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Dibenzyl trisulfide (DTS) is the major active ingredient expressed in Petiveria alliacea L., a shrub widely used for a range of conditions, such as, arthritis, asthma and cancer. Given its use alone and concomitantly with prescription medicines, we undertook to investigate its impact on the activities of important drug metabolizing enzymes, the cytochromes P450 (CYP), a key family of enzymes involved in many adverse drug reactions. DTS and seven standardized extracts from the plant were assessed for their impact on the activities of CYPs 1A2, 2C19, 2C9, 2D6 and 3A4 on a fluorometric assay. DTS revealed significant impact against the activities of CYPs 1A2, 2C19 and 3A4 with IC50 values of 1.9, 4.0 and 3.2µM, respectively, which are equivalent to known standard inhibitors of these enzymes (furafylline, and tranylcypromine), and the most potent interaction with CYP1A2 displayed irreversible enzyme kinetics. The root extract, drawn with 96% ethanol (containing 2.4% DTS), displayed IC50 values of 5.6, 3.9 and 4.2µg/mL respectively, against the same isoforms, CYPs 1A2, 2C19 and 3A4. These investigations identify DTS as a valuable CYP inhibitor and P. alliacea as a candidate plant worthy of clinical trials to confirm the conclusions that extracts yielding high DTS may lead to clinically relevant drug interactions, whilst extracts yielding low levels of DTS, such as aqueous extracts, are unlikely to cause adverse herb-drug interactions.

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BACKGROUND: Vernonia divaricata is one of five endemic Vernonia species of Jamaica. The ethno-medicinal uses of other species have been established, however, scientific validation of this species has not yet been done and as such this paper is aimed at identifying the anti-cancer activity of V divaricata against leukaemia, breast and prostate cancer cell lines. METHODS: Leaves and stems of V divaricata were dried and milled into powder. The crude hexane and methanol extracts of the leaves and stems were obtained and bio-assayed using WST-1 cell proliferation assay against leukaemia, breast and prostate cancer cell lines. RESULTS: The crude hexane and methanol extracts of V divaricata were able to significantly retard the growth of the MCF-7 (breast), HL-60 (leukaemia) and the PC-3 (prostate) cancer cell lines. The crude methanol extract of the stem was the strongest, exhibiting anti-proliferation activity with IC50 values of 10.14, 12.63 and 9.894 µg/ml for the HL-60, MCF-7 and PC-3 cancer cell lines, respectively, with the most potent toward prostate cancer. CONCLUSION: The medicinal use of V divaricata as an anti-cancer agent was corroborated as the crude hexane and methanol extracts demonstrated potent anti-proliferation activity and as such hold potential for further research and development into a drug to prevent or treat various cancers.

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In May 1996, the Georgia Division of Public Health was notified about a cluster of persons with Salmonella Enteritidis (SE) infections in Waycross, Georgia. A matched pair case-control study to determine risk factors for illness found a statistically significant association of SE infection with a history of having eaten at Restaurant A during the 5 days before onset of illness (relative risk = 13 [95% confidence interval (CI) = 3-62, P < 0.01]). In a second case-control study, to determine specific food exposures, consumption of a deep-fried Mexican dish (chile relleno) (4 of 21 cases vs. 0 of 26 controls, odds ratio undefined, 95% CI > 1.46, P = 0.034) was found to be significantly associated with SE infection. An environmental investigation found evidence of suboptimal food storage and cooking temperatures at Restaurant A; cross contamination of foods may have contributed to the low attributable risk identified for chile rellenos. Five of 37 Restaurant A food and environment specimens yielded SE strains. All five positive specimens were from chiles rellenos. Of the seven outbreak-associated strains (six patient isolates and one food isolate from Restaurant A) for which phage typing was conducted, all were phage type 34. A FDA traceback investigation through Restaurant A's single-egg supplier identified the potential source as three interrelated farms in South Carolina. Environmental culture from one of these farms yielded SE phage type 34. As a result of this outbreak, FDA helped institute a statewide egg quality-assurance programme in South Carolina to minimize SE contamination of eggs.

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Flight data obtained between 1990 and 1997 from the Cosmic Radiation Environment Monitors CREAM & CREDO carried on UoSAT-3, Space Shuttle, STRV-1a (Space Technology Research Vehicle) and APEX (Advanced Photovoltaic and Electronics Experiment Spacecraft) provide coverage over half a solar cycle. The modulation of cosmic rays and evolution of the South Atlantic Anomaly are observed, the former comprising a factor of three increase at high latitudes and the latter a general increase accompanied by a north-westward drift. Comparison of particle fluxes and linear energy transfer (LET) spectra is made with improved environment & radiation transport calculations which account for shield distributions and secondary particles. While there is an encouraging convergence between predictions and observations, significant improvements are still required, particularly in the treatment of locally produced secondary particles. Solar-particle events during this time period have LET spectra significantly below the October 1989 event which has been proposed as a worst case model.

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Flight data obtained between 1995 and 1997 from the Cosmic Radiation Environment Monitors CREAM & CREDO carried on UoSat-3, Space Shuttle, STRV-1a (Space Technology Research Vehicle) and APEX (Advanced Photovoltaic and Electronics Experiment Spacecraft) have been added to the dataset affording coverage since 1990. The modulation of cosmic rays and evolution of the South Atlantic Anomaly are observed, the former comprising a factor three increase at high latitudes and the latter a general increase accompanied by a westward drift. Comparison of particle fluxes and linear energy transfer spectra is made with improved environment & radiation transport calculations which account for shield distributions and secondary particles. While there is an encouraging convergence between predictions and observations, significant improvements are still required, particularly in the treatrnent of locally produced secondary particles.

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The Cosmic Radiation Environment and Dosimetry experiment (CREDO) has been operational on board the Advanced Photovoltaics & Electronics Experiment Spacecraft since August 1994. Extensive measurements of cosmic ray linear energy transfer spectra (using data to January 1996) and total dose (using data to November 1994) have been made, and compared with predictions of standard models. Detailed consideration of spacecraft shielding effects have been made. Predictions are shown to overestimate the measured linear energy transfer spectra. The CREAM experiment was flown on STS-63 in the SpaceHab module. Results show penetration of high energy electrons into the SpaceHab module.

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BACKGROUND: Unilateral neck exploration for primary hyperparathyroidism (PHPTH) is controversial because of concern about missed multiglandular disease. METHODS: In patients with sporadic PHPTH our approach has been arbitrarily to surgically explore the right neck first unless preoperative or intraoperative evidence suggests left-sided parathyroid pathologic condition. When an adenoma is identified and a normal ipsilateral gland is confirmed on histologic examination, the contralateral side is not explored. A 15-year series of 371 patients with sporadic PHPTH was reviewed retrospectively to determine the efficacy of this strategy. RESULTS: At operation unilateral exploration was possible in 125 patients (34%). Of these 122 had a single adenoma and two patients had parathyroid carcinoma. One patient with unrecognized hyperplasia required subsequent subtotal parathyroidectomy. There were no major complications. Bilateral surgical exploration was required in 246 patients including 18 with hyperplasia, 4 with double adenomas, and 4 with parathyroid cancer. Bilateral surgical exploration failed in 18 patients (14 persistent and 4 recurrent PHPTH) and was complicated by one recurrent nerve palsy and two cases of permanent hypocalcemia. Operative time was significantly shorter in the unilaterally explored group. CONCLUSIONS: When possible, unilateral exploration for PHPTH is safe and effective, avoids obliterative scarring of the contralateral neck, and may reduce morbidity and operative time.

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We studied the differential increase in FVIIIc and FVIII R:Ag after the intravenous infusion of 0.30 micrograms/kg DDAVP in 20 obligate hemophilia A carriers and in 20 female controls. FVIIIc increased in carriers (59.5 +/- 23.1 to 137.5 +/- 45.9) and in controls (98.0 +/- 20.7 to 259.9 +/- 57.4) (P less than 0.001), but the magnitude of the FVIIIc increase in carriers was less than that in controls by 51.9% (P less than 0.001). FVIII R:Ag increased comparably in carriers (105.2 +/- 30.4 to 171.9 +/- 25.4) and controls (92.1 +/- 33.0 to 165.2 +/- 20.6). Using the post-DDAVP instead of the standard FVIIIc/FVIII R:Ag ratio, hemophilia carrier detection was increased from 85% (with 10% false positive and 20% false negative assignments) to 95% (with 5% false positive and 5% false negative assignments). Toxicity associated with DDAVP infusion correlated linearly with doses greater than 10.5 +/- 1.3 micrograms/m2 (P less than 0.02) and with total doses greater than 17.0 +/- 4.5 micrograms (P less than 0.02). The use of DDAVP improves carrier detection in factor VIII-deficient hemophilia.

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