Obesity subtypes, related biomarkers & heterogeneity.

Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of this review was to examine heterogeneous links among the various phenotypes of obesity in adults. Proteins and associated genes in each group were analysed to differentiate between biomarkers. A variety of terms for classification and characterization within this pathology are currently in use; however, there is no clear consensus in terminology. The most significant groups reviewed include metabolically healthy obese, metabolically abnormal obese, metabolically abnormal, normal weight and sarcopenic obese. These phenotypes do not define particular genotypes or epigenetic gene regulation, or proteins related to inflammation. There are many other genes linked to obesity, though the value of screening all of those for diagnosis has low predictive results, as there are no significant biomarkers. It is important to establish a consensus in the terminology used and the characteristics attributed to obesity subtypes. The identification of specific molecular biomarkers is also required for better diagnosis in subtypes of obesity.

A preliminary study of platelet hyperactivity in the chronic indeterminate phase of Chagas' disease.

The chronic indeterminate phase of Chagas' disease is asymptomatic despite positive test results for antibodies specific to Trypanosoma cruzi. CD62P-APC (P-selectin) and PAC-1 FITC (GpIIb/IIIa) may improve diagnosis as biomarkers of platelet activity. Nine asymptomatic seropositive subjects, previously untreated, were selected from a blood bank within a year of Chagas' disease detection, in addition to a control group of four. All subjects were evaluated by flow cytometry for CD62P, PAC-1 and CD41, and in a complementary study, by Tissue Doppler Echocardiography for isovolumic relaxation times (IVRT) and E/A ratios. The subjects were classified as positive or negative for CD62P and PAC-1 by a cut off obtained from their mean±2SD. For IVRT and E/A ratios, cut offs were obtained from the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations. Fisher's exact test was used for associated findings. Pre-test and post-test probability, sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Abnormalities were expressed as platelet hyperactivity and ventricular dysfunction in CD62P, PAC-1, IVRT and E/A ratios. CD62P appears to have greater sensitivity (0.75) and PAC-1, more accurate specificity (0.75), which may explain thrombotic events in Chagas' disease. We recommend the use of CD62P and PAC-1 as biomarkers of platelet hyperactivity in patients in the chronic indeterminate phase of Chagas' disease.

Platelets and Platelet-Derived Microvesicles as Immune Effectors in Type 2 Diabetes.

The association between type 2 diabetes mellitus (T2DM) and systemic inflammation may increase platelet reactivity and the accelerated development of vascular disease. Platelets are able to modulate the function of immune cells via the direct release of growth factors and pro-inflammatory chemokines through the production of microvesicles. The microvesicles trigger a transcellular delivery system of bioactive molecules to other cells acting as vectors in the exchange of biological information. Here, we consider the influence of platelets and platelet-derived microvesicles on cells of the immune system and the implications in the pathogenesis of T2DM.

The relationship of aluminium and silver to neural tube defects; a case control.

OBJECTIVE: The purpose of this study was to identify the relationship of neurotoxic inorganic elements in the hair of patients with the diagnosis of Neural Tube Defects. Our initial hypothesis was that neurotoxic inorganic elements were associated with Neural Tube Defects. METHODS: Twenty-three samples of hair from newborns were obtained from the General Hospital, "Aurelio Valdivieso" in the city of Oaxaca, Mexico. The study group included 8 newborn infants with neural tube pathology. The control group was composed of 15 newborns without this pathology. The presence of inorganic elements in the hair samples was determined by inductively-coupled plasma spectroscopy (spectroscopic emission of the plasma). FINDINGS: THE POPULATION OF NEWBORNS WITH NEURAL TUBE DEFECTS SHOWED SIGNIFICANTLY HIGHER VALUES OF THE FOLLOWING ELEMENTS THAN THE CONTROL GROUP: Aluminium, Neural Tube Defects 152.77±51.06 µg/g, control group 76.24±27.89 µg/g; Silver, Neural Tube Defects 1.45±0.76, control group 0.25±0.53 µg/g; Potassium, Neural Tube Defects 553.87±77.91 µg/g, control group 341.13±205.90 µg/g. Association was found at 75 percentile between aluminium plus silver, aluminium plus potassium, silver plus potassium, and potassium plus sodium. CONCLUSION: IN THE HAIR OF NEWBORNS WITH NEURAL TUBE DEFECTS, THE FOLLOWING METALS WERE INCREASED: aluminium, silver. Given the neurotoxicity of the same, and association of Neural Tube Defects with aluminum and silver, one may infer that they may be participating as factors in the development of Neural Tube Defects.

Lectin activity of the coagulation factor VIII/von Willebrand complex.

The human coagulation factor VIII (FVIII) is essential in the intrinsic pathway of blood coagulation and circulates mainly as a non-covalently bound complex with the von Willebrand factor (VWF). This complex (FVIII/VWF) protects FVIII from degradation and cellular uptake, although no biological role has been identified yet for this complex. The FVIII/VWF complex was purified from a healthy donor's plasma by affinity chromatography on a Sepharose 4B-Concanavalin A column and was used to determine its capability to interact with erythrocytes and platelets. The purified FVIII/VWF complex at 6.0 and 12 microg/ml agglutinates rabbit and bovine erythrocytes, and showed negative agglutination with erythrocytes from other species including human ABO. Treatment of erythrocytes with Clostridium perfringens sialidase or trypsin increased four-fold the activity toward rabbit erythrocytes and positive agglutination for human A and B erythrocytes, suggesting the presence of FVIII/VWF-cryptic receptors in these erythrocytes. Goat, pig, or human O erythrocytes were not agglutinated even after enzymatic treatment. Fucose or N-acetyl-glucosamine (GlcNAc), at 10 mM, inhibited agglutinating activity of the complex with rabbit, human A and B erythrocytes, whereas galactose and N-acetyl-galactosamine, even at 200 mM, showed no effect on the complex activity. The FVIII/VWF complex, at 1.5 microg/200,000 platelets, significantly decreased platelet aggregation (p < 0.001) when compared with the effect of platelet-rich plasma; this effect was inhibited with 15 mM GlcNAc or fucose. ELISA assays on FVIII/VWF coated polystyrene plates confirmed specific binding to fucose- or biotinylated GlcNAc-dextran derivatives. We therefore propose that the FVIII/VWF complex possesses lectin activity.

Interaction of the protein C activation peptide with platelets.

The peptide NH(2)-DTEDQEDQVDPR-COOH is released during activation of protein C zymogen. We measured the effect of a synthetic peptide with an amino acid sequence similar to that of the natural peptide on platelets from healthy individuals using platelet aggregometry. We found that this synthetic peptide inhibits platelet aggregation induced by thrombin; furthermore, it diminishes mobilization of intraplatelet calcium. Molecular docking showed weak interaction between the synthetic peptide and thrombin. Our findings suggest that this synthetic peptide may interact with a receptor located on the platelet cell membrane.