Increased nitric oxide production in hepatocytes is involved in liver dysfunction following obstructive jaundice

BACKGROUND: Obstructive jaundice damages critical functions in the liver. However, the mechanisms involved in hepatic dysfunction are obscure. Nitric oxide is implicated in liver injury under various pathological conditions. We previously reported that proinflammatory cytokine interleukin-1beta (IL-1beta) stimulated the production of nitric oxide in hepatocytes, which was associated with mitochondrial dysfunction. Studies were performed to examine whether obstructive jaundice influences the production of nitric oxide in hepatocytes and alters hepatic energy metabolism. MATERIAL AND METHODS: Hepatocytes were isolated and cultured from a rat model of obstructive jaundice or sham control. Nitric oxide production, ATP content, and ketone body ratio (acetoacetate/beta-hydroxybutyrate; KBR) were compared between the two groups in the presence of IL-1beta. RESULTS: Hepatocytes obtained from obstructive jaundice rats markedly increased the levels of nitric oxide production stimulated by IL-1beta compared with those from sham control. Western blot analysis revealed that the enhancement of nitric oxide production was a posttranslational event, since protein levels of inducible nitric oxide synthase (NOS) were unchanged between the two groups. IL-1beta decreased cellular ATP content in obstructive jaundice but not in sham control. Further, the KBR, which is a marker of mitochondrial redox state, was lower in obstructive jaundice than in sham control. Addition of N(G)-monomethyl-L-arginine, an inhibitor of NOS, abolished the decreases in ATP content and KBR as well as the nitric oxide production. CONCLUSIONS: These results indicate that a priming of nitric oxide production following obstructive jaundice is associated with the alteration of hepatic energy metabolism in part through mitochondrial dysfunction. Regulation of nitric oxide production may be a useful therapy for preventing liver dysfunction in obstructive jaundice.     

Big snake,small snake: which wound is worse when bitten?

Snakebites in children and teenagers are relatively uncommon in the metropolitan city of Hong Kong. They are rarely fatal but may cause significant morbidity and fear. We report two cases of snakebites to illustrate that the spectrum of morbidity is independent of the size of the snakes. A 7-year-old boy was bitten in successions by a green snake. Envenomation occurred at the second bite site. He developed local and systemic signs that were promptly relieved with anti-venom therapy at the intensive care unit. An 18-year-old girl was bitten by a large python but only sustained minor local soft tissue injuries. This report serves to alert the public that snake may bite in successions and envenomation may occur with the subsequent bite.
Conclusion:  A small snake may be venomous and a large snake may not be. Avoidable risk factors associated with snakebites (such as avoiding areas known to harbour snakes in the evening in summer and autumn and wearing protective footwear) are highlighted.     

Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis

Background Recently, mutations in the filaggrin gene (FLG) have been shown to be a major predisposing factor for atopic dermatitis (AD). Objective In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals. Results We found a strong association of the FLG mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers. Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant asthma compared with those without this co‐morbidity. Conclusion Our data confirm and extend the knowledge of the influence of FLG mutations in AD.     

Impaired gist memory in patients with temporal lobe epilepsy and hippocampal sclerosis

Purpose: Temporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memory functions. We aimed to examine the effect of restricted hippocampal lesions on gist memory function in patients with TLE. Methods: Forty‐five patients with TLE and HS (16 left, 15 right, and 14 bilateral lesions) and 22 control subjects were recruited. Patients with magnetic resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal lesions were excluded. All participants performed a gist‐based recognition task following the Deese‐Roediger‐McDermott paradigm and were tested for verbal IQ and memory functions. We conducted hippocampal volumetry on MRI of all the participants. Results: Patients showed multidomain memory impairments. Gist memory was impaired in patients with bilateral HS and probably in patients with right HS. Hippocampal volumetry supported such findings that total volume of hippocampi and volume of right hippocampus correlated positively with gist memory function. Discussion: HS has a dose effect and a probable right dominance effect on gist memory; good item memory supports gist memory performance; and a disproportionate deficit was noted in tasks with high relational demand but not in tasks with simple association. We should develop memory skills for patients with TLE by enhancing performance of gist memory related to simple association task.