International migration of doctors from developing countries: need to follow the Commonwealth Code

There is an ongoing debate on the migration of doctors, especially psychiatrists, from developing countries. It is argued that these countries, which are already running short of psychiatrists, will further be jeopardized and their health systems will collapse if this migration and subsequent recruitment continue. In this paper the author presents a personal view of the ethics and human rights of this matter. He emphasises the importance of migration of doctors in view of the current situation in developing countries and advises that the Commonwealth Code be followed to address the problem of the shortage of psychiatrists in developing countries and psychiatrists' basic right to avail themselves of the opportunities in the developed world.     

Hepatic viral infections in Yemen between 2000--2005

OBJECTIVE: To determine the prevalence of hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies in Sanaa, and other governorates of Yemen. METHODS: By systematic review with meta-analysis we collected the research performed in different governorates of Yemen during the period 2000--2005. This included the published papers (peer reviewed), and the papers presented at Yemeni conferences. RESULTS: We identified 4 groups with separate prevalences. We found HBsAg to be 8% in healthy volunteers, 10.8% in blood donors, 12.3% in patients under dialysis, and 23% in patients with chronic liver diseases. Antibodies to HCV show different results, namely, 1.7% in healthy volunteers, 2.7% in blood donors, 33.8% in patients under dialysis, and 33.75% in patients with chronic liver diseases. The viral markers in different governorates showed significant differences in healthy and blood donor groups. The means of HBsAg and HCV antibodies in patients with liver diseases were recorded to be 26.2% for HBsAg, and 33.8% for HCV antibodies, with a total of 60%. The means in patients under dialysis, for HBsAg was 10.9%, and for HCV antibodies was 33.8%, with a total mean of 44.7%. CONCLUSION: Hepatitis B and C appear to be a major health problem in our community. Our study results indicate an intermediate level risk of hepatitis B virus infection. There are some geographic areas in the country that may be at high risk. Control strategies should take these differences into account.     

A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling

Stat5 proteins are critical signaling molecules activated by many cytokines. Within the immune system, Stat5 plays important roles related to the development of thymocytes and proliferation of T cells. Stat5 has been implicated in malignant transformation, and moreover, the activated tyrosine phosphorylated form of Stat5 is frequently observed in human lymphomas. We previously demonstrated the oncogenic potential of Stat5, with thymic lymphoblastic lymphomas developing in a significant proportion of transgenic (TG) mice overexpressing Stat5a or Stat5b in lymphocytes. In addition, immunization or expression of a T-cell receptor (TCR) transgene augmented the rate of tumor formation. Here, we investigate the mechanism of Stat5-mediated lymphomagenesis by exploring the contributions of major histocompatibility complex (MHC)/TCR and pre-TCR signals. We present data demonstrating that Stat5b TG mice unexpectedly develop CD8(+) lymphoma even in the absence of either pre-TCR signaling or normal thymic selection. Indeed, acceleration of Stat5b transgene-mediated lymphoma occurred on TCRalpha(-/-) and pre-TCRalpha(-/-) backgrounds. In light of these data, we propose a model in which alterations in T-cell development at the double-negative/double-positive (DN/DP) stages cooperate with cytokine-mediated pathways in immature thymocytes to give rise to lymphoblastic T-cell lymphomas in Stat5b TG mice.     

Effect of beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins on mortality in patients with implantable cardioverter-defibrillators

Nine hundred sixty-five patients (mean age 70 years) with implantable cardioverter-defibrillator were followed for 32 +/- 33 months for all-cause mortality. Death occurred in 73 of 515 patients (13%) treated with beta blockers (group 1), in 84 of 494 patients (17%) treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (group 2), in 56 of 402 patients (14%) treated with statins (group 3), in 40 of 227 patients (18%) treated with amiodarone (group 4), in 5 of 26 patients (19%) treated with sotalol (group 5), and in 64 of 265 patients (24%) treated with no beta blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, statin, amiodarone, or sotalol (group 6) (p <0.001 for group 1 vs group 6 and group 3 vs group 6, p <0.02 for group 2 vs group 6). In conclusion, patients with implantable cardioverter-defibrillators should be treated with beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins to reduce mortality.     

Synthesis, microsome-mediated metabolism, and identification of major metabolites of environmental pollutant naphtho[8,1,2-ghi]chrysene

Naphtho[8,1,2- ghi]chrysene, commonly known as naphtho[1,2- e]pyrene (N[1,2- e]P) is a widespread environmental pollutant, identified in coal tar extract, air borne particulate matter, marine sediment, cigarette smoke condensate, and vehicle exhaust. Herein, we determined the ability of rat liver microsomes to metabolize N[1,2- e]P and an unequivocal assignment of the metabolites by comparing them with independently synthesized standards. We developed the synthesis of both the fjord region and the K-region dihydrodiols and various phenolic derivatives for metabolite identification. The 12-OH-N[1,2- e]P, fjord region dihydrodiol 14 and diol epoxide 15 were synthesized using a Suzuki cross-coupling reaction followed by the appropriate manipulation of the functional groups. The K-region trans-4,5-dihydrodiol ( 18) was prepared by the treatment of N[1,2- e]P with OsO 4 to give cis-dihydrodiol 16, followed by pyridinium chlorochromate oxidation to quinone 17, and finally reduction with NaBH 4 to afford the dihydrodiol 18 with the desired trans stereochemistry. The 9-OH-N[1,2- e]P ( 30) and N[1,2- e]P trans-9,10-dihydrodiol ( 32) were also synthesized following a Suzuki cross-coupling approach starting from 1,2,3,6,7,8-hexahydropyrene-4-boronic acid. The metabolism of N[1,2- e]P with rat liver microsomes led to several dihydrodiol and phenolic metabolites as assessed by the HPLC trace. The 11,12-dihydrodiol and 4,5-dihydrodiol were identified as major dihydrodiol metabolites. The synthesized 9,10-dihydrodiol, on the other hand, did not match with any of the peaks in the metabolism trace. Among the phenols, only 12-OH-N[1,2- e]P was identified in the metabolism. The other phenolic derivatives synthesized, that is, the 4-/5-, 9-, 10-, and 11-hydroxy derivatives, were not detected in the metabolism trace. In summary, N[1,2- e]P trans-11,12-dihydrodiol was the major metabolite formed along with N[1,2- e]P 4,5- trans-dihydrodiol and 12-OH-N[1,2- e]P on exposure of rat liver microsomes to N[1,2- e]P. The presence of N[1,2- e]P in the environment and formation of fjord region dihydrodiol 14 as a major metabolite in in vitro metabolism studies strongly suggest the role of N[1,2- e]P as a potential health hazard.     

Ligand activation of peroxisome proliferator-activated receptor-beta/delta inhibits cell proliferation in human HaCaT keratinocytes

Although there is strong evidence that ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta induces terminal differentiation and attenuates cell growth, some studies suggest that PPARbeta/delta actually enhances cell proliferation. For example, it was suggested recently that retinoic acid (RA) is a ligand for PPARbeta/delta and potentiates cell proliferation by activating PPARbeta/delta. The present study examined the effect of ligand activation of PPARbeta/delta on cell proliferation, cell cycle kinetics, and target gene expression in human HaCaT keratinocytes using two highly specific PPARbeta/delta ligands [4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy acetic acid (GW0742) and 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy-acetic acid (GW501516)] and RA. Both PPARbeta/delta ligands and RA inhibited cell proliferation of HaCaT keratinocytes. GW0742 and GW501516 increased expression of known PPARbeta/delta target genes, whereas RA did not; RA increased the expression of known retinoic acid receptor/retinoid X receptor target genes, whereas GW0742 did not affect these genes. GW0742, GW501516, and RA did not modulate the expression of 3-phosphoinositide-dependent protein kinase or alter protein kinase B phosphorylation. GW0742 and RA increased annexin V staining as quantitatively determined by flow cytometry. The effects of GW0742 and RA were also examined in wild-type and PPARbeta/delta-null primary mouse keratinocytes to determine the specific role of PPARbeta/delta in modulating cell growth. Although inhibition of keratinocyte proliferation by GW0742 was PPARbeta/delta-dependent, inhibition of cell proliferation by RA occurred in both genotypes. Results from these studies demonstrate that ligand activation of PPARbeta/delta inhibits keratinocyte proliferation through PPARbeta/delta-dependent mechanisms. In contrast, the observed inhibition of cell proliferation in mouse and human keratinocytes by RA is mediated by PPARbeta/delta-independent mechanisms and is inconsistent with the notion that RA potentiates cell proliferation by activating PPARbeta/delta.     

Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines

The development of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPARbeta/delta promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPARbeta/delta ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPARbeta/delta on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPARbeta/delta ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPARbeta/delta target gene angiopoietin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPARbeta/delta inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPARbeta/delta ligands are not mitogenic in human cancer cell lines.     

The Effect of Manual Acupressure (Point UB32) on Pain Associated with Intramuscular Injections of Magnesium Sulfate

The aim of this study was determining the effect of acupressure on the severity of pain associated with intramuscular injections of magnesium sulfate administered by the Z-track technique in patients with eclampsia and preeclampsia. Forty-eight patients participated in this single-group clinical trial, which was conducted in three stages. For each patient, three intramuscular injections were administered by the Z-track technique. The first injection was administered by the conventional method. The second injection at a sham control point and the third injection using acupressure (BL32) were administered. Pain severity was measured on a visual analogue scale. The mean pain intensity was 7.22 in the first, 4.75 in the second and 1.94 in the third injections (p < 0.001). The results of the study showed that acupressure at the BL32 point before intramuscular injection of magnesium sulfate significantly reduced the injection-related pain.     

Dendrimer-mediated approaches for the treatment of brain tumor

Worldwide, the cancer appeared as one of the most leading cause of morbidity and mortality. Among the various cancer types, brain tumors are most life threatening with low survival rate. Every year approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed. The dendrimeric approaches have a huge potential for diagnosis and treatment of brain tumor with targeting abilities of molecular cargoes to the tumor sites and the efficiency of crossing the blood brain barrier and penetration to brain after systemic administration. The various generations of dendrimers have been designed as novel targeted drug delivery tools for new therapies including sustained drug release, gene therapy, and antiangiogenic activities. At present era, various types of dendrimers like PAMAM, PPI, and PLL dendrimers validated them as milestones for the treatment and diagnosis of brain tumor as well as other cancers. This review highlights the recent research, opportunities, advantages, and challenges involved in development of novel dendrimeric complex for the therapy of brain tumor.