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Neurological diseases continue to increase in prevalence worldwide. Combined with the lack of modifiable risk factors or strongly efficacious therapies, these disorders pose a significant and growing burden on healthcare systems and societies. The development of neuroprotective or curative therapies is limited by a variety of factors, but none more than the highly selective blood-brain barrier. Intranasal administration can bypass this barrier completely and allow direct access to brain tissues, enabling a large number of potential new therapies ranging from bioactive peptides to stem cells. Current research indicates that merely administering simple solutions is inefficient and may limit therapeutic success. While many therapies can be delivered to some degree without carrier molecules or significant modification, a growing body of research has indicated several methods of improving the safety and efficacy of this administration route, such as nasal permeability enhancers, gelling agents, or nanocarrier formulations. This review shall discuss promising delivery systems and their role in expanding the clinical efficacy of this novel administration route. Optimization of intranasal administration will be crucial as novel therapies continue to be studied in clinical trials and approved to meet the growing demand for the treatment of patients with neurological diseases. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the influence of verapamil‐mediated inhibition of P‐glycoprotein (P‐gp) on the pharmacokinetics of ivermectin (IVM) given orally and subcutaneously (SC) to rabbits. Twenty New Zealand rabbits were allotted to 4 groups (n = 5) and received IVM either orally or SC (0.4 mg/kg) alone or co‐administered with verapamil (2 mg/kg SC, 3 times at a 12‐hr interval). Plasma, fecal, and urine samples were collected over 30 days after medication to assess IVM concentrations in these samples. No significant differences were observed in the pharmacokinetic parameters of IVM between oral and SC administrations. The area under the plasma concentration–time curve was higher (p <.05) after IVM (oral)/verapamil treatment, compared with oral IVM alone. Moreover, the time to the Cmax of IVM was shorter (p <.05), whereas the elimination half‐life and the mean residence time were longer (p <.05) in the presence of verapamil. The IVM/verapamil combination administered orally or SC reduced fecal IVM concentrations, compared with IVM alone. In conclusion, the significant changes by verapamil on the pharmacokinetics of IVM, likely due to the inhibition of a P‐gp‐mediated intestinal secretion, may change IVM's antinematodal activity. [ABSTRACT FROM AUTHOR]

The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals and remains threatened as a result of intense environmental and anthropogenic pressure. The transformation and specialization of the giant panda's diet into a herbivorous diet have resulted in unique adaptabilities in many aspects of their biology, physiology and behavior. However, little is known about their adaptability at the molecular level. Through comparative analysis of the giant panda's genome with those of nine other mammalian species, we found some genetic characteristics of the giant panda that can be associated with adaptive changes for effective digestion of plant material. We also found that giant pandas have similar genetic characteristics to carnivores in terms of olfactory perception but have similar genetic characteristics to herbivores in terms of immunity and hydrolytic enzyme activity. Through the analysis of gene family expansion, 3752 gene families were found, which were enriched in functions such as digestion. A total of 93 genes under positive selection were screened out and gene enrichment identified these genes for the following processes: negative regulation of cellular metabolic process, negative regulation of nitrogen compound metabolic process, negative regulation of macromolecule metabolic process and negative regulation of metabolic process. Combined with the KEGG pathway, it was found that genes such as CREB3L1, CYP450 2S1, HSD11B2, LRPAP1 play a key role in digestion. These genes may have played a key role in the pandas' adaptation to its bamboo diet. [ABSTRACT FROM AUTHOR]

Little is known about the effect of the macronutrient composition of foods on cephalic phase response of gastrointestinal hormones. In addition, the metabolomics of cephalic phase response has not been studied before. The objective of the present study was to assess cephalic phase endocrinological and metabolomic responses following modified sham feeding (MSF) of foods with different macronutrient compositions. Ten healthy males attended four separate test sessions after overnight fasting, for a 3-min MSF of water, high-fat, high-carbohydrate or high-protein food, respectively, in a randomized order. Blood samples were collected at baseline and at regular time points for 10min following the completion of MSF and assayed for plasma glucose, insulin, ghrelin and glucose-dependent insulinotropic peptide. 1H nuclear magnetic resonance was used to acquire metabolomic profiles of the plasma samples. Plasma glucose increased after MSF of all test foods, but there were no differences due to the macronutrient composition of the test foods. MSF of the high-carbohydrate food elicited significantly higher insulin, and the high-protein food resulted in higher ghrelin compared to other test sessions. No significant change in glucose-dependent insulinotropic peptide was found. Analysis of plasma metabolomic profiles revealed concentrations of lipids were lower after MSF while plasma glucose increased after MSF. There was also a macronutrient-dependent change in certain amino acids. In conclusion, short-term oral exposure to foods with different macronutrient compositions can induce a macronutrient-specific cephalic change in insulin and ghrelin, as well as metabolomic profiles. [ABSTRACT FROM AUTHOR]

Abstract: Aging is associated with a reduction in appetite. Older adults require a higher number of chews to form a bolus before swallowing. However, whether this ingestive behavior contributes to the reduced appetite in this population is unknown. Fifteen males aged 65years or older participated in this randomized cross-over trial and attended two test sessions. After an overnight fast, they consumed a fixed-amount meal (2050kJ) by chewing each portion of food 15 or 40 times before swallowing. Subjective appetite was measured using visual analogue scales at regular intervals for 3h after completion of the meal. Blood samples were collected at the same time for measurement of glucose, insulin, and glucose-dependent insulinotropic peptide (GIP). Participants were provided an ad libitum meal 3h later. Compared with 15 chews, chewing food 40 times before swallowing resulted in significantly lower postprandial hunger (P =0.003), preoccupation with food (P <0.001), and desire to eat (P <0.001). Plasma concentrations of glucose, insulin, and GIP were significantly higher at meal completion when 40 chews were made (all P <0.01), and became significantly lower during the late postprandial period (all P <0.05). Food intake at the subsequent ad libitum meal did not differ significantly between test sessions. Our findings suggested that increased number of chews reduced postprandial hunger and desire to eat, and modulated glucose metabolism in older males. The number of chews made during a fixed-amount meal may influence short-term appetite; how this ingestive behavior contributes to energy balance in the long term warrants further investigation. [Copyright &y& Elsevier]

Understanding the impact of rheological properties of food on postprandial appetite and glycemic response helps to design novel functional products. It has been shown that solid foods have a stronger satiating effect than their liquid equivalent. However, whether a subtle change in viscosity of a semi-solid food would have a similar effect on appetite is unknown. Fifteen healthy males participated in the randomized cross-over study. Each participant consumed a 1690 kJ portion of a standard viscosity (SV) and a high viscosity (HV) semi-solid meal with 1000 mg acetaminophen in two separate sessions. At regular intervals during the three hours following the meal, subjective appetite ratings were measured and blood samples collected. The plasma samples were assayed for insulin, glucose-dependent insulinotropic peptide (GIP), glucose and acetaminophen. After three hours, the participants were provided with an ad libitum pasta meal. Compared with the SV meal, HV was consumed at a slower eating rate (P = 0.020), with postprandial hunger and desire to eat being lower (P = 0.019 and P<0.001 respectively) while fullness was higher (P<0.001). In addition, consuming the HV resulted in lower plasma concentration of GIP (P<0.001), higher plasma concentration of glucose (P<0.001) and delayed gastric emptying as revealed by the acetaminophen absorption test (P<0.001). However, there was no effect of food viscosity on insulin or food intake at the subsequent meal. In conclusion, increasing the viscosity of a semi-solid food modulates glycemic response and suppresses postprandial satiety, although the effect may be short-lived. A slower eating rate and a delayed gastric emptying rate can partly explain for the stronger satiating properties of high viscous semi-solid foods. [ABSTRACT FROM AUTHOR]

To understand the influence of food form on satiety, 19 male participants attended two separate test sessions to consume either a liquid-solid meal (LS), which consisted of whole pieces of vegetable in a broth, or a liquid version of the same ingredients [liquid meal (LM)]. Following this meal, appetite questionnaires and blood samples were collected at regular intervals over 3 h. An ad libitum meal was then served and the amount eaten recorded. Fullness and preoccupation with food were higher following the LM compared with the LS ( p = 0.001 and p = 0.031, respectively). Postprandial plasma concentration of cholecystokinin ( p < 0.001) and insulin ( p <  0.001) was higher and plasma glucose concentration was lower ( p = 0.003) following the LM compared with the LS. However, there was no difference in the food intake at the subsequent meal. These results suggest that food form has a limited effect on satiety; however, the influence of the postprandial insulin response warrants further attention. [ABSTRACT FROM AUTHOR]

Studies effect of bradykinin on insulin release, through performance of rat pancreas perfusion. Bradykinin increase at perfusate glucose concentration of 6nM; Bradykinin induced insulin elimination by HOE-140 (0.1 uM) antagonist.

The isoxazolines are a novel class of ectoparasiticides with potent inhibitory activity on glutamate‐ and gamma‐aminobutyric acid‐gated chloride channel located in nervous system of invertebrates. In recent years, studies have been performed to evaluate the efficacy and safety of isoxazolines against various types of ectoparasites, including fleas, ticks, and mites. As more single and combined isoxazoline products have been approved by the United States Food and Drug Administration and European Medicines Agency, a more comprehensive understanding of isoxazolines becomes essential for veterinary clinical practitioners. This article provides a complete review of isoxazolines with respect to pharmacodynamics, pharmacokinetics, ectoparasiticidal efficacy, and safety, which will provide veterinarians information to allow them to make the best choice of ectoparasiticide for their clients' specific needs. [ABSTRACT FROM AUTHOR]

Giant pandas consume different structural parts of bamboo (shoots, leaves and culms) during different seasons. Previous research showed different bamboo parts have varying nutritional content and that a long-term diet consisting of a single part of bamboo resulted in remarkable metabolic changes within captive giant pandas. However, the effects on the gut microbiome of giant pandas, as a result of a single bamboo part diet, have not been investigated. Here, we evaluated the changes in gut microbial communities based on single bamboo part diets and their potential implications by using 16S rRNA gene-based amplicon sequencing and metagenome shotgun sequencing. We found that the composition and function of the gut microbiome from captive giant pandas fed exclusively culms were significantly different from that of individuals fed shoots or leaves. During the culm feeding period, the gut microbiome showed strongest digestive capabilities for cellulose, hemicellulose and starch, and had the highest potential abilities for the biosynthesis of bile acids, fatty acids and amino acids. This suggests the microbiome aids in breaking down culm, which is more difficult for giant pandas to digest, as a means to compensate for the nutrient poor content of the culm. Genes related to fatty acid metabolism and tricarboxylic acid cycle enzymes were more abundant during the leaf stage diet than that in the shoot and culm stages. Thus, the microbiome may help giant pandas, which typically have low lipase levels, with fat digestion. These results illustrate that adaptive changes in the gut microbiome community and function may be an important mechanism to aid giant panda digestion when consuming different structural parts of bamboo. [ABSTRACT FROM AUTHOR]

Amitraz is presently the only FDA-approved treatment for demodicosis in dogs in the United States. Amitraz treatment involves a protracted course of administration and risks of severe adverse effects such as sedation, bradycardia, and respiratory depression, which are caused by activation of α2-adrenergic receptors. Other treatment options include macrocyclic lactones and lime sulfur, but these products have varied efficacy and high risks of adverse effects. Several recent studies have indicated that isoxazolines are capable of reducing Demodex mite counts in canine and feline patients with demodicosis by ≥ 99% in as little as 1 month with few adverse effects. This article reviews the status of isoxazolines in regard to labeled uses in dogs and cats in the United States, extralabel clinical use for treatment of demodicosis in these species, and safety of orally administered formulations of these drugs. [ABSTRACT FROM AUTHOR]

H 1 -antihistamines are widely used in treating allergic disorders, e.g., conjunctivitis, urticaria, dermatitis and asthma. The first-generation H 1 -antihistamines have a much greater sedative effect than the second-generation H 1 -antihistamines. Researchers could not offer a satisfactory explanations until late 1990s when studies showed that second-generation H 1 -antihistamines were substrates of P-glycoprotein. P-glycoprotein, expressed in the blood–brain barrier, acts as an efflux pump to decrease the concentration of H 1 -antihistamines in the brain, which minimizes drug effects on the central nervous system and results in less sedation. P-glycoprotein is found in the apical side of the epithelium. It consists of transmembrane domains that bind substrates/drugs and nucleotide-binding domains that bind and hydrolyze ATP to generate energy for the drug efflux. This review mainly discusses interactions between P-glycoprotein and commonly used second-generation H 1 -antihistamines. In addition, it describes other possible determining factors of minimal sedating properties of second-generation H 1 -antihistamines. [ABSTRACT FROM AUTHOR]

Intracellular Ca 2+ signaling is important for stem cell differentiation and there is evidence it may coordinate the process. Arginine vasopressin (AVP) is a neuropeptide hormone secreted mostly from the posterior pituitary gland and increases Ca 2+ signals mainly via V1 receptors. However, the role of AVP in adipogenesis of human adipose-derived stem cells (hASCs) is unknown. In this study, we identified the V1a receptor gene in hASCs and demonstrated that AVP stimulation increased intracellular Ca 2+ concentration during adipogenesis. This effect was mediated via V1a receptors, Gq-proteins and the PLC-IP 3 pathway. These Ca 2+ signals were due to endoplasmic reticulum release and influx from the extracellular space. Furthermore, AVP supplementation to the adipogenic medium decreased the number of adipocytes and adipocyte marker genes during differentiation. The effect of AVP on adipocyte formation was reversed by the V1a receptor blocker V2255. These findings suggested that AVP may function to inhibit adipocyte differentiation. [ABSTRACT FROM AUTHOR]

Arginine vasopressin (AVP), released from the CNS, plays an important role in regulating several aspects of CNS functions including aggression, anxiety, and cognition. In this study, we report a novel finding that AVP induces glutamate release from astrocytes isolated from the cerebral cortex and hippocampus. We also investigated the types of AVP receptors involved in the AVP-induced increase in glutamate release from astrocytes isolated from the hippocampus and cortex of neonatal rats. We showed that the AVP (0.1–1000 nmol/L) induced increase in glutamate release and [Ca2+]i is brought about by two distinct subtypes of V1 receptors (V1a and V1b). Our results suggested that V1b receptors are predominantly expressed in astrocytes isolated from the hippocampus and V1a receptors are solely expressed in astrocytes isolated from the cerebral cortex of neonatal rats. The results of the western blot analyses confirmed these pharmacological data. In addition, the AVP-induced increase in glutamate did not contribute to an increase in [Ca2+]i, as blockade of metabotropic glutamate receptors did not alter the AVP-induced increase in [Ca2+]i. In addition, the administration of a phospholipase A2 inhibitor failed to alter AVP-induced [Ca2+]i increase suggesting the lack of involvement of this enzyme. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the antihyperglycemic effect of p-methoxycinnamic acid (p-MCA), a cinnamic acid derivative, on plasma glucose and insulin concentrations, activities of hepatic glucose-regulating enzymes and hepatic glycogen content in normal and streptozotocin (STZ)-induced diabetic rats. p-MCA (10–100 mg/kg, PO) dose-dependently decreased plasma glucose concentration in both normal and diabetic rats in the oral glucose tolerance test. To investigate the chronic effects of p-MCA on glucose metabolism, p-MCA (40 mg/kg, PO) was administered to normal and diabetic rats once a day for 4 weeks. p-MCA reduced plasma glucose concentration in diabetic rats, which was observed during the 4-week study. However, p-MCA treatment did not change plasma glucose concentrations in normal rats during the 4-week study. p-MCA also reduced the excessive activities of hepatic glucose-6-phosphatase, hepatic hexokinase, glucokinase and phosphofructokinase in diabetic rats and increased hepatic glycogen in these rats. In p-MCA-treated normal rats, there were no changes in the activities of hepatic glucose-regulating enzymes, hepatic glycogen and glucose-6-phosphate. Our findings suggested that p-MCA exert its antihyperglycemic effect by increasing insulin secretion and glycolysis, and by decreasing gluconeogenesis. [Copyright &y& Elsevier]

PGF2α in semen has been shown to induce uterine contractions, thereby, facilitating sperm transport during fertilization. Previously, we demonstrated that extended boar semen used in artificial insemination does not increase myometrial contractility, but PGF2α supplementation did. In this study, we determined the concentrations of endogenous PGF2α in pre-sperm and sperm-rich fractions of the boar ejaculate and examined whether changes in the concentration of exogenous PGF2α occurred when added to extended boar semen after 72-h incubation at a 17 °C storage temperature.Concentrations of endogenous PGF2α (n=10 boars) in pre-sperm and sperm-rich fractions were 69.6±7.6 and 58.9±4.4 pg/ml, respectively. No differences were observed in the concentrations of exogenous PGF2α in the extended boar semen at 0 h (59.3±3.3 μg/ml) and after a 72-h incubation period (52.0±2.1 μg/ml). These results suggest that the concentration of endogenous PGF2α in boar semen used for artificial insemination is <100 pg/ml. The concentration of exogenous PGF2α in the extended boar semen did not differ after 72 h, which indicates that it is not metabolized during this period of time. [Copyright &y& Elsevier]

Amyloid β-peptide (Aβ) has been shown to impair glucose uptake in cultured hippocampal neurons and shortens their survival time. Aβ appears to inhibit neuronal glucose uptake by activating Gs-coupled receptors and the cAMP-PKA system. In this study, Aβ inhibition of neuronal glucose uptake was studied by assaying translocation of glucose transporter isoform GLUT3, transcription of GLUT3 mRNA, and fusion of GLUT3-containing vesicles with the plasma membrane. Cultured hippocampal neurons exposed to 10 μM Aβ25–35 or Aβ1–40 for 3 or 24 h showed a significant decrease in glucose uptake. To assess the regulatory role of Aβ on neuronal glucose uptake, translocation of GLUT3 from the cytosol to the plasma membrane was studied by the plasma membrane lawn assay and transcription of GLUT3 mRNA by in situ hybridization. In spite of a decrease in glucose uptake, Aβ25–35 and Aβ1–40 (10 μM) markedly promoted GLUT3 translocation to the plasma membrane by 30 min. Aβ25–35 also up-regulated transcription of GLUT3 mRNA by 12 h. High extracellular K+ increased immunolabeling of the exofacial (i.e., extracellular) epitope of GLUT3 at the plasma membrane and Aβ25–35 inhibited this increase. Based on these data we propose that Aβ increases translocation of GLUT3-containing vesicles, but inhibits their fusion with the plasma membrane. [Copyright &y& Elsevier]

Presents a study which examined the lethal and sublethal effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus. Information on the lethal concentrations of ivermectin; Involvement of chlorine channels using picrotoxin; Analysis of the electrophysiological effects of ivermectin on giant nerve fiber pathways.

The pharmacokinetics of tylosin were investigated in 3 groups of ducks (n = 6). They received a single dose of tylosin (50 mg/kg) by intravenous (IV), intramuscular (IM), and oral administrations, respectively. Plasma samples were collected at various time points to 24 hr post‐administration to evaluate tylosin concentration over time. Additionally, tylosin residues in tissues and its withdrawal time were assessed using 30 ducks which received tylosin orally (50 mg/kg) once daily for 5 consecutive days. After IV administration, the volume of distribution, elimination half‐life, area under the plasma concentration–time curve, and the total body clearance were 7.07 ± 1.98 L/kg, 2.04 hr, 19.47 µg hr/ml, and 2.82 L hr−1 kg−1, respectively. After IM and oral administrations, the maximum plasma concentrations were 3.70 and 2.75 µg/ml achieved at 1 and 2 hr, and the bioavailability was 93.95% and 75.77%, respectively. The calculated withdrawal periods of tylosin were 13, 8, and 5 days for kidney, liver, and muscle, respectively. For the pharmacodynamic profile, the minimum inhibitory concentration for tylosin against M. anatis strain 1,340 was 1 µg/ml. The calculated optimal oral dose of tylosin against M. anatis in ducks based on the ex vivo pharmacokinetic/pharmacodynamic modeling was 61 mg kg−1 day−1. [ABSTRACT FROM AUTHOR]

Neurological diseases are becoming increasingly prominent worldwide due to rapidly aging populations, which greatly contributes to increasing healthcare costs. The development of neuroprotective drugs has so far proven exceptionally difficult due to the blood-brain barrier. One novel approach to address this challenge is to administer drugs intranasally to noninvasively bypass the blood-brain barrier. The intranasal route can thus transport drugs directly to the brain from the nasal cavity along the olfactory and trigeminal nerves. The purpose of this review is to describe the details of this mechanism to better direct future research. The intranasal route is composed of two pathways, one being intracellular while the other being extracellular. The intracellular pathway begins with endocytosis by olfactory sensory cells, followed by axonal transport to their synaptic clefts in the olfactory bulb where the drug is exocytosed. This transynaptic process is repeated by olfactory neurons, thereby distributing the drug to other brain regions. In the extracellular mechanism, drugs are transported directly into the cerebral spinal fluid by first passing through the paracellular space across the nasal epithelium, then through the perineural space to the subarachnoid space of the brain. With a growing body of evidence and trials in both rodent and human models, this is an exciting area for research as therapeutics come to market. [ABSTRACT FROM AUTHOR]

Monoclonal anti-idiotypic antibody (Mab2-5G2) raised against idiotypic antibodies to membrane glycoprotein GP5 of porcine reproductive and respiratory syndrome virus (PRRSV). The variable regions of the heavy chain (VH) and light chain (VL) of Mab2-5G2 were cloned and connected with a (Gly 4 Ser) 3 linker. The recombinant scFv gene was cloned into the pEasy-E1 vector and expressed in E. coli as inclusion bodies. The expressed scFv-His proteins renatured in a pH and urea gradient buffer retained the same immunological properties as that of Mab2-5G2. Renatured scFv-His protein retained the same characteristics as that of Mab2-5G2 by recognizing and binding to Marc-145 cells. Furthermore, renatured scFv-His along with Mab2-5G2 were used to immunize rabbits to produce anti-anti-idiotypic antibodies (Ab3) that neutralized PRRSV infection of Marc-145 cells. These results demonstrated that the expressed scFv-His protein possessed the same characteristics of Mab2-5G2 and will be suitable for future investigations of Mab2-5G2 antibody structure and its ability to interact with potential PRRSV cellular receptor as well as immunological properties against PRRSV infection. [ABSTRACT FROM AUTHOR]

Virus replication depends upon host-cell processes in infected cells, and this is true for porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of PRRS that is a worldwide threat to the swine industry. Heme oxygenase-1 (HO-1) is a ubiquitously expressed inducible isoform of the first and rate-limiting enzyme for heme degradation. Our previous research suggested that HO-1 may play an important role in PRRSV infection. However, the function of HO-1 in PRRSV infection is unclear. In the present study, Marc-145, PK-15 CD163 cell lines and porcine alveolar macrophages (PAMs) were used to evaluate the effects of HO-1 induction and over-expression on the replication of two different PRRSV strains. Induction of HO-1 markedly decreased the replication of PRRSV strains in the different cells. Similarly, adenoviral-mediated over-expression of HO-1 also greatly decreased the replication of PRRSV. In contrast, ablation of HO-1 using small interfering RNA concomitantly increased PRRSV replication. Therefore, the data were consistent with HO-1 acting as an antiviral factor and these findings suggested that over-expression or induction of HO-1 may provide a potential therapeutic strategy against PRRSV infection. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV), the causative agent of hepatitis E, is classified into four major genotypes (1 to 4) and swine is the main natural reservoir for genotypes 3 and 4. In this study, a total of 106 bile samples from a slaughterhouse in the Shandong province of China were tested for the partial ORF2 gene of HEV by RT-nPCR to determine the virus genotypes, and two indirect ELISA were developed for the detection of swine HEV specific IgM and IgG antibodies in 980 serum samples from 24 farms, in order to investigate the seroprevalence. Thirty-two out of 106 (30.2%) bile samples were positive for HEV and a high degree of partial ORF2 sequence similarity (86.8-100%) was observed among 20 samples. The viral sequences belonged to genotype 4, subtypes 4a and 4d. One complete genome sequence of a subtype 4d HEV was further determined and characterized. The seroprevalence of HEV IgG and IgM antibodies was 100% (24/24) and 41.7% (10/24) for herds, and 66.4% (651/980) and 1.6% (16/980) for the individual pigs, respectively. These results suggested a high prevalence of genotype 4 of swine HEV infection both in swine farms and at the slaughterhouse in Shandong province, which further raise public-health concerns for zoonosis and pork safety. [ABSTRACT FROM AUTHOR]

Highlights: [•] We develop a bELISA for detection of antibodies against avian hepatitis E virus. [•] Cut-off value of bELISA is 20.7%. [•] The bELISA had a sensitivity of 98.3%. [•] The compliance rates of the bELISA with iELISA and Western blot were 83.7% and 93.3%, respectively. [•] The bELISA shows high reproducibility compared with iELISA and Western blot. [ABSTRACT FROM AUTHOR]

Abstract: Avian hepatitis E virus (HEV) is an emerging virus associated with the big liver and spleen disease or hepatitis-splenomegaly syndrome in chickens and subclinical infections by the virus are also common. The complete genome of avian HEV contains three open-reading frames (ORFs) in which ORF2 protein is part of virus particles and thus contains primary epitopes. Antigenic epitopes of avian HEV ORF2 protein have been described but those associated with the ORF3 have not. To analyze the antigenic domains and epitopes in the ORF3 protein of a Chinese isolate of avian HEV (CaHEV), we generated a series of antigens comprised of the complete ORF3 and also five truncated overlapping ORF3 peptides. The antibodies used in this study were mouse antisera and monoclonal antibodies against ORF3, positive chicken sera from Specific Pathogen Free chickens experimentally infected with CaHEV and clinical chicken sera. Using these antigens and antibodies, we identified three antigenic domains at amino acids (aa) 1–28, 55–74 and 75–88 in which aa 75–88 was a dominant domain. The dominant domain contained at least two major epitopes since field chickens infected with avian HEV produced antibodies against the domain and epitopes. These results provide useful information for future development of immunoassays for the diagnosis of avian HEV infection. [Copyright &y& Elsevier]

Highlights: [•] PiggyBac transposon-mediated PK-15CD163 cell line was generated. [•] PK-15CD163 cell line was stable for more than 60 passages. [•] PK-15CD163 cells were susceptible for different PRRSV strains with high titers. [•] PB transposed PK-15CD163 cell line is suitable for PRRSV biology study. [ABSTRACT FROM AUTHOR]

Objective--To evaluate the effect of IV administration of polymyxin B on clinical and serum biochemical variables in foals with experimental endotoxemia. Design--Prospective experimental study. Animals--14 healthy neonatal foals. Procedures--Foals were randomly assigned to a treatment or control group and were administered a single dose of lipopolysaccharide (0.5 (ig/kg [0.23 pg/lb]) IV over 30 minutes. The treatment group received polymyxin B (6,000 U/kg [2,727 U/Ib], IV) immediately after completion of lipopolysaccharide infusion; the control group was administered an equal volume of saline (0.9% NaCI) solution. Subsequent doses of polymyxin B or saline solution were administered IV at 8 and 16 hours. Blood was collected at various time points, and outcome variables, including heart rate, respiratory rate, rectal temperature, attitude score, WBC count, neutrophil count, lymphocyte count, monocyte count, platelet count, Hct, blood lactate concentration, blood glucose concentration, serum tumor necrosis factor-a concentration, and plasma thromboxane B2 concentration, were measured. Urine was collected prior to and after experimentation to determine whether nephrotoxicosis was associated with treatment. Results--The treatment group had significantly lower blood lactate concentration and serum tumor necrosis factor-a and plasma thromboxane B2 concentrations and had higher blood glucose concentrations and better attitude scores, compared with the control group, at various time points during the study. No other significant differences and no evidence of overt nephrotoxicosis were detected. Conclusions and Clinical Relevance--Administration of polymyxin B IV in healthy neonatal foals challenged with lipopolysaccharide attenuated some clinical and serum biochemical derangements associated with endotoxemia. [ABSTRACT FROM AUTHOR]

Objective:To evaluate baseline plasma cortisol and ACTH concentrations and responses to low:dose ACTH stimulation testing in ill foals. Design:Cross:sectional study. Animals:58 ill foals. Procedures:Baseline cortisol and ACTH concentrations and cortisol concentrations after administration of a low dose of cosyntropin were determined within 6 hours after admission. Foals were assigned to 4 groups on the basis of age (≤ 24 hours vs 1 to 56 days) and presence of septicemia (yes vs no). Values were compared among groups and with values previously reported for healthy foals. Results:Plasma cortisol concentrations 30 and 60 minutes after cosyntropin administration in foals ≤ 24 hours old were significantly higher than corresponding cortisol concentrations in older foals. In all 4 groups, plasma cortisol concentration 30 minutes after cosyntropin administration was significantly higher than baseline cortisol concentration or concentration 60 minutes after cosyntropin administration. No differences in baseline cortisol or ACTH concentration or in the ACTH:to:cortisol ratio were detected between groups or when ill foals were compared with healthy foals. A small number of ill foals had low baseline cortisol and ACTH concentrations or low responses to cosyntropin administration, compared with healthy foals. Conclusions and Clinical Relevance:Results indicated that most ill foals in the present study population had adequate responses to cosyntropin administration. However, a small subset of ill foals appeared to have dysfunction of the hypothalamic:pituitary:adrenal axis. [ABSTRACT FROM AUTHOR]

This study investigated the effect of p-methoxycinnamic acid ( p-MCA) on plasma glucose and insulin concentrations in normal and streptozotocin-induced diabetic rats. In both fasting and glucose-loading conditions, an oral administration of p-MCA (40–100 mg/kg) significantly decreased plasma glucose and also increased plasma insulin concentrations in both normal and diabetic rats. The onset of the p-MCA-induced antihyperglycaemia/hypoglycaemia was observed at 1 hr after administration. In perfused rat pancreas, p-MCA (10–100 µM) stimulated insulin secretion about 1.4- and 3.1-fold of basal–control group. In addition, p-MCA (10 µM) enhanced glucose-induced insulin secretion. Moreover, p-MCA stimulated insulin secretion and increased intracellular Ca2+ concentration ([Ca2+]i) in insulinoma-1 cells. Taken together, our findings suggested that p-MCA exerted antihyperglycaemic/hypoglycaemic effect by stimulating insulin secretion from pancreas and could be developed into a new potential for therapeutic agent used in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Somatostatin (SS) is a peptide hormone that inhibits insulin secretion in β-cells by activating its Gi/o-coupled receptors. Our previous work indicated that a βγ-dimer of Gi/o coupled to SS receptors can activate phospholipase D1 (PLD1) (Cheng, H., Grodnitzky, J. A., Yibchok-anun, S., Ding, J., and Hsu, W. H. (2005) Mol. Pharmacol. 67, 2162-2172). The aim of the present study was to elucidate the mechanisms underlying SS-induced PLD activation. We demonstrated the presence of ADP-ribosylation factor Arf1 and Arf6 in clonal β-cells, HIT-T15. We also determined that the activation of PLD1 was mediated through Arf6. Overexpression of dominant-negative (dn) Arf6 mutant, Arf6(T27N), and suppression of mRNA levels using siRNA, both abolished SS-induced PLD activation, while overexpression of wild type Arf6 further enhanced this PLD activation. In contrast, overexpression of dn-Arf1 mutant Arf1(T31N) or dn-Arf5 mutant Arf5(T31N) failed to reduce SS-induced PLD activation. These findings suggested that Arf6, but not Arf1 or Arf5, mediates the effect of SS. We further determined the involvement of the Arf6 guanine nucleotide exchange factor (GEF) EFA6A, a GEF previously thought to be found predominantly in the brain, in the activation of PLD1 in HIT-T15 cells. Using Northern and Western blot analyses, both mRNA and protein of EFA6A were found in these cells. Overexpression of dn-EFA6A mutant, EFA6A(E242K), and suppression of mRNA levels using siRNA, both abolished SS-induced PLD activation, whereas overexpression of dn-EFA6B mutant, EFA6B(E651K), failed to reduce SS-induced PLD activation. In addition, overexpression of dn- ARNO mutant, ARNO(E156K), another GEF of Arf6, had no effect on SS-induced activation of PLD. Taken together, these results suggest that SS signals through EFA6A to activate Arf6- PLD cascade. [ABSTRACT FROM AUTHOR]

An investigation was undertaken to assess whether polyclonal convalescent and hyperimmune sera obtained from pigs inhibit Mycoplasma hyopneumoniae induced increases in intracellular calcium [Ca2+]i in ciliated porcine tracheal cells. Basal [Ca2+]i in the tracheal cells was 97 ± 13 nM (n = 22 cells in four experiments) and after exposure to M. hyopneumoniae (300 µg/mL or 1011 CCU/mL), [Ca2+]i increased by 246 ± 56 nM within 100 s. After pre-treatment with hyperimmune or convalescent serum, M. hyopneumoniae increased [Ca2+]i by 196 ± 43 and 223 ± 65 nM, respectively. It was found that neither hyperimmune nor convalescent serum significantly prevented the increase in [Ca2+]i compared with M. hyopneumoniae alone. It was concluded that polyclonal antibodies produced by mycoplasma vaccination or exposure to the pathogen do not prevent M. hyopneumoniae-induced increase in [Ca2+]i. [ABSTRACT FROM AUTHOR]

Abstract: Somatostatin (SST) inhibits pancreatic endocrine secretion. It is generally accepted that SSTR2 and SSTR5 mediate the inhibition of glucagon and insulin release, respectively. The present study was performed to test the hypothesis that SSTR2, but not SSTR5, mediates SST-induced inhibition of insulin release in hamster β-cells. Both hamster clonal β-cells HIT-T15 and pancreatic islets were used to test this hypothesis. Both SST and a nonpeptide SSTR2 agonist L-779,976 (1–100 nM) inhibited insulin release from HIT-T15 and islets in a concentration-dependent manner. In contrast, nonpeptide agonists for SSTR1, 3, 4 and 5 at the highest concentration studied (1 μM) failed to inhibit insulin release. PRL-2903, a peptide SSTR2 antagonist (0.1–1 μM), antagonized SST-induced inhibition of insulin release in a concentration-dependent manner. Taken together, we conclude that, in hamster β-cells, SST inhibits insulin release via SSTR2 but not SSTR5. [Copyright &y& Elsevier]

The purpose of this study was to investigate the role of arginine vasopressin (AVP) on glucagon secretion in both normal and diabetic rats. Diabetes was induced by intravenous administration of 50 mg/kg streptozotocin, 14 days before pancreatic perfusion. Diabetic rats were maintained on insulin replacement therapy until ∼48 h before the perfusion experiments. Both glucagon and AVP were determined in the effluent of the perfused pancreas using RIA. Both normal and diabetic rats had similar basal glucagon secretion. AVP (3–30 pM) increased glucagon secretion from both normal and diabetic rats in a concentration-dependent manner. However, diabetic subjects were more sensitive to AVP administration than normal subjects with regard to glucagon secretion. By comparison of the areas under the curves, AVP-induced glucagon secretion in diabetic rats was ∼2-fold that of the normal rats. In addition, immunoreactive AVP was detected in the effluent of the perfused pancreas, and diabetic rats had 70% higher AVP concentrations in the pancreatic effluent than normal rats. We conclude that AVP is secreted from the pancreas and diabetic rats can secrete more AVP from the pancreas than normal rats. Consequently, AVP may have a greater impact on glucagon secretion in diabetic subjects than normal ones. AVP might play an important role in the hypersecretion of glucagon in diabetic subjects. [Copyright &y& Elsevier]

The effects of somatostatin (SRIF) are mediated through the seven transmembrane receptor family that signals via Gi/Go. To date, five distinct SRIF receptors have been characterized and designated SSTR1-5. We have characterized the SRIF receptor that mediates the increase in [Ca2+]i and insulin secretion in HIT-T15 cells (Simian virus 40-transformed Syrian hamster islets) using high affinity, subtype selective agonists for SSTR1 (L-797,591), SSTR2 (L-779,976), SSTR3 (L-796,778), SSTR4 (L-803,087), SSTR5 (L-817,818) and PRL-2903, a specific SSTR2 antagonist. In the presence of arginine vasopressin (AVP), SRIF increased [Ca2+]i and insulin secretion. Treatment with the SSTR2 agonist L-779,976 resulted in similar responses to SRIF. In addition, L-779,976 increased both [Ca2+]i and insulin secretion in a dose-dependent manner. Treatment with L-779,976 alone did not alter [Ca2+]i or basal insulin secretion. In the presence of AVP, all other SRIF receptor agonists failed to increase [Ca2+]i and insulin secretion. The effects of SRIF and L-779,976 were abolished by the SSTR2 antagonist PRL-2903. Our results suggest that the mechanism underlying SRIF-induced insulin secretion in HIT-T15 cells be mediated through the SSTR2. [Copyright &y& Elsevier]

Examines the role of rosiglitazone (RSG) in enhancing insulin secretory response via phosphatidylinositol 3-kinase pathway (PI3K). Inhibition of the effect of RSG on insulin secretion; Potentiation of glucose-induced insulin secretion by RSG; Role of PI3K pathway in RSG.