Allopurinol-induced DRESS syndrome mimicking biliary obstruction

An 84-year-old man was admitted to our hospital with fever, jaundice, and itching. He had been diagnosed previously with chronic renal failure and diabetes, and had been taking allopurinol medication for 2 months. A physical examination revealed that he had a fever (38.8℃), jaundice, and a generalized maculopapular rash. Azotemia, eosinophilia, atypical lymphocytosis, elevation of liver enzymes, and hyperbilirubinemia were detected by blood analysis. Magnetic resonance cholangiography revealed multiple cysts similar to choledochal cysts in the liver along the biliary tree. Obstructive jaundice was suspected clinically, and so an endoscopic ultrasound examination was performed, which ruled out a diagnosis of obstructive jaundice. The patient was diagnosed with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome due to allopurinol. Allopurinol treatment was stopped and steroid treatment was started. The patient died from cardiac arrest on day 15 following admission.     

Hepatitis B e antigen‐negative mutations in the precore and core promoter regions in Korean patients

Most patients with hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B have variants of the hepatitis B virus (HBV) that include mutations in the precore or core promoter regions of the HBV genome. The aim of this study was to investigate the patterns of precore and core promoter mutations and their relationship to HBeAg expression in Korean patients. Four hundred seventy‐five Korean patients with chronic HBV infection between February 1995 and December 2003 were enrolled in this study. There were 236 HBeAg‐positive and 239 HBeAg‐negative patients. Blood samples were tested for HBsAg, anti‐HBs, HBeAg, hepatitis B e antibody (anti‐HBe), liver function tests, and serum HBV DNA. Mutations in the precore and core promoter regions were determined by direct sequencing. In the core promoter region, the C1740, C1753, T1762/A1764, and T1766 mutations were associated with HBeAg escape (all; P < 0.05). In the precore region, a higher frequency of the C1802, A1828, T1846, A1850, C1858, T1862, and A1896 mutations was found in HBeAg‐negative patients (all; P < 0.05). In particular, the A1896 mutation was associated with high serum levels of ALT and HBV DNA in HBeAg‐negative patients (P = 0.014 and 0.026, respectively). Mutations around the Kozak sequence (nucleotides 1809–1812) were found in 6.7% of patients and were not associated with undetectable HBeAg (P = 0.13). In Korean patients, various mutations in the precore and core promoter regions were associated with HBeAg escape and amelioration of hepatic inflammation in HBeAg‐ negative patients. Only the A1896 mutation contributed to HBeAg‐negative chronic hepatitis B. J. Med. Virol. 81:594–601, 2009 © 2009 Wiley‐Liss, Inc.     

Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma

Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross‐sectional case–control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age‐, sex‐, and hepatitis B e antigen (HBeAg) status‐matched patients without HCC (non‐ HCC group). Age and sex were also matched between HBeAg‐positive and ‐negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box α region, the A1689 mutation in between the box α and β regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non‐HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001). Among HBeAg‐negative patients, the frequency of the T1653 mutation was higher in the HCC group. Regardless of HBeAg status, the prevalence of the A1689, and T1762/A1764 mutations was higher in the HCC group than in the non‐HCC group. However, no association was observed between mutations in the precore region and HCC. Upon multivariate analysis, the presence of the T1653, A1689, and T1762/A1764 mutations was an independent predictive factor for HCC. The addition of the T1653 or A1689 mutation to T1762/A1764 increased the risk of HCC. In conclusion, the T1653, A1689, and/or T1762/A1764 mutations were associated with the development of HCC in Korean patients infected with HBV/C2. J. Med. Virol. 81:1002–1008, 2009. © 2009 Wiley‐Liss, Inc.     

Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats

The hepatoprotective activities of Lycium chinense Miller (LC) fruit extract and its component betaine were investigated under carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. The treatment of LC fruit extract significantly suppressed the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera of CCl₄ injured rats, and restored the decreased levels of anti-oxidant enzymes such as total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and suppressed the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2. To visualize the potential activity of betaine, a component of LC fruit, betaine was substituted for LC extract in CCl₄ injured rats. The biochemical profile in CCl₄ injured rats co-treated with betaine matched those of LC fruit treated CCl₄ injured rats. The ameliorative effects of LC extract, as well as betaine, were also confirmed by histopathological examination. Collectively, the present findings imply that LC fruit, via its component betaine, mitigate CCl₄-induced hepatic injury by increasing antioxidative activity and decreasing inflammatory mediators including iNOS and COX-1/COX-2.     

A Case of Embryonal Sarcoma of the Liver Mimicking a Hydatid Cyst in an Adult

An undifferentiated (embryonal) liver sarcoma (ULS) originates from a primitive mesenchymal cell, with a predilection for childhood and very rare occurrence in adults. We report a case of a ULS that was incidentally found in a 53-year-old female. Our case was initially interpreted as a large hydatid cyst, which was later suspected to be a neoplastic lesion because its size was increasing and a solid portion was newly detected after shrinkage of the cyst following drainage. The patient underwent successful right hepatic lobectomy with complete resection, and is currently disease-free without adjuvant therapy. Although it is difficult to diagnose a hepatic cyst as a ULS due to its rare occurrence in adulthood and lack of specific findings, its possibility should be considered, especially when its size is increasing, because early diagnosis and curative resection are necessary for a favorable outcome.     

Effects of ethanol on the tonicity of corporal tissue and the intracellular Ca^2＋ concentration of human corporal smooth muscle cells

Heavy alcohol consumption is associated with an increased risk of erectile dysfunction （ED）; however, the acute effects of ethanol （EtOH） on penile tissue are not fully understood. We sought to investigate the effects of EtOH on corporal tissue tonicity, as well as the intracellular Ca^2＋ concentration （[Ca^2＋]i） and potassium channel activity of corporal smooth muscle. Strips of corpus cavernosum （CC） from rabbits were mounted in organ baths for isometric tension studies. Electrical field stimulation （EFS） was applied to strips precontracted with 10 μmol L^-1 phenylephrine as a control. EtOH was then added to the organ bath and incubated before EFS. The [Ca^2＋]i levels were monitored by the ratio of fura-2 fluorescence intensities using the fura-2 loading method. Single-channel and whole-cell currents were recorded by the conventional patch-clamp technique in short-term cultured smooth muscle cells from human CC tissue. The corpus cavernosal relaxant response of EFS was decreased in proportion to the concentration of EtOH. EtOH induced a sustained increase in [Ca^2＋]i in a dose-dependent manner, Extracellular application of EtOH significantly increased whole-cell K^＋ currents in a concentration-dependent manner （P 〈 0.05）. EtOH also increased the open probability in cell-attached patches; however, in inside-out patches, the application of EtOH to the intracellular aspect of the patches induced slight inhibition of Ca^2＋-activated potassium channel （KCa） activity. EtOH caused a dose-dependent increase in cavemosal tension by alterations to [Ca^2＋]i. Although EtOH did not affect KCa channels directly, it increased the channel activity by increasing [Ca^2＋]i. The increased corpus cavemosal tone caused by EtOH might be one of the mechanisms of ED after heavy drinking.     

Lancemaside A ameliorates colitis by inhibiting NF-κB activation in TNBS-induced colitis mice

Purpose  

In a preliminary study, we found that lancemaside A, which is a main constituent of Codonopsis lanceolata used as an herbal medicine for inflammatory diseases, potently inhibits lipopolysaccharide (LPS)-stimulated, TLR-4-linked NF-κB activation of NF-κB luciferase reporter gene-transfected 293-hTLR4-hemagglutinin (HA) cells. Therefore, we investigated its inhibitory effect in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice.     

Aquaporin-2 Urinary Excretion in Cirrhosis: Relationship to Vasopressin and Nitric Oxide

The aquaporin (AQP) water channel plays an important role in the regulation of water. AQP2 is expressed in the collection duct of the kidney, serving as the final channel that helps to regulate water excretion in the kidneys and affecting the regulation of water and hyponatremia in cirrhotic patients. So far, research on aquaporin expression in cirrhosis has had various results. The purpose of this study is to investigate the factors that affect the regulation of expression of AQP in patients with cirrhosis. The study comprised 81 cirrhosis patients and 18 control subjects. In each group, 24-h urine was collected and nitric oxide and vasopressin levels were measured in the blood. The amount of urinary AQP was measured by Western blot. In this study, the positivity rate and amount of expression of AQP was higher in the cirrhotic group than that of the control group. AQP expression in urine was also compared between the groups with use of diuretics and the groups with no use of diuretics. A 57.4% positivity was observed with the former, whereas a 51.5% was seen in the latter. No significance was found between the groups (P = 0.581). Expression of AQP in compensated cirrhotic patients is significantly higher than decompensated cirrhotic patients and is especially higher in cirrhotic patients with ascites than with no ascites. There is no relationship between the concentration of vasopressin and expression of AQP. Concentration of serum NOx is higher in cirrhotic patients than the control group and there is a positive association between the concentration of serum nitric oxide and AQP in urine. In conclusion, expression of AQP is increased in cirrhotic patients and is significantly higher in patients with ascites. There is a positive association between the expression of AQP and concentration of serum nitric oxide.