Bifidogenic factors as drug preparations

The review of new data on the study of bifidobacterial factors of different origin and the probable mechanisms of their favorable action on the microflora of the intestinal tract if presented. The main emphasis is made on the analysis of data on the use of oligosaccharides, including fructo-oligosaccharides, as compounds stimulating the growth and development of bifidobacteria both in pure cultures and in intestinal microflora. Methods for the treatment of natural compounds with a view to enhancing their bifidogenic effect are presented. The possibilities and/or advantages of using bifidogenic factors in vivo and in vitro as medicinal preparations either alone or incorporated in probiotic compositions are evaluated. Suggestion has been made that the choice of the method for using bifidogenic factors may depend on the kind and severity of disturbances in indigenous microflora.     

Molecular aspects of plant adaptation to life in the Chernobyl zone

With each passing year since the Chernobyl accident of 1986, more questions arise about the potential for organisms to adapt to radiation exposure. Often this is thought to be attributed to somatic and germline mutation rates in various organisms. We analyzed the adaptability of native Arabidopsis plants collected from areas with different levels of contamination around the Chernobyl nuclear power plant from 1986 to 1992. Notably, progeny of Chernobyl plants resisted higher concentrations of the mutagens Rose Bengal and methyl methane sulfonate. We analyzed the possible molecular mechanisms of their resistance to mutagens and found a more than 10-fold lower frequency of extrachromosomal homologous recombination, significant differences in the expression of radical scavenging (CAT1 and FSD3) and DNA-repair (RAD1 and RAD51-like) genes upon exposure to mutagens (Rose Bengal and x-rays), and a higher level of global genome methylation. This data suggests that adaptation to ionizing radiation is a complex process involving epigenetic regulation of gene expression and genome stabilization that improves plants' resistance to environmental mutagens.     

Expression of erythropoietin receptor mRNA in mouse brain hemispheres

Now there is a growing evidence that erythropoietin receptors (Epo-R) are present also in some nonhematopoietic tissues such as endothelial cells and fetal cells of neural origin, although the physiological role of Epo-R at these sites is unclear. There are some speculations that Epo-R may be expressed on cells only in the developing CNS. The objective of this study was to determine whether Epo-R mRNA may be expressed in the brain hemispheres of Balb/c mice of different age groups: 1) newborn mice, 2) young 2 months old mice, 3) old 1.8 year old mice. We also studied the in vivo effect of recombinant erythropoietin on the expression of Epo-R mRNA in the brain hemispheres of (CBA x C57BL)F1 mice by RT-PCR. We have detected the existence of Epo-R mRNA expression in brain hemispheres of all the groups, but in old mice this expression was significantly higher. We have discovered a decrease in Epo-R mRNA expression in brain hemispheres of (CBA x C57BL)F1 mice 24 h after in vivo administration of recombinant erythropoietin. The Epo-R mRNA expression in the left brain hemispheres of (CBA x C57BL)F1 was considerably higher than in the right one.     

Serious adverse events following treatment with ivermectin for onchocerciasis control: a review of reported cases

This paper presents a summary of reported cases of Serious Adverse Events (SAEs) following treatment with Mectizan^® (ivermectin, Merck, Sharpe &; Dohme) in onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001 through a passive surveillance system. A total of 207 SAE cases were reported out of approximately 165 million reported treatments delivered during the period under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000 reported treatments. The mean age was 40 years and 70% of the cases were males. The mean time between ivermectin intake and onset of illness was 1 day. For 57% of the cases (n = 118), that was their first exposure to ivermectin. The majority of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence of SAE reporting in 1989–1991 and 1994–1995 when the program expanded to ivermectin-naïve populations. Fifty-five percent of the cases from Cameroon (i.e. 97 out of 176 cases) were encephalopathic and were reported from the central-southern region of the country; two-thirds of these cases were 'probable' or 'possible' cases of Loa loa encephalopathy temporally related to ivermectin treatment. Reporting bias may explain some but not all of the differences in SAE reporting between the 34 onchocerciasis-endemic countries that have, or have had, mass treatment programs. Further research is needed to understand the apparent clustering of encephalopathy cases in central-southern Cameroon since L. loa infection alone probably does not explain the increased incidence of this type of SAE from this region.     

The Laptev Sea walrus Odobenus rosmarus laptevi: an enigma revisited

The walrus ( Odobenus rosmarus ) is in some current systematic schemes divided into three subspecies: O. r. rosmarus in the North Atlantic, O.   r. divergens in the North Pacific and O.   r. laptevi in the Laptev Sea. These three subspecies have been described as differing in body size, but the taxonomic status of O.   r. laptevi is disputed. The current study applies molecular and morphometric methods to assess the taxonomic status of O.   r. laptevi and to analyse the systematic and phylogeographic relationships between the three purported walrus subspecies. Tusk length and tusk circumference were measured from the few skulls available of O.   r. laptevi , and the obtained values were within the ranges reported for Pacific walruses. Thus, morphologically, subspecies status for O.   r. laptevi is not supported according to the Amadon–Mayr '75% rule'. Phylogenetic analyses and haplotype networks based on mitochondrial nucleotide sequence data of NADH dehydrogenase 1, 16S rRNA, cytochrome oxidase I and the d -loop of the control region of the historic O.   r. laptevi bone material and contemporary O.   r. rosmarus and O.   r. divergens showed that the Laptev Sea walrus groups with individuals from the North Pacific. Thus, the mitochondrial sequence data do not support the recognition of three walrus subspecies as reciprocally monophyletic evolutionary units with independent evolutionary histories. Only O.   r. rosmarus and O.   r. divergens meet this criterion with the present sampling. Accordingly, we recommend that Odobenus r. laptevi be abandoned and the Laptev walrus instead be recognized as the westernmost population of the Pacific walrus, Odobenus r. divergens. However, further research is recommended to assess whether the Laptev walrus could be considered as a significant unit in terms of conservation and management, since it is unique in several ecological parameters.     

Inhibition of MDR1 expression with altritol-modified siRNAs

Altritol-modified nucleic acids (ANAs) support RNA-like A-form structures when included in oligonucleotide duplexes. Thus altritol residues seem suitable as candidates for the chemical modification of siRNAs. Here we report that ANA-modified siRNAs targeting the MDR1 gene can exhibit improved efficacy as compared to unmodified controls. This was particularly true of ANA modifications at or near the 3′ end of the sense or antisense strands, while modification at the 5′ end of the antisense strand resulted in complete loss of activity. Multiple ANA modifications within the sense strand were also well tolerated. Duplexes with ANA modifications at appropriate positions in both strands were generally more effective than duplexes with one modified and one unmodified strand. Initial evidence suggests that the loss of activity associated with ANA modification of the 5′-antisense strand may be due to reduced phosphorylation at this site by cellular kinases. Treatment of drug resistant cells with MDR1-targeted siRNAs resulted in reduction of P-glycoprotein (Pgp) expression, parallel reduction in MDR1 message levels, increased accumulation of the Pgp substrate rhodamine 123, and reduced resistance to anti-tumor drugs. Interestingly, the duration of action of some of the ANA-modified siRNAs was substantially greater than that of unmodified controls. These observations suggest that altritol modifications may be helpful in developing siRNAs with enhanced pharmacological effectiveness.     

Death of the killer whale <Emphasis Type="Italic">Orsinus orca</Emphasis> from bacterial pneumonia in 2003

A killer whale was captured in Avacha Gulf (Kamchatka) on September 26, 2003. It was transported to the Utrish Sea Station (Black Sea) on October 6. However, the animal died in 13 days. As a result of microbiological analysis of the internal organs of dead animal, a bacterial culture was isolated that was identified as Pseudomonas aeruginosa. The infection by this opportunistic pathogen caused abscessing pneumonia that resulted in the death of the killer whale.     

Using thin-layer chromatography of fecal bile acids to study the leopard (<Emphasis Type="Italic">Panthera pardus ciscaucasica</Emphasis>) population

Thin-layer chromatography (TLC) of fecal bile acids has been used to confirm visual identification of scat samples found in Armenia in 2004–2005 and attributed to the leopard (Panthera pardus ciscaucasica). The results of TLC do not differ significantly from those of visual identification, confirming the reliability of the latter method. Taking into account the frequency and distribution of fresh scats, two priority areas for leopard conservation have been identified: the Central and Khachadzor districts of the Khosrov Reserve and the Nuvadi-Shvanidzor area in eastern Meghri Ridge.     

Mutations in HPCA Cause Autosomal-Recessive Primary Isolated Dystonia

Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as “DYT2 dystonia,” have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether “DYT2 dystonia” is a genetically homogeneous condition or not.