Genetics of Exercise and Diet-Induced Fat Loss Efficiency: A Systematic Review.

Physical exercise and dieting are well-known and effective methods for fat loss and improving cardiovascular health. However, different individuals often react differently to the same exercise regimen or dietary plan. While specific individuals may undergo substantial fat loss, others may observe only limited effects. A wide range of inter-individual variability in weight gain and changes in body composition induced by physical exercises and diets led to an investigation into the genetic factors that may contribute to the individual variations in such responses. This systematic review aimed at identifying the genetic markers associated with fat loss resulting from diet or exercise. A search of the current literature was performed using the PubMed database. Forty-seven articles met the inclusion criteria when assessing genetic markers associated with weight loss efficiency in response to different types of exercises and diets. Overall, we identified 30 genetic markers of fat-loss efficiency in response to different kinds of diets and 24 in response to exercise. Most studies (n = 46) used the candidate gene approach. We should aspire to the customized selection of exercise and dietary plans for each individual to prevent and treat obesity.

Identification of Optimal Reference Genes for qRT-PCR Normalization for Physical Activity Intervention and Omega-3 Fatty Acids Supplementation in Humans.

The quantitative polymerase chain reaction (qRT-PCR) technique gives promising opportunities to detect and quantify RNA targets and is commonly used in many research fields. This study aimed to identify suitable reference genes for physical exercise and omega-3 fatty acids supplementation intervention. Forty healthy, physically active men were exposed to a 12-week eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation and standardized endurance training protocol. Blood samples were collected before and after the intervention and mRNA levels of six potential reference genes were tested in the leukocytes of 18 eligible participants using the qRT-PCR method: GAPDH (Glyceraldehyde-3-phosphate dehydrogenase), ACTB (Beta actin), TUBB (Tubulin Beta Class I), RPS18 (Ribosomal Protein S18), UBE2D2 (Ubiquitin-conjugating enzyme E2 D2), and HPRT1 (Hypoxanthine Phosphoribosyltransferase 1). The raw quantification cycle (Cq) values were then analyzed using RefFinder, an online tool that incorporates four different algorithms: NormFinder, geNorm, BestKeeper, and the comparative delta-Ct method. Delta-Ct, NormFinder, BestKeeper, and RefFinder comprehensive ranking have found GAPDH to be the most stably expressed gene. geNorm has identified TUBB and HPRT as the most stable genes. All algorithms have found ACTB to be the least stably expressed gene. A combination of the three most stably expressed genes, namely GAPDH, TUBB, and HPRT, is suggested for obtaining the most reliable results.

DNA Methylation of the Dopamine Transporter DAT1 Gene-Bliss Seekers in the Light of Epigenetics.

DNA methylation (leading to gene silencing) is one of the best-studied epigenetic mechanisms. It is also essential in regulating the dynamics of dopamine release in the synaptic cleft. This regulation relates to the expression of the dopamine transporter gene (DAT1). We examined 137 people addicted to nicotine, 274 addicted subjects, 105 sports subjects and 290 people from the control group. After applying the Bonferroni correction, our results show that as many as 24 out of 33 examined CpG islands had statistically significantly higher methylation in the nicotine-dependent subjects and athletes groups compared to the control group. Analysis of total DAT1 methylation revealed a statistically significant increase in the number of total methylated CpG islands in addicted subjects (40.94%), nicotine-dependent subjects (62.84%) and sports subjects (65.71%) compared to controls (42.36%). The analysis of the methylation status of individual CpG sites revealed a new direction of research on the biological aspects of regulating dopamine release in people addicted to nicotine, people practicing sports and people addicted to psychoactive substances.

Inhibition of LPS-stimulated ecto-adenosine deaminase attenuates endothelial cell activation.

Vascular inflammation is an important factor in the pathophysiology of cardiovascular diseases, such as atherosclerosis. Changes in the extracellular nucleotide and in particular adenosine catabolism may alter a chronic inflammation and endothelial activation. This study aimed to evaluate the relation between vascular ecto-adenosine deaminase (eADA) activity and endothelial activation in humans and to analyze the effects of LPS-mediated inflammation on this activity as well as mechanisms of its increase. Moreover, we investigated a therapeutic potential of ADA inhibition by deoxycofromycin (dCF) for endothelial activation. We demonstrated a positive correlation of vascular eADA activity and ADA1 mRNA expression with endothelial activation parameters in humans with atherosclerosis. The activation of vascular eADA was also observed under LPS stimulation in vivo along with endothelial activation, an increase in markers of inflammation and alterations in the lipid profile of a rat model. Ex vivo and in vitro studies on human specimen demonstrated that at an early stage of vascular pathology, eADA activity originated from activated endothelial cells, while at later stages also from an inflammatory infiltrate. We proposed that LPS-stimulated increase in endothelial adenosine deaminase activity could be a result of IL-6/JAK/STAT pathway activation, since the lack of IL-6 in mice was associated with lower vascular and plasma eADA activities. Furthermore, the inhibitors of JAK/STAT pathway decreased LPS-stimulated adenosine deaminase activity in endothelial cells. We demonstrated that cell surface eADA activity could be additionally regulated by transcytosis pathways, as exocytosis inhibitors including lipid raft inhibitor, methyl-ß-cyclodextrin decreased LPS-induced eADA activity. This suggests that cholesterol-dependent protein externalization mediated by lipid rafts could be an important factor in the eADA increase. Moreover, endocytosis inhibitors and exocytosis activators increased this activity on the cell surface. Furthermore, the inhibition of adenosine deaminase in endothelial cells in vitro attenuated LPS-mediated IL-6 release and soluble ICAM-1 and VCAM-1 concentration in the incubation medium through the restoration of the extracellular adenosine pool and adenosine receptor-dependent pathways. This study demonstrated that the vascular endothelial eADA activity remains under control of inflammatory mediators acting through JAK/STAT pathway that could be further modified by dyslipidemic-dependent exocytosis and transcytosis pathways. Inhibition of eADA blocked endothelial activation suggesting a crucial role of this enzyme in the control of vascular inflammation. This supports the concept of eADA targeted vascular protection therapy.

Adenosine deaminase inhibition suppresses progression of 4T1 murine breast cancer by adenosine receptor-dependent mechanisms.

The activity of a cell-surface ecto-adenosine deaminase (eADA) is markedly increased in the endothelial activation and vascular inflammation leading to decreased adenosine concentration and alterations in adenosine signalling. Depending on the specific pathway activated, extracellular purines mediate host cell response or regulate growth and cytotoxicity on tumour cells. The aim of this study was to test the effects of adenosine deaminase inhibition by 2'deoxycoformycin (dCF) on the breast cancer development. dCF treatment decreased a tumour growth and a final tumour mass in female BALB/c mice injected orthotopically with 4T1 cancer cells. dCF also counteracted cancer-induced endothelial dysfunction in orthotopic and intravenous 4T1 mouse breast cancer models. In turn, this low dCF dose had a minor effect on immune stimulation exerted by 4T1 cell implantation. In vitro studies revealed that dCF suppressed migration and invasion of 4T1 cells via A2a and A3 adenosine receptor activation as well as 4T1 cell adhesion and transmigration through the endothelial cell layer via A2a receptor stimulation. Similar effects of dCF were observed in human breast cancer cells. Moreover, dCF improved a barrier function of endothelial cells decreasing its permeability. This study highlights beneficial effects of adenosine deaminase inhibition on breast cancer development. The inhibition of adenosine deaminase activity by dCF reduced tumour size that was closely related to the decreased aggressiveness of tumour cells by adenosine receptor-dependent mechanisms and endothelial protection.

AMP deaminase 1 gene polymorphism and heart disease-a genetic association that highlights new treatment.

Nucleotide metabolism and signalling is directly linked to myocardial function. Therefore analysis how diversity of genes coding nucleotide metabolism related proteins affects clinical progress of heart disease could provide valuable information for development of new treatments. Several studies identified that polymorphism of AMP deaminase 1 gene (AMPD1), in particular the common C34T variant of this gene was found to benefit patients with heart failure and ischemic heart disease. However, these findings were inconsistent in subsequent studies. This prompted our detailed analysis of heart transplant recipients that revealed diverse effect: improved early postoperative cardiac function associated with C34T mutation in donors, but worse 1-year survival. Our other studies on the metabolic impact of AMPD1 C34T mutation revealed decrease in AMPD activity, increased production of adenosine and de-inhibition of AMP regulated protein kinase. Thus, genetic, clinical and biochemical studies revealed that while long term attenuation of AMPD activity could be deleterious, transient inhibition of AMPD activity before acute cardiac injury is protective. We suggest therefore that pharmacological inhibition of AMP deaminase before transient ischemic event such as during ischemic heart disease or cardiac surgery could provide therapeutic benefit.

Analysis of Industrial Bacillus Species as Potential Probiotics for Dietary Supplements.

So far, Bacillus species bacteria are being used as bacteria concentrates, supplementing cleaning preparations in order to reduce odor and expel pathogenic bacteria. Here, we discuss the potential of Bacillus species as 'natural' probiotics and evaluate their microbiological characteristics. An industrially used microbiological concentrates and their components of mixed Bacillus species cultures were tested, which may be a promising bacteria source for food probiotic preparation for supplementary diet. In this study, antagonistic activities and probiotic potential of Bacillus species, derived from an industrial microbiological concentrate, were demonstrated. The cell free supernatants (CFS) from Bacillus licheniformis mostly inhibited the growth of foodborne pathogenic bacteria, such as Escherichia coli O157:H7 ATCC 35150, Salmonella Enteritidis KCCM 12021, and Staphylococcus aureus KCCM 11335, while some of Bacillus strains showed synergistic effect with foodborne pathogenic bacteria. Moreover, Bacillus strains identified by the MALDI TOF-MS method were found sensitive to chloramphenicol, kanamycin, and rifampicin. B. licheniformis and B. cereus displayed the least sensitivity to the other tested antibiotics, such as ampicillin, ampicillin and sulfbactam, streptomycin, and oxacillin and bacitracin. Furthermore, some of the bacterial species detected extended their growth range from the mesophilic to moderately thermophilic range, up to 54 °C. Thus, their potential sensitivity to thermophilic TP-84 bacteriophage, infecting thermophilic Bacilli, was tested for the purpose of isolation a new bacterial host for engineered bionanoparticles construction. We reason that the natural environmental microflora of non-pathogenic Bacillus species, especially B. licheniformis, can become a present probiotic remedy for many contemporary issues related to gastrointestinal tract health, especially for individuals under metabolic strain or for the increasingly growing group of lactose-intolerant people.

Correction: Lubkowska et al. Analysis of Industrial Bacillus Species as Potential Probiotics for Dietary Supplements. Microorganisms 2023, 11, 488.

There was an error in the original publication [...].

Association Between the rs4680 Polymorphism of the COMT Gene and Personality Traits among Combat Sports Athletes.

Physical performance has been the focus of studies examining genetic influences in martial arts. There has been little quantitative analysis of the interaction between psychological traits and gene variants in athletes. This study aimed to determine whether the rs4680 polymorphism of the COMT gene (catechol-O-methyltransferase) was linked to other sports phenotypes such as temperament, mental toughness, and stress tolerance. In our study, we concentrated on the case-control analysis of athletes in the aspect of their personality traits in association with the COMT gene polymorphism. Participants comprised 258 combat sports athletes and 278 healthy male individuals as a control group. Psychometric properties were assessed with the Revised Temperament and Character Inventory (TCI-R). COMT polymorphism testing was performed using real-time PCR. We found a statistically significant effect of a complex factor COMT rs4680 genotype with combat athletes/controls and novelty seeking (F2,530 = 5.958, p = 0.0028, η2 = 0.022), self-management (F2,530 = 6.772, p = 0.0012, η2 = 0.025), and with self-transcendence skills (F2,530 = 9.387, p = 0.00009, η2 = 0.034). The results are important for encouraging further studies on the genetic makeup of athletes in conjunction with personality traits. Due to the multigene and multifactorial nature of determinants of sports predispositions, we propose to take into account also other features, especially when studying genes related to cerebral neurotransmission. It is a holistic departure, and it clearly illustrates the relationship between the given characteristics of an athlete.

Polyphenol Supplementation and Antioxidant Status in Athletes: A Narrative Review.

Antioxidants in sports exercise training remain a debated research topic. Plant-derived polyphenol supplements are frequently used by athletes to reduce the negative effects of exercise-induced oxidative stress, accelerate the recovery of muscular function, and enhance performance. These processes can be efficiently modulated by antioxidant supplementation. The existing literature has failed to provide unequivocal evidence that dietary polyphenols should be promoted specifically among athletes. This narrative review summarizes the current knowledge regarding polyphenols' bioavailability, their role in exercise-induced oxidative stress, antioxidant status, and supplementation strategies in athletes. Overall, we draw attention to the paucity of available evidence suggesting that most antioxidant substances are beneficial to athletes. Additional research is necessary to reveal more fully their impact on exercise-induced oxidative stress and athletes' antioxidant status, as well as optimal dosing methods.

Transmission Distortion of MCT1 rs1049434 among Polish Elite Athletes.

BACKGROUND: To date, nearly 300 genetic markers were linked to endurance and power/strength traits. The current study aimed to compare genotype distributions and allele frequencies of the common polymorphisms: MCT1 rs1049434, NRF2 rs12594956, MYBPC3 rs1052373 and HFE rs1799945 in Polish elite athletes versus nonathletes. METHODS: The study involved 101 male elite Polish athletes and 41 healthy individuals from the Polish population as a control group. SNP data were extracted from whole-genome sequencing (WGS) performed using the following parameters: paired reads of 150 bps, at least 90 Gb of data per sample with 300 M reads and 30× mean coverage. RESULTS: All the analyzed polymorphisms conformed to Hardy-Weinberg equilibrium (HWE) in athletes and the control group, except the MCT1 rs1049434, where allele T was over-represented in the elite trainers' group. No significant between-group differences were found for analyzed polymorphisms. CONCLUSIONS: The MCT1 rs1049434 transmission distortion might be characteristic of Polish athletes and the effect of strict inclusion criteria. This result and the lack of statistically significant changes in the frequency of other polymorphisms between the groups might result from the small group size.

Association of Interleukin Genes IL10 and IL10RB with Parameters of Overweight in Military Students.

BACKGROUND: To date, nearly 300 single-nucleotide polymorphisms (SNPs) associated with BMI, waist-to-hip ratio, and other adiposity traits have been identified by GWAS. With regards to IL10, at least 49 IL10-associated polymorphisms have been reported. However, little is known regarding the relationship between SNPs of the IL10 gene and the risk of obesity in young men. The aim of the present study was to investigate the relationship between SNPs of the IL10 and IL10RB genes and the risk of obesity in young men. METHODS: A cohort of 139 male students were enrolled and the following IL10 and IL10RB SNPs were analyzed: IL10 (rs1518110), IL10 (rs3024491), IL10RB (rs2834167). The subjects were divided into groups depending on obesity parameters: body mass index (BMI), fat mass index (FMI) and fat percentage (Fat%). Statistical analysis was conducted for a single locus and haplotypes, an association between SNPs and body composition parameters was tested with four genetic models: dominant, recessive, codominant and overdominant mode of inheritance (MOI). RESULTS: Significant association was found for interaction IL10 (rs1518110) × IL10RB (rs2834167) with Fat% value exceeding 20 in codominant (p-value = 0.03, OR = 0.34, 95% CI 0.08 1.44) and dominant model (p-value = 0.03, OR = 0.34, 95% CI 0.08 1.44) Conclusion: Our study shows for the first time that there is a correlation between the occurrence of specific polymorphisms of IL10 gene (rs1518110, rs3024491 and rs2834167) and the possibility of obesity.

Are COL22A1 Gene Polymorphisms rs11784270 and rs6577958 Associated with Susceptibility to a Non-Contact Anterior Cruciate Ligament Injury in Polish Athletes?

Understanding the risk factors and etiology of ACL ruptures (anterior cruciate ligament) is crucial due to the injury's high occurrence, significant financial cost to the healthcare sector, and clinical consequences. In this study, we investigated the hypothesis that rs11784270 A/C and rs6577958 C/T SNPs (single gene polymorphism) within COL22A1 are associated with ACL ruptures (ACLR) in Polish soccer players. Methods: 228 athletes with ACLR (157 male, age 26 ± 4, 71 female, age 26 ± 6) and 202 control athletes (117 male, age 26 ± 6, 85 female, age 29 ± 2) engaged in the study. The buccal cell swabs were genotyped using TaqMan® pre-designed SNP genotyping assays, following the manufacturer's recommendations. The R program and SNPassoc package were used to determine the genotype and allele frequency distributions under the various inheritance models (co-dominant, dominant, recessive, and over-dominant). Further, p-values of <0.05 were considered statistically significant. We found no association between the analyzed polymorphisms and the risk of non-contact ACL ruptures in any of the studied models. Although the genetic variants investigated in this study were not associated with the risk of non-contact ACL ruptures, we assumed that the COL22A1 gene remains a candidate for further investigations in musculoskeletal injuries.

Genome-Wide Association Study of Exercise-Induced Fat Loss Efficiency.

There is a wide range of individual variability in the change of body weight in response to exercise, and this variability partly depends on genetic factors. The study aimed to determine DNA polymorphisms associated with fat loss efficiency in untrained women with normal weight in response to a 12-week aerobic training program using the GWAS approach, followed by a cross-sectional study in athletes. The study involved 126 untrained young Polish women (age 21.4 ± 1.7 years; body mass index (BMI): 21.7 (2.4) kg/m2) and 550 Russian athletes (229 women, age 23.0 ± 4.1; 321 men, age 23.9 ± 4.7). We identified one genome-wide significant polymorphism (rs116143768) located in the ACSL1 gene (acyl-CoA synthetase long-chain family member 1, implicated in fatty acid oxidation), with a rare T allele associated with higher fat loss efficiency in Polish women (fat mass decrease: CC genotype (n = 122) -3.8%; CT genotype (n = 4) -31.4%; p = 1.18 × 10-9). Furthermore, male athletes with the T allele (n = 7) had significantly lower BMI (22.1 (3.1) vs. 25.3 (4.2) kg/m2, p = 0.046) than subjects with the CC genotype (n = 314). In conclusion, we have shown that the rs116143768 T allele of the ACSL1 gene is associated with higher fat loss efficiency in response to aerobic training in untrained women and lower BMI in physically active men.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04). INTERPRETATION: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. FUNDING: German Federal Ministry of Health.

Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro.

Adult cardiac tissue undergoes a rapid process of dedifferentiation when cultured outside the body. The in vivo environment, particularly constant electromechanical stimulation, is fundamental to the regulation of cardiac structure and function. We investigated the role of electromechanical stimulation in preventing culture-induced dedifferentiation of adult cardiac tissue using rat, rabbit and human heart failure myocardial slices. Here we report that the application of a preload equivalent to sarcomere length (SL) = 2.2 µm is optimal for the maintenance of rat myocardial slice structural, functional and transcriptional properties at 24 h. Gene sets associated with the preservation of structure and function are activated, while gene sets involved in dedifferentiation are suppressed. The maximum contractility of human heart failure myocardial slices at 24 h is also optimally maintained at SL = 2.2 µm. Rabbit myocardial slices cultured at SL = 2.2 µm remain stable for 5 days. This approach substantially prolongs the culture of adult cardiac tissue in vitro.

Vascular extracellular adenosine metabolism in mice correlates with susceptibility to atherosclerosis.

Animal models are widely used in atherosclerosis research. The most useful, economic and valid is mouse genetic model of this pathology. Purinergic signaling is an important mechanism regulating processes involved in the vascular inflammation and atherosclerosis. The aim of this study was to measure vascular activities of nucleotide and adenosine-degrading ecto-enzymes in different strains of mice and to compare them to atherosclerotic susceptibility. The vascular extracellular nucleotide catabolism pathway was analyzed in 6-month-old male genetically unmodified mouse strains: FVB/NJ, DBA/2J, BALB/c, C57Bl/6J and mouse knock-outs on C57Bl/6J background for LDLR (LDLR-/-) and for ApoE and LDLR (ApoE-/-LDLR-/-). LDLR-/- mice were a model of moderate hypercholesterolemia, while ApoE-/-LDLR-/- mice, a model of severe hypercholesterolemia with advanced atherosclerosis. FVB/NJ, DBA/2J and BALB/c mice showed high rates of vascular extracellular AMP hydrolysis and low activity of adenosine deamination. In turn, all mice with the C57Bl/6J background expressed diminished activity of vascular AMP hydrolysis. Mice with genetically-induced hyperlipidemia and atherosclerosis on the C57Bl/6J background revealed increased ecto-adenosine deaminase activity. Mouse strains that were resistant to atherosclerosis (FVB/NJ, DBA/2J, BALB/c) exhibited a protective extracellular vascular ecto-enzyme pattern directed toward the production of anti-inflammatory and anti-atherosclerotic adenosine. In turn, mice with genetically induced hypercholesterolemia and atherosclerosis expressed disturbed activities of ecto-5'nucleotidase and ecto-adenosine deaminase related to decreased production and increased degradation of extracellular adenosine.

Cardioprotective effect of N-methylnicotinamide salt of pyruvate in experimental model of cardiac hypoxia.

BACKGROUND: Pyruvate improves contractility of normal, hypoxic, and post-ischemic myocardium. However, sodium overload is a major problem with its therapeutic application if sodium pyruvate is used. Development of alternative forms such as N-1-methylnicotinamide (MNA) pyruvate may help to overcome this problem. The aim of the study was to investigate the effect of MNA pyruvate in a murine model of cardiac ischemia. METHODS: Seven month old male ApoE-/-LDLr-/- mice that develop myocardial infarction when exposed to hypoxic stress, were used in this study. Hypoxia (8% O2 in inspired air) was maintained for 8min and was followed by reoxygenation (21% O2 in inspired air). Four groups of mice were treated 10min before the hypoxic event by intravenous injection of MNA, MNA pyruvate, sodium pyruvate, and saline as control. The myocardial ischemia and damage was recorded by ECG. Four hours following the hypoxic episode serum troponin T and creatine kinase activity were measured. RESULTS: Significant hypernatremia was found in the sodium pyruvate group. During hypoxia, control and MNA group developed profound STU depressions on ECG while no changes were observed in MNA pyruvate and sodium pyruvate group. Creatine kinase activity and troponin T content in the mice plasma were significantly higher in the control and MNA group as compared to the MNA pyruvate and sodium pyruvate group. CONCLUSIONS: This study demonstrated that administration of MNA pyruvate prior to a hypoxia-induced cardiac event was cardioprotective. This intervention did not cause hypernatremia in contrast to sodium pyruvate.

From breathing difficulty to dyspnea: The translation process from the patient's story to the doctor's report in interactive medical case reports.

The aim of this paper is to study the 'translation process' (Fleischman 2001) from the patient's story into the doctor's report in interactive case reports from professional medical journals. Interactive case reports are a relatively new development in the genre, which has been postulated by, and adopted in, several publication outlets. The novelty of the variety is the possibility for readers to comment on a published case as well as the optional Patient's perspective section, in which the patient can share their experience of illness and treatment. In the present paper, a collection of interactive case reports derived from professional medical journals will be examined. The material under study can be seen as a contact situation between the lay discourse of a patient's narration and the professional discourse of medical description. The comparison and qualitative analysis of the two discourses referring to the same disease event will point to different communicative accents, different means and different effects. Drawing on the tradition of Rhetorical Genre Studies, the paper will also emphasise the many social practices in which the variety is, and can be, used.

Effects of 4-Pyridone-3-carboxamide-1ß-D-ribonucleoside on adenine nucleotide catabolism in the aortic wall; Implications for atherosclerosis in ApoE-/-LDLR-/- mice.

4-Pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) is an endogenously produced nucleoside that had been identified as a substrate for intracellular phosphorylation to form intracellular nucleotides. Previous studies demonstrated that 4PYR adversely affects metabolism of endothelial cells that is known risk factor for atherosclerosis. The purpose of this study was to evaluate effects of 4PYR on the progression of atherosclerosis and changes in extracellular nucleotides degradation on the surface of the vessel wall in the murine model. METHODS: Two month old ApoE-/-LDLR-/- mice were subcutaneously injected with 4PYR (4P) twice per day for one month or with saline in controls (C). Then, at the age of eight month hydrolysis rates of ATP, AMP and adenosine were evaluated in the intact aorta sections by HPLC based assays. Oil Red O (ORO) staining that indicates lipid deposition was quantified spectrophotometrically after extraction from the vessel. Serum amyloid A (SAA) content was analyzed with ELISA. RESULTS: Adenosine deamination rate (activity of eADA) increased from 8.7±1.4 nmol/min/cm2 in C to 16.0±2.6 nmol/min/cm2 in 4P (p<0.05). AMP dephosphorylation rate (activity of e5NT) and ATP hydrolysis rate (activity of eNTPD) were not different between C and 4P. ORO staining in the aorta of 4P mice increased by 75% as compared to C (p<0.01) while SAA content was similar in both groups. CONCLUSIONS: This data demonstrated that prolonged exposure to 4PYR of ApoE-/-LDLR-/- mice results in sustained elevation of vascular eADA activity and increased ORO staining indicating endothelial impairment and accelerated atherosclerosis.