Serum CGRP, VIP, and PACAP usefulness in migraine: a case-control study in chronic migraine patients in real clinical practice.

Calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypetide-38 (PACAP-38) have relevant roles in migraine pathophysiology. Their serum levels have been proposed as biomarkers for migraine. Our aim was to assess their diagnostic value in real clinical practice in a cohort of chronic migraine (CM), episodic migraine (EM) and healthy controls (HC). We recruited subjects with CM, EM and HC at two medical centers. Blood samples were drawn under fasting conditions in the interictal period, immediately centrifuged and stored at - 80 ºC. Serum levels were determined by ELISA. Neuropeptide levels, the effect of preventatives, correlations with clinical and demographic variables, and their diagnostic value were studied among clinical categories. 296 age- and sex-matched subjects (101 CM, 98 EM and 97 HC) were included. All three neuropeptide serum levels were higher in CM [median and IQ for CGRP = 18.023 pg/ml (14.4-24.7); VIP = 121.732 pg/ml (48.72-186.72) and PACAP = 204.931 pg/ml (101.08-597.64)] vs EM [CGRP = 14.659 pg/ml (10.29-17.45); VIP = 75.603 pg/ml (28.722-107.10); and PACAP = 94.992 pg/ml (65.77-128.48)] and vs HC [CGRP = 13.988 pg/ml (10.095-17.87); VIP = 84.685 pg/ml (35.32-99.79), and PACAP = 103.142 pg/ml (59.42-123.97)]. Using multinomial modeling, only VIP (OR 1.011, 95% CI 1.003-1.018, p = 0.005) and PACAP (OR 1.003, 95% CI 1.001-1.005, p = 0.002) increased the risk for CM, but not for EM. CGRP did not predict CM or EM. This model could correctly classify only 62/101 (61.38%) of CM, 75/98 (76.53%) of EM, and 5/97 (4.12%) of HC [globally 147/296 (49.8%)]. Individually, PACAP performed the best for classifying clinical categories [global accuracy 150/296 (50.67%)]. In CM, neuropeptide levels were higher in those OnaBT-treated than in no-treated patients. Although interictal serum CGRP and VIP were higher in CM than both EM or HC, their utility to discriminate migraine categories was low. Contrary to other studies, PACAP serum levels were also higher in CM than in EM or HC and had more discriminative capability to distinguish CM from EM and HC. Further investigation is needed for determination technique standardization.

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3ß-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis.

Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3ß-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.

Foraging strategy of a carnivorous-insectivorous raptor species based on prey size, capturability and nutritional components.

Optimal foraging theory has typically paid little attention to species feeding on mobile prey and has emphasised energy intake rather than the nutritional contribution of food. The difficulty of capturing food has rarely been included in foraging models, even when it is a potentially important modulator of time devoted to foraging. From the central place foraging and provisioning perspectives, it is posited that at high levels of prey selectivity, the time spent to capture prey is longer than at low levels of prey selectivity. Furthermore, in the case of carnivorous predators, it is thought that nutritional composition does not influence foraging strategies. To explore these issues, we investigated the influence of abundance, size, difficulty of capture, gross energy and nutritional composition (fat, protein, protein-fat ratio and amino acid contents) of prey species on the foraging behaviour of a predator species, the common kestrel Falco tinnunculus, in a region of high diversity of prey species. Our results show that capturability index and load-size explain the foraging behaviour of kestrels. Preferred prey take longer to be provisioned, both selectivity and capturability might explain this result. It is also shown that specific nutritional components, such as protein and amino acid contents, are likely to explain food preference in this carnivorous-insectivorous species.

Thelepamide: an unprecedented ketide-amino acid from Thelepus crispus, a marine annelid worm.

Thelepamide (1) was characterized during a program to study cytotoxic substances from an unusual source, the tidal zone-derived annelid Thelephus crispus. Its structure contains a tetraketide and a tripeptide subunit and possesses striking atom diversity, consisting of 17 carbons and 8 heteroatoms. The relative configurations at four chiral sites were elucidated via ROESY, J-based configurational analysis, and DFT calculations. It was modestly active against leukemia cells (IC50 = 5 µg/mL) and inactive against solid tumor cell lines.