Evaluation of the field efficacy of an avirulent live Lawsonia intracellularis vaccine in foals.

Equine proliferative enteropathy caused by Lawsonia intracellularis is an emerging disease with as yet unaddressed preventative measures. The hypothesis of this study was that vaccination will prevent clinical and sub-clinical disease. Weanling Thoroughbreds (n=202) from Central Kentucky were randomly assigned into two groups (vaccinated and non-vaccinated). Vaccinated foals received 30 mL of an avirulent, live L. intracellularis vaccine intra-rectally twice, 30 days apart. Foals were monitored for clinical disease, total solids and average weight gain until yearling age. There was an overall decreased disease incidence on the farms involved in the study that did not differ significantly between the groups. This decreased disease prevalence in the study population may be associated with the ongoing vaccine trial on these farms, as disease prevalence in Central Kentucky did not change in 2009 compared to 2008.

Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis.

We have shown previously that numerous IgE(+) macrophage-like cells are present in the villous stroma of full term placenta and that there was no difference in the amount of IgE(+) cells between allergic and non-allergic mothers. The presence of such an abundant number of IgE(+) cells in the placenta in allergic as well as non-allergic women suggests that the IgE is of some importance for a successful pregnancy outcome. Here we have investigated the IgE-pattern in 59 placentas from second and third trimesters from Sweden with different degrees of chorioamnionitis and 27 full term placentas from Ghana with and without malaria parasites. The immunohistochemical staining pattern for IgE looked similar to our previous study, with the IgE located on Hofbauer-like cells. We could not find any difference in the amount or distribution of IgE(+) cells between malaria-infected and non-infected placentas, nor between different degrees of chorioamnionitis. The IgE score in the placenta did not correlate with the levels of IgE in maternal serum or plasma. However, the IgE score was significantly higher in second- compared to third-trimester placentas (P = 0.03). This might reflect a maturation time-point in the fetus and in the intrauterine environment during the second trimester, or it might be associated with the increased number of intrauterine fetal deaths in the second trimester.

A new test for immunological infertility: an ELISA based on prostasomes.

Antisperm antibodies (ASA) are present in patients with immunological infertility, but the antigens are poorly characterized. Prostasomes adhere to sperm cells and are recognized as antigens for ASA. This investigation aimed to study the prevalence of antiprostasome antibodies in ASA-classified sera. We studied the reactivity of ASA-positive sera from 116 immunoinfertile patients. Ninety-seven per cent (113 of 116) of the patients' sera contained IgG antibodies against seminal prostasomes. Accordingly, prostasomes are one of the major targets for ASA. An enzyme-linked immunosorbent assay based on prostasomes is simpler to perform than ASA tests presently in use. It is also easier to achieve reproducible and standardized results.

Effects of modifying topoisomerase II levels on cellular recovery from radiation damage.

Effects of Modifying Topoisomerase II Levels on Cellular Recovery from Radiation Damage. Experiments were performed with the budding yeast, Saccharomyces cerevisiae, to test whether DNA topoisomerase II is involved in repair of DNA damage induced by ionizing radiation. Topoisomerase II was inactivated by use of a temperature-sensitive mutation. Enzyme inactivation increased cellular radiosensitivity, blocked the restitution of broken chromosomes, assayed by pulsed-field gel electrophoresis, and prolonged the induction of a DNA damage-inducible gene (RNR3). Overexpression of the topoisomerase II gene did not alter cellular radiosensitivity. The data support a role for topoisomerase II in the repair of DNA strand breaks.

Is it necessary to suture all lacerations after a vaginal delivery?

BACKGROUND: Midwives tend to leave minor perineal lacerations to heal spontaneously, and clinical experience and studies show that women can suffer from their stitched lacerations. The study purpose was to determine any differences in the healing process and experience of minor perineal lacerations when they were sutured or not sutured. METHODS: Eighty term pregnant primiparas with minor perineal lacerations of grades I-II were randomized after childbirth. The experimental group was nonsutured and the control group was sutured. A follow-up examination was performed at 2 to 3 days, 8 weeks, and 6 months after the delivery. Participants were asked about the type of discomfort, and the effect of the laceration on breastfeeding and sexual intercourse. RESULTS: No significant differences were found in the healing process. The type of pain differed between the groups, but the amount of discomfort was the same. The sutured group had to visit the midwife more often because of discomfort from the stitches. Sixteen percent of the women in the sutured group, but none in the nonsutured group (p = 0.0385), considered that the laceration had had a negative influence on breastfeeding. CONCLUSIONS: Minor perineal lacerations can be left to heal spontaneously. The benefits for the woman include the possibility of having a choice, avoiding the discomfort of anesthesia and suturing, providing positive affects on breastfeeding.

Syntheses of some polyunsaturated sulfur- and oxygen-containing fatty acids related to eicosapentaenoic and docosahexaenoic acids.

With the aim of enhancing selectively the beneficial biological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) a number of polyunsaturated fatty acids containing sulfur or oxygen atoms in the chain has been synthesized starting from EPA and DHA, respectively. Oxidative degradation of these acids led to the corresponding aldehydes all-(Z)-3,6,9,12-pentadecatetraenal and all-(Z)-3,6,9,12,15-octadecapentaenal. Reactions with DBU converted these aldehydes quantitatively into the conjugated isomers (2E,6Z,9Z,12Z)-pentadecatetraenal and (2E,6Z,9Z,12Z,15Z)-octadecapentaenal, respectively. The four aldehydes were transformed by a sequence of reactions comprising reduction to the alcohols, halogenation and substitution with mercapto esters into the corresponding sulfur containing polyunsaturated fatty acid esters. The oxygen containing esters were prepared from the respective alcohol by boron trifluoride catalysed reaction with ethyl diazoacetate.

Enhanced hepatic fatty acid oxidation and upregulated carnitine palmitoyltransferase II gene expression by methyl 3-thiaoctadeca-6,9,12,15-tetraenoate in rats.

This study reports the effects of a novel polyunsaturated 3-thia fatty acid, methyl 3-thiaoctadeca-6,9,12,15-tetraenoate on serum lipids and key enzymes in hepatic fatty acid metabolism compared to a saturated 3-thia fatty acid, tetradecylthioacetic acid. Palmitic acid treated rats served as controls. Fatty acids were administered by gavage in daily doses of 150 mg/kg body weight for 10 days. The aim of the present study was: (a) To investigate the effect of a polyunsaturated 3-thia fatty acid ester, methyl 3-thiaoctadeca-6,9,12,15-tetraenoate on plasma lipids in normolipidemic rats: (b) to verify whether the lipid-lowering effect could be consistent with enhanced fatty acid oxidation: and (c) to study whether decreased activity of esterifying enzymes and diversion to phospholipid synthesis is a concerted mechanism in limiting the availability of free fatty acid as a substrate for hepatic triglyceride formation. Repeated administration of the polyunsaturated 3-thia fatty acid ester for 10 days resulted in a reduction of plasma triglycerides (40%), cholesterol (33%) and phospholipids (20%) compared to controls. Administration of polyunsaturated and saturated 3-thia fatty acids (daily doses of 150 mg/kg body weight) reduced levels of lipids to a similar extent and followed about the same time-course. Both mitochondrial and peroxisomal fatty acid oxidation increased (1.4-fold- and 4.2-fold, respectively) and significantly increased activities of carnitine palmitoyltransferase (CPT) (1.6-fold), 2,4-dienoyl-CoA reductase (1.2-fold) and fatty acyl-CoA oxidase (3.0-fold) were observed in polyunsaturated 3-thia fatty acid treated animals. This was accompanied by increased CPT-II mRNA (1.7-fold). 2,4-dienoyl-CoA reductase mRNA (2.9-fold) and fatty acyl-CoA oxidase mRNA (1.7-fold). Compared to controls, the hepatic triglyceride biosynthesis was retarded as indicated by a decrease in liver triglyceride content (40%). The activities of glycerophosphate acyltransferase, acyl-CoA: 1,2-diacylglycerol acyltransferase and CTP:phosphocholine cytidylyltransferase were increased. The cholesterol lowering effect was accompanied by a reduction in HMG-CoA reductase activity (80%) and acyl-CoA:cholesterol acyltransferase activity (33%). In hepatocytes treated with methyl 3-thiaoctadeca-6,9,12,15-tetraenoate, fatty acid oxidation was increased 1.8-fold compared to controls. The results suggest that treatment with methyl 3-thiaoctadeca-6,9,12,15-tetraenoate reduces plasma triglycerides by a decrease in the availability of fatty acid substrate for triglyceride biosynthesis via enhanced fatty acid oxidation, most likely attributed to the mitochondrial fatty acid oxidation. It is hypothesized that decreased phosphatidate phosphohydrolase activity may be an additive mechanism which contribute whereby 3-thia fatty acids reduce triglyceride formation in the liver. The cholesterol-lowering effect of the polyunsaturated 3-thia fatty acid ester may be due to changes in cholesterol/cholesterol ester synthesis as 60% of this acid was observed in the hepatic cholesterol ester fraction.

Docosahexaenoic acid shows no triglyceride-lowering effects but increases the peroxisomal fatty acid oxidation in liver of rats.

The effect of docosahexaenoic acid (DHA) on mitochondrial and peroxisomal fatty acid oxidation and on key enzymes in triglyceride metabolism was investigated in the liver of rats fed a standard diet, a cholesterol diet, and a pelleted chow diet. Unexpectedly, in all three rat models repeated administration of highly purified DHA (92% pure) at different doses and times, at a dose of 1000 mg/day per kg body weight, resulted in no significant decrease of hepatic and plasma concentration of triglycerides. The serum concentrations of cholesterol and phospholipids showed an increase in a time-dependent manner in rats fed the pelleted chow diet. The hepatic concentration of cholesterol was increased in rats fed the cholesterol diet and pelleted chow diet after administration of DHA compared to palmitic acid. In all rat models, treatment with DHA tended to increase the peroxisomal beta-oxidation. This was accompanied with a significant increase (1.5-fold) of fatty acyl-CoA oxidase activity. The mitochondrial fatty acid oxidation system and carnitine palmitoyl-transferase activity, however, were almost unchanged. Moreover, palmitoyl-CoA synthetase activity was increased, whereas the palmitoyl-CoA hydrolase activity was decreased. Neither microsomal phosphatidate phosphohydrolase activity nor cytosolic phosphatidate phosphohydrolase activity was affected by DHA feeding in the three rat models. Acyl-CoA:1,2-diacylglycerol acyltransferase activity was also unaffected. In contrast to docosahexanoic acid feeding, eicosapentaenoic acid (EPA) administration possessed a hypotriglyceridemic effect and resulted in an increase of mitochondrial and peroxisomal oxidation of fatty acids. Carnitine palmitoyltransferase activity was also stimulated. Phosphatidate phosphohydrolase activity was unaffected whereas diacylglycerol acyltransferase activity was increased by EPA treatment compared with palmitic acid feeding. The results indicate that docosahexaenoic acid, in contrast to eicosapentaenoic acid, does not inhibit the synthesis and secretion of triglycerides in the liver. In addition, the results emphasize the importance that stimulation of peroxisomal beta-oxidation by these n-3 fatty acids is not sufficient to decrease the serum levels of triglycerides. In addition, increased mitochondrial beta-oxidation of fatty acids and thereby decreased availability of nonesterified fatty acids may be a mechanism by which EPA inhibits triglyceride, and subsequently very low density lipoprotein-triglyceride, production. Whether DHA and EPA possess different metabolic properties should be considered.

On the effect of peroxisomal beta-oxidation and carnitine palmitoyltransferase activity by eicosapentaenoic acid in liver and heart from rats.

Repeated administration of highly purified eicosapentaenoic acid (as ethyl ester) resulted in a decrease in plasma triglycerides and high density lipoprotein (HDL) cholesterol. This was accompanied by a stimulation in the activities of carnitine palmitoyltransferase, fatty acyl-CoA oxidase and peroxisomal beta-oxidation in the liver. The results suggest that the triglyceride-lowering effect observed with eicosapentaenoic acid may be due to a reduced supply of fatty acids for hepatic triglyceride synthesis because of increased fatty acid oxidation. Eicosapentaenoic acid feeding marginally affected the triglyceride content of heart and mitochondrial and peroxisomal enzyme activities.

The guinea pig I region. II. Functional analysis.

We have examined whether an association exists between specific Ia antigen genes and Ir genes which are encoded within the same haplotype. Functionally monospecific sera to the Ia antigens of the guinea pig MHC were selective in their ability to inhibit antigen-specific T-cell proliferation and we were thus able to demonstrate an association between individual Ia specificities and specific Ir genes. The results of these studies in inbred animals were confirmed by examining the association of Ir genes and Ia antigens in the outbred guinea pig population. Of great interest was the observation that antisera made against cross-reactive Ia antigens of strains lacking specific Ir genes would still inhibit immune responses of strains possessing the Ir gene, if the Ir gene was associated with that Ia antigen in the responder strain.