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The endemic juvenile cardiomyopathy known as Keshan disease occurs in regions of China with poor selenium nutrition, but a role for an infectious agent was suggested by seasonal changes in disease incidence. Mice fed a selenium-deficient diet suffered more heart damage than normal mice when infected with a myocarditic coxsackievirus B3 (CVB3/20). Increased heart damage was also observed when CVB3/20 was inoculated into vitamin E-deficient mice. Feeding diets deficient in either vitamin E or selenium allowed an amyocarditic coxsackievirus (CVB3/0) to become myocarditic. When CVB3/0 was harvested from deficient mice, passed through HeLa cells and inoculated into normal (non-deficient) mice, it retained its increased cardiovirulence. Virus obtained from the selenium- deficient mice contained six nucleotide changes in the genome compared with the input strain. This is the first report of a nutritional deficiency driving changes in a viral genome. Host nutritional status could have important public health implications for the spread of influenza, hepatitis, polio and perhaps even AIDS.
Author: LEVANDER OA, ARS, NUTR REQUIREMENTS & FUNCT LAB, BELTSVILLE HUMAN
NUTR RES CTR, USDA, BELTSVILLE, MD
Source: FOOD CHEMISTRY 1996 SEP;57(1):47-49
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Hepatitis, alcohol consumption, cigarette smoking, and hepatocellular carcinoma in Los Angeles.
M. C. Yu, T. Mack, R. Hanisch, R. L. Peters, B. E. Henderson & M. C. Pike
Seventy-eight black patients and white patients with primary hepatocellular carcinoma (PHC), 70 years or younger at diagnosis, and 78 age-, sex-, and race-matched neighborhood controls were interviewed. Information sought included usual dietary and drinking habits, cigarette smoking habits, prior medical conditions including a history of hepatitis, prior exposure to blood products, and occupational history. Cigarette smoking was a risk factor for PHC; the relative risk (RR) for current smokers of more than one pack/day compared to nonsmokers was 2.6. Alcohol consumption was also a significant risk factor for PHC; individuals who drank 80 g or more of ethanol per day had a RR of 4.2 compared to those drinking less than 10 g/day. In addition, a history of hepatitis (RR = 13.0) and a history of blood transfusions (RR = 7.0) were significant risk factors for PHC. Each of these factors remained significant after adjustment was made for the others.
HepC BC Source: PR Newswire
http://www.prnewswire.com [12-19-96 at 12:00 EST, PR Newswire]
SAN MATEO, Calif., Dec. 19 /PRNewswire/ via Individual Inc. - SciClone Pharmaceuticals, Inc. (Nasdaq-NNM: SCLN), an international biopharmaceutical company, today reported that its lead product, ZADAXIN(R) thymosin alpha 1, achieved strong results in a hepatitis C trial led by Dr. Guido Rasi of the Institute of Experimental Medicine in Rome. A report on the trial appears in the current issue of Gut, the journal of the British Society of Gastroenterology.
Fifteen patients with chronic hepatitis C were enrolled in the trial. All patients enrolled had biopsy confirmed chronic hepatitis, raised alanine transaminase (ALT) values equal to or greater than 1.5 times the upper normal limit, positive serum hepatitis C virus ("HCV RNA") by polymerase chain reaction ("PCR") testing, and compensated liver disease. Thirteen patients had HCV RNA genotype 1b which in published reports on the treatment of hepatitis C is often associated with cirrhosis, liver cancer and a poor response to treatment with single agent alpha interferon, currently the only FDA approved therapy for chronic hepatitis C. The patients in Rasi's trial received a combination of lymphoblastoid alpha interferon and thymosin alpha 1 therapy for one year and were followed for an additional six months. The treatment protocol included a "loading dose" of thymosin alpha 1 (1.0 mg subcutaneously) for four consecutive days, followed on the fourth day by the first interferon injection (three million units). For the next 51 weeks, the patients received 1.0 mg of thymosin alpha 1 twice weekly, and three million units of interferon three times per week. A response to treatment was defined at 12 months as a negative serum HCV RNA by PCR. A sustained response was defined as a negative serum HCV RNA by PCR six months after completion of treatment.
After six months of treatment, 47 percent of the patients were found to be HCV RNA negative. After one year of treatment, 73 percent of the patients were HCV RNA negative. After the six month follow-up period, 40 percent of the patients showed a sustained response to treatment and continued to be HCV RNA negative. Among the HCV genotype 1b patients, 69 percent were HCV RNA negative after one year of treatment with 39 percent exhibiting sustained response after the six-month follow-up.
"These trial results, both the response to treatment and sustained response rates, are very exciting, particularly the difficult to treat genotype 1b response rates," said Donald R. Sellers, President and Chief Executive Officer of SciClone Pharmaceuticals. "These results support our belief that thymosin alpha 1 has significant potential as a treatment for chronic hepatitis C."
ZADAXIN, SciClone's lead product, is a synthetically produced peptide that the Company believes stimulates the immune system's disease-fighting properties. ZADAXIN clinical trials continue to support the safety and efficacy of the treatment. In addition to being investigated as a possible treatment for hepatitis C, ZADAXIN is being investigated as a potential treatment for HIV and has been cleared for marketing in several countries as a treatment for hepatitis B.
The statements made in this press release contain certain forward-looking statements, including conclusions regarding the results of clinical studies and the potential of thymosin alpha 1, that involve a number of risks and uncertainties. Actual events or results may differ from the Company's expectations. In addition to the matters described in this release, future actions by the Food and Drug Administration or equivalent regulatory authorities in foreign countries, results of pending or future clinical trials, as well as the risk factors listed from time to time in the Company's SEC reports, including but not limited to its Annual Report on Form 10-K, may affect the actual results achieved by the Company. SciClone Pharmaceuticals is an international biopharmaceutical company engaged in the acquisition, development and commercialization of pharmaceuticals worldwide. SciClone's focus is on therapeutics for diseases that are chronic and life-threatening, including hepatitis B and C, immune system disorders and cancer. SOURCE SciClone Pharmaceuticals Inc.
/CONTACT: Mark Culhane, Chief Financial Officer of SciClone Pharmaceuticals, Inc., 415-358-3456/ (SCLN) CO: SciClone Pharmaceuticals Inc. ST: California
IN: MTC SU: PDT CW-KL -- LATH025 -- 9219 12/19/96 09:00 EST
HepC BC Scand J Gastroenterol 1997 May;32(5):433-438
Konturek PC, Konturek SJ, Brzozowski T, Dembinski A, Zembala M, Mytar B, Hahn EG
Dept. of Physiology, Jagiellonian University School of Medicine, Cracow, Poland.
BACKGROUND: Melatonin, a pineal hormone that is biosynthesized from L-tryptophan, is known to scavenge oxygen free radicals and to be present in the gut, but little is known about the role of this hormone and its precursor, L-tryptophan, in protecting the gastric mucosa from damage accompanied by increase in the generation of oxygen radicals. METHODS: This study was designed to determine the effects of melatonin and L-tryptophan on the formation of acute gastric lesions induced by stress and ischaemia reperfusion and, for comparison, by topical irritants such as 100% ethanol or acidified acetylsalicylic acid. RESULTS: It was found that pretreatment with melatonin in doses ranging from 1.2 to 10 mg/kg dose-dependently reduced the stress-induced gastric lesions and was accompanied by a reduction in blood-free radicals and by attenuation of the fall in gastric blood flow. L-tryptophan applied intragastrically in doses ranging from 1 to 100 mg/kg also reduced dose-dependently the lesions induced by stress; this effect too was accompanied by a rise in gastric blood flow. Pretreatment with indomethacin, to block the biosynthesis of prostaglandins, significantly augmented the lesions produced by stress and completely abolished the protective effects of melatonin or L-tryptophan. Both melatonin and tryptophan reduced the formation of acute gastric lesions provoked by ischaemia reperfusion; this was accompanied by an increase in gastric blood flow. In contrast, melatonin and L-tryptophan failed to influence acute gastric lesions induced by topical irritants such as 100% ethanol or acidified aspirin. CONCLUSIONS: Melatonin and L-tryptophan protect the gastric mucosa from damage by stress and ischaemia reperfusion, and this action is mediated, at least in part, by the limitation in the free radicals, the stimulation of mucosal generation of PG and by the increase in gastric blood flow.
PMID: 9175203, MUID: 97318244
HepC BC Eur J Pharmacol 1997 Mar 12;322(1):73-77
Konturek PC, Konturek SJ, Majka J, Zembala M, Hahn EG
Department of Physiology, Jagiellonian University School of Medicine, Krakow, Poland.
Melatonin, a pineal hormone, is known to scavenge oxygen free radicals and to be present in the gut but little is known about its role in the protection of gastric mucosa against the damage accompanied by a marked increase in these radicals. This study was designed to determine the effects of melatonin on the formation of acute gastric lesions induced by ischemia-reperfusion and, for comparison, by a topical irritant such as 100% ethanol. It was found that pretreatment with melatonin at a dose of 5 mg/kg given intragastrically reduced significantly gastric lesions induced by ischemia-reperfusion and this was accompanied by a reduction in free radicals in the blood and by attenuation of the fall in gastric blood flow. In contrast, melatonin failed to affect acute gastric lesions induced by 100% ethanol. We conclude that melatonin is capable of protecting gastric mucosa from the damage caused by ischemia-reperfusion and that this action is mediated, at least in part, by limitation of the generation of free radicals and by attenuation of the fall in gastric blood flow.
PMID: 9088873, MUID: 97244062
HepC BC SOURCE: American Journal of Gastroenterology, March 1996;91(3):498-505.
Alcoholism; "Alcoholism Is Associated with Hepatitis C but Not Hepatitis B in an Urban Population."
Hepatitis Weekly via Individual Inc. : According to the authors' abstract of an article published in American Journal of Gastroenterology, "OBJECTIVES: Previous studies have suggested an association of viral hepatitis with alcoholism, although the role of confounding risk factors (e.g., i.v. drug use) has not been adequately excluded. We therefore compared the seroprevalences of hepatitis B and C in alcoholic patients to that of a nonalcoholic control group. METHODS: Hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody, and hepatitis C virus antibody testing (second generation ELISA and a confirmatory recombinant immunoblot assay) was performed in 150 consecutive alcoholics admitted for detoxification and in 166 randomly selected patients attending a general medical clinic who were screened for alcoholism. RESULTS: Hepatitis B and C seropositivities in actively drinking alcoholics were 49.3% and 35.3%, respectively, and were significantly associated with a history of i.v. drug abuse. Out of 166 general medicine clinic patients, 93 were classified as nonalcoholic (by both self-report and collateral verification), 46 patients had a history of alcoholism, and 27 were indeterminate. In the subgroup of patients without known viral hepatitis risk factors, there was no significant difference in hepatitis B seropositivity among nonalcoholic general medicine clinic patients, alcoholic general medicine clinic patients, and alcoholic patients admitted for detoxification (22.1%, 30.3%, and 27.6%, respectively). In contrast, anti-HCV recombinant immunoblot assay seropositivity in alcoholic patients admitted for detoxification without risk factors was significantly greater than in nonalcoholic general medicine patients without risk factors (10 vs 0%, p<0.01). Stepwise logistic regression analysis revealed that alcoholism requiring detoxification was a significant risk factor for hepatitis C but not for hepatitis B seropositivity. CONCLUSIONS: The increased seroprevalence of hepatitis C in actively drinking alcoholic patients without known risk factors suggests that alcoholism, in some way, is a predisposing factor for HCV infection."
The corresponding author for this study is: CS Lieber, Vet ADM Med Ctr, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. For subscription information for this journal contact the publisher: Williams & Wilkins, 351 West Camden St, Baltimore, MD 21201-2436.
AUTHORS: Rosman, A.S.; Waraich, A.; Galvin, K.; Casiano, J.; Paronetto, F.; Lieber, C.S.
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