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Clinical Experience with Chitosan Matrix and Cultured Fibroblasts for Burns
Get PDFIntroduction. Burns are an important public health challenge due to the frequency of getting burns in day-to-day life, occupational hazards, and catastrophes. Treatment of burns is complex and is associated with high morbidity and mortality. Duration and complexity of burn treatment require finding new ways of curing and rehabilitating burns. The result of burn treatment plays a significant role in post-traumatic status of a patient and his or her consequent adaptation in society. Chitosan is a natural safe non-toxic product compatible with human tissues, characterized by hydrosorbid, anticoagulant, antibacterial, and wound healing features. The study aims to show a clinical application of chitosan-pectin scaffold with cultured human skin fibroblasts in the treatment of deep burns.Methods. The substrate was prepared by dissolving 3% chitosan in 0.5N acetic acid, which was then mixed with 3% solution of pectin dissolved in distillated water. Chitosan film was formed in a Petri dish for 20-24 hours at 20-25 °C. After drying the film, cultured allogeneic fibroblasts (patent number RK-25091) were seeded on its surface.Results. The results from an in vitro culture study showed that human allogeneic fibroblasts could adhere well and grow on the selected scaffold with a typical morphology. During autodermoplasty surgery, cultured allogeneic fibroblasts were applied on granulating wounds of 9 patients with IIIA to IVB degree burns and limited donor resources. Wounds treated with the fibroblast-seeded scaffold among all patients provided the highest level of re-epithelialization (day 5), in comparison to cell-free scaffold (day 7) and untreated surface of wounds (day 10).Conclusion. Our results indicate the potential use of chitosan for wound healing due to its allogenic fibroblast adherence to scaffolding as well as high epithelization. This warrants further studies on chitosan for use in wounds resulting from third and fourth degree burns
Pre-clinical Evaluation of an Adult Extracoproreal Carbon Dioxide Removal System for Pediatric Application
Get PDFIntroduction. Adult extracorporeal carbon dioxide removal (ECCO2R) systems and pediatric ECMO share the common objectives of having a low blood flow rate and low priming volume while safely maintaining sufficient respiratory support. The Hemolung is a highly simplified adult ECCO2R system intended for partial respiratory support in adult patients with acute hypercapnic respiratory failure. The objective of this work was to conduct pre-clinical feasibility studies to determine if a highly efficient, active-mixing, adult ECCO2R system can safely be translated to the pediatric population. Methods. 14 healthy nonsedated juvenile sheep were used for acute (2 animals) and 7-day chronic (12 animals) in-vivo studies to evaluate treatment safety independently of respiratory related injuries. In all evaluations, we hypothesized that gas exchange capabilities of the Hemolung RAS in this model would be equivalent to the adult configuration performance at similar blood flows - minimum CO2 removal of 50 mL/min at a venous partial pressure of CO2 equal to 45 mmHg. Target blood flow rates were set to a minimum of 280 mL/min. Swan Ganz catheters were used under general anesthesia in the two acute subjects to evaluate blood gas status in the pulmonary artery.Results. The Hemolung RAS was found to have adequate gas exchange and pumping capabilities for full respiratory support for subjects weighing 3 – 25 kg. The Hemolung device was estimated to provide a partial respiratory support for subjects weighing 27 – 34 kg. The seven-day studies in juvenile sheep demonstrated that veno-venous extracorporeal support could be provided safely at low flows with no significant adverse reactions related to device operation.Conclusion. The study outcomes suggest the potential use of the Hemolung RAS in a veno-venous pediatric configuration to safely provide respiratory support utilizing a significantly less complex system than traditional pediatric ECMO.
Heart and Lungs Protection Technique for Cardiac Surgery with Cardiopulmonary Bypass
Get PDFIntroduction: Cardioplegic cardiac arrest with subsequent ischemic-reperfusion injuries can lead to the development of inflammation of the myocardium, leucocyte activation, and release of cardiac enzymes. Flow reduction to the bronchial arteries, causing low-flow lung ischemia, leads to the development of a pulmonary regional inflammatory response. Hypoventilation during cardiopulmonary bypass (CPB) is responsible for development of microatelectasis, hydrostatic pulmonary edema, poor compliance, and a higher incidence of infection. Based on these facts, prevention methods of these complications were developed. The aim of this study was to evaluate constant coronary perfusion (CCP) and the “beating heart” in combination with pulmonary artery perfusion (PAP) and “ventilated lungs” technique for heart and lung protection in cardiac surgery with CPB.Methods. After ethical approval and written informed consent, 80 patients undergoing cardiac surgery with normothermic CPB were randomized in three groups. In the first group (22 patients), the crystalloid cardioplegia without lung ventilation/perfusion techniques were used. In the second group (30 patients), the CCP and “beating heart” without lung ventilation/perfusion techniques were used. In the third group (28 patients), the CCP with PAP and lung ventilation techniques were used. Clinical, functional parameters, myocardial damage markers (CK MB level), oxygenation index, and lung compliance were investigated.Results. There were higher rates of spontaneous cardiac recovery and lower doses of inotrops in the second and third groups. Myocardial contractility function was better preserved in the second and third groups. The post-operative levels of CK-MB were lower than in control group. Three hours after surgery CK-MB levels in the second and third groups were lower by 38.1% and 33.3%, respectively. Eight hours after surgery, CK-MB levels were lower in the second and third groups by 45.9% and 47.7%, respectively. 24 hours after surgery, CK-MB levels were lower in the second and third groups by 42.0% and 42.6%, respectively, and lower by 29.7% and 27.4% 48 hours after surgery, respectively. Normalization of CK-MB levels were registered earlier in second and third groups (within 24 hours) than the control group. Oxygenation index and lung compliance were significantly higher in the third group after CPB.Conclusion. Our technique improved myocardial and lung function in patients, but larger prospective randomized trials are needed to definitively assess the protective effects of this technique
Polyphenol Concentrate from Kazakhstan Cabernet Sauvignon Collection of Grapes
Get PDFIntroduction. Nowadays, most of the research in the field of gerontology is focused on the effects of the grape polyphenols. In particular, resveratrol has been shown to increase life expectancy of various living organisms, including mammals. Resveratrol also plays an important role in cancer prevention and decreases the risk of developing cardiovascular disease. In our research, we proposed the development of the therapeutic product from Cabernet Sauvignon grapes that would exhibit the beneficial properties of polyphenols. Standard operating procedures were developed in our laboratories to collect alcohol free concentrate of polyphenols from the Kazakhstan Cabernet Sauvignon collection of grapes. The purpose of the study was to investigate the composition, biological safety, and potential therapeutic effects of the polyphenol concentrate.Methods. The total polyphenol amount was determined using the Enology Analyzer Y15 (BioSystems, Spain). HPLC analysis of the polyphenol composition was performed using Agilent 1290 chromatograph. The polyphenol concentrate was analyzed for the microbiological purity and the presence of the toxic elements. The cytoprotective effect of the polyphenol concentrate was studied in experimental models of diabetes, toxic hepatitis, doxorubicin cardiomyopathy, and acute radiation sickness.Results. The total polyphenol amount in one sample was 12,819 mg/l. Polyphenol composition analysis showed presence of the following polyphenols: catechin, epicatechin, gallic acid, quercetin, miricetin, 3-glucosylkaempferol, epicatechin gallate, 3-(3,4-Dihydroxyphenyl)-2-propenoic acid, catechin gallate, pitseid, kaempferol, n-hydroxy-cinnamic acid, resveratrol and chlorogenic acid. The concentrate was proven to be biologically safe and acceptable for use as a dietary supplement. The polyphenol concentrate demonstrated high antioxidant activity against ABTS and DPPH radicals in vitro. It also showed the following impacts on the various experimental models in vivo: reduction of sugar levels in diabetes; regeneration of the structure and function of the heart tissue in cardiomyopathy; regeneration of the nephron structure and function in nephropathy; regeneration of liver in toxic hepatitis; recovery of the antioxidant status in oxidative stress; and recovery of the hematopoiesis in acute radiation sickness.Conclusion. The polyphenol concentrate from Kazakhstan Cabernet Sauvignon collection of grapes was proved to be biologically safe and acceptable for use as a dietary supplement. The concentrate showed high antioxidant, antiradiation activity, and regenerative effect in diabetes, cardiomyopathy, nephropathy, and hepatitis in the corresponding organs.
Emerging Infectious Diseases, Antimicrobial Resistance and Millennium Development Goals: Resolving the Challenges through One Health
Get PDFMost emerging infectious diseases are zoonoses, which could severely hamper reaching the targets of millennium development goals (MDG). Five out of the total eight MDG’s are strongly associated with the Emerging Infectious Diseases (EIDs). Recent emergence and dissemination of drug-resistant pathogens has accelerated and prevent reaching the targets of MDG, with shrinking of therapeutic arsenal, mostly due to antimicrobial resistance (AMR). World Health Organization (WHO has identified AMR as 1 of the 3 greatest threats to global health.Until now, methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) have been observed in hospital-acquired infections. In India, within a span of three years, New Delhi metallo-?-lactamase prevalence has risen from three percent in hospitals to twenty- fifty percent and is found to be colistin resistant as well. Routine use of antimicrobials in animal husbandry accounts for more than 50% in tonnage of all antimicrobial production to promote growth and prophylaxis. This has consequences to human health and environmental contamination with a profound impact on the environmental microbiome, resulting in resistance. Antibiotic development is now considered a global health crisis. The average time required to receive regulatory approval is 7.2 years. Moreover, the clinical approval success is only 16%. To overcome resistance in antimicrobials, intersectoral partnerships among medical, veterinary, and environmental disciplines, with specific epidemiological, diagnostic, and therapeutic approaches are needed. Joint efforts under “One Health”, beyond individual professional boundaries are required to stop antimicrobial resistance against zoonoses (EID) and reach the MDG
Study of genetic markers of cardiac arrhythmias in Kazakhstan
Get PDFIntroduction: Cardiac arrhythmias are the most common cause of mortality and sudden cardiac death worldwide. In the past decade, genetic factors underlying arrhythmogenic diseases have been revealed and given novel insights in to the understanding and treatment of arrhythmias predisposing one to sudden cardiac death.Material and methods: We conducted a pilot genetic screening of two patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and 14 patients with ventricular tachycardia (VT) for genetic variants in the human ryanodine receptor gene 2 (hRYR2). The most relevant 45 hot-spot exons of hRYR2 were amplified by polymerase chain reaction (PCR) and directly sequenced.Results: One novel mutation in a CPVT patient (c.A13892T; p.D4631V) and a novel mutation in a VT patient (c.G5428C; p.V1810L) were identified. Both variants are located at phylogenetically conserved positions and predicted pathogenesis. Three known synonymous SNPs (rs3765097, rs2253273, and TMP ESp1 237664067) were detected in the study group. No further variants within the target regions were detected in the study group.Conclusion: The results of study can be applied to risk asssessment for life-threatening arrhythmias and assist in development of appropriate strategies for prevention of sudden cardiac death. The implementation of these strategies would assist in the management of patients with genetically determined arrhythmias in Kazakhstan
Oligomeric Amyloid-? Peptide on Sialylic Lewisx–Selectin Bonding at Cerebral Endothelial Surface
Get PDFIntroduction: Alzheimer’s disease (AD) is a chronic neurodegenerative disorder, which affects approximately 10% of the population aged 65 and 40% of people over the age 80. Currently, AD is on the list of diseases with no effective treatment. Thus, the study of molecular and cellular mechanisms of AD progression is of high scientific and practical importance. In fact, dysfunction of the blood-brain barrier (BBB) plays an important role in the onset and progression of the disease. Increased deposition of amyloid b peptide (A?) in cerebral vasculature and enhanced transmigration of monocytes across the BBB are frequently observed in AD brains and are some of the pathological hallmarks of the diseases. Since the transmigration of monocytes across the BBB is both a mechanical and a biochemical process, the expression of adhesion molecules and mechanical properties of endothelial cells are the critical factors that require investigation.Methods: Because of recent advances in the biological applications of atomic force microscopy (AFM), we applied AFM with cantilever tips bio-functionalized by sLex in combination with the advanced immunofluorescent microscopy (QIM) to study the direct effects of A?42 oligomers on the selectins expression, actin polymerization, and cellular mechanical and adhesion properties in cerebral endothelial cells (mouse bEnd3 line and primary human CECs) and find a possible way to attenuate these effects. Results: QIM results showed that A?42 increased the expressions of P-selectin on the cell surface and enhanced actin polymerization. Consistent with our QIM results, AFM data showed that A?42 increased the probability of cell adhesion with sLex-coated cantilever and cell stiffness. These effects were counteracted by lovstatin, a cholesterol-lowering drug. Surprisingly, the apparent rupture force of sLex-selectin bonding was significantly lower after treatment with A?42, as compared with the control (i.e. no treatment). Similar results were also obtained when cells were treated with latruculin A (F-actin-disrupting drug). These results suggest that the decrease in the apparent rupture force of sLex-selectin bonding is the consequence of the dissociation of adhesion between the cytoskeleton and the bilayer membrane induced by A?42. The major causes of excess mortality in the first group were neoplams (30.6%), hypertension (23.8%), and myocardial infarction (22.6%). The effects of radiation influenced mortality in the second group were 2-2.5 times lower than the first group. Conclusion: The studies of the effects of A?42 on the adhesion properties of cerebral endothelial cells and how pharmacological agents (e.g. statin) counteract these effects should prove to provide insights into the mechanism of inflammation in Alzheimer’s brains and the design of therapeutic treatments of the disease
Lifestyle intervention as a treatment for obesity in school-age-children in Celaya, Guanajuato: An experimental study
Get PDFIntroduction: Obesity is a risk factor in chronic diseases, and its frequency among children in Mexico is increasing. Objective: To determine the effect of lifestyle intervention as a treatment for obesity in school-age-children from Celaya, Mexico.Methodology: For this experimental study, four schools were randomly selected. Children and parents participated voluntarily and signed consent forms. Two schools were chosen as the experimental group and the other two formed the control group. Age, gender, weight, height, BMI and blood pressure were recorded for each participant. Intervention: Children and parents were asked to walk in their schools for 30 minutes a day Monday through Friday and to attend 8 instructional sessions over a period of four months dedicated to the selection and preparation of meals. Statistical Analysis: The OR and 95% CI were calculated to determine the effect of the intervention; a Z-test for two proportions for overweight and obesity in the control and experimental groups were carried out for comparison.Results: 157 children were included in the experimental group and 144 in the control group. To compare the proportions of the overweight and the obese between the groups, a Z-test = - 0.36 (p-value 0.72) were obtained showing no effect of the intervention in lifestyle; OR =1.09, 95% CI (0.67, 1.77). It was adjusted according to the attendance to the sessions resulting in an OR = 2.00, 95% CI (0.69, 5.77), demonstrating that not attending the sessions was a confounder.Conclusions: Intervention in lifestyle should be measured over a longer period of time in order to determine what effects it may have on changes in body mass index
The Impact of Global Institutions on National Health HIV/AIDS Policy Making in Developing Countries
Get PDFThis article explores the relationship of global institutions such as the International Monetary Fund, World Trade Organization, World Bank, and individual developing countries in social health policy making in terms of HIV and AIDS. We examine the role of IGOs and NGOs in regarding to HIV/AIDS issues then analyse the TRIPs agreement as a tool for developing countries to negotiate with International organisations in global health policy decisions
BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.
Get PDFBackground: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women.Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer.Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing.Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05); higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations.Conclusions:Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation.