Catch me if you can: are catechol- and indoleamine genes pleiotropic QTLs for common mental disorders?

The aim of this study was to determine the effect of a short-term ethinyl estradiol/levonorgestrel medication on blood flow in the uterine arteries in postmenopausal women in a prospective placebo-controlled double-blind study. Twenty-one healthy postmenopausal woman at least 2 years after menopause received 60 micrograms ethinyl estradiol (EE) for 14 days followed by 40 micrograms EE plus 125 micrograms levonorgestrel (LNG) for 12 days (total treatment period 26 days). Sonographically, uterine volume, endometrial thickness, and blood flow in the uterine arteries [as reflected by pulsatility (PI) and resistance indices (RI)] were measured. Uterine size increased from 44 to 80 mL (day 14, p < 0.001) and 87 mL (day 26, p = NS). Endometrium grew from 3 to 8 mm (day 14, p < 0.001) and 11 mm (day 26, p = NS). Uterine arterial PI fell from 2.76 to 1.37 (day 14, p < 0.001) and 1.34 (day 26, p = NS), whereas RI fell from 0.9 to 0.68 (day 14 and day 26, p < 0.001). In conclusion, short-term treatment with LNG does not antagonize the vascular effect of EE on the uterine arteries as reflected by PI and RI. This result might have clinical significance in the selection of the progestin used in hormonal replacement therapy.     

Logistic regression analysis of twin data: estimation of parameters of the multifactorial liability-threshold model

This study with the rat evaluated the contribution of omega-conotoxin GVIA-(omega-CgTx) and verapamil-sensitive Ca2+ channels in behavioural, antinociceptive and thermoregulatory responses to intracerebroventricular (i.c.v.) injection of [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and dynorphin A-(1-17), which are selective agonists for putative mu, delta and kappa-opioid receptors, respectively. The rats treated with omega-CgTx (8-32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothermia which gradually disappeared within 4 h. The behaviour of the rats was normal by 24 h. Histological examination of brain sections showed morphological alterations of neurons in the hippocampus, medial-basal hypothalamus and pyriform cortex. antinociception, catalepsy and thermoregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were significantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or omega-CgTx (8 pmol 24 h before). Antinociception and hypothermia induced by DPDPE were antagonized by verapamil and omega-CgTx, whereas only omega-CgTx prevented the behavioural arousal observed after DPDPE. Similarly, hypothermia induced by dynorphin A-(1-17) (5.0 nmol) and by the kappa-opioid receptor agonist U50,488H (215 nmol) was antagonized by the two Ca2+ channel blockers but only omega-CgTx prevented the barrel rolling and bizarre postures caused by the opioid peptide.     

Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3 ligands

The 2-isopropyl thiazolyl group is a highly optimized P3 ligand for C2 symmetry-based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we report that incorporation of this P3 ligand into a piperazine hydroxyethylamine series also yielded novel, highly potent inhibitors. In tissue culture assays, the presence of human serum was less deleterious to the activity of these inhibitors than to that of ritonavir. Furthermore, potent activity against ritonavir resistant HIV was observed.     

Iron‐Oxide‐Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Small interfering RNA (siRNA) holds promise as a new class of therapeutics for HCC, as it can achieve sequence‐specific gene knockdown with low cytotoxicity. However, the main challenge in the clinical application of siRNA lies in the lack of effective delivery approaches that need to be highly specific and thus incur low or no systemic toxicity. Here, a nonviral nanoparticle‐based gene carrier is presented that can specifically deliver siRNA to HCC. The nanovector (NP‐siRNA‐GPC3 Ab) is made of an iron oxide core coated with chitosan‐polyethylene glycol (PEG) grafted polyethyleneimine copolymer, which is further functionalized with siRNA and conjugated with a monoclonal antibody (Ab) against human glypican‐3 (GPC3) receptor highly expressed in HCC. A rat RH7777 HCC cell line that coexpresses human GPC3 and firefly luciferase (Luc) is established to evaluate the nanovector. The nanoparticle‐mediated delivery of siRNA against Luc effectively suppresses Luc expression in vitro without notable cytotoxicity. Significantly, NP‐siLuc‐GPC3 Ab administered intravenously in an orthotopic model of HCC is able to specifically bound to tumor and induce remarkable inhibition of Luc expression. The findings demonstrate the potential of using this nanovector for targeted delivery of therapeutic siRNA to HCC.     

Characteristics,Stability, and Release of Peanut Sprout Extracts in Powdered Microcapsules by Spray Drying

This study was carried out to investigate the characteristics of powdered microcapsules from peanut sprout extracts prepared by spray drying. The microcapsules were made from medium-chain triglyceride (MCT) as primary coating material and whey protein concentrate (WPC) or maltodextrin (MD) as selected secondary coating materials. The microcapsule studies conducted were microphotograph, scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR), particle size, moisture contents, sorption, zeta potential, storage stability, and in-vitro study. The surface of microcapsules coated with WPC were rough and smooth, and particle size ranged from 2.86 to 8.59 µm. An FT-IR study revealed that absorption bands at 1,537 and 1,657 cm^?1 of microcapsules can be attributed to the protein amide I and II bands of WPC overlapped by the conjugated C?C. The moisture content was 1.33% in the microcapsules coated with WPC. The moisture sorption increased until 18% at the 90% RH. The yield of peanut sprout extracts from microcapsules was 89.01%. In the in-vitro study, the microcapsules released 2.48 and 6.01% at pH 2.0 and 4.0, respectively, in simulated-gastric fluid, and 61.07 and 89.24% at pH 6.0 and 8.0, respectively, in simulated-intestinal fluid. The preservation rate of the microcapsules dropped down to 60.43% from 89.01% during six months of storage. The stability of peanut sprout extracts in the microcapsules was over 80% at 4 and 20°C during 10-day storage. The zeta-potential of microcapsules was stable with ?30 mV. Based on the data obtained from the present study, the powdered peanut-sprout-extract microcapsules coated with WPC exhibited high stability during storage. Therefore, the powdered microcapsules by spray drying may be useful as a functional ingredient.