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Satisfaction with surgical correction of stress urinary incontinence in women: A pilot study in Almaty, Kazakhstan
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The Investigations of Nitric Oxide Influence on Lifespan of Fruit Fly D. melanogaster Transgenic Strain dNOS4
Introduction. Aging and longevity control are among the greatest problems in biology and medicine. The fruit fly Drosophila melanogaster is a nice model organism for longevity investigations because of its biological features. Many D. melanogaster genes have their orthologs, similar in other eukaryotes, including human. The role of nitric oxide (NO) in the D. melanogaster lifespan has been analyzed.Methods. Virgin flies of dNOS4 transgenic strain were used for the experiment. This strain contains non-functional additional copies of nitric oxide synthase (NOS) gene under heat shock promoter. For promoter activation, transgenic flies on their second day of life were exposed to heat shock (37°C) for an hour. After heat shock, flies were maintained on standard medium temperatures at 25°C, with females separate from males. Two types of control were used: Oregon R wild-type strain and Oregon R strain exposed to heat shock. The average lifespan was evaluated.Results. It was revealed that the longevity of females was significantly higher than males in each series of experiments (p < 0.05). The survival rate of females and males was similar in the first month of their life, but in the second month the mortality among males was much higher than among females in all series of experiments. The average lifespan of dNOS4 imago was 31 days (34 days for females and 28 days for males), maximum lifespan was 63 days. In controls, the average lifespan of Oregon R flies was 54 days (58 days for females and 50 days for males), and the maximum lifespan was 94 days. The average lifespan of Oregon R flies exposed to heat shock was 45 days (48 days for females and 41 days for males), and the maximum lifespan was 72 days. The difference between average lifespan in all studied groups is statistically significant (p < 0.05).Conclusion. Thus, NOS-transgene activation results in formation of non-functional dNOS4-transcripts and NO deficiency. In turn, NO deficiency decreases dNOS4 imago lifespan.
Association Between the P2RY12 Receptor Gene Polymorphism and Aspirin Resistance in Patients with Coronary Artery Disease
Introduction. Platelet activation and aggregation are key elements in the development of coronary atherosclerosis. Recent studies have shown that the two polymorphisms of platelet ADP receptor P2RY12 (haplotypes H2 and 34T) are associated with increased platelet aggregation and atherothrombotic risk. It was shown that these polymorphisms promote reduced body response to antiplatelet therapy.Aim. We investigated the association of P2RY12 gene polymorphisms with aspirin resistance in patients with coronary artery disease (CAD).Methods. This case-control study included 100 cases with CAD (mean age 57.6 ± 2.8 years) treated in the cardiology department of the city hospital Semey, Kazakhstan, 90 of whom suffered from myocardial infarction. The control group (n = 100) were healthy people without a history of CAD, matched on sex and age. Genotyping of polymorphisms H1/H2 in P2RY12 gene was performed by PCR. Statistical analysis was performed using SPSS v.19.0.Results. The distribution of H1/H2 genotypes P2RY12 was 42%, 34%, and 24%, respectively, in cases and 42%, 58%, and 0%, respectively, in controls. All allele frequencies were consistent with the Hardy Weinberg equilibrium (p = 0.0036 and p = 0.0001 in cases and controls, respectively). Genotype H2 was associated with risk of CAD with aspirin resistance (co-dominant model: OR = 3.75, 95% CI 0.14 - 99.88, p = 0.05 and dominant model: OR = 2.78, 95% CI 0.11 - 70.93, p = 0.05). We found significant differences in the distribution of the mutant genotype H2 between CAD patients with aspirin resistance and healthy controls (?2 = 30.3, p < 0.05).Conclusion. We found an association of H2 haplotype in P2RY12 gene with aspirin resistance in patients with CAD. However, in order to obtain definitive conclusions about the role of genetic variants with the development of aspirin resistance in patients with CAD, there is a need for further research with a larger sample size as well as the use of selective thromboxane receptor antagonists for studying functional effects of genetic variants
Application of Cellular Technologies to the Experimental Treatment of Destructive Inflammatory Arthropathies
Introduction. The treatment of destructive inflammatory joint diseases (arthropathies) is one of the issues of current interest in modern medicine. In destructive inflammatory diseases, the regenerative ability of cartilaginous tissue proves to be inadequate for neogenesis of joints. The goal of this study is to determine the efficacy of bone marrow-derived mononuclear cell fraction (MNC) and multipotent mesenchymal stromal cells (MMSC) in the treatment of destructive inflammatory joint diseases.Materials and methods. The study subjects consisted of 15 male rabbits weighing 3-4 kg with experimental destructive inflammatory knee joint disease. The test animals were divided into 3 groups: reference group without treatment, first test group – introduction of autologous MNC from rabbit bone marrow into the affected joint, and second test group – introduction of cultured MMSC from rabbit bone marrow into the joint.Results. A morphological examination of the synovial membranes in the reference group on the 40th day of the experiment revealed chronic synovitis with destruction of synoviocytes, thickening and inflammatory infiltration of the underlying connective tissue (subintima). During examination of synovial membranes in the first test group the patches of thickened regenerating inner layer (intima) made up by large proliferating synoviocytes were observed. The layer of loose connective tissue (subintima) contained a large number of small blood vessels and was only slightly infiltrated by inflammatory cells. The morphological examination of synovial membranes in the second test group discovered thickened regenerating intimal layer sitting on hypertrophied subintima with dense vascular network. Elastic collagenous layers of synovial membrane adjoined proliferating elements in cartilage plates.Conclusion. Both autologous MNC fraction and MMSC from bone marrow proved effectiveness in the treatment of destructive inflammatory joint diseases which stimulate neoangiogenesis. At the same time, it must be noted that the introduction of MMSC diminished destructive changes and accelerated proliferative process
Diagnostics of Cognitive Function in Women of Menopausal Period at Level of Primary Health Care
Introduction. In the medical community, there is no consensus on whether or not climacteric changes are pathologic and require treatment. One of the main problems related to menopause is misperception of menopause; consequently, there is no consensus on treatments for psychological dysfunction and cognitive deficits in menopausal women. Timely diagnosis and adequate treatment of psychological disorders and cognitive dysfunction are imperative and complicated. The purpose of this study was to evaluate physician perceptions of cognitive and psychological deficits in menopausal women in outpatient settings.Methods. 215 obstetricians-gynecologists working in out-patient services were surveyed using a multiple choice questionnaire assessing perceptions and knowledge of menopausal transition.Results. Of total respondents, 42.0% ± 2.5 of physicians found it hard to define menopausal period, and 67.5% ± 3.2 could not give a clear definition of hormone replacement therapy. On the question “cognitive function includes…,” 62.5% ± 2.1 of physicians selected “memory,” 32.3% ± 1.8 selected attention, 77.5% ± 3.2 selected mood and/or imagination, 37.4% selected intellect, 36.3% ± 3.1 of respondents selected character traits, and 6.2% ± 1.7 selected speech. Regarding the question “how do you study memory status function?” it was estimated that 71.2% ± 2.5 of study participants have studied the memory only on the basis of subjective complaints, and none of the respondents (100%) have ever used neuropsychological tests.Conclusion. The survey allows us to ascertain that primary medical care services lack the ability to appropriately recognize and diagnose cognitive deficits in women of menopausal age. Based on these data, we can assume that proper mental care is not provided. Thus, the study indicates a need to create training programs for general practitioners and other specialists (cardiologists, neurologists, and endocrinologists) to fulfill this need. Implementation of a standard of care, testing, and treatment of cognitive and psychological function, such as the use of neuropsychological tests and questionnaires, in an out-patient setting for menopausal women would improve the quality of life during a woman’s transition period
Application of Clinical Aging Indicators for the Assessment of Neurological Health via Screening Among Residents of the Almaty Region
Introduction. Life expectancy at birth is considered to be a primary indicator of public health success. However, an increase in life expectancy is meaningless if it is not accompanied by an equivalent increase in the number of life years without disability such as physical, cognitive, and psychological abilities. The main consequences of disease leading to neurological dysfunction are directly related to issues such as the inability to walk, talk, learn, live in society, or take care of oneself. The objective of the study was to conduct a medical examination of elderly people as a part of the scientific program "Development of a model (program) of anti-aging to provide active longevity of elderly people of Kazakhstan.”Methods. As part of a pilot study, we assessed the presence of the following clinical indicators of aging: cognitive impairment (MMSE test), pyramidal symptoms,and ataxia. We conducted medical examination (screening) among 150 elderly persons in Almaty City Polyclinic #8 and 287 elderly persons in Central Regional Clinic of Rayimbek Area, Almaty region aged 45 and above.Results. The results show that the intensity of changes is directly dependent on the age of the study groups. The cognitive function is the most affected and depends on the age of examinees. The changes are more expressed among residents of Almaty region. The average MMSE score in Almaty was 28.2 (age group of 45-49 years) and 25.8 (age group of 80 and above), and 27.3 and 24.0 respectively in Almaty region. The various symptoms among residents of Almaty tend to stabilize after 65 years, however, the frequency of ataxia continues to grow and increases significantly after 75 years.Conclusions. Considering that important risk factors of neurological disorders are cerebrovascular diseases of various origins (primarily hypertension, atherosclerosis, and diabetes), an adequate treatment of these diseases will increase a healthy lifespan. Furthermore, it is necessary to conduct additional research for possible methods of reducing existing morbidities so that healthy aging can be achieved
A 24-hour dietary recall for assessing the intake pattern of choline among Bangladeshi pregnant women at their third trimester of pregnancy
Maternal choline intake during the third trimester of human pregnancy can modify systemic and local epigenetic marks in fetal-derived tissues, promoting better pregnancy outcomes, increased immunity, as well as improved mental and physical work capacity with proper memory and cognitive development. 103 pregnant women presenting to the antenatal care of Azimpur Maternity Hospital of Dhaka, Bangladesh in their third trimester of pregnancy were randomly selected for this cross sectional study exploring dietary intake patterns of choline. A dietary recall form was administered to estimate frequency and amount of food consumption of foods for the previous 24 hours. Most women reported diets that delivered less than the recommended choline intake (mean ± SD; 189.5 ± 98.2) providing only 42.72% of total RDA value. The results of this study may indicate that dietary choline among pregnant, Bangladeshi women may not be adequate to meet the needs of both, the mother and fetus. Further studies are warranted to determine clinical implications.
Herbal extracts in the treatment of Diabetic Foot Syndrome
Introduction: One of the most serious complications of diabetes is the formation of Diabetic Foot Syndrome. Herbal extracts that combine high antioxidant and antimicrobial properties can be used to treat the resulting neuropathy.The aim of this study was to determine antimicrobial and antioxidant activities of crude extracts isolated from plants growing in Kazakhstan, which could be used to develop products for treatment of Diabetic Foot Syndrome.Method: Different solvents, including dichloromethane and ethanol, were used to prepare plant extracts. The crude extracts from the plants were tested for antimicrobial activity using a modified version of the CLSI/NCCLS methods. All organisms were obtained from American Type Culture Collection. These included the fungi Candida glabrata ATTC 90030, the bacteria Staphylococcus aureus ATCC 29213, and Methicillin-resistant S. aureus ATCC 43300. The 2,2-diph?nyl-1-picrylhydrazyl (DPPH) assay, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assay were used to analyzed the antioxidant capacity.Results: The results clearly indicate that antibacterial and antifungal activities vary with plant species. Dichloromethane extracts produced favorable results in all assays. Epilobium hirsutum, Rhodiola quadrifida, Rumex confertus showed antifungal activity against Candida glabrata in all extracts where IC50 less than 3 ?g/ml. Rumex confertus, Glycyrrhiza Uralensis and Vexibia alopecuroides showed anti-fungal activity against Staphylococcus aureus (IC50 =10.80 ?g/ml), (IC50 =11.10 ?g/ml), (IC50 =3.05 ?g/ml) and Methicillin-resistant S. aureus (IC50 =16.20 ?g/ml), (IC50 =11.00 ?g/ml), (IC50 =2.90 ?g/ml) respectively. In spite of this, Vexibia alopecuroides extract showed no antioxidant activity. The other extracts showed a dose dependent ABTS scavenging activity. IC50 values were for the following: 6.6 ?g/ml Epilobium hirsutum; 4.5 ?g/ml Rumex confertus; 3.8 ?g/ml Rhodiola quadrifida, 5.7 ?g/ml Glycyrrhiza Uralensis. Extracts of Epilobium hirsutum and Rumex confertus had high antioxidant activity greater than 85% inhibition of DPPH (P ? 0.05).Conclusion: The demonstrated antimicrobial and antioxidant activities showed evidence supporting the use of herbal extracts to treat Diabetic Foot Syndrome
Peptidoglycan Hydrolases of Local Lactic Acid Bacteria from Kazakh Traditional Food
Introduction: Peptidoglycan (PG) is a major component of the cell wall of Gram-positive bacteria and is essential for maintaining the integrity of the bacterial cell and its shape. The bacteria synthesize PG hydrolases, which are capable of cleaving the covalent bonds of PG. They also play an important role in modeling PG, which is required for bacterial growth and division. In an era of increasing antibiotic-resistant pathogens, PG hydrolases that destroy these important structures of the cell wall act as a potential source of new antimicrobials. The aim of this study is to identify the main PG hydrolases of local lactic acid bacteria isolated from traditional foods that enhance probiotic activity of a biological preparation.Methods. Lactococcus lactis 17? and Lactococcus garvieae 19? were isolated from the traditional sausage-like meat product called kazy. They were isolated according to standards methods of microbiology. Genetic identification of the isolates were tested by determining the nucleotide sequences of 16S rDNA. The Republican collection of microorganisms took strains of Lactobacillus casei subsp. Rhamnosus 13-P, L. delbrueckii subsp. lactis CG-1 B-RKM 0044 from cheese, Lactobacillus casei subsp. casei B-RKM 0202 from homemade butter. They used the standard technique of renaturating polyacrylamide gel electrophoresis to detect PG hydrolases activity.Results. According to the profiles of PG hydrolase activity on zymograms, the enzymes of Lactococci 17A and 19A in kazy are similar in electrophoretic mobility to major autolysin AcmA, while the lactobacilli of industrial and home-made dairy products have enzymes similar to extracellular proteins p40 and p75, which have probiotic activity.Conclusions. Use of peptidoglycan hydrolases seems to be an interesting approach in the fight against multi-drug resistant strains of bacteria and could be a valuable tool for the treatment of diseases caused by these microorganisms in Kazakhstan
Genomic research perspectives in Kazakhstan
Introduction: Technological advancements rapidly propel the field of genome research. Advances in genetics and genomics such as the sequence of the human genome, the human haplotype map, open access databases, cheaper genotyping and chemical genomics, have transformed basic and translational biomedical research. Several projects in the field of genomic and personalized medicine have been conducted at the Center for Life Sciences in Nazarbayev University. The prioritized areas of research include: genomics of multifactorial diseases, cancer genomics, bioinformatics, genetics of infectious diseases and population genomics. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. Results: To further develop genomic and biomedical projects at Center for Life Sciences, the development of bioinformatics research and infrastructure and the establishment of new collaborations in the field are essential.Widespread use of genetic tools will allow the identification of diseases before the onset of clinical symptoms, the individualization of drug treatment, and could induce individual behavioral changes on the basis of calculated disease risk. However, many challenges remain for the successful translation of genomic knowledge and technologies into health advances, such as medicines and diagnostics.It is important to integrate research and education in the fields of genomics, personalized medicine, and bioinformatics, which will be possible with opening of the new Medical Faculty at Nazarbayev University. People in practice and training need to be educated about the key concepts of genomics and engaged so they can effectively apply their knowledge in a matter that will bring the era of genomic medicine to patient care. This requires the development of well-equipped laboratories, bioinformatics, as well as qualified trained physicians and laboratory staff