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*While Chemwatch has taken all efforts to ensure the accuracy of information in this publication, it is not intended to be comprehensive or to render advice. Websites rendered are subject to change. Gene therapy of severe combined immunodeficiency disease: Proof of principle of efficiency and safety issues Gene therapy, primary immunodeficiencies, retrovirus, lentivirus, genome 2006-05-01
This literature reviews the severe combined immunodeficiency disease(SCID) to assess the effectiveness of gene therapy. Retroviral vectors have been
successfully used ex vivo to transduce hematopoietic precursors from patients with 2 forms of SCID, namely X-linked SCID and ADA deficiency. Fifteen out
of 16 patients with XL-SCID and 4 out of 4 patients with ADA deficiency have benefited from gene therapy. Correction of the immunodeficiency has
been maintained now for 6 years in the first patients to be treated. These results provide clear-cut proof of the principle of gene therapy in relevant
clinical models. However, 3 patients with XL-SCID have developed a severe complication after gene therapy, consisting of leukemia-like clonal lymphocyte proliferation. One of the 3 patients has died from this complication. It is due
to provirus insertion within or close to proto-oncogenes, and to the enhancer activity of the viral LTR on targeted proto-oncogenes. The authors conclude that vector modifications, based mostly on inactivating the enhancer activity of the LTR, should preserve efficacy while improving safety. Authors: Fischer, Alain; Hacein-Bey-Abina, Salima; Lagresle, Chantal; Garrigue, Alexandrine; Cavazana-Calvo, MarinaFull Source: Bulletin de l’Academie Nationale de Medecine (Paris, France) 2005, 189(5), 779-788 (Fr)
Efficacy and Safety of Fasudil in Patients With Stable Angina 2006-05-01 This study evaluated the efficacy and safety of fasudil, an orally available rhokinase inhibitor, in patients with stable angina. Several small, nonplacebo- controlled trials suggest that fasudil reduces myocardial ischemia in patients with stable or vasospastic angina. 206 patients were screened and 84 with reproducible exercise times were randomized 1:1 fasudil or placebo. Where needed nitroglycerin and a beta- or calcium-channel blocker were allowed. Fasudil or matching placebo was force-titrated from 20 mg three times daily to 80 mg twice daily with 20 mg twice-daily increments every two weeks. Symptom-limited exercise testing was performed after two, four, six, and eight weeks of treatment. The results showed that Fasudil up to 80 mg three times daily significantly increased the ischemic threshold of angina patients during exercise with a trend toward increased exercise duration. The authors concluded that further investigation of fasudil doses >80 mg three times daily is indicated. Authors: Vicari, Ralph M.; Chaitman, Bernard; Keefe, Deborah; Smith, William B.; Chrysant, Steven G.; Tonkon, Melvin J.; Bittar, Neville; Weiss, Robert J.; Morales-Ballejo, Hugo; Thadani, Udho Full Source: Journal of the American College of Cardiology 2005, 46(10), 1803- 1811 (Eng) Sustained-release Bupropion Versus Naltrexone in the Treatment of Pathological Gambling: A Preliminary Blind- rater Study 2006-05-01 Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotheraputic agents, including
selective serotonin reuptake inhibitors, mood stabilizers, and opioid
antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the
obsessive-compulsive spectrum disorders and addictive disorders. This study investigates the effectiveness of sustained-release bupropion versus
naltrexone in the treatment of PG observing thirty-six male pathological gamblers. A comprehensive psychiatric diagnostic evaluation was
performed prior to administering the drugs. The patients were screened for symptoms of gambling, depression, and anxiety and completed a self-report
questionnaire about their demographic status. Patients were randomized in 2 groups and received either naltrexone or sustained-release bupropion
for 12 weeks. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which and also assessed for the presence of gambling behavior via an unstructured interview. The results showed twelve
of 17 patients in the sustained-release bupropion group completed the 12-wk study, and 13 of 19 naltrexone patients completed the study. Nine (75%)
of the 12 completers were rated as full responders in the sustained-release bupropion group vs. 10 (76%) of 12 in the naltrexone group. Full response
was defined as the absence of gambling for a 2-wk duration together with improvement on the Clinical Global Impression-Improvement Scale. The
authors concluded that this preliminary study shows that sustained release bupropion may be effective as naltrexone in the treatment of PG; however,
further studies are needed to confirm our findings. Authors: Dannon, Pinhas N.; Lowengrub, Katherine; Musin, Ernest;
Gonopolski, Yehudit; Kotler, Moshe Full Source: Journal of Clinical Psychopharmacology 2005, 25(6), 593-596
The effect of short-contact topical tretinoin therapy for foot ulcers in patients with diabetes
2006-05-01in this study, the efficacy and safety of a short-course of topical tretinoin
on foot ulcers in patients with diabetes was determined. The study was a randomized, double-blind, placebo-controlled trial with observed twenty-
four volunteers with diabetic foot ulcers but without evidence of peripheral arterial disease or infection. Patients were either treated with topical 0.05% tretinoin solution (Retin-A) or placebo saline soln for 4 weeks. Photographs and assessment of wound size and appearance were assessed every 2 wk for a total of 16 wk. The results showed twenty-two patients, with a total of 24 foott ulcers, completed the study. At the end of 16weeks, 2 (18%) of 11 ulcers in the control group and 6 (46%) of 13 ulcers in the tretinoin treatment group healed completely. Topical tretinoin therapy significantly decreased ulcer area and depth compared with placebo treatment over the 16 wk of the study. Adverse effects mainly consisted of mild pain at the ulcer site. The authors concluded that short-contact application of topical tretinoin improved the healing of foot ulcers in patients with diabetes and was generally well tolerated, without serious local or systemic adverse effects. Authors: Tom, Wynnis L.; Peng, David H.; Allaei, Atabak; Hsu, Daniel; Hata, Tissa R. Full Source: Archives of Dermatology 2005, 141(11),1373-1377 (Eng)
Impact of environmental endocrine disruption on the reproductive system for human health 2006-05-01 Endocrine disrupters (EDs) are environmental chemicals that interfere with physiological systems, adversely affecting hormone balance (endocrine system), or disrupting normal function in the organs which hormones regulate or modulate, i.e., the female and male reproductive systems. This review summarizes the interference of environmental EDs on reproductive development and function, and introduces biomarkers and screening methods for Eds in in vitro and in vivo models, in particular, female reproductive system. This was determined by studying of the uterine expression of Calbindin-D9k (CaBP-9k), a cytosolic calcium binding protein regulated by estrogenic or progestogenic compounds In addition, the effect of exposure to multiple EDs on reproductive functions is highlighted, and brings attention to major sources of exposure. Authors: Choi, Kyung-Chul; Jeung, Eui-Bae; Leung, Peter C. K. Full Source: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry 2006, 6(1), 3-13 (Eng), Bentham Science Publishers Ltd. Relationship between urinary thiocyanate and health effects of cyanide exposure 2006-05-01
This study observed the relationship between the urinary thiocyanate (USCN) and main complaints, physical signs and other health effects in workers
exposed to cyanide was studied to verify the feasibility of taking USCN as the bio-marker in health surveillance of cyanide exposure. 106 Male and
19 female cyanide exposed workers employed in a chemical factory were observed. The indexes, such as subjective symptoms, ultrasonic and ECG
examination and so on were analyzed. The urine samples were randomly collected in a routine physical examinations for USCN measurement. The results showed the mean value of USCN was 3.0 mg/L. The USCN
in smokers was twice as much as that in non-smokers. The WBC count went up and the PLT count went down when the USCN level ascended.
There was no statistical relationship between USCN and main complaints, physical signs and other health effects. The authors concluded that USCN
of random urine specimen of cyanide exposed workers was not associated with effects, physical signs and other adjuvant examinations.
Authors: Zhou, Yuanling; Lu, Rongzhu; Fan, Wei; Zhang, Zhaoben; Zhu, Ruijuan; Ying, Qi; Jin, FushengFull Source: Gongye Weisheng Yu Zhiyebing 2004, 30(6), 325-328 (Ch)
Biosensor Recognition of Thyroid-Disrupting Chemicals Using Transport Proteins 2006-05-01 This literature describes the surface plasmon resonance-based biosensor assays for the bioeffect-related screening of chemicals with thyroid-disrupting activity. Two thyroid transport proteins (TPs), thyroxine binding globulin (TBG) and recombinant transthyretin (rTTR), were applied in an inhibition assay format in a Biacore 3000 using CM5 biosensor chips coated with L- thyroxine (T4), the main hormone of the thyroid system. Assay conditions were optimized for the natural thyroid hormones, and known thyroid disruptors and structurally related compounds were selected as model compounds to be tested in both assays for their relative potency (RP) compared to T4. The chosen compounds were halogenated phenols, halogenated bisphenols,
bisphenol A, 3,5-dichlorobiphenyl, and its hydroxylated metabolite 4-hydroxy-3,5-dichlorobiphenyl (4-OH PCB 14).The result demonstrated that the TBG-based assay was highly specific for T4, and the rTTR-based assay was sensitive toward several compounds. The highest sensitivity being obtained with 4-OH PCB 14, followed by tetrabromobisphenol A (RP ) 1.5) and tetrachlorobisphenol A. The authors concluded that for the bioeffect-related screening of known and identification of possible new thyroid disruptors, the TPs-based biosensor assays were more sensitive for the rTTR,.easier to perform, and faster alternatives (10 min/sample) than the currently used methods such as radioligand binding assays and immunopptn.-HPLC. Authors: Marchesini, Gerardo R.; Meulenberg, Eline; Haasnoot, Willem; Mizuguchi, Mineyuki; Irth, Hubertus Full Source: Analytical Chemistry 2006, 78(4), 1107-1114 (Eng)
Quantification of six herbicide metabolites in human urine 2006-05-01 In this study, a sensitive, selective and precise method for measuring herbicide metabolites in human urine was developed using automated liquid delivery of internal standards and acetate buffer and a mixed polarity polymeric phase solid phase extension of a 2 mL urine sample. The eluate was analyzed using high performance liquid chromatography-tandem mass spectrometry. Isotope dilution calibration is used for quantification of all analytes. Precision was similar with samples fortified with 0.1 and 0.25 ng/ mL that were analyzed in each run. The authors concluded that this method produced results that were in agreement, with no significant bias observed. Authors: Norrgran, Jessica; Bravo, Roberto; Bishop, Amanda M.; Restrepo, Paula; Whitehead, Ralph D.; Needham, Larry L.; Barr, Dana B. Full Source: Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences 2006, 830(2), 185-195 (Eng)
Fitocomposti e dieta: quale efficacia nelle dislipidemie Lesi C., Valeriani L., Fabozzi M.T., Giaquinto E., D’Atri A., Zoni L. U.O.C. di Dietologia e Nutrizione Clinica ,P.O. Bellaria-Maggiore, AUSL di Bologna U.O.C. di Dietologia e Nutrizione Clinica, P.O. Bellaria-Maggiore , AUSL di Bologna Tel +390516478689 Fax+390516478727 E-mail [email protected] Riassunto . Le di
Published Cell lines used in perfusion cultures with the BioSep, Acoustic cell retention device. Cell line Viable Cell Aver. conc density (c/ml) DUKX B11- derived CHO (6) DUKX CHO (11) Human (27) recombinant CHO High Five Cells (9) TB/C3 Mouse (1) mouse Hybridoma Mouse mouse Hybridoma (8) Hybridoma (23) Mouse human (30) human hybridoma Hybrido
May 19, 2006
Gene therapy of severe combined immunodeficiency 
selective serotonin reuptake inhibitors, mood stabilizers, and opioid
antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the
obsessive-compulsive spectrum disorders and addictive disorders. This study investigates the effectiveness of sustained-release bupropion versus
naltrexone in the treatment of PG observing thirty-six male pathological gamblers. A comprehensive psychiatric diagnostic evaluation was
performed prior to administering the drugs. The patients were screened for symptoms of gambling, depression, and anxiety and completed a self-report
questionnaire about their demographic status. Patients were randomized in 2 groups and received either naltrexone or sustained-release bupropion
for 12 weeks. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which and also assessed for the presence of gambling behavior via an unstructured interview. The results showed twelve
of 17 patients in the sustained-release bupropion group completed the 12-wk study, and 13 of 19 naltrexone patients completed the study. Nine (75%)
of the 12 completers were rated as full responders in the sustained-release bupropion group vs. 10 (76%) of 12 in the naltrexone group. Full response
was defined as the absence of gambling for a 2-wk duration together with improvement on the Clinical Global Impression-Improvement Scale. The
authors concluded that this preliminary study shows that sustained release bupropion may be effective as naltrexone in the treatment of PG; however,
further studies are needed to confirm our findings.
Impact of environmental endocrine disruption on the 
bisphenol A, 3,5-dichlorobiphenyl, and its hydroxylated metabolite 4-hydroxy-3,5-dichlorobiphenyl (4-OH PCB 14).The result demonstrated that the TBG-based assay was highly specific for T4, and the rTTR-based assay was sensitive toward several compounds. The highest sensitivity being obtained with 4-OH PCB 14, followed by tetrabromobisphenol A (RP ) 1.5) and tetrachlorobisphenol A. The authors concluded that for the bioeffect-related screening of known and identification of possible new thyroid disruptors, the TPs-based biosensor assays were more sensitive for the rTTR,.easier to perform, and faster alternatives (10 min/sample) than the currently used methods such as radioligand binding assays and immunopptn.-HPLC.