The 13C-glucose breath test is a valid non-invasive screening tool to identify metabolic syndrome in adolescents.

BACKGROUND: Metabolic syndrome (MS) is an important risk factor in pediatric population for the early onset of type 2 diabetes mellitus and cardiovascular disease. New non-invasive tools are required to identify MS in at risk populations; the aim of this study was to determine an optimal cut-off point for the 13C-glucose breath test (13C-GBT) for the diagnosis of MS in adolescents. METHODS: A total of 136 adolescents between 10 and 16 years old were recruited. MS was defined as: waist circumference >90th percentile and at least two of the following; high density lipoprotein-cholesterol (HDL-C) <50 mg/dL, triglycerides >110 mg/dL, diastolic and/or systolic blood pressure >90th percentile adjusted by age, gender and height, and/or fasting glucose >100 mg/dL. After the ingestion of a glucose load of 1.75 g/kg of body weight (up to 75 g) and an oral dose of 1.5 mg of universally labeled 13C-glucose/kg dissolved in water, breath samples were taken at baseline, 30, 60, 90, 120, 150 and 180 min. Exhaled 13CO2 in breath samples was measured by isotope ratio mass spectrometry. RESULTS: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD) at 180 min, was significantly higher in the healthy subjects group (17.72%±4.9%) in comparison with subjects with ≥3, 2 or 1 components of the MS (9.95%±4.73%, 14.3%±4.47% and 14.62%±4.62%, respectively). The optimal cut-off point for the A% OD was 16.09, with a sensitivity of 81.5% and a specificity of 66.7%. CONCLUSIONS: Our results demonstrate that the 13C-glucose breath test could be a valid screening method to identify MS in adolescents.

Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells.

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/- 0.370 mg/kg, and the cells' metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new "easy-to-make" nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.

Norcantharidin toxicity profile: an in vivo murine study.

Norcantharidin (NCTD) is the demethylated analog of cantharidin, with allegedly reduced toxicity. However, there is still limited information regarding its posology and potential risk in its use in cancer treatment. Healthy BDF1 mice were intraperitoneally administered with norcantharidin (0, 3, 6, 12, and 25 mg/kg) every 24 h for 6 days. Survivor mice were euthanized, and the brain, lungs, kidneys, spleen, and liver were procured for enzymatic and histopathological analysis in the liver and kidney. DL50 were 8.86 mg/kg for females and 11.77 mg/kg for males. The treatments with 3.0 mg/kg and 6.0 mg/kg significantly modified the phosphorylase, alanine transaminase, and γ-glutamyl transferase activities; however, an organ-specific response was detected. A significant dose-dependent decrease was observed in the kidney for ROS, while the liver had the opposite effect. Histopathological analysis revealed a significant elevation in hepatocytes' nuclei average size and total area (3 mg/kg), as well as centrilobular vein and adjacent sinusoidal capillaries showed a significant difference. The portal triad presented a significant difference in veins and capillarity count in 6 mg/kg. Renal samples showed cortex convoluted tubules' average size significantly augmented in both doses' groups, and tubule count was found augmented in 6 mg/kg. These physiological effects of NCTD can be exploited as treatment strategies if able to operate in an established posology and proper testing.