Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Although sirtuin 1 (SIRT1) over-expression and resveratrol exert anti-inflammatory and proinflammatory effects, their effects and the mechanism of action on human gingival fibroblast (HGF)-mediated inflammation are unknown. The aim of this study was to demonstrate the effects of activating SIRT1 using resveratrol and recombinant adenovirus encoding SIRT1 (Ad-SIRT1) on the expression of proinflammatory cytokines and to elucidate its mechanism of action of lipopolysaccharide (LPS) and nicotine stimulated-HGF. MATERIAL AND METHODS: Cytotoxicity and the production of reactive oxygen species (ROS) were measured using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The amount of prostaglandin E2 (PGE2 ) released into the culture medium was measured by radioimmunoassay. mRNA and protein levels were analyzed using RT-PCR and western blotting, respectively. RESULTS: Nicotine and LPS up-regulated the expression of SIRT1 mRNA and SIRT1 protein in a time- and concentration-dependent manner. Resveratrol and Ad-SIRT1 decreased LPS and nicotine-induced cytotoxicity, ROS and PGE2 production, and expression of cyclooxygenase-2 in HGFs. Resveratrol and Ad-SIRT1 inhibited nicotine and LPS-mediated protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), p38, ERK, JNK, MAPK and nuclear factor-kappa B (NF-κB) activation. CONCLUSION: This study is the first to show that the anti-inflammatory and cytoprotective effects of SIRT1 activation in HGFs occur through the PKC, PI3K, MAPK and NF-κB pathways.

The C-caffeine breath test distinguishes significant fibrosis in chronic hepatitis B and reflects response to lamivudine therapy.

BACKGROUND: The 13C-caffeine breath test is a non-invasive, quantitative test of liver function. AIM: To determine the utility of the 13C-caffeine breath test in chronic hepatitis B virus and its ability to monitor response to lamivudine. METHODS: Forty-eight chronic hepatitis B virus patients and 24 controls underwent the 13C-caffeine breath test. In 28 patients commenced on lamivudine, 13C-caffeine breath tests were performed at 1 week (n = 12) and after 1 year of therapy. RESULTS: Patients with Metavir F0-1 fibrosis (2.30 +/- 1.02 Delta per thousand per 100 mg caffeine) had a 13C-caffeine breath test similar to controls (2.31 +/- 0.85, P = 0.96). However, patients with F2-3 fibrosis (1.59 +/- 0.78, P = 0.047) and cirrhotic patients (0.99 +/- 0.33, P = 0.001) had a decreased 13C-caffeine breath test. Fibrosis correlated best with the 13C-caffeine breath test (r(s) = -0.62, P < 0.001). The 13C-caffeine breath test independently predicted significant (F > or = 2) and advanced (F > or = 3) fibrosis and yielded the greatest area under the receiver operating characteristic curve (0.91 +/- 0.04) for predicting advanced fibrosis. The 13C-caffeine breath test was unaltered by 1 week of lamivudine but improved by 61% (P < 0.001) in responders to long-term lamivudine, whereas in those with viraemia and elevated alanine aminotransferase, values remained stable or deteriorated. CONCLUSION: The 13C-caffeine breath test distinguishes chronic hepatitis B virus-related fibrosis and detects improvement in liver function in response to long-term lamivudine.

Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum.

Herbal preparations are widely available and generally regarded by the public as harmless remedies for a variety of medical ailments. We report the first case in Australia of acute hepatitis associated with the Chinese herbal medicine Shou-Wu-Pian, prepared from Polygonum multiflorum. Cholestatic hepatitis developed in a Chinese woman taking this preparation for the greying of her hair, and liver biopsy was consistent with a toxic reaction. Clinical and biochemical resolution occurred following cessation of the drug.

Aspartate aminotransferase: alanine aminotransferase ratio in chronic hepatitis C infection: is it a useful predictor of cirrhosis?

BACKGROUND: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST:ALT > or = 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST:ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. METHODS: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST:ALT. RESULTS: In 30 patients with cirrhosis, the mean AST:ALT (0.99 +/- 0.06) was higher than in 123 patients without cirrhosis (0.60 +/- 0.02; P < 0.001). A ratio > or = 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. CONCLUSION: Although relatively insensitive, an AST:ALT > or = 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients.

Electronic memory aids for outpatient brain injury: follow-up findings.

The introduction of highly portable computers extends the range of tools potentially useful to persons with functional impairments of prospective memory resulting from brain injury. This study reviews the experience of 12 patients with brain injury undergoing outpatient treatment using palmtop computers to assist with memory dependent activities in their everyday lives. During the initial supervised trial period, each was provided a palmtop computer based memory aid capable of generating audible and visible reminder cues. Subsequently, patients were contacted for follow-up between 2 months and 4 years after initial trial usage, and surveyed as to the utility of the computer. Nine patients found palmtop computers were useful during supervised trials. Seven of nine patients actually continued to use such devices after the usage trials had ended. Experience with this technology has shown it to be useful in a high proportion of patients for assisting with memory dependent functions.