Activator of G protein signaling 3 null mice: I. Unexpected alterations in metabolic and cardiovascular function

Activator of G protein signaling (AGS)-3 plays functional roles in cell division, synaptic plasticity, addictive behavior, and neuronal development. As part of a broad effort to define the extent of functional diversity of AGS3-regulated-events in vivo, we generated AGS3 null mice. Surprisingly, AGS3 null adult mice exhibited unexpected alterations in cardiovascular and metabolic functions without any obvious changes in motor skills, basic behavioral traits, and brain morphology. AGS3 null mice exhibited a lean phenotype, reduced fat mass, and increased nocturnal energy expenditure. AGS3 null mice also exhibited altered blood pressure control mechanisms. These studies expand the functional repertoire for AGS3 and other G protein regulatory proteins providing unexpected mechanisms by which G protein systems may be targeted to influence obesity and cardiovascular function.     

Associations of the infancy body mass index peak with anthropometry and cardiometabolic risk in Mexican adolescents

Background: Early-life growth dynamics are associated with future health. Little is known regarding timing and magnitude of the infancy body mass index (BMI) peak with adiposity and metabolic biomarkers during adolescence.

Aim: To examine associations of the infancy BMI peak with anthropometry and cardiometabolic risk during peripuberty.

Methods: Among 163 ELEMENT participants, this study estimated age and magnitude of the infancy BMI peak from eight anthropometric measurements from birth–36?months using Newton’s Growth Models, an acceleration-based process model. Associations were examined of the infancy milestones with anthropometry and cardiometabolic risk at 8–14?years using linear regression models that accounted for maternal calcium supplementation and age; child’s birthweight, sex, and age; and the other infancy milestone.

Results: Median age at the infancy BMI peak was 9.6?months, and median peak BMI was 16.5?kg/m². Later age and larger magnitude of the peak predicted higher BMI z-score, waist circumference, and skinfold thicknesses; i.e. each 1?month of age at peak and each 1?kg/m² of peak BMI corresponded with 0.04 (0.01–0.07) and 0.33 (0.17–0.48) units of higher BMI z-score, respectively. Later age at peak was also a determinant of worse glycaemia and higher blood pressure.

Conclusion: Later age and larger magnitude of the infancy BMI peak are associated with higher adiposity at 8–14?years of age. Later age but not magnitude of the BMI peak are related to a worse cardiometabolic profile during peripuberty.     

The extent of perfusion-F18-fluorodeoxyglucose positron emission tomography mismatch determines mortality in medically treated patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to assess the determinants of mortality in a large group of patients with ischemic cardiomyopathy who are treated medically and the impact of the extent of viable tissue on prognosis. BACKGROUND: Whether the presence of viability drives mortality in patients with ischemic cardiomyopathy who are treated medically and whether the extent of viability is important are issues that are currently unclear. METHODS: Two hundred sixty-one patients with ischemic cardiomyopathy underwent positron emission tomography (PET) for assessment of viability. Prospective follow-up was obtained. RESULTS: Ninety-four patients were revascularized and 167 were not. The cardiac death rate was significantly less in the revascularized patients as compared with medically treated patients (13% vs. 24%, p < 0.05). In the revascularized patients, there was a trend toward better survival in patients with viable myocardium as compared with nonviable myocardium (3.5-year survival, 85% and 75% respectively, p = NS). In the medically treated group, age (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.2 to 3.7), presence of left bundle branch block (HR 3.4, 95% CI 1.6 to 7.2) and extent of perfusion-metabolism mismatch on PET (HR 1.36, 95% CI 1.1 to 1.6) predicted cardiac death during a median follow-up period of 2.1 years. The risk of cardiac death was not significantly increased when the extent of mismatch was < or =20% (HR 0.97, 95% CI 0.46 to 2.05) but was significantly increased when the extent of mismatch was >20% (HR 3.21, 95% CI 1.38 to 7.49). CONCLUSIONS: Medically treated patients with ischemic cardiomyopathy and large areas of viable myocardium on PET are at high risk for cardiac death.     

Short‐Term Effects of 2% Atorvastatin Dentifrice as an Adjunct to Periodontal Therapy: A Randomized Double‐Masked Clinical Trial

Background: The pleiotropic effects of statins, such as immunomodulation and anti‐inflammatory effects, may also improve periodontal conditions. The aim of the present study is to assess the effectiveness of a dentifrice medicated with 2% atorvastatin in improving clinical periodontal parameters as a complement to non‐surgical periodontal treatment (NSPT). Methods: A randomized, double‐masked clinical trial was performed with two parallel groups: 1) atorvastatin group (NSPT plus medicated 2% atorvastatin dentifrice) and 2) placebo group (NSPT plus placebo dentifrice). The effectiveness of these treatments was assessed using periodontal measurements obtained at baseline and 1 month later. The measurements were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), and periodontal inflamed surface area (PISA). Multiple linear regression models were used to compare outcome variables after adjusting for sex, diabetes, and tobacco use. Results: A total of 36 individuals participated in this study (atorvastatin group, n = 18; placebo group, n = 18). Both groups showed improvements in periodontal parameters. The atorvastatin group showed a decrease of 297.63 mm² in PISA (95% confidence interval = 76.04 to 519.23; P = 0.01), which was significantly greater than the reduction observed in the placebo group. There was also a significantly greater reduction in mean PD, percentage of sites with PD ≥5 mm, mean CAL, percentage of sites with CAL ≥5 mm, BOP, and GI in the atorvastatin group compared with the placebo group. Conclusion: NSPT plus 2% atorvastatin medicated dentifrice was more effective in improving clinical periodontal parameters than NSPT plus a placebo dentifrice.     

Steroid hyperglycemia: Prevalence,early detection and therapeutic recommendations: A narrative review

Steroids are drugs that have been used extensively in a variety of conditions. Although widely prescribed for their anti-inflammatory and immunosuppressive properties, glucocorticoids have several side effects, being hyperglycemia one of the most common and representative. In the present review, we discuss the main epidemiologic characteristics associated with steroid use, with emphasis on the identification of high risk populations. Additionally we present the pathophysiology of corticosteroid induced hyperglycemia as well as the pharmacokinetics and pharmacodynamics associated with steroid use. We propose a treatment strategy based on previous reports and the understanding of the mechanism of action of both, the different types of glucocorticoids and the treatment options, in both the ambulatory and the hospital setting. Finally, we present some of the recent scientific advances as well as some options for future use of glucocorticoids.     

Bacterial Biofilm Formation Using PCL/Curcumin Electrospun Fibers and Its Potential Use for Biotechnological Applications

Electrospun nanofibers are used for many applications due to their large surface area, mechanical properties, and bioactivity. Bacterial biofilms are the cause of numerous problems in biomedical devices and in the food industry. On the other hand, these bacterial biofilms can produce interesting metabolites. Hence, the objective of this study is to evaluate the efficiency of poly (Ɛ- caprolactone)/Curcumin (PCL/CUR) nanofibers to promote bacterial biofilm formation. These scaffolds were characterized by scanning electron microscopy (SEM), which showed homogeneous fibers with diameters between 441–557 nm; thermogravimetric analysis and differential scanning calorimetry (TGA and DSC) demonstrated high temperature resilience with degradation temperatures over >350 °C; FTIR and ¹H-NMR serve as evidence of CUR incorporation in the PCL fibers. PCL/CUR scaffolds successfully promoted the formation of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa biofilms. These results will be valuable in the study of controlled harvesting of pathogenic biofilms as well as in metabolites production for biotechnological purposes.