Our studies reveal that UVB and reactive oxygen species stimulate the expression of IL-31 in PBMCs and skin, especially in T cells, monocytes and monocyte-derived dendritic cells.
The hypothalamic melanocortin system regulates feeding in part through interaction of the appetite stimulating peptide, agouti-related protein (AGRP), and the anorectic peptide, alpha-melanocyte stimulating hormone, a peptide derived from the pro-opiomelanocortin (POMC) polyprotein. Central administration of AGRP induces hyperphagia and increased gain in body weight in rodents, but may also exert metabolic effects even when hyperphagia is prevented. In the present studies, the effects of AGRP on hypothalamic neuropeptide gene expression and metabolism were examined in the rat. Central administration of AGRP for 3- and 7-day periods resulted in hyperphagia, increased body weight and increased plasma leptin and insulin concentrations compared to saline-injected controls. Hypothalamic concentrations of Pomc mRNA were also increased by 27% and 44% (in 3- and 7-day experiments, respectively). The hypothalamic concentration of Agrp mRNA was unchanged after 3 days, but was significantly decreased by 33% after 7 days of AGRP infusion. To determine if these changes were dependent upon AGRP-induced hyperphagia, pair-fed rats with restricted food intake receiving central administration of AGRP were also studied. In the absence of hyperphagia, intracerebralventricular administration of AGRP caused significant increases in plasma leptin and insulin concentrations (two-fold and 1.5-fold, respectively) and fat pad mass. A significant increase in hypothalamic Pomc mRNA concentrations was not detected in pair-fed rats. In contrast, Agrp mRNA concentrations remained suppressed by 45% in the pair-fed group after 7 days of AGRP infusion despite equal body weight compared to saline controls. The ratio of hypothalamic Pomc to Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats, which is consistent with increased stimulation of central melanocortin signalling pathways. Thus, central administration of AGRP exerts changes in hypothalamic neuropeptide gene expression and metabolic effects that are independent of the effects on food intake and body weight.
Illicit drugs are widely used by inner city patients and their use by pregnant women has increased in recent years. The aim of this study was to determine the prevalence of polysubstance abuse among parturients at our institution who received no prenatal care ('unbooked') and to determine the accuracy of the Ontrak TesTcup an in vitro immunodiagnostic assay. We prospectively analysed urine from 50 'unbooked' parturients and found that 26 (52%) tested positive for cocaine. Of these, six patients (23%) were also positive for morphine. All TesTcup results were confirmed by the hospital laboratory using alternate chemical methods. When comparing TesTcup to the hospital laboratory, there were no false positive or negative results. Given the high frequency of concomitant opioid abuse in cocaine-abusing parturients, anyone suspected of cocaine abuse should be tested for other illicit substances. TesTcup is a clinically accurate test that allows the rapid assessment of several drugs of abuse, which may impact on anaesthetic care.
techniques for evaluation of cardiac allograft rejection have been evaluated. In this study, we aim to compare the efficacy of two non-invasive methods of detecting rejection against the gold standard of EMB; gene expression profiling with AlloMap and echocardiographic doppler tissue imaging (DTI). Methods: This was a single-center, retrospective analysis. Electronic medical records of all patients who underwent orthotopic heart transplant at our institution and had at least two concomitant measurements of Allo-Map, echocardiogram DTI and endomyocardial biopsy from January 1 st , 2015 to December 31 st , 2017 were reviewed. Statistical analyses were performed to calculate sensitivity, specificity, negative predictive value (NPV) and positive predictive value. Rejection for EMB was defined using ISHLT guidelines and was considered present with either acute cellular rejection of 1R or greater or antibody mediated rejection pAMR1 or greater. For non-invasive studies, we considered an AlloMap score of > 34 and a DTI <0.016 m/sec as rejection. Results: A total of 107 patients with available data were reviewed. 77% were male. Mean age was 57 years old § 13 years with a range of 22-77 years. AlloMap and DTI performed similarly in our cohort and had NPV of 92% and 88%, respectively when compared to similarly timed EMB. Positive predictive value was 9% for AlloMap and 8% for DTI. Sensitivity was 37% for AlloMap and 18% for DTI and specificity was 65% for AlloMap and 74% for DTI. Conclusion: In our cohort, AlloMap and DTI performed similarly and demonstrated excellent NPV in ruling out rejection. AlloMap has known excellent NPV and has been well-validated for this purpose. The NPV of DTI has been less studied, but performed similarly and is highly cost effective. This could have implications on future screening protocols. This study is limited by the inherent errors of a single-center, retrospective analysis. Further prospective studies to validate this data are ongoing.
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