Tissue-Specific Inactivation of Type 2 Deiodinase Reveals Multilevel Control of Fatty Acid Oxidation by Thyroid Hormone in the Mouse

Type 2 deiodinase (D2) converts the prohormone thyroxine (T4) to the metabolically active molecule 3,5,3′-triiodothyronine (T3), but its global inactivation unexpectedly lowers the respiratory exchange rate (respiratory quotient [RQ]) and decreases food intake. Here we used FloxD2 mice to generate systemically euthyroid fat-specific (FAT), astrocyte-specific (ASTRO), or skeletal-muscle-specific (SKM) D2 knockout (D2KO) mice that were monitored continuously. The ASTRO-D2KO mice also exhibited lower diurnal RQ and greater contribution of fatty acid oxidation to energy expenditure, but no differences in food intake were observed. In contrast, the FAT-D2KO mouse exhibited sustained (24 h) increase in RQ values, increased food intake, tolerance to glucose, and sensitivity to insulin, all supporting greater contribution of carbohydrate oxidation to energy expenditure. Furthermore, FAT-D2KO animals that were kept on a high-fat diet for 8 weeks gained more body weight and fat, indicating impaired brown adipose tissue (BAT) thermogenesis and/or inability to oxidize the fat excess. Acclimatization of FAT-D2KO mice at thermoneutrality dissipated both features of this phenotype. Muscle D2 does not seem to play a significant metabolic role given that SKM-D2KO animals exhibited no phenotype. The present findings are unique in that they were obtained in systemically euthyroid animals, revealing that brain D2 plays a dominant albeit indirect role in fatty acid oxidation via its sympathetic control of BAT activity. D2-generated T3 in BAT accelerates fatty acid oxidation and protects against diet-induced obesity.     

The ‘Variant Normal’ Electrocardiogram of the Professional Football Player

The ECGs of highly trained athletes reveal variants that may incorrectly be called abnormal.     

Diagnosis and Management of Infectious Complications of Childhood Rheumatic Diseases

Progress in the diagnosis and management of pediatric rheumatic disease has improved complications from underlying disease and the survival of children. However, as a consequence, infection has now become one of the leading causes of morbidity and mortality. Differentiating between infections and disease flares in children with rheumatic conditions can often pose diagnostic quandaries. Children with rheumatic diseases are at risk of infection, not only because of the use of immune-modulating medications but also because of underlying immune dysfunction associated with their disease. Although bacterial infections are the most common, any organism can potentially be a causative agent and, at times, more invasive measures of diagnosis, for example bronchoscopy and tissue biopsies may be necessary. Maintaining a high index of suspicion of infection with prompt diagnosis and treatment are important to further improve patient outcomes.     

Evaluación de la función de la mano en las enfermedades reumáticas. Validación y utilidad de los cuestionarios AUSCAN,m-SACRAH,DASH y Cochin en Español

IntroductionQuestionnaires to evaluate hand function are variable in the number of items, domains and diseases in which they had been previously used.Objectivesa) To translate to Spanish and validate the m-SACRAH and AUSCAN questionnaires; b) to do a transcultural adaptation of DASHe, previously validated in Spain), and c) to compare them and the Cochin questionnaire (previously validated in México), in rheumatic patients with variable impairment of hand function.Material and methodsm-SACRAH, AUSCAN and DASH were translated/retro-translated and adapted. The final version was revised to determine content validity and them, plus Cochin were applied to 10 healthy subjects (pilot study) with a variable educational level and in 16 rheumatic patients with variable diagnoses and degrees of hand function impairment; all patients answered 4 questionnaires and were evaluated clinically by blinded investigators.ResultsSeventy six percent were women, mean age 45.7 ± 11.4 years. Cronbach?s alpha > 0.90; time to answer went from 2.3 ± 0.087 (AUSCAN) to 3.5 ± 0.36 minutes (DASH). There was good correlation among them (r = 0.0683 AUSCAN-m-SACRAH to r = 0.889 AUSCAN-DASH) and good capability for discrimination between patients with mild VS moderate to severe impairment was also demonstrated; patients with mild impairment needed less time to answer them and there were no significant differences among questionnaire scores. Patients prefered AUSCAN (10/16), Cochin (4/16) and m-SACRAH (2/16).ConclusionThe 4 questionnaires are useful to evaluate hand function in rheumatic patients and have good discrimination capability. More patients preferred AUSCAN.     

In Vitro Antiplasmodial Activity of Phospholipases A2 and a Phospholipase Homologue Isolated from the Venom of the Snake Bothrops asper

The antimicrobial and antiparasite activity of phospholipase A₂ (PLA₂) from snakes and bees has been extensively explored. We studied the antiplasmodial effect of the whole venom of the snake Bothrops asper and of two fractions purified by ion-exchange chromatography: one containing catalytically-active phospholipases A₂ (PLA₂) (fraction V) and another containing a PLA₂ homologue devoid of enzymatic activity (fraction VI). The antiplasmodial effect was assessed on in vitro cultures of Plasmodium falciparum. The whole venom of B. asper, as well as its fractions V and VI, were active against the parasite at 0.13 ± 0.01 µg/mL, 1.42 ± 0.56 µg/mL and 22.89 ± 1.22 µg/mL, respectively. Differences in the cytotoxic activity on peripheral blood mononuclear cells between the whole venom and fractions V and VI were observed, fraction V showing higher toxicity than total venom and fraction VI. Regarding toxicity in mice, the whole venom showed the highest lethal effect in comparison to fractions V and VI. These results suggest that B. asper PLA₂ and its homologue have antiplasmodial potential.     

Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti‐thrombotic drugs

Background and Aim: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti‐thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. Methods: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti‐thrombotic therapy. VCE studies were re‐evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti‐thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti‐thrombotic therapy was resumed before the VCE study. Results: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty‐two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti‐thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20–60.42, P = 0.032). Conclusions: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti‐thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.