Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention (HIPOCRATES Study).

BACKGROUND: Pretreatment with high-dose statins given before percutaneous coronary intervention (PCI) has been shown to have beneficial effects, in particular by reducing peri-procedural myocardial infarction. The mechanism of these lipid-independent beneficial statin effects is unclear. Circulating endothelial progenitor cells (EPCs) have an important role in the process of vascular repair, by promoting re-endothelization following injury. We hypothesized that statins can limit the extent of endothelial injury induced by PCI and promote re-endothelization by a positive effect on EPCs. We, therefore, aimed to examine the effect of high-dose statins given prior to PCI on EPCs profile. METHODS: Included were patients, either statin naïve or treated chronically with low-dose statins, with stable or unstable angina who underwent PCI. Patients were randomized to receive either high-dose atorvastatin (80 mg the day before PCI and 40 mg 2-4 h before PCI) or low- dose statin. EPCs profile was examined before PCI and 24 h after it. Circulating EPCs levels were assessed by flow cytometry as the proportion of peripheral mononuclear cells co-expressing VEGFR-2+ CD133+ and VEGFR-2+ CD34+. The capacity of the cells to form colony forming units (CFUs) was quantified after 7 days of culture. RESULTS: Twenty three patients (mean age 61.4 ± 7.4 years, 87.0% men) were included in the study, of which 12 received high-dose atorvastatin prior to PCI. The mean number of EPC-CFUs before PCI was higher in patients treated with high-dose atorvastatin vs. low-dose statins (165.8 ± 58.8 vs. 111.7 ± 38.2 CFUs/plate, respectively, p < 0.001). However, 24 h after the PCI, the number of EPC-CFUs was similar (188.0 ± 85.3 vs. 192.9 ± 66.5 CFUs/plate in patients treated with high-dose atorvastatin vs. low- dose statins, respectively, p = 0.15). There were no statistical significant differences in FACS analyses between the 2 groups. CONCLUSIONS: The current study showed higher EPC- CFUs levels in patients treated with high-dose atorvastatin before PCI and a lower increment in EPC-CFUs after PCI. These findings could account for the beneficial effects of statins given prior to PCI, yet further investigation is required.

Stepping from traditional to integrative medicine: perspectives of Israeli-Arab patients on complementary medicine's role in cancer care.

BACKGROUND: Limited research is available on the perspectives of patients with cancer regarding integration of complementary medicine (CM) in conventional supportive cancer care. The purpose of this study was to explore patients' perspectives concerning CM integration within conventional oncology settings. PATIENTS AND METHODS: A 27-item questionnaire was constructed and administered to a convenient sample of Arab patients receiving cancer care in three oncology centers in northern Israel. RESULTS: Of the 324 respondents (94.7% response rate), 124 of 313 (39.6%) reported the use of CM for cancer-related outcomes. A logistic regression model indicated that CM was used with active chemo- or radiotherapy treatment [EXP [B], 2.926, 95% confidence interval (CI) 1.276-6.708; P=0.011] and a higher degree of spiritual quest (EXP [B], 3.425, 95% CI 1.042-11.253; P=0.043). Herbal medicine was the leading CM modality (87.9% of CM users), which included the use of 28 plants and traditional remedies, of which 17 were used to improve QOL, with 5 of the herbs having potential interactions with chemotherapy. 83.1% of respondents stated that they would consult with a CM provider if CM were to be integrated into the oncology department. Patients' expectation of CM consultation was clearly associated with expectations of QOL improvement, coping with cancer, and alleviating chemotherapy's side-effects when compared with expectations of cancer cure (P<0.0001). The three leading concerns which patients expected to be improved by integrative CM treatment were gastrointestinal symptoms (63.2%), fatigue (51.9%), and pain (40.5%). CONCLUSIONS: Integrative CM consultations should focus on the improvement of QOL concomitant with safety concerns regarding potential drug-herb interactions. The need to integrate a nonjudgmental yet evidence-based CM consultation service may also be applicable to oncology institutions challenged with culturally diverse populations with a high prevalence of traditional medicine use.

Integrative oncology in the Middle East: from traditional herbal knowledge to contemporary cancer care.

BACKGROUND: Based on traditional, historical, ethnobotanical, laboratory, and clinical findings, we present research framework aiming to identify Middle Eastern herbs that are worthy of further research for their anticancer potential. METHODS: A comprehensive research project was developed by a multinational team comprising family physicians, medicine specialists, oncologists, an Islamic medicine history specialist, a traditional medicine ethnobotanist, and a basic research scientist. The project followed two consecutive phases: (i) historical and ethnobotanical search for cancer-related keywords and (ii) Medline search for in vitro and in vivo studies. RESULTS: This search yielded 44 herbs associated with cancer care. The Medline search yielded 34 herbs of which 9 herbs were reported in various clinical studies. CONCLUSIONS: This multidisciplinary survey was found to be a valuable way to identify herbs with potential clinical significance in cancer care. Based on this pilot study, it is suggested that the Middle East can serve as a valuable region for future multicultural-oriented cancer research.

The Jerusalem Balsam: from the Franciscan Monastery in the old city of Jerusalem to Martindale 33.

The Jerusalem Balsam, a remedy based on an ethanolic extract of a herbal mixture, was formulated in 1719 in the pharmacy of the Saint Savior monastery in the old city of Jerusalem. Having gained fame, the Jerusalem Balsam was replicated and prepared in Europe. One can still find variations of the formula in current pharmacopoeias (B.P., 1998. The Stationary Office, London, p. 1510; Sweetman, S.C., Blake, P.S., McGlashan, J.M., Parsons, A.V., 2002. Martindale: The Extra Pharmacopeia, 33rd ed. Pharmaceutical Press, London, p. 1101). We report here, five different formulas, all referred to as "The Jerusalem Balsam". Three of those formulas were translated and two of these translations are presented in the text. A third one is available as Supplementary data online. As the formulas originate from different historical periods, the Jerusalem Balsam may be a good case study of the development of pharmaceutical formulations over a 250 years period. One of the formulas, found in a manuscript form in the archive of the monastery, contains four plants: olibanum (Boswellia spp.), myrrh (Commiphora spp.), aloe (Aloe sp.) and mastic (Pistacia lentiscus L.). We conducted pharmacological assays on this four-plant formula. It showed anti-inflammatory, as well as anti-oxidative, and anti-septic properties.

Ethnopharmacological survey of traditional drugs sold in Israel at the end of the 20th century.

This report deals with the results of a study of present day uses of traditional medicinal materials in Israel. The survey covered selected markets in medicinal materials, belonging to various religious and ethnic communities, and also included questioning of the sellers and buyers about the healing characteristics of the various materials. The survey yielded information on many and varied medicinal materials, of which 310 are identified according to the following classifications, 264 species of plants (85.1%); 20 species of animals (6.5%); 19 kinds of minerals (6.5%); and seven materials of other or mixed origin (2.3%). Analysis of the data showed that a significant proportion of the materials were of local origin (51.5%) and some were imported from other countries. These data demonstrate that there is still a flourishing and well developed trade in these materials - a trade which is the remnant of a rich and ancient medical culture, which is disappearing from the modern world.

Annexin II and bleeding in acute promyelocytic leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid. METHODS: We studied a newly described receptor for fibrinolytic proteins, annexin II, in cells from patients with APL or other leukemias. We examined initial rates of in vitro generation of plasmin by tissue plasminogen activator (t-PA) in the presence of APL cells that did or did not have the characteristic translocation of APL, t(15;17). We also determined the effect of all-trans-retinoic acid on the expression of annexin II and the generation of cell-surface plasmin. RESULTS: The expression of annexin II, as detected by a fluorescein-tagged antibody, was greater on leukemic cells from patients with APL than on other types of leukemic cells (mean fluorescence intensity, 6.9 and 2.9, respectively; P<0.01). The t(15;17)-positive APL cells stimulated the generation of cell-surface, t-PA-dependent plasmin twice as efficiently as the t(15;17)-negative cells. This increase in plasmin was blocked by an anti-annexin II antibody and was induced by transfection of t(15;17)-negative cells with annexin II complementary DNA. The t(15;17)-positive APL cells contained abundant messenger RNA for annexin II, which disappeared through a transcriptional mechanism after treatment with all-trans-retinoic acid. CONCLUSIONS: Abnormally high levels of expression of annexin II on APL cells increase the production of plasmin, a fibrinolytic protein. Overexpression of annexin II may be a mechanism for the hemorrhagic complications of APL.