The efficacy and outlook for the study of live vaccines for the prevention of melioidosis]

The effect of immunization with Burkholderia pseudomallei, (Pur- and Ts), heterologous vaccines and the recombinant culture of Francisella tularensis RM2, carrying a plasmid with fragments of B. pseudomallei chromosome, was studied on four species of experimental animals, essentially differing by their sensitivity to melioidosis. B. pseudomallei mutants formed the statistically significant level of protection in subcutaneously challenged animals, moderately sensitive to melioidosis, but were not effective when tested, under the same conditions, in animals, highly sensitive to melioidosis. The effect produced by the experimental vaccines under study in animals of all species, subjected to aerogenic challenge, was leveled. The study showed good prospects for the use of tularemia vaccine with a view to create heterologous immunity to melioidosis and the possibility of its use as the basis of bivalent gene engineering vaccine.     

Various properties of erythromycin basicity]

Erythromycin (Er) as a weak base showed some specific properties when dissolved in aqueous solutions. The basic ability of Er had a tendency to become weaker during storage in the room settings and especially at high temperatures. The temperature gradient within the ranges of 10 to 25 degrees C was dpH/dt = -0.03 (for 2 x 10(-3) M Er solution). However, the basic properties of the Er base partly renewed when Lewis' bases such as dimethyl carboxide, dimethylformamide and dimethyl sulfoxide were added to Er aqueous solutions previously stored for days or weeks. In chloroform solutions, either the thermodynamics or the kinetics of Er protonization showed no abnormalities as compared to nitric bases. It was supposed that in aqueous solutions of Er base there was transformation linked with intramolecular or extramolecular interactions which provoked shielding of the tertiary basic atom of nitrogen due to formation of the nitrogen linkage.     

The effect of the acid exopolysaccharide produced by the causative agent of melioidosis on macrophage function]

Acid exopolysaccharide of the melioidosis agent, isolated from the slime of alysogenic strain of Pseudomonas pseudomallei SVBDO-141 inhibits the capture of sheep erythrocytes--55Fe by mouse peritoneal macrophages. Administration of the sheep erythrocytes--55Fe, sensibilized by acid exopolysaccharide was proved not to have an antiphagocytic effect. Inhibition of phagocytic macrophagal activity depends on the conditions of isolation of acid exopolysaccharide.     

The action of short-range low-intensity infrared laser irradiation on the functional and metabolic parameters of the isolated rat myocardium in hypoxia

It was found that infrared laser radiation (IRL) reduces the sparing action of acute hypoxia on ventricular transport function of low-resistant animals and accelerates the recovery of the function during the post-hypoxia period. The effect was caused by the IRL affecting directly the speed of perfusion through the myocardium and thus the latter's breathing rate. The protective effect of the IRL was practically absent in highly resistant animals, which may be indicative of the existence of basic differences in the regulatory systems which is responsible for local vasodilation and supply of oxygen to cells, and which participates in the formation of resistance of cardiomyocytes to oxygen shortage.     

The trimeric coiled‐coil HSBP1 protein promotes WASH complex assembly at centrosomes

The Arp2/3 complex generates branched actin networks that exert pushing forces onto different cellular membranes. WASH complexes activate Arp2/3 complexes at the surface of endosomes and thereby fission transport intermediates containing endocytosed receptors, such as α5β1 integrins. How WASH complexes are assembled in the cell is unknown. Here, we identify the small coiled‐coil protein HSBP1 as a factor that specifically promotes the assembly of a ternary complex composed of CCDC53, WASH, and FAM21 by dissociating the CCDC53 homotrimeric precursor. HSBP1 operates at the centrosome, which concentrates the building blocks. HSBP1 depletion in human cancer cell lines and in Dictyostelium amoebae phenocopies WASH depletion, suggesting a critical role of the ternary WASH complex for WASH functions. HSBP1 is required for the development of focal adhesions and of cell polarity. These defects impair the migration and invasion of tumor cells. Overexpression of HSBP1 in breast tumors is associated with increased levels of WASH complexes and with poor prognosis for patients.     

The Mectizan® Donation Program – highlights from 2005

Through the Mectizan^® Donation Program, Merck & Co., Inc. has donated Mectizan (ivermectin, MSD) for the treatment of onchocerciasis worldwide since 1987. Mectizan has also been donated for the elimination of lymphatic filariasis (LF) since 1998 in African countries and in Yemen where onchocerciasis and LF are co-endemic; for LF elimination programs, Mectizan is co-administered with albendazole, which is donated by GlaxoSmithKline. The Mectizan Donation Program works in collaboration with the Mectizan Expert Committee/Albendazole Coordination, its scientific advisory committee. In 2005, a total of 62,201,310 treatments of Mectizan for onchocerciasis were approved for delivery via mass treatment programs in Africa, Latin America, and Yemen. Seventy-seven percent and 20% of these treatments for onchocerciasis were for countries included in the African Programme for Onchocerciasis Control (APOC) and the former-Onchocerciasis Control Programme in West Africa (OCP), respectively. The remaining 3% of treatments approved were for the six onchocerciasis endemic countries in Latin America, where mass treatment is carried out twice-yearly with the goal of completely eliminating morbidity and eventually transmission of infection, and for Yemen. All 33 onchocerciasis endemic countries where mass treatment with Mectizan is indicated have ongoing mass treatment programs. In 2005, 42,052,583 treatments of co-administered albendazole and Mectizan were approved for national Programs to Eliminate LF (PELFs) in Africa and Yemen. There are ongoing PELFs using albendazole and Mectizan in nine African countries and Yemen; these represent 35% of the total number of countries expected to require the co-administration of these two chemotherapeutic agents for LF elimination. In Africa, the expansion of existing PELFs and the initiation of new ones have been hampered by lack of resources, technical difficulties with the mapping of LF endemicity, and the co-endemicity of LF and loiasis. Included in this review are recommendations recently put forward for the co-administration of albendazole and Mectizan in areas endemic for LF, loiasis, and onchocerciasis.