Current status of the foci and morbidity of tick-borne relapsing fever in Uzbekistan

The contemporary state of settlement nidi of tick-borne relapsing fever is discussed on the material collected in the Namanganskaya and Andizhanskaya regions of Uzbek SSR. Despite the control measures and rise of the sanitary culture of population the conditions are still preserved for the maintenance of nidi. As in ancient estates, classical nidi of tick-borne relapsing fever, so in modern ones there are preserved conditions for existence of flourishing populations of vectors, i.e. favourable habitats and the availability of hosts. The analysis of factors is given affecting the contemporary level of sick-rate with tick-borne relapsing fever. Within the limits of the distribution area of the vector a higher sick-rate should be expected than it is registered.     

Specific Features of Digestive Function Development in Larvae of Some Salmonid Fish

We studied the activities of digestive enzymes responsible for the digestion of food carbohydrate and protein components in plant-eating fish at various stages of larval development. The activities of all digestive enzymes tend to rise during larval development. Species specific features of the alimentary canal functioning have been described.     

Dystrophin gene expression in patients with Duchenne muscular dystrophy after myoblast transplantation

Based on originally designed technique of myoblast cultivation and in accordance with the approved by the Russian Ministry of Health "one muscle treatment" protocol of myoblast transplantation to the Duchenne muscular dystrophy patients, the first in Russia clinical trial of this gene correction method was carried out. Immonologically related myoblast cultures (30 to 90 million cells per patient) were injected after all preliminary procedures into tibialis anterior muscles of four boys selected from a group of volunteer recipients (Duchenne muscular dystrophy patients) based on the analysis of a number of surface antigens in donor-recipient pairs. The condition of the patients remained satisfactory during the whole period of post-transplantation follow-up (from 6 months to 1.5 years). Six months after myoblast transplantation the presence of donor DNA or dystrophin synthesis was demonstrated in muscle biopsies of three out of four patients. This result confirms efficacy and safety of the procedure used.     

Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

Background

For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen.

Methods and Findings

We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005–2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16–23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients’ baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph.In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09–1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65–2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48–1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18–1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09–1.76, per drug when three effective drugs present in regimen).The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse.

Conclusions

MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.     

The effect of CpG-rich DNA fragments on the development of hypertension in spontaneously hypertensive rats (SHR)

In this study we have investigated properties of blood plasma extracellular DNA (cell-free DNA, cfDNA) from patients with essential arterial hypertension (AH). Concentration of cell-free DNA was basically the same as in healthy donors, however, the content of the marker, CpG-rich cell-free DNA fragments (CpG-DNA) of the transcribed area of the ribosomal repeat (TArDNA, CpG-DNA) was higher in AH patients. For evaluation of the effect of CpG-DNA on the development of arterial hypertension 2-day-old SHR rat pups and corresponding controls of normotensive WKY rats received a single subcutaneous injection of human TArDNA (700 ng) to generate anti-CpG-DNA antibodies (and thus to alter the CpG-DNA content in total cfDNA). After 9 weeks blood pressure (BP) in SHR rats immunized with CpG-DNA was significantly lower than in control SHR rats and was basically the same as in WKY rats. However, subsequently, BP of the immunized SHR exhibited age-related increase, which reached the stably high values typical for mature SHR 8 weeks later compared with control SHR. Analysis of cfDNA has shown that in 17-week-old immunized SHR rats concentrations of cell-free DNA and its small DNA fragments are lower and the content of CpG-DNA (rat TArDNA) is higher than in corresponding controls. These changes were accompanied by a 3.5-fold increase in blood endonuclease activity and the decrease in content of free (unbound to cfDNA) anti-CpG-DNA antibodies. Total content of anti-CpG-DNA antibodies in the immunized rats was the same as in control animals. Thus, the delayed age-related increase in stable BP observed in immunized SHR rats is obviously not associated with increased generation of anti-CpG-DNA antibodies. Possible reasons of this effect are discussed.     

Production of reactive oxygen species and antioxidant enzymes of pea and soybean plants under hypoxia and high CO<Subscript>2</Subscript> concentration in medium

Generation of reactive oxygen species (ROS) and activities of antioxidant enzymes (catalase, peroxidase, ascorbate peroxidase) in pea (Pisum sativum L.) and soybean (Glycine max L.) under hypoxia (3–24 h) and high CO₂ concentration in medium were studied. In sensitive to hypoxia pea seedlings, hypoxia enhanced markedly production of superoxide anion-radical, hydroperoxides, and especially hydrogen peroxide. In more tolerant soybean plants, these changes were less pronounced. During first hours of hypoxia, activity of lipoxygenase in plant cells increased. This allows a suggestion that this enzyme is involved in the processes of hydroperoxide accumulation in plant tissues under oxygen deficit. In pea and soybean plants, a correlation between tolerance to hypoxia, the rate of ROS generation, and antioxidant enzyme activities was established. During the first hours of hypoxia, the catalase activity in soybean plants increased stronger than in sensitive to hypoxia pea plants. At longer exposure to hypoxia (24 h), peroxidases started to play the higher role in cell defense against hypoxia, but only in soybean plants. The medium with the higher CO₂ content induced higher changes in the processes of ROS accumulation and activities of lipoxygenase and antioxidant enzymes. This permits us to refer CO₂, accumulated as a product of respiration in the cells, to low-molecular signal molecules switching on plant adaptation to hypoxic stress.     

Dry medium for determining the beta-galactosidase activity of enterobacteria

Differential diagnosis of enterobacteria is based on the determination of beta-galactosidase enzyme, hydrolyzing lactose in the nutrient substrates; however, the tests suggested for its determination are time consuming and their use in practice is limited. Dry nutrient medium prepared by the authors containing o-nitrophenyl-betaD-pyranoside was tested on 1625 strains of enterobacteria in comparison with the Le Minor's ONPS test used at present. The results of beta-galactosidase determination by the, mentioned methods proved to coincide (significance level greater than 95%); this permits to recommend the method described--in dry nutrient medium--as a differential-diagnostic test for the identification of enterobacteria.