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Journal Article 2012; 33(Suppl 2): 43-49 PubMed PMID: 23183509 Citation  Keywords:  Animals, Animals, Congenic, Chromosomes, Mammalian, Disease Models, Animal, Glucose Intolerance:drug therapy, Hypertension:drug therapy, Lipids:blood, Male, Metabolic Syndrome X:drug therapy, Ondansetron:pharmacology, Polydactyly:genetics, Rats, Rats, Inb.   

OBJECTIVES: Ondansetron is an antagonist of 5-HT3 receptors mostly used as an antiemetic yet known to modulate metabolism and appetite. We tested the metabolic effects of ondansetron in newly derived congenic rat strain, carrying limited chromosome 8 regions of (PD) Brown Norway (BN) and polydactylous (PD) strain origins (including variant serotonin receptor Htr3b gene) within the genomic background of highly inbred model of metabolic syndrome, the spontaneously hypertensive rat (SHR).

METHODS: Adult, standard diet-fed male rats of SHR and the congenic SHR.(PD/BN)8 strains received ondansetron (2mg/kg body weight/day) or vehicle (n=6/strain/treatment) via oral gavage for 14 days while we followed their metabolic and morphometric profiles including glucose tolerance and triacylgycerol and cholesterol concentrations in 20 lipoprotein fractions.

RESULTS: We fine-mapped the chromosome 8 differential segment in the new SHR.(PD/BN)8 congenic strain: it comprises BN-derived region together with an adjacent 422kb stretch of PD origin. The SHR.(PD/BN)8 rats were heavier than SHR, the fasting glucose was significantly higher in ondansetron-treated congenic than in SHR (post-hoc Tukey's HSD p=0.02). Compared to SHR, ondansetron induced significantly more robust increases of cholesterol and triacylglycerol concentrations in total, chylomicron, VLDL and HDL particles in the SHR.(PD/BN)8 congenic strain.

CONCLUSION: We established new congenic model with distinct pharmacogenetic profile related to metabolic effects of ondansetron, facilitating thus the search for responsible genetic variants within the limited genomic region demarcated by the differential segment....

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Journal Article 2012; 33(Suppl 2): 26-31 PubMed PMID: 23183506 Citation  Keywords:  Adult, Atherosclerosis:blood, Biomarkers:blood, Dyslipidemias:blood, Endothelium, Vascular:metabolism, Fatty Acid-Binding Proteins:blood, Female, Homeostasis:physiology, Humans, Intercellular Adhesion Molecule-1:blood, Linear Models, Male, Middle Aged, Mu.   

OBJECTIVES: Some findings support the role of serum adipocyte fatty acid-binding protein (A-FABP) as a key pro-inflammatory mediator that links obesity with cardiovascular diseases. The aim of the study was to evaluate the association of A-FABP with endothelial/hemostatic markers [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator (t-PA), soluble intercellular cell adhesion molecule-1 (s-ICAM-1) and soluble vascular cell adhesion molecule-1 (s-VCAM-1)] in asymptomatic dyslipidemic subjects.

DESIGN: We examined 105 dyslipidemic patients (with apolipoprotein B concentration ≥1.2 g/l and/or triglyceride (TG) concentration ≥1.5 mmol/l) without clinical manifestation of atherosclerosis and 50 normolipidemic healthy subjects, who served as a control group. Except of endothelial/hemostatic markers, anthropometric and lipid parameters, markers of insulin resistance and inflammation were assessed.

RESULTS: In dyslipidemic patients, A-FABP positively correlated with age (p<0.05), TG (p<0.05), insulin (p<0.05), homeostatic model assessment (HOMA) index (p<0.05), body mass index (p<0.001), waist circumference (p<0.05), high sensitivity C reactive protein (p<0.01), and vWF (p<0.05) and negatively with male gender (p<0.05). There were no correlations between A-FABP and PAI-1, t-PA, s-VCAM-1 or s-ICAM-1. By using linear multivariate regression analysis the positive association between A-FABP and vWF was independent of age, gender, insulin resistance, and visceral obesity.

CONCLUSION: Study displayed an independent positive association of A-FABP with vWF in clinically asymptomatic dyslipidemic subjects. Contribution of A-FABP in the process of endothelial dysfunction could help to explain the role of obesity in cardiovascular damage....

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Controlled Clinical Trial 2012; 33(6): 651-659 PubMed PMID: 23160228 Citation  Keywords:  Aged, Biomechanical Phenomena:drug effects, Chondroitin Sulfates:administration & dosage, Disease Progression, Female, Glucosamine:administration & dosage, Humans, Hyaluronic Acid:administration & dosage, Knee Joint:drug effects, Male, Middle Aged, Models.   

OBJECTIVES: This study seeks to demonstrate the influence of pharmacological substances from the SYSADOA group on the progression of osteoarthritis in the human knee. The quantification methods were direct measurement of the rheological properties of the knee joints in vivo and standard WOMAC index questionnaires.

MATERIALS AND METHODS: The drugs were administered orally to 34 probands with second degree gonarthrosis for 13 weeks. The untreated control group consisted of 10 probands. The rheological properties of the joints were determined by a biorheometer, and subjective assessment of the knees by patients (WOMAC) before and after medication, and for a further 13 weeks. Changes in the calculated parameters over time were compared.

RESULTS: During the audited perioda slight deterioration in all of the parameters was observed in the untreated group. The treated group, however, improved in all the parameters and some indicators showed statistically significant differences. The positive effects of the SYSADOA persisted for 3 months after the end of treatments. Partial correlation was found between the results of the WOMAC questionnaire and the rheological measurements.

CONCLUSIONS: This study shows the positive effects of the preparation on arthritic changes in the knee joint, but due to the large variance of the collected data, this conclusion is on the borderline of statistical significance. The method of measuring the rheological properties of the joints is suitable for evaluating the progression of OA....

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Journal Article 2012; 33(5): 536-545 PubMed PMID: 23090273 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Body Mass Index, Carcinoembryonic Antigen:blood, Female, Humans, Life Style, Lipid Peroxidation:physiology, Logistic Models, Middle Aged, Neoplasms:metabolism, Obesity:metabolism, Oxidative Stress:physiology, Risk Factors, .   

BACKGROUND: Non-communicable diseases (NCDs) constitute leading cause of morbidity, disability and premature mortality. Oxidative processes are involved in the pathogenesis of NCDs.

OBJECTIVES: To investigate the relationship between lipid peroxidation (LPO), an index of oxidative damage to membrane lipids, or carcinoembryonic antigen (CEA), a tumor marker, and potential risk factors for NCDs in women at midlife and beyond.

METHODS: Data on lifestyle, such as dietary habits, smoking, physical activity, etc. and medical history, were assessed by a questionnaire in 323 female outpatients of the Regional Centre of Menopause and Osteoporosis - Outpatient Department of Endocrinology, Lodz (Poland), at midlife and beyond. Blood serum LPO and CEA levels, as well as anthropometric measurements were evaluated.

RESULTS: Positive correlations between LPO level and body mass or body mass index or hip circumference were found. LPO level was increased in women who did not declare regular menstrual cycles. CEA level was increased in women who smoked (and positively correlated with duration of smoking), who consumed pickled food every day and over-consumed animal fats, who had not breastfed in the past, as well as in women with malignancy in anamnesis. Logistic regression analysis has revealed that LPO constitutes the independent positive determinant, whereas CEA constitutes the independent negative determinant, of obesity. Moreover, CEA was independently associated with malignancy in anamnesis, cigarette smoking and animal fat over-consumption.

CONCLUSION: Both LPO and CEA are independently associated with certain modifiable risk factors for NCDs....

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Journal Article 2012; 33(5): 471-476 PubMed PMID: 23090262 Citation  Keywords:  Algorithms, Brain:physiology, Entropy, Humans, Magnetic Resonance Imaging:methods, Models, Neurological, Signal-To-Noise Ratio,.   

: Entropy is a measure of information content or complexity. Information-theoretic modeling has been successfully used in various biological data analyses including functional magnetic resonance (fMRI). Several studies have tested and evaluated entropy measures on simulated datasets and real fMRI data. The efficiency of entropy algorithms has been compared to classical methods based on the linear model. Here we explain and summarize entropy algorithms that have been used in fMRI analysis, their advantages over classical methods and their potential use in event-related and block design fMRI....

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Journal Article 2012; 33(3): 318-320 PubMed PMID: 22635092 Citation  Keywords:  Animals, Chronobiology Phenomena:physiology, Circadian Rhythm:physiology, Light, Melatonin:physiology, Models, Animal, Photoperiod, Translational Medical Research:methods,.   

: That light and melatonin rhythms provide both clock and calendar information in humans and numerous other species is beyond dispute; this holds true for all stages of life, including the very early ones. Experimental evidence elucidates that exposure to light and melatonin titres are keys for the very development of circadian and seasonal rhythms. As evinced by a 2011 publication in Nature Neuroscience such awareness could impact considerably on the design and conduct of experimental studies as well as their subsequent analyses, interpretations and comparisons. Therefore "when and how experimental animals were bred, developed and raised" may be critical when experimenting with animals generally, and not just rodents. As long as the suggested imprinting of circadian system stability via light cues is not falsified, the perinatal season or perinatal experimental light:dark [L:D] conditions that an animal was kept under should be routinely recorded, published and considered in analysing and interpreting study data....

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Journal Article 2012; 33(3): 294-297 PubMed PMID: 22635087 Citation  Keywords:  Aged, Aged, 80 and over, Brain Ischemia:epidemiology, Coronary Artery Disease:epidemiology, Female, Humans, Logistic Models, Male, Middle Aged, Recurrence, Retrospective Studies, Risk Factors, Stroke:epidemiology,.   

BACKGROUND: Coronary artery disease (CAD) is a leading cause of long-term mortality in Europe and it negatively influences the outcome after stroke. However, its influence on stroke recurrence which endangers stroke patients mostly in the first months following stroke, is unclear. Previous studies have found no association between CAD and ischemic stroke recurrence. However, assessment of the relationship was not the primary endpoint of these investigations. The aim of this study was to assess the possible association between CAD and stroke recurrence.

PATIENTS AND METHODS: In a hospital-based, retrospective study, the set consisted of 190 patients - 105 patients with a first ever stroke (48 males; age 37-88, mean 70.7±12.5 years) and 85 patients with stroke recurrence (36 males; age 46-94, mean 88.0±9.6 years). CAD was correlated with the following other risk factors (age, sex, occurrence of arterial hypertension, atrial fibrillation, diabetes mellitus, plasma levels of total cholesterol, triglycerides, low-density cholesterol, high-density cholesterol, body mass index, presence of carotid plaques). Logistic regression analysis was used for the statistical evaluation.

RESULTS: No significant association was found between CAD and stroke recurrence. Of all of the other observed risk factors, only age showed a significant association with stroke recurrence (OR 1.04, 95% CI: 1.02-1.07).

CONCLUSION: The results of the presented study indicate that CAD does not influence stroke recurrence....

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Journal Article 2012; 33(1): 26-33 PubMed PMID: 22467108 Citation  Keywords:  Adenomatous Polyposis Coli, Animals, Disease Models, Animal, Genes, APC, Germ-Line Mutation, Mice, Mutation, Phenotype,.   

OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by the presence of hundreds to thousands of benign polyps in the colon. If not removed prophylactically they represent a risk of developing malignant cancer with an almost 100% penentrance. FAP is induced by germline mutation in the APC gene. Tumorigenesis launched a second somatic mutation of APC gene allele, leading to synthesis of non-functional APC protein. One of the possibilities of cancer prevention could be an alternative gene therapy using bacteria as vectors for delivery of therapeutic protein molecules.

MATERIAL AND METHODS: For this purpose mice model APC+/APC1638N with mutation in one allele murine homolog of the APC gene were used. Mice were fed orally commercial nutrition enriched with 0.5 ml PBS buffer with 5% milk containing 5×108 recombinant bacterial cells DE3plys6 bearing plasmid with cloned APC gene twice a week during 42 weeks. Afterwords mice were killed by thiopental, gastrointestinal tracts were removed, microscopically, macroscopically inspected for polyps/neoplastic lesions and immunohistochemically investigated with polyclonal rabbit antibody against APC protein.

RESULTS: We have cloned full-lenght APC gene into vector for expression in bacterial cells Escherichia coli BL21(DE3) and BL21(DE3) pLysS. Expression of the APC protein, induced by IPTG, was detected in protein extracts of three bacterial clones: DE3104-11, DE3pLys5, DE3pLys6. APC protein was identified by Western blot analysis using monoclonal and polyclonal antibodies against the APC protein. Bacteria of clone DE3pLys6 were orally administered to APC+/APC1638N mice with mutations in the APC gene. All transgenic mice without therapy developed adenomatous polyps in the gastrointestinal tract. Transgenic mice treated by oral administration of bacteria expressing functional APC protein developed polyps in 33.3%. The remaining four mice 66.7% were without polyps development.

CONCLUSION: Administration of APC gene expressing by bacteria to transgenic mice with mutation in APC gene leads to reduction in the number of mice developing polyps in the gastrointestinal tract. The effect of bacterially expressed APC protein in elimination of intestinal polyps or tumors has been monitored. These are our preliminary results and for possible confirmation of our hypotheses still more research is needed....

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