Protective effects of glutamine on lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice.

Fulminant hepatitis remains a critical health problem owing to its high mortality rate and the lack of effective therapies. An increasing number of studies have shown that glutamine supplementation provides protective benefits in inflammation-related disorders, but the pharmacological significance of glutamine in lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis remains unclear. In the present study, the potential effects of glutamine on LPS/D-Gal-induced fulminant hepatitis were investigated. Pretreatment with glutamine decreased plasma activities of alanine and aspartate aminotransferases, and ameliorated hepatic morphological abnormalities in LPS/D-Gal-exposed mice. Glutamine pretreatment also inhibited LPS/D-Gal-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production. In addition, glutamine pretreatment decreased the level of cleaved cysteinyl aspartate-specific proteinase 3 (caspase-3), suppressed the activities of caspase-3, caspase-8, and caspase-9, and reduced the number of cells positive for TdT-mediated dUTP nick-end labeling in LPS/D-Gal-challenged mice. Interestingly, post-treatment with glutamine also provided protective benefits against LPS/D-Gal-induced acute liver injury, although these effects were less robust than those of glutamine pre-treatment. Thus, glutamine may have potential value as a pharmacological intervention in fulminant hepatitis.

Forsythia Fruit Prevents Fulminant Hepatitis in Mice and Ameliorates Inflammation in Murine Macrophages.

Forsythia Fruit (FF), the fruit of Forsythia suspensa, has been used since ancient times as an herbal medication in East Asia to treat inflammation, gonorrhea, and pharyngitis. However, the efficacy of FF against liver damage due to inflammation has not been studied. Here, we explored the protective effects of FF in a mouse hepatitis model induced by lipopolysaccharide (LPS)/D-galactosamine (GalN) treatment. We measured inflammatory cytokine and aminotransferase levels in mouse blood and analyzed the effects of FF on inflammatory gene and protein expression levels in liver tissue. Our results show that FF treatment effectively lowers inflammatory cytokine and serum aminotransferase levels in mice and inhibits the expression of hepatic cytokine mRNA and inflammatory proteins. Furthermore, treatment with FF activated the antioxidant pathway HO-1/Nrf-2 and suppressed severe histological alteration in the livers of LPS/D-GalN-treated mice. Further investigation of the effects of FF on inflammatory reactions in LPS-stimulated macrophages showed that pretreatment with FF inhibits inflammatory mediator secretion and activation of inflammatory mechanisms both in a mouse macrophage RAW 264.7 cells and in primary peritoneal macrophages. These results show that FF has potential worth as a candidate for the treatment of fulminant inflammatory reactions and subsequent liver injury.

First Case Report of Fulminant Hepatitis After Laparoscopic Sleeve Gastrectomy Associated with Concomitant Maximal Therapeutic Dose of Acetaminophen Use, Protein Calorie Malnutrition, and Vitamins A and D, Selenium, and Glutathione Deficiencies.

Nonalcoholic fatty liver disease (NAFLD) is increasingly being linked to obesity. Although laparoscopic sleeve gastrectomy (LSG) is effective for weight loss that can ultimately resolve NAFLD, an initial transient deterioration of liver functions could be observed during the first few months post-operatively, after which a subsequent improvement of the liver functions might occur. Rapid weight loss, nutritional deficiencies, and protein malnutrition can all contribute to hepatic dysfunction and can affect the metabolism of medications such as acetaminophen leading to more insult to a compromised liver. We report acute liver failure after LSG associated with protein calorie malnutrition, multiple nutritional deficiencies in addition to concomitant use of therapeutic doses of acetaminophen. Treatment with N-acetylcysteine, and replacement of deficient multivitamins and trace elements resulted in significant improvement in liver functions.

Therapeutic potential of genipin in various acute liver injury, fulminant hepatitis, NAFLD and other non-cancer liver diseases: More friend than foe.

Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis. For decades, genipin is the focus of studies as a versatile compound in the treatment of various pathogenic conditions. In particularly, Gardenia jasminoides Ellis has long been used in traditional Chinese medicine for the prevention and treatment of liver disease. Mounting experimental data has proved genipin possesses therapeutic potential for cholestatic, septic, ischemia/reperfusion-triggered acute liver injury, fulminant hepatitis and NAFLD. This critical review is a reflection on the valuable lessons from decades of research regarding pharmacological activities of genipin. Of note, genipin represents choleretic effect by potentiating bilirubin disposal and enhancement of genes in charge of the efflux of a number of organic anions. The anti-inflammatory capability of genipin is mediated by suppression of the production and function of pro-inflammatory cytokines and inflammasome. Moreover, genipin modulates various transcription factor and signal transduction pathway. Genipin appears to trigger the upregulation of several key genes encoding antioxidant and xenobiotic-metabolizing enzymes. Furthermore, the medicinal impact of genipin extends to modulation of regulated cell death, including autophagic cell death, apoptosis, necroptosis and pyroptosis, and modulation of quality of cellular organelle. Another crucial effect of genipin appears to be linked to dual role in targeting uncoupling protein 2 (UCP2). As a typical UCP2-inhibiting compound, genipin could inhibit AMP-activated protein kinase or NF-κB in circumstance. On the contrary, reactive oxygen species production and cellular lipid deposits mediated by genipin through the upregulation of UCP2 is observed in liver steatosis, suggesting the precise role of genipin is disease-specific. Collectively, we comprehensively summarize the mechanisms and pathways associated with the hepatoprotective activity of genipin and discuss potential toxic impact. Notably, our focus is the direct medicinal effect of genipin itself, whereas its utility as a crosslinking agent in tissue engineering is out of scope for the current review. Further studies are therefore required to disentangle these complicated pharmacological properties to confer this natural agent a far greater potency.

What risks do herbal products pose to the Australian community?

Traditional herbal products are widely used in Australia to treat a broad range of conditions and diseases. It is popularly believed that these products are safer than prescribed drugs. While many may be safe, it is worrying that the specific effects and harmful interactions of a number of their components with prescription medications is not well understood. Some traditional herbal preparations contain heavy metals and toxic chemicals, as well as naturally occurring organic toxins. The effects of these substances can be dire, including acute hepatic and renal failure, exacerbation of pre-existing conditions and diseases, and even death. The content and quality of herbal preparations are not tightly controlled, with some ingredients either not listed or their concentrations recorded inaccurately on websites or labels. Herbal products may also include illegal ingredients, such as ephedra, Asarum europaeum (European wild ginger) and endangered animal species (eg, snow leopard). An additional problem is augmentation with prescription medications to enhance the apparent effectiveness of a preparation. Toxic substances may also be deliberately or inadvertently added: less expensive, more harmful plants may be substituted for more expensive ingredients, and processing may not be adequate. The lack of regulation and monitoring of traditional herbal preparations in Australia and other Western countries means that their contribution to illness and death is unknown. We need to raise awareness of these problems with health care practitioners and with the general public.

Decreased hepatic phosphorylated p38 mitogen-activated protein kinase contributes to attenuation of thioacetamide-induced hepatic necrosis in diet-induced obese mice.

We previously reported that thioacetamide (TA)-induced hepatocellular necrosis was attenuated in mice fed a high-fat diet (HFD mice) compared with mice fed a normal rodent diet (ND mice). In this study, we investigated whether p38 mitogen-activated protein kinase (p38 MAPK) was involved in this attenuation. Western blot analysis revealed that hepatic phosphorylated p38 MAPK protein decreased at 8 and 24 hours (hr) after TA dosing in the HFD mice, while it decreased only at 24 hr in the ND mice in comparison to the time- and diet-matched, vehicle-treated mice. p38 MAPK regulates various biological functions including inflammation, therefore, hepatic metabolomics analysis focusing on pro-inflammatory lipid mediators was performed. At 24 hr after TA dosing, only one pro-inflammatory mediator, 12-hydroxyeicosatetraenoic acid (HETE), was higher in the HFD mice. On the other hand, in addition to 12-HETE, 15-HETE and 12-hydroxyeicosapentaenoic acid (HEPE) were higher and omega-3/omega-6 polyunsaturated fatty acids ratios were lower in the ND mice at 24 hr. These results of metabolomics indicated that less pro-inflammatory state was seen in HFD mice than in ND mice at 24 hr. Finally, to confirm whether the observed decrease in phosphorylated p38 MAPK could attenuate TA-induced hepatocellular necrosis, we showed that SB203580 hydrochloride, an inhibitor of p38 MAPK, partially attenuated TA-induced hepatic necrosis in ND mice. Collectively, these results suggest that a prompt decrease in phosphorylation of p38 MAPK after TA administration is one of the factors that attenuate TA-induced hepatic necrosis in HFD mice.

Lethal hepatocellular necrosis associated with herbal polypharmacy in a patient with chronic hepatitis B infection.

Following a short treatment for irritable bowel with the following herbs: Astragalus propinquus, Codonopsis pilosula, Paeonia sp., Atractylodes macrocephala, Pueraria sp., Poria cocos, Dioscorea opposita, Patriniae, Psoralea corylifolia, Alpinia katsumadai, Glycyrrhiza uralensis and Dolomiaea souliei sp. a 43-year-old woman developed acute severe liver failure requiring liver transplantation. Histopathological examination of the liver showed massive hepatic necrosis in keeping with drug/chemical toxicity. Surgery was followed by multiorgan failure and death. While numerous studies have evaluated the effect of polypharmacy, the study of multiple concurrent herb use is only just emerging, despite the popularity of herbal medicine use in the western world. As this case demonstrates that fulminant hepatic failure and death may be caused by the concomitant use of a number of herbal products, the possibility of untoward effects from herbal polypharmacy must be increasingly considered in the evaluation of medicolegal cases.

Paciente con hepatitis aguda fulminante / Clinical case: coping strategies used by the family of a patient with acute fulminant hepatitis

Dentro del cuidado integral al paciente, la familia debe ocupar una parte indispensable puesto que también se ve afectada por la situación. Por ello, la labor de enfermería debe ir dirigida tanto al individuo como a su entorno, siendo de gran ayuda identificar sus necesidades para cubrirlas adecuadamente. Además, dentro del proceso de convalecencia, la familia atraviesa varias fases de afrontamiento y cada una de ellas tiene unas características propias que hacen que las intervenciones de enfermería deban adecuarse. El objetivo de este artículo es evidenciar la importancia de la atención a la familia, identificando las fases de afrontamiento, reconociendo sus necesidades y detectando los cuidados pertinentes. Para ello, se desarrolla un caso clínico que aborda la situación de una familia con un miembro ingresado en una unidad de cuidados intensivos por una hepatitis aguda fulminante. Los instrumentos utilizados para llevar a cabo el análisis del caso son: las necesidades de la familia descritas por Leske y otros autores, las fases de afrontamiento identificadas por Kubler-Ross y la escala de modos de afrontamiento desarrollada por Lazarus y Folkman. Las enfermeras tienen un rol privilegiado por su contacto cercano con las personas; esto contribuye a ser un agente facilitador en la interacción del paciente y su familia con el ambiente hospitalario. Un enfoque holístico requiere evaluar las necesidades de las familias para posteriormente desarrollar estrategias de intervención efectivas(AU)

In the holistic care to the patient, the family should be an important part because its members are also affected by the situation. Therefore, nursing work should be directed to both the individual and his environment, being of great help to identify family’s needs in order to meet their specific needs accurately. Also in the process of recovery, the family goes through several stages of coping, each of them have its own characteristics and nurses' interventions should be adapted to them. The aim of this paper is to evidence the importance of caring for the family, identifying the stages of coping, recognizing their needs and identifying relevant care. For this, a clinical case of a family with a relative hospitalised in an Intensive Care Unit because of an acute fulminant hepatitis was developed. The instruments used to carry out the analysis of the case are: family's needs described by Leske et al., coping stages identified by Kubler-Ross, and ways of coping scale developed by Lazarus and Folkman. Nurses have a relevant role due to their close contact with people; this helps to become a factor which facilitates the interaction of patient and family within the hospital environment. A holistic approach of nursing care involves assessing the needs of families to develop strategies for effective interventions(AU)

Renal cortex copper concentration in acute copper poisoning in calves / Concentração de cobre no córtex renal na intoxicação aguda de cobre em bezerros

The aim of this study was to estimate the diagnostic value of renal cortex copper (Cu) concentration in clinical cases of acute copper poisoning (ACP). A total of 97 calves that died due to subcutaneous copper administration were compiled in eleven farms. At least, one necropsy was conducted on each farm and samples for complementary analysis were taken. The degree of autolysis in each necropsy was evaluated. The cases appeared on extensive grazing calf breeding and intensive feedlot farms, in calves of 60 to 200 kg body weight. Mortality varied from 0.86 to 6.96 percent, on the farms studied. The first succumbed calf was found on the farms between 6 and 72 hours after the susbcutaneous Cu administration. As discrepancies regarding the reference value arose, the local value (19.9 parts per million) was used, confirming the diagnosis of acute copper poisoning in 93 percent of the analyzed kidney samples. These results confirm the value of analysis of the cortical kidney Cu concentration for the diagnosis of acute copper poisoning.

O objetivo deste trabalho foi estimar o valor diagnóstico de concentração de cobre (Cu) no córtex do rim em casos clínicos da intoxicação cobre aguda (ACP). Um total de 97 bezerros foi compilado em onze fazendas. Pelo menos, uma necropsia foi realizada em cada caso e foram colhidas amostras para análise complementar. O grau de autólise em cada necropsia foi avaliado. Os casos aparecem em criação extensiva e também em fazendas de confinamento intensivo. Os pesos dos animais variavam de 60 até 200 kg. Mortalidade variou entre 0,86 e 6,96 por cento, em todas as fazendas estudadas, o primeiro animal morto foi observado entre 6 e 72 horas após à administração parenteral de Cu. Surgirem discrepâncias em relação ao valor de referência a ser usado. O valor local (19. 9 partes por milhão) foi usado, confirmando o diagnóstico de intoxicação aguda de cobre em 93 por cento das amostras analisadas nos rins. Estes resultados confirmam o valor diagnóstico da concentração de Cu no rim córtex para o diagnóstico de ACP.