Palmitate differentially regulates Spexin, and its receptors Galr2 and Galr3, in GnRH neurons through mechanisms involving PKC, MAPKs, and TLR4.

The function of the gonadotropin-releasing hormone (GnRH) neuron is critical to maintain reproductive function and a significant decrease in GnRH can lead to disorders affecting fertility, including hypogonadotropic hypogonadism. Spexin (SPX) is a novel hypothalamic neuropeptide that exerts inhibitory effects on reproduction and feeding by acting through galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3). Fatty acids can act as nutritional signals that regulate the hypothalamic-pituitary-gonadal (HPG) axis, and elevated levels of circulating saturated fatty acids associated with high fat diet (HFD)-feeding have been shown to induce neuroinflammation, endoplasmic reticulum stress and hormonal resistance in the hypothalamus, as well as alter neuropeptide expression. We previously demonstrated that palmitate, the most common saturated fatty acid in a HFD, elevates the expression of Spx, Galr2 and Galr3 mRNA in a model of appetite-regulating neuropeptide Y hypothalamic neurons. Here, we found that Spx, Galr2 and Galr3 mRNA were also significantly induced by palmitate in a model of reproductive GnRH neurons, mHypoA-GnRH/GFP. As a follow-up to our previous report, we examined the molecular pathways by which Spx and galanin receptor mRNA was regulated in this cell line. Furthermore, we performed inhibitor studies, which revealed that the effect of palmitate on Spx and Galr3 mRNA involved activation of the innate immune receptor TLR4, and we detected differential regulation of the three genes by the protein kinases PKC, JNK, ERK, and p38. However, the intracellular metabolism of palmitate to ceramide did not appear to be involved in the palmitate-mediated gene regulation. Overall, this suggests that SPX may play a role in reproduction at the level of the hypothalamus and the pathways by which Spx, Galr2 and Galr3 are altered by fatty acids could provide insight into the mechanisms underlying reproductive dysfunction in obesity.

Prevalence of smoking and other smoking-related behaviors reported by the Global Youth Tobacco Survey (GYTS) in Thailand.

INTRODUCTION: Thailand ratified the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) on November 8, 2004. The WHO FCTC requires all parties to inform all persons of the health consequences of tobacco consumption and exposure to tobacco smoke. Each party has agreed to develop, implement and evaluate effective tobacco control programs to measure progress in reaching the goals of the WHO FCTC. METHODS: The Global Youth Tobacco Survey (GYTS) was developed to provide data on youth tobacco use to countries for their development of youth-based tobacco control programs. Data in this report can be used as baseline measures for future evaluation of the tobacco control programs implemented by the Ministry of Public Health. RESULTS: Overall, about 1 in 10 Thai students are current smokers, this number including 4 times more boys than girls (17% versus 3.9%). Almost 2 in 10 Thai students start smoking before the age of 10, and almost 7 in 10 students are reported to have been exposed to smoke from others in public places. About 4 in 10 students are reported to have an object with a cigarette brand logo on it. CONCLUSION: The key for Thailand is to implement and enforce the provisions on indirect tobacco advertising, smoking in public places, selling tobacco to youths under 18 years of age, and to use the data from the GYTS to monitor progress toward achieving the goals of the WHO FCTC. When these goals are met, tobacco consumption and exposure in Thailand will have declined substantially.

Clinicopathologic features and treatment outcomes in Woringer-Kolopp disease.

Woringer-Kolopp disease, also known as pagetoid reticulosis, is an exceedingly rare variant of mycosis fungoides. Accurate diagnosis and effective treatment is essential to prevent progression to debilitating disease. We identified 7 patients with Woringer-Kolopp disease treated at our institution. We review the major clinical and pathologic characteristics of this disease, focusing on treatment strategies and patient outcomes. All of our patients were successfully treated with skin-directed therapies including topical steroids, topical nitrogen mustard, psoralen plus ultraviolet A, narrow-band ultraviolet B, and radiation therapy. Our observations confirm that Woringer-Kolopp disease carries an excellent prognosis, and support that the most effective and appropriate treatment for recalcitrant or severe Woringer-Kolopp disease is localized radiation therapy.