Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions: studies in human leukemic cells

The use of low density lipoprotein (LDL) as drug carrier in acute myeloblastic leukemia chemotherapy is attractive due to high LDL uptake by leukemic cells. Lipid-based formulations, such as liposomes or microemulsions are promising alternatives. In the current study, we incorporated N-trifluoroacetyl-adriamycin-14-valerate (AD32), a lipophilic derivative of daunorubicin (DNR), and WB4291, a lipophilic alkylating agent, into LDL or lipid microemulsions and evaluated their cytotoxic activities towards leukemic cell lines using as references DNR and melphalan. The incorporation of AD32 into LDL or emulsion resulted in complexes with poor cytotoxicity. WB4291-LDL and WB4291-emulsion exerted, on the other hand, promising cytotoxic effects towards parental and resistant K562 and HL60 cell lines.     

Male infertility in Zimbabwe

OBJECTIVES: There are very few studies on male infertility in sub-Saharan Africa. Sub-Saharan countries tend not to research male infertility because of economic reasons and, possibly, the psychological denial of the problem. METHODS: The participants in the present study were 311 men with infertility problems who had been referred to the Andrology Clinic of the University of Zimbabwe. They were investigated by means of a clinical interview, a clinical examination, semen analysis and various endocrine tests. RESULTS: It was found that 78% of the respondents had ever had a sexually transmitted disease. Most of the respondents reported that their infertility caused them stress and reported signs of mild depression. Most men mentioned also to seek treatment based on traditional methods. Men blamed that their wife was the reason of their childlessness. CONCLUSION: This study shows the importance of understanding both the cultural and the medical aspects of male infertility. Male infertility is a significant medical and psychological problem in Zimbabwe. PRACTICE IMPLICATION: Men should promptly be diagnosed and treated for STIs. Health education and teaching people about STDs and HIV in general about this are essential to the process of preventing male infertility.     

Effects of montelukast and salmeterol on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction

STUDY OBJECTIVES: To compare the effect of montelukast and the long-acting beta(2)-agonist salmeterol on cardiopulmonary exercise economy and physical performance in adult patients with asthma during exercise. DESIGN AND PATIENTS: Asthmatic patients (n = 18), aged 18 to 35 years with exercise-induced bronchoconstriction (EIB), using a double-blind, double-dummy cross-over design. Montelukast, 10 mg/d, was compared to inhaled salmeterol, 50 microg bid. The study medication was administered for at least 5 days prior to testing, with a washout period of at least 5 days. Treadmill exercise tests (5.3% inclination, -15 degrees C ambient temperature) were performed at work loads of 80% of maximal oxygen uptake (Vo(2)max) [6 min], rest (4 min), 60% of Vo(2)max (6 min), and finally step increments until exhaustion. MEASUREMENTS AND RESULTS: We investigated parameters of gas exchange, physical performance, and lung function. After montelukast, the oxygen pulse was higher than after salmeterol, at 80% of Vo(2)max (p = 0.035), and 6 min at 60% of Vo(2)max (p = 0.011). Lung function during exercise, running time to exhaustion, Borg score, lactate levels, Vo(2)max, carbon dioxide elimination, minute ventilation, ventilatory equivalents, respiratory exchange ratio, and heart rate were not significantly different between the two treatments. The maximal postexercise fall in FEV(1) from baseline occurred 2 min after run to exhaustion, and was greater after salmeterol than after montelukast: mean, 16.2% (SD, 11.0) vs 10.0% (SD, 12.2) [p < 0.001]. CONCLUSIONS: In adult asthmatics with EIB, montelukast may have a more favorable effect on the oxygen pulse, thus suggesting improved gas exchange during exercise.     

Patterns of TH1/TH2 cytokines predict clinical response in multiple sclerosis patients treated with glatiramer acetate

The patterns of Th1/Th2 cytokines in relapsing-remitting multiple sclerosis were analyzed to evaluate their relevance as biomarkers of therapy response to glatiramer acetate (GA). Serum interferon-γ (IFN-γ), osteopontin and interleukin (IL)-2, IL-4, and IL-10 were measured in 19 relapsing-remitting multiple sclerosis patients treated with GA in a prospective study over 3 years. The quotient (IL-2 + IFN-γ)/(IL-4 + IL-10) was elevated in patients with relapses as compared to relapse-free patients after 12 (p = 0.04), 24 (p = 0.02) and 36 months (p = 0.04). Our study indicates that specific patterns of Th1/Th2 cytokines predict the response to GA therapy.