Pyruvate attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity

Pyruvate, a potent endogenous antioxidant and an important metabolic fuel is essential for the cardiac function and tissue defense mechanism. The present study was evaluated to investigate whether pyruvate attenuates the development of cardiotoxicity in isoproterenol (ISO)-induced myocardial infarction by assessing hemodynamic, biochemical and histopathological parameters. Subcutaneous injection of ISO (85 mg/kg) administered for 2 days at an interval of 24 h was used for induction of cardiotoxicity. ISO administration significantly decreased arterial pressure indices, heart rate, contractility {(+)LVdP/dt} and relaxation {(?)LVdP/dt} and increased left ventricular end-diastolic pressure. In addition, a significant reduction in activities of myocardial creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels along with increase in thiobarbituric acid reactive substances were also observed following ISO administration. However, pretreatment with pyruvate (0.25, 0.5 and 1.0 g/kg, p.o.) favorably modulated all most every studied parameters in ISO-induced myocardial injury. Furthermore, protective effect of pyruvate was confirmed by histopathological studies. Rats pretreated only with pyruvate did not produce significant change in hemodynamic, biochemical and histopathological parameters. Pyruvate at 0.50 and 1.0 g/kg doses was found to exert optimal cardioprotective effect against ISO-induced myocardial infarction. The results of our study suggest that pyruvate possessing antioxidant activity has a significant cardioprotective effect against ISO-induced myocardial injury.     

Venous thromboembolism and ethnicity

Venous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non-Western countries, and the low incidence of hereditary thrombophilia in those of non-Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non-Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.     

Does the rate of inappropriate therapy differ in implantable cardioverter–defibrillators from different manufacturers?

Objective We conducted this study to compare the rate of ≥1 inappropriate therapy between ICDs from two manufacturers which use different discriminatory protocols. Method One hundred sixty two patients (mean age 58 ± 13 years, 126 male) who received ICDs between January 2001 and 2005 were included in the study. Clinical, electrocardiographic, and ICD stored data and electrograms were collected and analyzed. Immediately after implantation all the detection and discrimination criteria were activated with the nominal values in order to compare the two discriminatory protocols under the default manufacturer’s settings. Results During the follow up period of 14.3 ± 10 months, 49 (30%) patients received ≥1 inappropriate ICD therapy. The rate of ≥1 inappropriate ICD therapy in manufacturer A and B ICDs was 26% (n = 29) and 41% (n = 20), respectively. Comparing the rate of ≥1 inappropriate ICD therapy between the two groups by Kaplan–Meier analysis and the log rank test resulted in P = 0.04. Conclusion Having all discriminatory variables activated with the nominal values, discriminatory performance differs between the two manufacturers. Further larger-scale studies are warranted to prospectively compare the performance of various available ICDs’ discriminatory protocols, and define the optimum combination of discriminators in each ICD to decrease the rate of inappropriate therapy.     

Barriers to obesity treatment

Obesity, one of the most prevalent health problems in the Western world, is a chronic and progressive condition. Therefore, as with other chronic diseases, patients with obesity require lifelong treatment. Long-term efficacy and effectiveness of obesity treatments is notoriously poor. This may in part be attributable to the substantial barriers that undermine long-term obesity management strategies. These can include lack of recognition of obesity as a chronic condition, low socioeconomic status, time constraints, intimate saboteurs, and a wide range of comorbidities including mental health, sleep, chronic pain, musculoskeletal, cardiovascular, respiratory, digestive and endocrine disorders. Furthermore, medications used to treat some of these disorders may further undermine weight-loss efforts. Lack of specific obesity training of health professionals, attitudes and beliefs as well as coverage and availability of obesity treatments can likewise pose important barriers. Health professionals need to take care to identify, acknowledge and address these barriers where possible to increase patient success as well as compliance and adherence with treatments. Failure to do so may further undermine the sense of failure, low self esteem and self efficacy already common among obese individuals. Addressing treatment barriers can save resources and increase the prospect of long-term success.     

Intellectual and Developmental Status in Children With Hyperphenylalaninemia and PKU Who Were Screened in a National Program

Background:

Hyperphenylalaninemia (HPA) and Phenylkeonuria (PKU) are metabolic errors caused by deficiency of phenylalanine hydroxylase enzyme, which results in increased level of phenylalanine. This increase is toxic to the growing brain.

Objectives:

The purpose of this study was to compare the intellectual and developmental status in HPA and PKU children with normal population in national screening program.

Patients and Methods:

In a historical cohort study, 41 PKU patients who had the inclusion criteria and 41 healthy children were evaluated. Wechsler preschool and primary scale of intelligence-3rd edition (WPPI-3) was used in order to assess the intellectual status of children 4 years and older and Ages and stages questionnaire (ASQ) was used to assess the developmental status of children 5 years and younger.

Results:

In intellectual test comparison, the two groups showed significant difference in Wechsler’s performance intelligence score and some performance subscales (P-value < 0.01). In comparison of developmental status, no significant difference was observed between the two groups (P-value > 0.05).

Conclusions:

Even with early diagnosis and treatment of PKU patients, these children show some deficiencies intellectually compared to normal children. This study emphasizes on necessity for screening intellectual and developmental status of PKU patients so that effective medical or educational measures can taken in case of deficiencies.     

Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p‐values (p < 1 × 10^?4). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (β ± SE = ?0.25 ± 0.05, p = 6.23 × 10^?6). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p‐value < 1 × 10^?4). The best association was observed on chromosome 9 with rs59902911 (β ± SE = 0.86 ± 0.17, p = 1.01 × 10^?6), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.