IL18 rs360717 and rs187238 genetic variants are associated with migraine diagnosis.

BACKGROUND: Migraine is a genetically determined disorder that predisposes to recurrent episodes of headache. Interleukin (IL)-18 is a pro-inflammatory cytokine that seems to play a role in migraine pathophysiology, and its genetic variants could potentially impact susceptibility to migraine. OBJECTIVE: To investigate the association between IL18 rs360717 and rs187238 genetic variants with migraine diagnosis and its clinical characteristics. METHODS: A case-control study was conducted with 152 people with migraine and 155 healthy controls, matched by sex, age, ethnicity, and body mass index. Clinical characteristics of migraine, as well as validated questionnaires regarding disability and impact of migraine, presence of allodynia, anxiety, depression, and hyperacusis were collected. Genotyping for IL18 rs360717 and rs187238 variants was performed using real-time polymerase chain reaction (qPCR) and TaqMan™ method. RESULTS: The IL18 rs360717A and rs187238G alleles were associated with increased chance of being diagnosed with migraine (OR = 1.53, 95%CI 1.05-2.24, p = 0.028 and OR = 1.46, 95%CI 1.00-2.14, p = 0.049, respectively). In the dominant model, the rs360717GA + AA genotypes were also associated with a higher chance of migraine than the GG genotype (OR = 1.69, 95%CI 1.05-2.73, p = 0.030). In women, in addition to the previous associations, there was also an effect of the variants on the chance of migraine in the codominant models and dominant models. Furthermore, among women, there was an influence on the prevalence of postdrome perception with rs360717GA + AA (OR = 3.04, 95%CI 1.10-8.42, p = 0.032) and rs187238CG + GG (OR = 2.97, 95%CI 1.08-8.21, p = 0.035). CONCLUSION: IL18 rs360717 and rs187238 variants were associated with migraine diagnosis and postdrome symptoms, especially in women. SIGNIFICANCE: This study has demonstrated that IL18 rs360717 and rs187238 variants play a role in migraine, influencing the chance of being diagnosed with migraine, particularly among women. There are prospects that IL18 variants could be considered potential genetic biomarkers for migraine.

Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8.

Cutaneous leishmaniasis (CL) is a neglected parasitic disease conventionally treated by multiple injections with systemically toxic drugs. Aiming at a more acceptable therapy, we developed lipid-core nanocapsules (LNCs) entrapping the potent antileishmanial chalcone (CH8) for topical application. Rhodamine-labeled LNC (Rho-LNC-CH8) was produced for imaging studies. LNC-CH8 and Rho-LNC-CH8 had narrow size distributions (polydispersity index <0.10), with similar mean sizes (~180 nm) by dynamic light scattering. In vitro, Rho-LNC-CH8 was rapidly internalized by extracellular Leishmania amazonensis parasites macrophages in less than 15 min. LNC-CH8 activated macrophage oxidative mechanisms more efficiently than CH8, and was more selectively toxic against the intracellular parasites. In vivo, topically applied Rho-LNC-CH8 efficiently permeated mouse skin. In L. amazonensis-infected mice, LNC-CH8 reduced the parasite load by 86% after three weeks of daily topical treatment, while free CH8 was ineffective. In conclusion, LNC-CH8 has strong potential as a novel topical formulation for CL treatment.

Mitochondria Superoxide Anion Production Contributes to Geranylgeraniol-Induced Death in Leishmania amazonensis.

Here we demonstrate the activity of geranylgeraniol, the major bioactive constituent from seeds of Bixa orellana, against Leishmania amazonensis. Geranylgeraniol was identified through (1)H and (13)C nuclear magnetic resonance imaging and DEPT. The compound inhibited the promastigote and intracellular amastigote forms, with IC(50) of 11 ± 1.0 and 17.5 ± 0.7 µg/mL, respectively. This compound was also more toxic to parasites than to macrophages and did not cause lysis in human blood cells. Morphological and ultrastructural changes induced by geranylgeraniol were observed in the protozoan by electronic microscopy and included mainly mitochondria alterations and an abnormal chromatin condensation in the nucleus. These alterations were confirmed by Rh 123 and TUNEL assays. Additionally, geranylgeraniol induces an increase in superoxide anion production. Collectively, our in vitro studies indicate geranylgeraniol as a selective antileishmanial that appears to be mediated by apoptosis-like cell death.