Splenic ischemic preconditioning attenuates oxidative stress induced by hepatic ischemia-reperfusion in rats

Abstract Purpose: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. Methods: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. Results: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. Conclusion: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.

Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Elastografía transicional (fibroscan): nuevo método para la evaluación no invasiva de la fibrosis hepática / Transitional elastography (fibroscan): new method for noninvasive assessment of liver fibrosis

Los grandes avances realizados en la biomedicina y biotecnología durante la última década han puesto en escenamétodos rápidos e incruentos que desafían el ôgold standardõ de los procedimientos diagnósticos y terapéuticos invasivos. Algunos ejemplos de esto incluyen estudioscomo la angiografía coronaria mediante tomografía computada (TC), la resonancia magnética cardíaca (RMcardíaca) para la evaluación no invasiva de las miocardiopatías, y la colonoscopia virtual mediante TC.De esta forma, varios grupos de investigación han desarrolladométodos de imágenes para evaluar la elasticidad de los tejidos de manera no invasiva, teniendo en cuenta las propiedades mecánicas de estos. La elastografía transicional (TE) fue el primer método utilizado, hace unosocho años, en pacientes con enfermedad hepática crónica.Muchos estudios han evaluado la eficacia de este método para el diagnóstico de la fibrosis hepática y la cirrosis, y el Fibroscan es ahora una herramienta utilizada por hepatólogos de todo el mundo, teniendo en cuenta que el pronóstico y tratamiento de las enfermedades crónicas del hígado dependen en gran medida de la extensión y progresión de la fibrosis.

A criança com hepatopatia crônica: abordagem diagnóstica inicial / The child with chronic liver disease: initial diagnostic approach

Um amplo espectro de doenças hepáticas crônicas pode se manifestar na faixa etária pediátrica, seja ao nascimento, nos primeiros anos de vida ou mais tardiamente. As hepatopatias crônicas acarretam impacto importante na morbimortalidade, o que enfatiza a necessidade de diagnóstico precoce. Este artigo aborda a conduta diagnóstica inicial frente a uma criança com quadro sugestivo de hepatopatia crônica. (AU)

A wide spectrum of chronic liver disease can manifest in childhood: either at birth, in the first few years of life, or later. Chronic Liver disease mean significant impact on mortality and morbidity, thus early diagnosis is very important. This article discusses the initial diagnostic approach of a child with chronic liver disease. (AU)

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage.

Hepatoprotective activity of six polyherbal formulations in CCl4-induced liver toxicity in mice.

To evaluate pretreatment of six polyherbal liquid formulations (PLFs) commercially available in India, on CCl4-induced liver injury, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil at a dose of 1 ml/kg. The serum biochemical parameters such as alanine transaminases, aspartate transaminases and alkaline phosphatase were estimated. Phenobarbitone-induced sleeping time and liver histopathology were also carried out. CCl4-treated animals showed significant increase in the levels of liver enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and centrizonal necrosis on histological examination of liver indicating hepatic damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the CCl4-induced changes were significantly reversed. The pretreatment with PLFs can prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it is suggested that a dose adjustment of these PLFs may be necessary for their optimal effects in human liver diseases.

Preventive effect of garlic on histopathology of liver and markers of hepatic injury in streptozotocin-induced diabetic rats

Diabetes mellitus is associated with biochemical, physiological, and pathologic alterations in the liver. In this study, we investigated the preventive effect of garlic juice on changes in the structure of rat liver and serum activities of alanine and aspartate aminotransferases after streptozotocin injection. Forty rats were divided into five groups of 8 rats each: a] Normal group [N], b] Normal+Garlic group [N+G] received 1 ml of garlic juice/100g BW/day for 6 weeks, c] Diabetic group [D] was injected with streptozotocin [60rng/kg BW, i.p.], d] Diabetic+Garlic_before group [D+Gb] received garlic juice for 3 weeks before STZ injection and continued for another 3 weeks, e] Diabetic+Garlic - after group [D+Ga] received garlic juice for 3 weeks after being injected with STZ. Hepatic histological changes were assessed with hematoxylin-eosine staining using a light microscope. In diabetic rats, the activities of serum ALT and AST were significantly increased [p < 0.05] compared to other groups. In D+Gb and D+Ga rats the activity of serum ALT was significantly decreased compared to the D group. The activity of serum AST in D+Gb group had no significant difference with the N and N+G groups and was significantly decreased compared to the D group. In the D group, separated necrosis of hepatocytes, anarchism of liver plates, and lymphocytic inflammation were observed; in the D+Gb and D+Ga groups compared to the D group, all of previous signs improved. Garlic juice was found to influence changes of aminotransferases and prevent the histopathological changes of liver associated with STZ diabetes in rats

Melatonin prevents cyclosporine- induced hepatotoxicity in rats

Cyclosporine A [CsA] is a widely used immuno-suppressive agent that is implicated in the formation of free oxygen radicals. Melatonin is known to be a free radical scavenger and an antioxidant agent. This study was designed to investigate the effects of melatonin on CsA-induced liver damage by histopathological examination. Thirty-two male rats of Sprague-Dawley origin were divided into 4 groups of 8 and treated for 28 days as follows: group 1 received daily doses of 0.1 ml/kg olive oil s.c.; group 2 received 4mg/kg of melatonin; group 3 received 10mg/kg CsA diluted in 0.1 ml/kg olive oil; group 4 was treated with 4 mg/kg melatonin i.p. and 10 mg/kg CsA s.c. Finally, the rats were sacrificed by terminal anesthesia, and liver tissue specimens were processed for light microscopy, stained with HE and examined under a light microscope. Specimens of the control group showed normal liver histology, whereas group 3 showed major histopathological changes, such as cytoplasmic vacuolization, dilatation of the sinusoids, apoptosis and many mitotic figures. In group 4, the normal histology of the liver was preserved, although apoptosis, mitotic figures and cytoplasmic vacuolization were still infrequently observed. Nevertheless, there were significant differences between group 2 [melatonin] and group 3 [CsA] and between group 3 [CsA] and group 4 [CsA + melatonin] concerning these 3 parameters [vacuolization, sinusoidal dilatation and apoptosis]. The results of this study suggest that CsA-related liver toxicity in rats could be significantly reduced by melatonin adminstration

Hyperbaric oxygen therapy aggravates liver reperfusion injury in rats / Oxigenoterapia hiperbárica agrava lesão de reperfusão hepática em ratos

PURPOSE: To evaluate the effects of hyperbaric oxygen (HO) therapy in the protection against liver ischemia/reperfusion injury. METHODS: Thirty-two male Wistar rats were divided into four groups of eight animals each: group A - laparotomy and liver manipulation, group B - liver ischemia and reperfusion, group C - HO pretreatment for 60 min followed by liver ischemia and reperfusion, and group D - pretreatment with ambient air at 2.5 absolute atmospheres for 60 min followed by liver ischemia and reperfusion. Plasma was assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Intra-arterial blood pressure was monitored continuously. Myeloperoxidase activity in the liver and lung was assessed 30 min after reperfusion. RESULTS: Plasma AST, ALT and LDH increased after reperfusion in all animals. Plasma ALT values and myeloperoxidase activity in the liver parenchyma were higher in HO-pretreated animals than in groups A, B and D. HO had a negative hemodynamic effect during liver reperfusion. CONCLUSION: Liver preconditioning with hyperbaric oxygen therapy aggravated liver ischemia/reperfusion injury in rats as demonstrated by plasma ALT and liver myeloperoxidase activity.

OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (OH) como método preventivo da lesão de isquemia e reperfusão (LIR) do fígado. MÉTODOS: Trinta e dois ratos machos Wistar foram distribuídos em quatro grupos de oito animais cada: A - laparotomia e manipulação hepática, B - isquemia e reperfusão hepática, C - pré-tratamento com OH por 60 minutos seguido de isquemia e reperfusão hepática e D - pré-tratamento com ar ambiente a 2,5 atmosferas absolutas por 60 minuto e isquemia e reperfusão hepática. Dosagens seriadas de AST, ALT e DHL foram realizadas. A pressão intra arterial foi monitorizada continuamente. O grau de infiltração leucocitária no fígado e pulmões foi inferido pela dosagem de mieloperoxidade tecidual. RESULTADOS: O nível sérico de AST, ALT e DHL aumentou em todos animais. Os animais expostos a OH apresentaram níveis de ALT e infiltração leucocitária hepática maior que os demais. A OH apresentou efeitos hemodinâmicos negativos durante a reperfusão hepática. CONCLUSÃO: O pré-condicionamento hepático por oxigenoteraia hiperbárica agrava a lesão de isquemia e reperfusão hepática em ratos.

Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70 percent hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.

Consumo dietético de macronutrientes e de micronutrientes e a sua relação com a gravidade da doença hepática / Dietary consumption of macronutrients and micronutrients and their relationship to the severity of hepatic disease

The reduction of the dietary intake in the chronic liver disease can occur as a consequence of the disease treatment or adoption of distorted dietary habits after the diagnosis, which contributes to aggravate the patient ́s nutritional status. The aim of the present work was to characterize the alimentary profile of 147 patients, both male and female, suffering from hepatitis, cirrhosis and hepatocellular carcinoma, through the evaluation of the dietary intake of macronutrients and micronutrients with antioxidant function, represented by vitamins, A, C, and E, besides the intake of minerals, zinc and selenium by patients with chronic liver disease assisted at the University Hospital Clementino Fraga Filho - UFRJ. The food consumption was evaluated through the method of Quantity-Frequency Questionnaire, the dietary intakes of micronutrients were compared to the Recommended Daily Intakes (RDI),and the intakes of macronutrients were compared to the Espenre commendations. The severity of the liver disease was assessed using the Child-Pugh classification (1973). The energy intake decreased along with the disease aggravation. Concerning lipid consumption, an important in adequacy in the consumption of polyunsaturated and mono un saturated fats appears, while the consumption of saturated fat was above the adequate(p<0.05). All the evaluated antioxidant nutrients presented a high percentage of inadequacy. However, no significant differences in the percentages of intake inadequacy according to the different stages of the disease were observed. A significant number of patients informed to have excluded some type of food item from their diets after the diagnosis. We recommend that more attention should be paid to the dietary intake of patients with chronic liver disease in order to improve their life quality and expectancy and prevent the aggravation of their nutritional status, reducing complications and hospitalization costs

La reducción de la ingestión dietética en las hepatopatias crónicas es consecuencia del tratamento de la enfermedad o de la adopción de hábitos alimenticios inadecuados después del diagnóstico y contribuye para el agravamiento del estado nutricional de estos pacientes. En este estudio se caracterizó el perfil alimenticio de 147 pacientes de ambos sexos, portadores de hepatitis, cirrosis o carcinoma hepatocelular (CHC), a través de la evaluación de la ingestión dietética de los macro y micronutrientes. Estos últimos representados por lavitamina A, E y C y los minerales, zinc y selenio de los pacientes portadores de enfermedad hepática crónica atendidos en el Hospital Universitario Clementino Fraga Filho - UFRJ. El consumo alimentar fue evaluado con el método de "Frecuencia d e Consumo Alimentar Semicuantitativo", la ingestión dietética de micronutrientes fue comparada con las recomendaciones de ingestión diaria ­IDR-pregonados por el Institute of Medicine (IOM, 2004) y los macronutrientes con las recomendaciones de la Espen (1997). La gravedad de la enfermedad hepática fue evaluada según la clasificación de Child y Pugh(1973). La ingestión calórica, de acuerdo con lo revelado, se presenta disminuida en correlación conel agravamiento de la enfermedad. Cuánto a la ingestión lipídica, hubo una inadecuación importante en el consumo de grasas poli y monoinsaturados, mientras que el consumo de grasas saturadas revelado estaba arriba del adecuado (p>0,05). Los alimentos antioxidantes evaluados presentan un alto porcentaje de inadecuación, sin embargo, las diferencias en los porcentajes de inadecuación observadas no fueron significativas observadas en relación a la fase de la enfermedad. Un número significativo de pacientes relató haber hecho exclusiones alimenticias después del diagnostico. La ingestión dietética de los pacientes portadores de hepatopatias crónicas necesita mayor atención, objetivando mejorar tanto la calidad como la expectativa de vida, previniendo la deterioración del estado nutricional, reduciendo complicaciones y costos con hopitalización

A diminuição da ingestão dietética nas hepatopatias crônicas ocorre por conseqüência do tratamento da doença ou pela adoção de hábitos alimentares distorcidos após o diagnóstico, contribuindo para o agravo do estado nutricional destes pacientes. O objetivo do trabalho foi caracterizar o perfil alimentar de 147 pacientes, de ambos os sexos, com hepatite, cirrose e carcinoma hepatocelular, através da avaliação da ingestão dietética de macronutrientes e micronutrientes representados pelas vitaminas A, E e C e os minerais, zinco e selênio dos pacientes portadores de doença hepática crônica atendidos no Hospital Universitário Clementino Fraga Filho­ UFRJ. O consumo alimentar foi avaliado através do método de Freqüência de Consumo Alimentar Semi-quantitativo, a ingestão dietética de micronutrientes foi comparada com as recomendações de ingestão diária - IDR preconizados pelo Institute of Medicine (IOM, 2004)e os macronutrientes foram comparados com as recomendações da Espen (1997). A gravidade da doença hepática foi avaliada segundo a classificação de Child e Pugh (1973). A ingestão calórica mostrou-se decrescente de acordo com o agravamento da doença. Quanto ao lipídio consumido, houve uma inadequação importante no consumo de gorduras poli e monoinsaturadas, enquanto, o consumo de gordura saturada mostrou-se acima do adequado (p<0,05). Os nutrientes antioxidantes avaliados apresentaram um elevado percentual de inadequação, porém, não foram observadas diferenças significativas nos percentuais de inadequação de ingestão de acordo com os estágios da doença. Um número significativo de pacientes relatou ter feito exclusões alimentares após o diagnóstico. Recomenda-se uma maior atenção à ingestão dietética dos pacientes portadores de hepatopatias crônicas, objetivando melhorar da qualidade e expectativa de vida, evitando o agravamento de seu estado nutricional, reduzindo complicações e custos com hospitalizações

Hepatoprotective effect of silybum marianum [L] gaertn and glycyrrhiza glabra L. in the rats

One of the major role of liver is metabolism of xenobiotics and detoxification. But sometimes during metabolism of xenobiotics produce active and more toxic agents which cause liver damage and disease. Use of nature products from vegetables. In the treatment of diseases and liver diseases have a long history, especially in Eastern medicine in this study we have investigate the protective effects of polyphenolic extracts of Silybum marianum and Cichorium intybus. Liver damage induced with hepatotoxin, thioacethamide. Extracts was injected every day for a duration of 3 days, to rats, at a doses of 25 mmg/kg body weight together with thioacetamide at a doses of 50 mg/kg body weight. In order to investigate the hepatoprotective effect of extracts against thioacetamide activities of serum aminotrasferases [SGOT and SGPT], alkalline Pbosphatase bilirubin, Na[+] and K[+] were measured.Activities of serum aminotrasferases [SGOT and SGPT], alkaline phosphatase and bilirubin were decreased significantly to rats treated with extracts compared to thioacetamide group. The results showed potent protective effects of these extracts against the thioacetamide induced hepatotoxicity that are due to antioxidant effect of polyphenolic compound

Protective effect of vitamin E on chronic liver damage induced by carbon-tetrachloride [ccl4] in rats

The objective of this study was undertaken to determine whether a sustained increase in hepatic vitamin E could prevent or reduce the extent of CCl4-induced chronic-liver damage and the cirrhotic process. Free radicals affect virtually all aspects of biological existence by reaction and modification of structural, metabolic and genetic material. Studies were performed to examine the mechanisms for the protective effect of free radicals scavengers and to investigate whether the oxidative damage produced in the liver exposed to CCl4 in rats and to find out the effect of antioxidant vitamin E and its ability to protect cell membrane from lipid peroxidation mediated damage and its synthetic derivatives is able to prevent the onset of cell damage consequent to the induction of oxidative stress in different systems in vitro and in experimental acute intoxication with CCl4. 4 groups of male albino rats were studied. The first served as control, the second was fed vitamin E supplemented diet, the third was treated with CCl4 and the last group was treated with CCl4 and after that was supplemented with vitamin E diet

Funcionalismo hepático en trabajadores expuestos a tolueno en una planta procesadora de hidrocarburos / Liver funcion in toluene-exposed workers from a hydrocarbon processing plant

Dado que existe controversia acerca del papel hepatotóxico que juega el tolueno en la industria petrolera y petroquímica en trabajadores expuestos a bajas concentraciones y en forma crónica, se planificó el presente estudio transversal en una población de 33 hombres no expuestos al tolueno, trabajadores de la industria respectiva (grupo control, edad: 33 ñ 4,88 años) comparados con un grupo de 33 hombres (grupo expuesto al tolueno, edad: 35 ñ 9,33 años) y con un tiempo mínimo de exposición de 6 meses y sin antecedentes de enfermedad hepática, a fin de dilucidar la situación en nuestro medio. Además de una minuciosa historia clínica médica-ocupacional, a cada trabajador de los 2 grupo le fue tomada una muestra de sangre venosa (para determinarción de protombina, bilirrubina total y fraccionada, proteínas totales y fraccionadas, transaminasas glutámico-oxalacética y pirúvica, fosfatasa alcalina y colesterol), y de orina (ácido hipúrico), analizados por metodología estandar establecida. Se determinó la concentración ambiental de tolueno en los sitios de trabajo mediante cromatografía de gases, la cual estuvo por debajo de los niveles ambientales permisibles en los lugares de trabajo. Aunque los parámetros analizados estuvieron dentro de los valores normales, se demostró que en los trabajadores expuestos al tolueno con antecedentes de ingesta de alcohol, los resultados se encontraron alterados. Se concluye que el tolueno posee un efecto sinergístico hepatotóxico con el alcohol en los trabajadores expuestos. El alcohol es considerado como factor de confusión y, por lo tanto no se puede descartar en la etiología de los cambios hepáticos detectados en el estudio

Prevention of gastrointestinal diseases.

The prevalence of gastrointestinal diseases markedly differs between developed and developing countries because of the poor sanitation, hygiene, impure water and food ingestion, widespread illiteracy and poverty in the developing world. The incidence of gastrointestinal diseases such as diarrhoea, cholera, typhoid, dysentery, viral hepatitis (A and E virus) can be substantially reduced by providing clean water and food to the population. Restricting consumption of tobacco and nonsteroidal anti-inflammatory drugs will reduce diseases and/or complications of the upper gastrointestinal tract. Diminishing alcohol intake and overuse of blood transfusion and improving blood banks would prevent many acute and chronic liver diseases. Costly passive and active immunoprophylaxis will become unnecessary if these measures are undertaken.

Biochemical mechanisms in hepatotoxicity: oxidative stress induced by xenobiotics and hormonal changes

Cytotoxicity induced by xenobiotics and hormonal changes is a complex event, comprising primary and secondary mechanisms whose joint operation may lead to irreversible molecular changes associated with cell death. In this respect, alcoholic liver cell necrosis may be conditioned either by the generation of ethanol-derived acetaldehyde leading to covalent binding to biomolecules and derangement of key metabolic functions, the production of hypoxic damage secondary to elevated O2 uptake, impairment of membrane functions upon reduction in membrane fluidity, and/or by the development of oxidative stress. The latter mechanism is involved in the hepatotoxic effects of lindane, involving both early direct actions related to the biotransformation of the insecticide and late adaptive changes derived from cytochrome P-450 induction. Thyroid calorigenesis involving an accelerated rate of O2 consumption in the liver determines an increased oxidative stress status due to higher rates of O2 and/or H2O2 production by microsomal, mitochondrial, and peroxisomal electron transport systems, with diminished antioxidant defenses. Hyperthyroidism-induced liver oxidative stress may be associated with cell injury, altered hepatic functions, and potentiation of toxicity by xenobiotics. Liver oxidative stress may be secondarily exacerbated by neutrophil infiltration and/or alterations in Kupffer cell function. These phagocytes release chemical mediators and respiratory burst-related reactive O2 species upon stimulation in the liver, which are potentially toxic for parenchymal cells. As the different factors underlying oxidative stress and the interrelationships between oxidative stress and other cytotoxic mechanisms become better defined preventive and protective interventions will become more clear.

Visceral leishmaniasis in the Dhofar region of Oman

The clinical presentation, frequency distribution of symptoms and signs and laboratory findings were studied in the suspected cases of kala azar admitted to the paediatric wards of sultan Qaboos Hospital, salalah, during period February 1992 to april 1994. response to therapy with sodium stibogluconate was excellent. Mortality in these cases were not encountered