosis y entre el 20% al 40% presentan otras complicaciones como fibrosis, hepatitis alcohólica y cirrosis; sin embargo, no todos los individuos con consumo crónico de alcohol desarrollan cirrosis, en parte debido al componente genético de cada individuo. El grado de actividad de las enzimas que metabolizan el alcohol está influenciado por polimorfismos presentes en los genes que codifican para estas enzimas, y corresponde a uno de los factores determinantes para el desarrollo de una hepatopatía terminal en respuesta al consumo de alcohol. Entre las enzimas implicadas en el metabolismo del alcohol están la alcohol deshidrogenasa (ADH), el citocromo P450 2E1 (CYP2E1) y la acetaldehído deshidrogenasa (ALDH), de las cuales se ha reportado que la mayor actividad de ADH y CYP2E1 y la menor actividad de ALDH pueden conferir riesgo en algunas poblaciones por la acumulación de acetaldehído, el cual es tóxico para el organismo. Se realizó una revisión en la literatura de los principales aspectos del metabolismo del alcohol y polimorfismos (genotipos) de enzimas que intervienen en el metabolismo del alcohol como factor de riesgo. Esto se hizo mediante la búsqueda de material bibliográfico a través de la base de datos PubMed desde 1990 hasta el 2013 utilizando las palabras claves alcohol liver disease, ADH, ALDH, CYP2E1 y polymorphism.

Liver cirrhosis is the third most common cause of death attributable to alcohol consumption throughout the world. More than 80% of chronic drinkers develop steatosis, and 20% to 40% develop other complications such as fibrosis, alcoholic hepatitis and cirrhosis. However, not everyone who chronically consumes alcohol develops cirrhosis. This is partly because of the genetic component of each individual. The level of activity of the enzymes that metabolize alcohol is influenced by polymorphisms of the genes that coding for these enzymes. This is one of the determining factors in the development of terminal liver disease in response to alcohol consumption. Among the enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1) and acetaldehyde dehydrogenase (ALDH). It has been reported that higher levels of activity of ADH and CYP2E1 and lower levels of activity of ALDH may be risk factors in some populations for accumulation of acetaldehyde which is toxic for the organism. This literature review covers the most important aspects of alcohol metabolism including polymorphisms (genotypes) of enzymes involved in the metabolism of alcohol as a risk factor. A search through the PubMed database from 1990 to be held 2013 was conducted using the keywords alcoholic liver disease, ADH, ALDH, CYP2E1, and polymorphism.

Enfermedad hepática por alcohol / Alcoholic liver disease

Excessive alcohol consumption is an important cause of preventable morbidity and mortality. We have to bealert to chronic alcohol usage or abuse. Simple tests (AUDIT, CAGE) can be applied quickly on outpatientcare. We highlight advances in understanding the immune and molecular mechanisms; there is disruptionof the intestinal barrier with bacterial translocation, as well as endotoxins which activate the liver’s innateimmunity, causing apoptosis, necrosis, inflammation and fibrosis. Alcoholic hepatitis is most common inpatients between 40 and 60 years of age, preferably male with jaundice, fever, ascites, hepatomegaly. Thediagnosis is confirmed with a history of alcoholic consumption, mild to moderate AST and ALT values,a AST/ALT ratio > 2, hyperbilirrubinemia and prolonged prothrombin time. There are scores to evaluatethe severity and the need of corticoid therapy, such as modified Maddrey discriminating function andMELD score. Lille score assesses the response to treatment in the seventh day. The risks and benefits ofliver biopsy should be evaluated individually. The cornerstone of treatment remains alcohol abstinence.Nutritional management must be carefully monitored. Proteins requirements are standardized based onweight. The use of corticoids with 40 mg of prednisolone each day is the most widely accepted therapy,indicated on patients with MMDF higher than 32 or MELD score higher than 21. If Lille score is higherthan 0.45 at the seven day under corticoid therapy, treatment must be interrupted. The use of pentoxifyllinewould only be effective for prevention of hepatorenal syndrome...

El consumo excesivo de alcohol es una causa importante de morbimortalidad prevenible. Debemos estaratentos en detectar a pacientes con dependencia o abuso crónico de alcohol. Test sencillos (AUDIT, CAGE)pueden aplicarse rápidamente en consulta ambulatoria. Destacamos avances en el conocimiento moleculare inmunológico, existe disrupción de la barrera intestinal con translocación bacteriana y endotoxinas conactivación del sistema inmune innato del hígado, produciendo apoptosis celular, necrosis e inflamación yfibrosis. La hepatitis alcohólica se presenta principalmente en pacientes entre 40 y 60 años, preferentementeen varones con ictericia, fiebre, ascitis, hepatomegalia. El diagnóstico se confirma con antecedentes deingesta alcohólica, GOT y GPT elevadas en forma leve o moderada, relación GOT/GPT mayor de 2, hiperbilirrubinemiay tiempo de protrombina prolongado. Existen scores para evaluar la gravedad y necesidad demanejo con corticoides como función discriminante de Maddrey modificada y MELD. El puntaje de Lilleevalúa respuesta del tratamiento al séptimo día. El riesgo/beneficio de la biopsia hepática se evalúa caso acaso. La piedra angular del tratamiento sigue siendo la abstinencia. Manejo nutricional debe ser riguroso.Requerimientos proteicos están estandarizados por peso. La terapia con corticoides (prednisolona 40 mg/día) es la más ampliamente aceptada, con indicación en pacientes con FDMm mayor a 32 o MELD mayora 21. Si el puntaje de Lille es mayor de 0,45 a los 7 días con corticoides, deben suspenderse. Pentoxifilinasólo tendría efecto en prevenir el desarrollo de síndrome hepatorrenal (SHR). Hay nuevas terapias enevaluación, como el uso de G-CSF...

Evaluation of the predictive indices for candidemia in an adult intensive care unit

INTRODUCTION: To evaluate predictive indices for candidemia in an adult intensive care unit (ICU) and to propose a new index. METHODS: A prospective cohort study was conducted between January 2011 and December 2012. This study was performed in an ICU in a tertiary care hospital at a public university and included 114 patients staying in the adult ICU for at least 48 hours. The association of patient variables with candidemia was analyzed. RESULTS: There were 18 (15.8%) proven cases of candidemia and 96 (84.2%) cases without candidemia. Univariate analysis revealed the following risk factors: parenteral nutrition, severe sepsis, surgical procedure, dialysis, pancreatitis, acute renal failure, and an APACHE II score higher than 20. For the Candida score index, the odds ratio was 8.50 (95% CI, 2.57 to 28.09); the sensitivity, specificity, positive predictive value, and negative predictive value were 0.78, 0.71, 0.33, and 0.94, respectively. With respect to the clinical predictor index, the odds ratio was 9.45 (95%CI, 2.06 to 43.39); the sensitivity, specificity, positive predictive value, and negative predictive value were 0.89, 0.54, 0.27, and 0.96, respectively. The proposed candidemia index cutoff was 8.5; the sensitivity, specificity, positive predictive value, and negative predictive value were 0.77, 0.70, 0.33, and 0.94, respectively. CONCLUSIONS: The Candida score and clinical predictor index excluded candidemia satisfactorily. The effectiveness of the candidemia index was comparable to that of the Candida score. .

Correlation Between Radiographic Area and Immunolocation of MMP-2 and MMP-9 in Unilocular Radiographic Lesions

Unilocular bone cysts are the most common entities affecting the maxillofacial region. The mechanism of proliferation and expansion remains unclear. Metalloproteinases (MMPs) are associated to diverse pathological conditions. The aim of the present study was to correlate the radiographic aspect (area) and the presence of MMP-2 and MMP-9 in dentigerous cysts, radicular cysts and keratocystic odontogenic tumors. The radiographic area of each lesion was calculated using the mathematical formula of the ellipse area. All specimens were subjected to immunohistochemical analysis for these enzymes. The average radiographic area was 284.17 mm2, 235.81 mm2 and 381.81 mm2, respectively. Statistical analyses revealed no association between the immunoreactivity of MMPs and radiographic area of the lesions in all pathologies studied, except for MMP-2 and radicular cysts, for which smaller lesions had increased immunostaining for this enzyme. The results demonstrate that quantities of MMP-2 and MMP-9 are especially involved with dentigerous and radicular cysts in expansion, whereas these enzymes seem to be related to the biological behavior of keratocystic odontogenic tumors, indicating invasion and cell proliferation. Moreover, there is an inverse association between MMP-2 and MMP-9 in keratocystic odontogenic tumors (p=0.03; rs=-0.660), indicating activity in different regions.

Cistos ósseos uniloculares são as entidades mais comuns que afetam a região maxilofacial. O mecanismo de proliferação e expansão permanece obscuro. As metaloproteinases (MMPs) estão associadas a diversas condições patológicas. O objetivo do presente estudo foi correlacionar o aspecto radiográfico (área) e a presença de MMP-2 e MMP-9 em cistos dentígeros, cistos radiculares e tumores odontogênicos queratocísticos. A área radiográfica de cada lesão foi calculada usando a fórmula matemática da área de elipse. Todas as amostras foram submetidas à análise imunoistoquímica para estas enzimas. A área radiográfica média foi de 284,17 mm2, 235,81 mm2 e 381,81 mm2, respectivamente. As análises estatísticas não mostraram associação entre a imunorreatividade de MMPs e área radiográfica das lesões em todas as patologias estudadas, exceto para MMP-2 e cistos radiculares, nas quais as lesões menores tinham maior imunomarcação para esta enzima. Os resultados demonstraram que a quantidade de imunomarcação da MMP-2 e MMP-9 estão envolvidos com cistos dentígeros e radiculares na expansão óssea, ao passo que estas enzimas parecem estar relacionados com o comportamento biológico dos tumores odontogénicos queratocísticos, indicando invasão e proliferação celular. Além disso, há uma relação inversa entre a MMP-2 e MMP-9 em tumores odontogénicos queratocísticos (p=0,03; rs= -0,660), indicando atividade em diferentes regiões.

Effects of Green Tea Application Time on Bond Strength after Enamel Bleaching

This study evaluated the effect of green tea application time on the bond strength of enamel after enamel bleaching. Enamel samples were obtained from 80 third molars and randomly divided into 7 experimental groups (G1-G7) and 1 group without treatment (G8): G1, bleached with 10% carbamide peroxide (CP); G2, CP + 10% sodium ascorbate gel (SA) for 15 min; G3, CP + SA for 30 min; G4, CP + SA for 60 min; G5, CP + 10% green tea gel (GT) for 15 min; G6, CP + GT for 30 min; G7, CP + GT for 60 min. The CP was applied onto the enamel surface for 8 h for 14 days. The SA was applied in groups 2, 3 and 4, and the GT was applied in groups 5-8 according to the above described application times. Immediately after treatment, the specimens were bonded with Adper Single Bond 2 and Filtek Z350XT. The specimens were prepared to microtensile bond strength analysis. Fracture mode analysis was performed using a stereoscopic loupe. The data were statistically analyzed by two-way analysis of variance, the Tukey's and Dunnett's tests (=5%). The means (standard deviation) were: G1, 23.3 (3.2); G2, 25.2 (3.9); G3, 26.4 (5.4); G4, 30.2 (4.5); G5, 26.6 (3.4); G6, 22.0 (5.4); G7, 31.4 (3.3); G8, 31.4 (3.2). All groups had a high percentage of adhesive failures. In conclusion, the bond strength values were higher than the value in the bleached group only when the antioxidants were applied for 60 min.

Este estudo avaliou o efeito do tempo de aplicação do chá verde na resistência de união do esmalte após o clareamento. Amostras de esmalte foram obtidas a partir de 70 terceiros molares e aleatoriamente divididas em 7 grupos experimentais (G1-G7) e um grupo sem tratamento (G8). Os 7 grupos experimentais foram tratados como segue: G1, clareado com peróxido de carbamida a 10% (PC); G2, PC + gel de ascorbato de sódio a 10% (AS) por 15 min; G3, PC + AS por 30 min; G4, PC + AS por 60 min; G5, PC + gel de chá verde a 10% (CV) por 15 min; G6, PC + CV por 30 min; G7, PC + CV por 60 min. O PC foi aplicado na superfície do esmalte por 8 h, durante 14 dias. O AS foi aplicado nos grupos 2, 3 e 4 e o CV foi aplicado nos grupos 5, 6 e 7 de acordo com os tempos de aplicação descritos acima. Imediatamente após o tratamento, foi realizado o procedimento adesivo utilizando Adper Single Bond 2 e Filtek Z350XT. Em seguida, as amostras foram preparadas para o teste de microtração. A análise do padrão de fratura foi realizada em lupa estereoscópica. Os dados foram analisados através de ANOVA (2 fatores), testes de Tukey e Dunnett (α=5%). As médias (desvio padrão) foram: G1: 23,29 (3,20); G2: 25,18 (3,95); G3: 26,41 (5,40); G4: 30,17 (4,46); G5: 26,63 (3,43); G6: 22,02 (5,41); G7: 31,40 (3,35); G8: 31,4 (3,2). Todos os grupos apresentaram maior porcentagem de falhas adesivas. Em conclusão, os valores de resistência de união foram maiores que os dos grupos clareados somente quando os antioxidantes foram aplicados por 60 min.

Percepção materna quanto aos filhos recém-nascidos hospitalizados / Maternal perception regarding hospitalized newborns / Percepción materna con respecto a hijos recién nacidos hospitalizados

Estudo transversal e descritivo, desenvolvido em unidade neonatal de um hospital público de ensino do estado de São Paulo, Brasil, em que se objetivou verificar a percepção das mães quanto aos filhos recém-nascidos hospitalizados. A amostra foi constituída por 100 mulheres, questionadas, por meio do Inventário de Percepção Neonatal de Broussard, sobre quanta dificuldade esperavam que os bebês da unidade, em geral, apresentassem para comportamentos como: chorar; alimentar; regurgitar ou vomitar; evacuar; dormir e estabelecer uma rotina. Em seguida, as mesmas perguntas foram repetidas sobre o próprio filho. Noventa mães consideraram os filhos com menos dificuldades que os outros bebês da unidade. As mulheres mais jovens e as mães de bebês com maiores pesos tenderam a considerar seus filhos com mais dificuldade. O Inventário é de fácil aplicação e pode ser útil no processo de avaliação da interação mãe-filho, embora seu resultado não possa ser considerado de forma isolada.

Cross-sectional descriptive study conducted in the neonatal unit of a public teaching hospital in the state of São Paulo, Brazil, which aimed to determine the perceptions of mothers about their newborns hospitalized children. The sample consisted of 100 women questioned, through the Neonatal Perception Inventory Broussard, about how much trouble was expected to be presented by babies of the general unit, on behaviors such as crying; feeding; regurgitate or vomit; evacuate; sleep and have a routine. Then, the same questions were repeated about their own babies. Ninety mothers considered their children with fewer difficulties than other babies at the unit. Younger women and mothers of infants with higher weights tended to consider their children with more difficulty. The Inventory is easy to apply and may be useful in the evaluation of mother-child interaction, although its result cannot be considered in isolation.

Estudio descriptivo transversal realizado en la unidad neonatal de un hospital público de enseñanza en el estado de São Paulo, Brasil, que tuve como objetivo determinar las percepciones de las madres con respecto a sus hijos recién nacidos hospitalizados. La muestra consistió en 100 mujeres a quien, a través del Inventario de Percepción Neonatal Broussard, se preguntó por la cantidad de problemas esperaban que los bebés de la unidad general presentasen respecto a comportamientos como el llanto; alimentos; regurgitar o vomitar; evacuar; dormir y establecer una rutina. Entonces, las mismas preguntas se repitieron a respecto de su propio hijo. Noventa madres consideraran a sus hijos con menos dificultad que los otros bebés en la unidad. Las mujeres más jóvenes y las madres de los recién nacidos con pesos mayores tendían a ver a sus hijos con más dificultades. El inventario es fácil de aplicar y puede ser útil en la evaluación del proceso de interacción madre-hijo, aunque sus resultados no pueden ser considerados aisladamente.

Tratamento da diabetes mellitus tipo 2 e comorbidades hepáticas: relato de caso e revisão da literatura / The challenge of treating diabetes mellitus type 2 oral antidiabetic agent whenliver comorbidities represent a problem: case report and literature review

JUSTIFICATIVA E OBJETIVOS: A resistência à insulina (RI) desempenha papel fundamental na etiopatogenia do diabetes mellitus tipo 2 (DM2). A hiperinsulinemia compensatória impede a adequada metabolização dos ácidos graxos, levando ao acúmulo de gordura no hepatócito. A doença hepática gordurosa não alcoólica (DHGNA), na qual a esteatose hepática é a expressão clínica mais comum, têm alta incidência entre os portadores de DM2. Este estudo teve como objetivo discutir os riscos de lesão hepatocelular quando o fígado é exposto a doenças graves e o potencial de hepatotoxicidade de um grupo específico de fármacos.RELATO DO CASO: Paciente do sexo masculino, 51 anos, portador de DM2 e de psoríase numular. História de uso moderado de bebidas alcoólicas por longo período com risco de desenvolver doença hepática alcoólica (DHA). Acresce sorologia positiva para hepatite pelo vírus C (VHC). O fígado palpável, a confirmação da hepatomegalia em exame ultrassonográfico e a elevação das aminotransferases denunciam afecção hepática. CONCLUSÃO: As interações entre o DM2, DHGNA, DHA, VHC e a psoríase, bem como a toxicidade potencial cruzada dos fármacos indicados para o tratamento dessas comorbidades, representam risco real de agressão hepatocelular. A análise comparativa do perfil de segurança dos antidiabéticos orais (ADO) permite eleger os inibidores da dipeptidilpeptidase 4 (i DPP4) como os fármacos de menor potencial de lesão hepática, considerando que não são, em geral, substratos para o sistema do citocromo CYP450 e não atuam como indutores ou inibidores deste sistema com ações metabolicamente apreciáveis.

BACKGROUND AND OBJECTIVES: Insulin resistance (IR) plays a key role in the pathogenesis of type 2 diabetes mellitus (DM2). Compensatory hyperinsulinemia prevents the proper metabolism of fatty acids, leading to accumulation of fat in hepatocytes. The non-alcoholic fatty liver disease (NAFLD) in which hepatic steatosis is the most common clinical expression, has a high incidence among DM2 patients. This paper aims to discuss the risk of hepatocellular injury when the liver is exposed to serious diseases, and the potential hepatotoxicity of a specific group of drugs. CASE REPORT: Male, 51 year-old patient, with DM2 and nummular psoriasis with a history of moderate use of alcoholic beverages for long periods at risk of developing alcoholic liver disease (ALD), and positive serology for hepatitis C virus (HCV). The liver was palpable, the confirmation of hepatomegaly in ultrasound and elevated aminotransferases show liver disease. CONCLUSION: The interactions between DM2, NAFLD,ALD, HCV and psoriasis, as well as the potential cross-toxicity of drugs indicated for the treatment of these comorbidities, represent real risk of hepatocellular injury. The comparative analysis of the safety profile of oral antidiabetic (OAD) drugs allows the election of dipeptidyl peptidase 4 inhibitors (DPP4 i) as the drugs of lower liver damage potential, considering that generally they are not substrates for the CYP450 system and do not work as inducers or inhibitors of this system with substantial metabolic actions.

Hfe mutations add iron overload in patients with alcoholic liver disease

Context Alcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003). Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, ...

Contexto A doença hepática alcoólica (DHA) está geralmente associada à sobrecarga de ferro, que pode contribuir para a sua patogênese, através do aumento do estresse oxidativo e dano celular. As descrições existentes na literatura sobre a associação entre mutações HFE e a gravidade da DHA nem sempre são concordantes. Objetivos Comparar a prevalência de mutações HFE entre um grupo de pacientes com DHA e uma população de controle. Avaliar a relação entre mutações HFE e os depósitos de ferro hepático. Avaliar se a presença dessas mutações está associada com a gravidade da DHA. Métodos Compararam-se 63 pacientes com DHA que efetuaram biopsia hepática com 52 controles saudáveis. A genotipagem HFE (wild type, C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M, W164X) e uma avaliação laboratorial de rotina (incluindo cinética do ferro) foram feitos em todos os indivíduos. Realizou-se regressão logística multivariada nos casos para avaliar se a presença de mutações HFE estava relacionada com risco aumentado de depósitos de ferro hepático aumentados, ferritina sérica anormal, fibrose hepática significativa ou atividade necroinflamatória. Resultados Os pacientes apresentaram ferritina sérica e saturação da transferrina mais elevadas que os controles, mas não existiram diferenças significativas na distribuição de mutações HFE entre pacientes e controles. Considerando apenas os pacientes, o risco relativo de estes apresentarem pelo menos uma mutação HFE e depósitos de ferro hepático significativos foi de 17.23 (CI 95% 2.09-142.34, P = 0.008). Contudo, a presença ...

Qualidade de vida e consumo de alcoólicos em hepatopatas do sexo masculino / Quality of life and alcohol consumption in male patients with liver diseases

CONTEXTO: O uso disfuncional de álcool é um problema com amplas consequências. Além disso, os efeitos do seu uso sobre a qualidade de vida não foram ainda muito estudados. OBJETIVO: Avaliar a qualidade de vida de hepatopatas e verificar suas possíveis associações com o consumo de alcoólicos e variáveis sociodemográficas. MÉTODO: Estudo transversal realizado com pacientes atendidos em ambulatório de hepatologia, entre abril e dezembro de 2009, avaliando homens entre 20 e 59 anos e escolaridade superior à 5ª série do ensino fundamental. Instrumentos: CAGE, AUDIT, WHOQOL-Bref e questionário sociodemográfico. RESULTADOS: Pacientes CAGE positivos tiveram médias mais baixas no domínio físico do WHOQOL (p = 0,027). Aqueles que nunca usaram alcoólicos tiveram médias mais altas no domínio social comparados aos consumidores de médio e alto risco ou provável dependência no ano (p-valores, respectivamente, 0,023 e 0,036). Abstêmios e usuários de baixo risco registraram médias mais elevadas no domínio social comparados aos usuários de médio risco no último ano (p = 0,031). CONCLUSÃO: Os mais baixos níveis de qualidade de vida nos domínios físico (CAGE) e social (AUDIT) registrados pelos pacientes que informaram consumo de alcoólicos de alto risco ou provável dependência são consistentes com achados da literatura.

BACKGROUND: Dysfunctional use of alcohol is a problem with broad consequences. Moreover, there exists little evidence about the impact of dysfunctional use on quality of life. OBJECTIVE: To evaluate the quality of life of patients with liver diseases and to verify its possible associations with alcohol consumption and sociodemographic variables. METHOD: Transverse study with masculine patients between 20 and 59 years of age and with at least 5 years of primary school completed, assessed between April and December 2009 in a hepatology service. Instruments: CAGE, AUDIT, WHOQOL-Bref and sociodemographic questionnaire. RESULTS: CAGE positive patients had a lower average in the physical domain of WHOQOL (p = 0.027). Those who never used alcohol had higher scores in the social domain compared to patients with medium and high risk consumption or probable dependence in the past year (p = 0.023 and p = 0.036 respectively). Abstainers and low-risk users recorded the highest average in the social domain compared to medium risk users in the past year (p = 0.031). DISCUSSION: The lowest levels of quality of life in the physical (CAGE) and social (AUDIT) domains reported by patients with alcohol consumption of high risk or probable dependence are consistent with findings in the literature.