Nootkatone improves anxiety- and depression-like behavior by targeting hyperammonemia-induced oxidative stress in D-galactosamine model of liver injury.

Acute or chronic liver injury is closely related to hyperammonemia, which will result in oxidative stress and damage to nerve cells, and these factors are vital to the development of anxiety and depression. In this study, the effect of Nootkatone (NKT) on the anxiety- and depression-like behavioral changes in mice induced by liver injury was investigated. Liver injury was induced by D-galactosamine (D-GalN; 350 mg/kg) three times a week for 4 weeks. NKT (5 mg/kg or 10 mg/kg) was given as co-treatment daily for 4 weeks. NKT (5 mg/kg) co-treatment remarkably ameliorates D-GalN-induced anxiety- and depression-like behaviors as evident from the results of sucrose preference test, forced swimming test, tail suspension test, and novelty suppressed feeding test. Results showed that NKT could induce an elevation in serum alanine transaminase and aspartate transaminase level, alleviate the oxidative stress induced by hyperammonemia through activating Keap1/Nrf2/HO-1 antioxidant pathways, decrease the expression of inducible nitric oxide synthase and NOX2 in hippocampus and prefrontal cortex, enhance the vitality of superoxide dismutase, catalase, and glutathione levels in serum, liver, and brain, and significantly reduce the generation of malondialdehyde. At the same time, NKT also reduces the level of ammonia in serum and brain and upgrades the activity of glutamine synthetase in the hippocampus and prefrontal cortex. Taken together, the present results suggested that NKT has a significant antidepressant effect through modulation of oxidative stress induced by D-GalN administration.

Depressive-like behaviors are induced by chronic liver injury in male and female mice.

Depression is a highly prevalent mental disease and increasingly become a global public health problem. Recent studies have shown that the dysfunction of liver was associated with depression. However, the previous studies have not been fully explained the relationship between depression and liver injury. The present study was aimed to investigate whether chronic liver injury could induce depressive-like behavior. Chronic liver injury was induced by intraperitoneal injection of carbon (CCl4), D-galactosamine (D-GalN) and thioacetamide (TAA), respectively. And the results showed that the serum activities of ALT in CCl4, D-GalN and TAA groups were significantly increased in both male and female mice compared with the control group, while the activities of AST increased only in CCl4 group. Meanwhile, H&E staining showed that CCl4, D-GalN and TAA induced hepatocytes injury in both male and female mice. Moreover, the sucrose preference was significantly decreased and the immobility time in forced swimming test and tail suspension test were significantly prolonged in CCl4 and D-GalN group compared with control group. Our findings demonstrated that chronic liver injury induced by CCl4 and D-GalN could induce depressive-like behaviors in mice.

Liver Transplantation for Acetaminophen-Induced Acute Liver Failure: Role of Psychiatric Comorbidity in Listing Decisions and Outcomes.

BACKGROUND: Psychiatric co-morbidities are thought to deter listing of patients with acetaminophen-induced acute liver failure (APAP-ALF) for liver transplantation (LT). We examined the listing process and short-term outcomes via a cohort study of APAP-ALF patients with and without psychiatric comorbidity. METHODS: We analyzed listing determinants, listing rates, and short-term (21-day) outcomes in APAP-ALF patients with and without psychiatric comorbidity (mental illness and/or substance abuse) enrolled in the ALFSG registry between 2000 and 2016. RESULTS: Of the 910 APAP-ALF patients, 801 (88%) had evidence of psychiatric comorbidity. There was no difference in listing between patients with (169/801, 21%) and without (26/109, 24%) psychiatric comorbidity (p = 0.59). Listed patients in both groups were younger with more severe admission clinical parameters than those not listed. Patients with and without psychiatric comorbidity had similar short-term outcomes: transplant rates among listed patients [57/169 (34%) vs 10/26 (39%), p = 0.80], spontaneous (transplant-free) survival (SS) [544/801 (68%) vs 73/109 (67%), p = 0.93], and overall death [207/801 (26%) vs 26/109 (24%), p = 0.74]. CONCLUSIONS: In our study, which is limited by informal psychiatric assessments, psychiatric comorbidity in APAP-ALF patients does not appear to impact listing, or short-term outcomes-SS, LT, or death. Transplant listing decisions primarily appear to be based on clinical severity of disease, rather than concern that APAP-ALF patients' psychiatric comorbidity will compromise outcomes.

P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet.

Chronic low-grade neuroinflammation is increasingly implicated in organ damage caused by alcohol abuse. Purinergic P2X7 receptors (P2X7Rs) play an important role in the generation of inflammatory responses during a number of CNS pathologies as evidenced from studies using pharmacological inhibition approach. P2X7Rs antagonism has not been tested during chronic alcohol abuse. In the present study, we tested the potential of P2X7R antagonist A804598 to reduce/abolish alcohol-induced neuroinflammation using chronic intragastric ethanol infusion and high-fat diet (Hybrid) in C57BL/6J mice. We have previously demonstrated an increase in neuroinflammatory response in 8 weeks of Hybrid paradigm. In the present study, we found neuroinflammatory response to 4 weeks of Hybrid exposure. A804598 treatment reversed the changes in microglia and astrocytes, reduced/abolished increases in mRNA levels of number of inflammatory markers, including IL-1ß, iNOS, CXCR2, and components of inflammatory signaling pathways, such as TLR2, CASP1, NF-kB1 and CREB1, as well in the protein levels of pro-IL-1ß and Nf-kB1. The P2X7R antagonist did not affect the increase in mRNA levels of fraktalkine (CX3CL1) and its receptor CX3CR1, an interaction that plays a neuroprotective role in neuron-glia communication. P2X7R antagonism also resulted in reduction of the inflammatory markers but did not alter steatosis in the liver. Taken together, these findings demonstrate how P2X7R antagonism suppresses inflammatory response in brain and liver but does not alter the neuroprotective response caused by Hybrid exposure. Overall, these findings support an important role of P2X7Rs in inflammation in brain and liver caused by combined chronic alcohol and high-fat diet. Graphical Abstract ᅟ.

Psychosocial and behavioral factors in acetaminophen-related acute liver failure and liver injury.

OBJECTIVES: Acetaminophen overdoses result in nearly 500 deaths annually and a much larger number of hospitalizations. Suicidal overdoses are exceeded in number in the United States by unintentional overdoses. We evaluated clinical, demographic and psychosocial factors among unintentional and intentional overdose patients whose acetaminophen (APAP) toxicity had resulted in acute liver failure. We hypothesized that APAP overdose patients would be more likely to suffer from behavioral health issues and display higher impulsivity scores than the general population. METHODS: Within 4days of admission and initial recovery of alertness, we administered a detailed questionnaire that included questions on APAP intake (e.g., dose taken, intent, other substances ingested), the Mini International Neuropsychiatric Interview modules on depression, alcohol use, substance use, and pain disorders and The Barratt Impulsiveness Scale-11. RESULTS: The group included 44 intentional (single time point ingestions with the intent to self-harm) and 51 unintentional (multiple time point ingestions to manage pain or other condition) APAP patients enrolled in the Acute Liver Failure Study Group registry between 2007 and 2013. Both groups were characterized by similar frequencies of chronic pain, depressive symptoms at time of ingestion and alcohol and substance use disorders, all at higher rates than the general population. Overall, APAP patients scored higher than the general population for Non-planning aspects of impulsivity, with no apparent differences between other impulsivity scores or between intentional and unintentional APAP patients. CONCLUSIONS: Depression, mismanagement of problematic chronic pain, frequent substance abuse, and increased impulsivity appear to provide the substrate for many APAP overdoses.

Interactions Between Platelets and Inflammatory Monocytes Affect Sickness Behavior in Mice With Liver Inflammation.

BACKGROUND & AIMS: Patients with inflammatory liver disease commonly develop debilitating symptoms, called sickness behaviors, which arise via changes in brain function. Monocytes that produce tumor necrosis factor interact with cerebral endothelial cells to activate microglial cells and promote sickness behavior. Platelets regulate inflammation, and aggregates of monocytes and platelets are increased in the circulation of patients with liver disease. We investigated the role of platelets in inducing inflammatory features of circulating monocytes and promoting sickness behaviors in mice with cholestatic liver injury. METHODS: We performed bile-duct ligations or sham surgeries on C57BL/6 or toll-like receptor 4 (TLR4)-knockout mice to induce liver inflammation. Liver inflammation was also induced in a separate group of mice by administration of concanavalin A. Circulating platelets, aggregates of monocytes and platelets, and activation of microglial cells were measured by flow cytometry. To deplete platelets, mice were given anti-thrombocyte serum or normal rabbit serum (control) 4 days after surgery. Interactions between monocytes and cerebral endothelial cells were analyzed by intravital microscopy. Sickness behaviors were quantified based on time spent by adult mice engaging in social behaviors toward a juvenile mouse, compared with time spent in nonsocial behavior or remaining immobile. RESULTS: Aggregates of monocytes and platelets in circulation of mice increased significantly following bile-duct ligation. Platelet-monocyte interactions were required for activation of inflammatory monocytes and production of tumor necrosis factor. Platelet depletion greatly reduced adhesive interactions between inflammatory monocytes and adhesive interactions with cerebral endothelial cells and activation of the microglia, as well as development of sickness behavior. Furthermore, TLR4 signaling was important for aggregation of monocytes and platelets, and development of sickness behavior following bile-duct ligation. These findings were confirmed in mice with concanavalin A-induced liver injury. CONCLUSIONS: In mice with liver inflammation, we found TLR4 and aggregates of monocytes and platelets to regulate microglial activation and development of sickness behavior. These findings might lead to new therapeutic strategies for liver disease-associated symptoms.

Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice.

Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison.

Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2.

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of inflammatory cells, degeneration, vacuolization, and necrosis of acinar cells and distention of pancreatic ducts. Extent of pancreatic damage and pancreatitis were scored 3.6 ± 0.4 (severe) for DBTC-treated in contrast to score 0 (normal) in sham-treated animals. The gall bladder became expanded with ductal distention, and occasional bile stones were detected along with microscopic hepatic lesions. DBTC-treated animals developed splenic hypertrophy with increased weight and length (P < 0.01) along with thymic atrophy (P < 0.001). Finally, colitic lesions and colitis were prominent in DBTC-treated animals and scored 3.4 ± 0.3 (moderately severe) vs 0 (normal) for the sham-treated animals. CONCLUSION: This is the first report of chronic inflammatory multiorgan hepatobiliary pancreatitis, along with fibrosis and calculi formation induced reliably utilizing oral DBTC administration in TNFR1/R2 deficient mice.

[A 36-year old schizophrenic patient with paracetamol intoxication]. / Intoxication au paracétamol chez une patiente schizophrène de 36 ans.

Paracetamol poisoning is by far the most common poisoning. Its diagnosis must be made promptly because it can lead to severe liver damage and even to death. Its management protocol uses N-acetylcysteine which must be administered before the onset of hepatic cytolysis. OBSERVATION: we report the case of a 36-year old female in a delusional paranoid state admitted to the emergency department with multifocal pains for whom paracetamol poisoning was finally diagnosed. The initial (clinical and biological) results were negative. An unexpectedly severe acute liver failure followed within 48 hours after having been admitted in the hospital. The diagnosis and therefore the administration of the antidote were delayed due to the psychiatric state of the patient which hindered the medical history evaluation. DISCUSSION: emergency doctors should take extra care when evaluating psychiatric patients since psychiatric symptoms can hinder good medical history taking thereby potentially misguiding the diagnosis and obscuring a potentially lethal disease. Repeated evaluation of these patients is essential.

L'intoxication au paracétamol est de loin l'intoxication la plus fréquente. Son diagnostic doit être établi précocement car el le peut conduire à une atteinte hépatique sévère voire au décès. Son protocole de prise en charge fait appel à la N-acétylcystéine. Celle-ci doit être administrée avant l'apparition de la cytolyse. OBSERVATION: nous rapportons le cas d'une dame de 36 ans admise aux urgences adultes pour des algies multifocales dans un tableau paranoïde délirant. Une intoxication au paracétamol est finalement diagnostiquée. Le bilan (organique et biologique) initial est négatif et se complique dans les 48 heures d'une insuffisance hépatique aiguë de sévérité inattendue en relation avec un surdosage en paracétamol. Le diagnostic et donc le traitement antidote sont retardés à cause du tableau psychiatrique qui interfère dans l'anamnèse. DISCUSSION: le report de cette observation est intéressant car il sert à rappeler aux urgentistes qu'un tableau psychiatrique peut faussement orienter un diagnostic en occultant une pathologie potentiellement létale. Une réévaluation systématique de ces patients est indispensable.

[Effect of silymarin on liver health and quality of life. Results of a non-interventional study]. / Einfluss von Silymarin auf Lebergesundheit und Lebensqualität.

BACKGROUND: Many drugs are known to have hepatotoxic side effects. The effect of silymarin on liver function and liver-injury-impaired quality of life under daily practice conditions in patients with elevated values of liver enzymes was evaluated in the present non-interventional study. METHOD: Patients with drug-induced elevated aminotransferase levels and indication for silymarin (Legalon forte) treatment for 2 to 3 months were documented prospectively over 4 months. At baseline, after 2 and 4 months, respectively, the following parameters were documented: alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase, total bilirubin, presence of liver-related skin symptoms and discoloured urine, severity of liver-related symptoms and quality of life. RESULTS: In total, 190 patients (53.2% male, median age 60.0 years [range 19-81]) from 48 centres participated in the non-interventional study. Among potentially hepatotoxic drugs, analgesics/anti-inflammatory drugs were used most frequently (45.8%). These drugs have been administered for a median period of 2.8 years (range 0.0-26.1). At baseline, all patients had elevated levels of ALT, AST or GGT. Fatigue, flatulence, upper abdominal discomfort, lethargy, and joint complaints were the most severe liver-related symptoms and prevalent in over 62% of patients. Quality of life was affected in 88.7% of patients. Significant reductions were achieved in all documented laboratory parameters (p < 0.001), leading to marked improvement in liver-related symptoms and increased quality of life already after 2 months. The percentage of patients with liver enzymes in the normal range increased considerably within 4 months. No adverse drug reactions were observed. CONCLUSIONS: Silymarin is a safe and efficacious treatment option for patients with elevated liver enzymes. A benefit in terms of liver-related symptoms as well as quality of life and performance was demonstrated already after 2 months of treatment.

Anxiety and depression propensities in patients with acute toxic liver injury.

AIM: To investigate anxiety and depression propensities in patients with toxic liver injury. METHODS: The subjects were divided into three groups: a healthy control group (Group 1, n = 125), an acute non-toxic liver injury group (Group 2, n = 124), and a group with acute toxic liver injury group caused by non-commercial herbal preparations (Group 3, n = 126). These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale (HADS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and the hypochondriasis scale. RESULTS: The HADS anxiety subscale was 4.9 ± 2.7, 5.0 ± 3.0 and 5.6 ± 3.4, in Groups 1, 2, and 3, respectively. The HADS depression subscale in Group 3 showed the most significant score (5.2 ± 3.2, 6.4 ± 3.4 and 7.2 ± 3.4 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). The BAI and BDI in Group 3 showed the most significant score (7.0 ± 6.3 and 6.9 ± 6.9, 9.5 ± 8.6 and 8.8 ± 7.3, 10.7 ± 7.2 and 11.6 ± 8.5 in Groups 1, 2, and 3, respectively) (BAI: P < 0.01 vs Group 1, P < 0.05 vs Group 2) (BDI: P < 0.01 vs Group 1 and 2). Group 3 showed a significantly higher hypochondriasis score (8.2 ± 6.0, 11.6 ± 7.5 and 13.1 ± 6.5 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). CONCLUSION: Psychological factors that present vulnerability to the temptation to use alternative medicines, such as herbs and plant preparations, are important for understanding toxic liver injury.

High-dose vitamin C: does it exacerbate the effect of psychosocial stress on liver? Biochemical and histological study.

AIM: Chronic stress has been implicated as a contributing factor in liver injury. However, other factors that can contribute to the severity of stress effect in liver injury have not been well characterized. In this study, the combined effect of chronic psychosocial stress and variable dosing levels of vitamin C on liver injury, have been studied. METHODS: Stress was chronically induced using intruder method. Vitamin C was administered by oral gavage. Both biochemical and histopathological measures were undertaken. RESULTS: The results showed that low (50mg/kg/day) and moderate (150 mg/kg/day) doses of vitamin C alone or in combination with chronic stress had no effect on liver. However, combination of high dose of vitamin C (500 mg/kg/day) and chronic stress induced various histopathological liver lesions in most of animals in the group that was stressed and supplemented with high dose vitamin C. CONCLUSION: Results of this study show a dose-dependent effect for vitamin C in exacerbating stress contribution to liver injury.

Duloxetine for depression and the incidence of hepatic events in adults.

Elevated hepatic enzyme levels and hepatic injuries have been associated with duloxetine use in clinical trials and spontaneous reports, but the association of duloxetine with a broad spectrum of hepatic outcomes has not been assessed observationally. This cohort study of adult duloxetine initiators between 2004 and 2006 based on the Ingenix Research Data Mart involved 6 matched comparator cohorts, including 4 antidepressant initiator groups (venlafaxine, nefazodone, selective serotonin reuptake inhibitors, and tricyclic antidepressants), depressed but untreated patients, and individuals without depression. The cohorts were followed up for hepatic events, and proportional hazards regression compared duloxetine initiators with comparator cohorts, whereas Poisson regression compared duloxetine usage categories to account for changed therapy during follow-up. Approximately 64,000 person-years among 21,457 duloxetine initiators and comparator cohorts yielded 51 hepatic outcome events. Venlafaxine initiators (incidence rate ratio [IRR] = 0.34; 95% confidence interval [CI], 0.12-0.95) and the cohort without depression (IRR = 0.30; 95% CI, 0.10-0.93) had lower incidences of combined hepatic events than duloxetine initiators, whereas no other differences in hepatic events were observed for duloxetine initiators relative to selective serotonin reuptake inhibitors, tricyclic antidepressants, and untreated depressed patients. In as-treated analyses, relative to nonuse, current (IRR = 4.30; 95% CI, 1.45-12.81) and recent (IRR = 5.93; 95% CI, 1.63-21.55) duloxetine use was associated with greater incidence of less severe hepatic outcomes but not hepatic-related death and potential acute hepatic failure. Although duloxetine does not seem to increase the risk of hepatic-related death or acute hepatic failure, it may be associated with an increased risk of certain less severe hepatic events.

Medical and psychiatric outcomes for patients transplanted for acetaminophen-induced acute liver failure: a case-control study.

BACKGROUND: Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure (ALF) in the UK. Patients often consume the drug with suicidal intent or with a background of substance dependence. AIMS AND METHODS: We compared the severity of pretransplant illness, psychiatric co-morbidity, medical and psychosocial outcomes of all patients who had undergone liver transplantation (LT) emergently between 1999-2004 for acetaminophen-induced ALF (n=36) with age- and sex-matched patients undergoing emergent LT for non-acetaminophen-induced ALF (n=35) and elective LT for chronic liver disease (CLD, n=34). RESULTS: Acetaminophen-induced ALF patients undergoing LT had a greater severity of pre-LT illness reflected by higher Acute Physiology and Chronic Health Evaluation II scores and requirement for organ support compared with the other two groups. Twenty (56%) acetaminophen-induced ALF patients had a formal psychiatric diagnosis before LT (non-acetaminophen-induced ALF=0/35, CLD=2/34; P<0.01 for all) and nine (25%) had a previous suicide attempt. During follow-up (median 5 years), there were no significant differences in rejection (acute and chronic), graft failure or survival between the groups (acetaminophen-induced ALF 1 year 87%, 5 years 75%; non-acetaminophen-induced ALF 88%, 78%; CLD 93%, 82%: P>0.6 log rank). Two acetaminophen-induced ALF patients reattempted suicide post-LT (one died 8 years post-LT). CONCLUSIONS: Despite a high prevalence of psychiatric disturbance, outcomes for patients transplanted emergently for acetaminophen-induced ALF were comparable to those transplanted for non-acetaminophen-induced ALF and electively for CLD. Multidisciplinary approaches with long-term psychiatric follow-up may contribute to low post-transplant suicide rates seen and low rates of graft loss because of non-compliance.

Antihepatotoxic potential of Trianthema portulacastrum in carbon tetrachloride-induced chronic hepatocellular injury in mice: reflection in haematological, histological and biochemical characteristics.

The effect of an ethanolic extract of the plant Trianthema portulacastrum L. on the CCl4-induced chronic hepatocellular damage of Swiss albino mice has been investigated. The normal mice received olive oil (0.2 ml/mouse) for five weeks. The CCl4 control mice, on the other hand, received CCl4 (0.05 ml/mouse) in olive oil for five weeks. The extract was administered at the dose of 100 mg/kg or 150 mg/kg for five weeks by gastric intubation in addition to CCl4 treatment. The CCl4 administration alone caused hepatocellular necrosis, severe anemia, leucopaenia, lymphocytopaenia, neutrophilia, eosinophilia and haemoglobinaemia along with the alterations of plasma albumin and globulin. The administration of plant extract (at 100 or 150 mg/kg) restored the CCl4-induced alterations of the haematological parameters to the normal level. The extract of T. portulacastrum elicited a marked protection against CCl4-induced hepatotoxicity as indicated by the several haematological parameters, related indices of formed elements, and different fractions of plasma protein. We also observed the dose-dependent antihepatotoxic effect of the extraction on these mice. The 150 mg/kg of extract was found to be more effective in normalizing the toxic effects of CCl4 on the above parameters of mice. These results suggest that the hepatoprotective effect of T. portulacastrum could be caused by its critical involvement in modulating several factors associated with erythropoiesis, and the boosting of general immunity of the host.

Paracetamol self-poisoning. Characteristics, prevention and harm reduction.

BACKGROUND: Paracetamol is now the most common drug used for self-poisoning in the UK and is associated with potentially fatal liver damage. Patients admitted to hospital because of paracetamol overdoses were studied in order to determine their characteristics and factors which might have deterred them from taking paracetamol or reduced the dangers of the overdose. METHOD: Eighty patients were studied in hospital using a structured interview schedule, measures of depression and suicidal intent, information collected through the Oxford Monitoring System for Attempted Suicide, and the results of liver function tests. RESULTS: Acute liver dysfunction (25 patients) was associated with consumption of more than 25 tablets (odds ration 4.46, 95% CI 1.31 to 17.41, P = 0.014). The proportionate use of tablets from blister packs (60%) and loose preparations (46%; 5 patients using both types) reflected their general availability. More of those who took tablets from a loose preparation consumed 25 or more tablets (69%) than those who used a blister-pack preparation (40%; odds ratio = 3.0, 95% CI 1.12 to 9.95, P = 0.028). Only 20 patients thought that any type of warning label would have deterred them from taking a paracetamol overdose. CONCLUSIONS: Establishing a maximum number of tablets (e.g. 25) that can be available in individual preparations is likely to reduce the dangers of paracetamol self-poisoning. The potential effects of other measures are uncertain.

[Drug-induced toxic hepatitis]. / Epatite tossica da farmaci.

The case is described of a woman with drug hepatotoxicity, who was a psychiatric patient. The case is reported because the diagnosis occurred by a "praecoxfeeling", in fact physician's intuition is a personal structure which is born from same external incitements instead of other. The diagnosis was confirmed by clinical tests and by subsequent clinical research.