Building complementary and alternative health care research capacity: workshop report

Lack of research into the safety and efficacy of CAM has been identified as a barrier to collaboration between conventional and CAM practitioners. As an initial step to address this issue, Health Canada held an invitational roundtable discussion with researchers, practitioners and policy makers to explore specific issues related to CAM research capacity and literacy. The objectives of this workshop were to identify and prioritize CAM research infrastructure and training needs; and to identify strategies for meeting high priority needs. Eleven individuals representing three CAM groups, university-based researchers with experience in CAM research, and policy makers attended. Discussion focussed around research literacy, capacity, funding and leadership. Several recommendations were made including an advisory group, a needs assessment, support for research networks, development of learning modules, a review of existing research programmes, support for centres of excellence in CAM research, and funding for research meetings.     

Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans

The possibility of direct transport of hydroxocobalamin from the nasal cavity into the cerebrospinal fluid (CSF) after nasal administration in rats was investigated and the results were compared with a human study. Hydroxocobalamin was given to rats (n=8) both intranasally (214 microg/rat) and intravenously (49.5 microg/rat) into the jugular vein using a Vascular Access Port (VAP). Prior to and after drug administration, blood and CSF samples were taken and analysed by radioimmunoassay. The AUCCSF/AUCplasma ratio after nasal delivery does not differ from the ratio after intravenous infusion, indicating that hydroxocobalamin enters the CSF via the blood circulation across the blood-brain barrier (BBB). This same transport route is confirmed by the cumulative AUC-time profiles in CSF and plasma, demonstrating a 30 min delay between plasma absorption and CSF uptake of hydroxocobalamin in rats and in a comparative human study. The present results in rats show that there is no additional uptake of hydroxocobalamin in the CSF after nasal delivery compared to intravenous administration, which is in accordance with the results found in humans. This indicates a predictive value of the used rat model for the human situation when studying the nose to CSF transport of drugs.     

Multi-resistance to antimicrobial agents for the ten most frequently isolated bacterial pathogens

Cross-resistance and multi-resistance to selected antibiotics was determined for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Amikacin-resistant Enterobacteriaceae often showed cross-resistance to ss-lactam antibiotics. Only 1% of the Escherichia coli isolates showed resistance to more than four antibiotics from a set of seven. This rate was higher for other Enterobacteriaceae and there were high levels of cross-resistance for P. aeruginosa. The cross-resistance of oxacillin with other antibiotics is well known in staphylococci. Penicillin-resistant pneumococcal isolates were cross-resistant to macrolides. Cross-resistance was only a minor problem in H. influenzae and M. catarrhalis. Cross- and multi-resistance are important problems for Gram-negative and Gram-positive bacteria but not for fastidious bacteria with the exception of penicillin-resistant S. pneumoniae.     

Chitosan and its derivatives as intestinal absorption enhancers

Chitosan is a non-toxic, biocompatible polymer that has found a number of applications in drug delivery including that of absorption enhancer of hydrophilic macromolecular drugs. Chitosan, when protonated (pH<6.5), is able to increase the paracellular permeability of peptide drugs across mucosal epithelia. Chitosan derivatives have been evaluated to overcome chitosan's limited solubility and effectiveness as absorption enhancer at neutral pH values such as those found in the intestinal tract. Trimethyl chitosan chloride (TMC) has been synthesized at different degrees of quaternization. This quaternized polymer forms complexes with anionic macromolecules and gels or solutions with cationic or neutral compounds in aqueous environments and neutral pH values. TMC has been shown to considerably increase the permeation of neutral and cationic peptide analogs across Caco-2 intestinal epithelia. The mechanism by which TMC is enhancing the intestinal permeability is similar to that of protonated chitosan. It reversibly interacts with components of the tight junctions, leading to widening of the paracellular routes. This chitosan derivative does not provoke damage of the cell membrane, and does not alter the viability of intestinal epithelial cells. Co-administrations of TMC with peptide drugs were found to substantially increase the bioavailability of the peptide in both rats and juvenile pigs compared with administrations without the polymer.     

Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions

Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD) is a neurodegenerative disease characterized by HIV infection and replication in brain tissue. HIV-1-infected monocytes overexpress inflammatory molecules that facilitate their entry into the brain. Prostanoids are lipid mediators of inflammation that result from cyclooxygenase-2 (COX-2) activity. Because COX-2 is normally induced during inflammatory processes, the aim of this study was to investigate whether COX-2 expression is up-regulated during monocyte-brain endothelium interactions. In vitro cocultures of HIV-infected macrophages and brain endothelium showed an up-regulation of COX-2 expression by both cell types. This up-regulation occurs via an interleukin-1beta (IL1beta)-dependent mechanism in macrophages and via an IL-1beta-independent mechanism in endothelial cells. Thus, interactions between HIV-infected monocytes and brain endothelium result in COX-2 expression and, as such, might contribute to the neuropathogenesis of HIV infection.     

Peanut butter intake, GSTM1 genotype and hepatocellular carcinoma: a case–control study in Sudan

Objective: Hepatocellular carcinoma (HCC) is one of the major cancers in the world. In Sudan the incidence is thought to be high and increasing. This study aims to assess the association between peanut butter intake, as a source of aflatoxins, and the GSTM1 genotype in the etiology of HCC. Method: A case–control study was conducted among 150 patients and 205 controls from two regions in Sudan. Food habits with special reference to peanut butter consumption, as well as peanut storage systems, have been investigated, as well as confounders such as hepatitis, drinking and smoking habits, and demographic characteristics. GSTM1 genotype was assessed in DNA extracted from blood samples (110 cases, 189 controls). Results: A positive association was observed for highest vs. lowest quartile of peanut butter intake, humid storage system and HCC, with ORs (95% CI) being 3.0 (1.6–5.5) and 1.6 (1.1–2.5) respectively. The positive association with peanut butter intake was essentially limited to subjects with GSTM1 null genotype with OR for highest vs. lowest quartile 16.7 (2.7–105). Conclusion: Peanut butter consumption has been identified as a strong risk factor of HCC in a region with endemic aflatoxin contamination in Sudan and was essentially limited to subjects with the GSTM1 null genotype.     

Observations on the iron status during pregnancy in rats. Iron transport from mother to fetus

The objective of the present study was to investigate a transfer of liver iron in rats from mother to fetus during pregnancy. A decrease in maternal liver iron and an increase in fetal liver iron, in groups of 10 rats, have been shown, based on iron analysis and specific activity of ⁵⁹Fe.     

MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23

We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.