Evidence for the presence of beta-3-adrenoceptors mediating relaxation in the human oviduct

Beta1- and beta2-adrenoceptors mediate relaxation in the oviductal smooth muscle. This study examines the existence and function of beta3-adrenoceptors in the human oviduct. Ring segments of the oviduct were set up for isometric tension recording. The effect of isoprenaline and BRL 37344 on smooth muscle tone was examined. The expression of beta3-adrenoceptors in the oviduct was also examined. Isoprenaline and BRL 37344 concentration-dependently relaxed circular muscles of the oviduct. BRL 37344 was less potent than isoprenaline and was a partial agonist. Propranolol shifted isoprenaline but not BRL 37344 concentration-response curve to the right without reducing the maximum response. Cyanopindolol (1 micromol/l), a beta3-adrenoceptor antagonist, shifted the isoprenaline concentration response curve to the right. The -log K(B) value of 7.8 indicates activation of beta3-adrenoceptors by isoprenaline. mRNA for beta3-adrenoceptors was expressed in the oviduct. These results suggest that beta3-adrenoceptors, mediating relaxation, are expressed in the human oviduct.     

Recombinant Ascaris 16-Kilodalton protein-induced protection against Ascaris suum larval migration after intranasal vaccination in pigs

We recently cloned a protective antigen that is commonly expressed in Ascaris species that infect humans and pigs. We evaluated the vaccinal effects of this 16-kilodalton protein (As16) in pigs, the natural host of Ascaris suum, by intranasal immunization. Pigs that received Escherichia coli-expressed recombinant As16 (rAs16) coupled with cholera toxin (CT) had significantly elevated levels of rAs16-specific serum immunoglobulin G (IgG) and mucosal-associated IgA antibodies. rAs16 evoked a type II immune response characterized by elevated levels of interleukin-4 and -10 in the culture supernatants of peripheral blood mononuclear cells of the vaccinated pigs. An increased level of rAs16-specific serum IgG1 was also detected. Pigs vaccinated with rAs16-CT were protected from migration of A. suum larvae through the lungs, as indicated by a 58% reduction in the recovery of lung-stage third-stage larvae (L3), compared with that in nonvaccinated controls. Purified immunoglobulin from rAs16-CT-vaccinated pigs inhibited survival of infective L3 and interrupted the molting of lung-stage L3. Immunofluorescence studies revealed that this immunoglobulin bound to the digestive tracts of L3, suggesting that it might inactivate functions of the gut tissues of Ascaris species. We conclude that rAs16 is a promising mucosal vaccine candidate for pig and human ascariasis.     

Antioxidant micronutrient profile (vitamin E, C, A, copper, zinc, iron) of colostrum: association with maternal characteristics

The study was conducted to investigate the micronutrient profile of human colostrum, and to assess the association of maternal characteristics to the micronutrients. Colostral concentrations of antioxidant vitamins E, C, and A were 21.34 +/- 8.47, 148.92 +/- 43.64, 0.79 +/- 0.42 micromol/l, respectively. The antioxidant minerals copper, zinc, and iron contents were 19.17 +/- 11.73, 63.69 +/- 12.82, 11.44 +/- 1.46 micromol/l, respectively. Maternal characteristics did not have any influence on the colostral micronutrients.     

Water and electrolyte salvage in an animal model of dehydration and malnutrition

BACKGROUND AND AIM: Recently, a new oral rehydration solution (ORS) called Resomal has been designed specifically for children with severe malnutrition. The aim of this study was to assess the effect of malnutrition on renal and intestinal responses to dehydration, and to compare intestinal water and electrolyte absorption from Resomal and from the standard World Health Organization-Oral Rehydration Solution (WHO-ORS). METHOD: Malnutrition was achieved in a rabbit model by feeding the animals daily for 30 days with half the amount of food that a well-nourished group of control animals had consumed on the previous day. Dehydration was achieved by water deprivation for 46 hours in both control and malnourished rabbits. At 46 hours, dehydration was assessed by changes in body weight, urinary volume and osmolarity, and blood urea nitrogen concentration. At that time active colonic and jejunal mucosal electrolyte transport in Ussing chambers was also measured. Small intestinal absorption of water, sodium, and potassium was measured in vivo during intestinal perfusion of the two ORSs and in vitro by measurement of mucosal electrogenic glucose-stimulated sodium absorption across intestinal patches. RESULTS: Compared to controls (C), well-nourished but dehydrated (C+D) animals lost 12% of their body weight, with an 87% reduction in urine volume, a 110% increase in urine osmolality, and a 94% increase in blood urea nitrogen. In the colon of C+D animals, short-circuit current (Isc) and net sodium transepithelial flux (JNa+ net) were increased. Almost identical results were obtained in malnourished and dehydrated (M+D) animals. In the jejunum, net in vivo absorption of water (JWater), sodium (JNa+), and potassium (JK+) were increased during standard ORS infusion in both dehydrated groups. During Resomal infusion, water absorption was the same as seen with WHO-ORS, but sodium absorption was reduced, and potassium absorption was increased in both well-nourished and malnourished dehydrated animals. In vitro, compared to controls, the glucose-stimulated short-circuit current (DeltaIsc), JNa+ net and G were increased in both dehydrated groups. CONCLUSION: During experimental dehydration, the kidney and large intestine salvage water and electrolytes, thus reducing the consequences of dehydration. These findings indicate that jejunal water absorption from Resomal and WHO-ORS is increased during dehydration, but Resomal allows for less sodium and more potassium to be absorbed, both in well-nourished and malnourished dehydrated rabbits.     

The proteome expression patterns in adult<Emphasis Type="Italic"> Ascaris suum</Emphasis> under exposure to aerobic/anaerobic environments analyzed by two-dimensional electrophoresis

We investigated the protein expression patterns (the proteome) in adult Ascaris suum under exposure to aerobic and anaerobic environments in vitro using two-dimensional polyacrylamide gel electrophoresis. Adult A. suum were cultured in RPMI-1640 in the absence of oxygen (anaerobic) or in its presence (aerobic), and whole worm extracts and their excretory-secretory (ES) products were prepared for protein analysis. More than 200 protein spots resolved in two-dimensional gels. A comparison of aerobic versus anaerobic cultures revealed two aerobic and three anaerobic specific spots differentially expressed in adult worm extracts. ES products released during aerobic/anaerobic cultures also exhibited one aerobic and seven anaerobic specific spots in two-dimensional maps. One of the anaerobic specific protein spot was analyzed for its internal amino acid sequence (1-LLAFELAPHGIR-12; 1-VNTVNPGAVD-10) and the protein was predicted to be a putative dehydrogenase. These findings suggest that the availability of oxygen or its absence in the environment may influence protein expression patterns in parasitic nematodes.     

Differential amplification and quantitation of Marek's disease viruses using real-time polymerase chain reaction

Quantitative real-time PCR (qPCR) assays for the three serotypes of Marek's disease virus (MDV) have been developed. An internal control qPCR assay that detects chicken alpha2 (VI) collagen gene was also developed to allow quantitation of MDV. To reduce costs and time, the assays for MDV1 and the internal control were combined into a duplex assay. The sensitivity, specificity, precision, and reproducibility of each assay are reported. The MDV qPCR assays were specific to their target gene when compared using Australian field and vaccine strains of MDV and 10-100-fold more sensitive than standard PCR. Using DNA from infected spleen tissue, the lower limit of detection of total DNA (viral and host combined) was 0.025 ng for the MDV1 and collagen assays, and 0.25 ng for the HVT and MDV2 assays. All assays were found to be highly reproducible for Ct values, but less so for calculated concentrations. MDV1 and HVT were quantitated in spleen tissue of twenty experimentally infected chickens 7-35 days after infection. The relative abundance of MDV1 exhibited a clear peak at day 14 post-infection, whereas HVT displayed an increasing trend over the 35 days post-infection. The duplex assay was optimized such that it was able to accurately quantitate MDV1 in samples of very high, medium, and very low relative abundance of MDV1. These qPCR assays will be useful for reliable differentiation and quantitation of MDV for a range of research and industry applications.     

Zinc status in well nourished Bangladeshi children suffering from acute lower respiratory infection

This study was done to investigate the association of zinc status of well nourished Bangladeshi children with Acute Lower Respiratory Infection (ALRI). In this case control study, simultaneous estimation of serum and hair zinc was performed in 35 well nourished children, aged 6-60 months suffering from ALRI and 38 normal matched controls. Serum zinc was low in children suffering from ALRI as compared to control (90 +/- 51 pg/dL vs 176 +/- 98 pg/dL, OR: 6, 95% CI: 1.83, 19.66;P <0.05) children. Hair zinc was also found significantly low in children suffering from ALRI as compared to control (158 + 48 1g/g vs 247 154 pg/g, OR: 3, 95% CI: 1.46, 10.04, P < 0.05). We conclude that Bangladeshi children suffering from pneumonia, have decreased levels of serum and hair zinc.     

The international suicide prevention trial (interSePT): rationale and design of a trial comparing the relative ability of clozapine and olanzapine to reduce suicidal behavior in schizophrenia and schizoaffective patients

Suicidal behavior in patients with psychotic disorders represents a seriously undertreated life-threatening condition. The International Suicide Prevention Trial (InterSePT) is the first large-scale, prospective study designed to evaluate the potential of antipsychotic medications to reduce suicidal behaviors in patients with schizophrenia or schizoaffective disorder who are known to be at high risk for suicide. The unique challenges to study design and the solutions identified for the InterSePT study are described. These challenges included defining suicidal behavior in patients with psychosis, endpoint selection, determination of analytic strategy, and development of scales to assess suicidal behavior. Given the life-threatening nature of suicidal behavior, ethical considerations required that the design minimize suicide attempts and deaths. While the study focused primarily on treatment of suicide, opportunities were used to collect data in related areas of interest, including suicide risk factors, other efficacy measures (e.g., Positive and Negative Syndrome Scale, Covi Anxiety Scale, Calgary Depression Scale), adverse events, pharmacoeconomics, and pharmacogenetics. Because of the complexity of the design issues, a steering committee, suicide monitoring board, and publication committee were established to assist with their management.