Factors associated with uterine functions in the mare

Delayed uterine clearance is the most common cause of subfertility in the mare. Previous studies have shown that mares that accumulate intrauterine fluid have impaired myometrial activity. Uterine contractility is a complex mechanism controlled by coordination of myogenic, neurogenic and hormonal factors. Despite the importance of the nervous system in controlling uterine contractility, there have been no studies on uterine innervation in the mare. Furthermore, there have been no detailed information on oxytocin release in mares during oestrus, the time when the uterus is challenged by breeding. The aims of this study were to investigate the factors which are associated with uterine contractility in mares. This study was designed to describe uterine innervation, to identify the presence and location of oxytocin in the equine endometrium, and to measure circulating concentrations of oxytocin around oestrus and after ovulation. The uterus of the mare was well supplied by a variety of nerve fibres. Using general neuronal marker, PAN-N and PGP 9.5, it showed a general view of equine uterine innervation. Within the regions of the uterus, nerve density score for both PGP-immunoreactive (IR) and PAN-N-IR was greatest in the myometrium. There were no marked differences between the supply to uterine horn or body, but nerve density was significantly greater (P<0.05) in the cervix. The nerve supply was predominantly adrenergic and was distributed throughout all regions of the uterus. With adrenergic nerves, the density score was the greatest in the myometrium within the structure and in the cervix within the regions. Peptidergic nerves were also seen and were slightly denser in the cervix than in the uterine horn or uterine body. Among the peptidergic nerves, neuropeptide Y was the most abundant, whereas vasoactive intestinal polypeptide and calcitonin gene-related peptide were less frequent. Substance P was rarely observed. The presence of oxytocin and neurophysin in the uterus was demonstrated using immunohistochemistry. Ultrastructural studies showed that these hormones were stored in the secretory vesicles of the luminal secretory cells and the secretory cells in the superficial endometrial glands. Ciliated cells in the luminal epithelium and endometrial glands did not show any positive staining for either oxytocin or neurophysin. Mean plasma oxytocin concentrations in genitally-normal mares (n=5) were significantly higher (P<0.02) in oestrus (day -5 to day -2) than the day of ovulation (day 0). On the day 1 post ovulation, mean plasma oxytocin concentrations were the lowest level. Plasma oxytocin concentrations in day 2 oestrus were significantly higher (P<0.01) in genitally-normal mares (n=5) than in mares with delayed uterine clearance (n=5). This study has provided fundamental information on factors associated with uterine contractile function. This information will be used in further studies to investigate mares with dysfunction in uterine contractility. Uterine innervation is a main key function to regulate myometrial contractility and is coordinated by hormones such as sex steroid hormones, oxytocin and PGF₂α- Studies are now needed to investigate further differences in uterine innervation, the distribution of α and ß adrenergic receptors, uterine oxytocin and oxytocin receptors in mares between genitally-normal mares and mares with delayed uterine clearance

Crude Extracts of Caenorhabditis elegans Suppress Airway Inflammation in a Murine Model of Allergic Asthma

Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses

Synthesis of Gold Nanoparticle with Aqueous Carbon Nano Colloid under Ultrasonication and Self-Assembled Carbon-Gold Nanoparticle Multilayer Films

The preparation of gold nanoparticle showed in carbon nano colloid under ultrasonic irradiation. The products of gold nanoparticle were well dispersed in carbon nano colloid investigated by UV-vis., SEM, TEM, EDX, and XRD spectra. Carbon nano colloid – gold nanoparticle films were self-assembled on the reactive surface of glass slides functionalized with 3-aminopropyltrimethoxysilane. Also, the self-assembled nanoparticle films were characterized using UV-vis. spectra

Antifungal and antiaflatoxigenic methylenedioxy-containing compounds and piperine-like synthetic compounds

Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure-activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 mu g/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 mu g/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes.ope

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

BackgroundGlucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.MethodsReverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.ResultsCoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.ConclusionOur data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored

A Functional Polymorphism on Chromosome 15q25 Associated with Survival of Early Stage Non–Small-Cell Lung Cancer

Introduction:The 15q25 region has been associated with lung-cancer risk and might also be associated with the prognosis of lung cancer. This study was conducted to determine the impact of a functional polymorphism in the CHRNA3 gene on chromosome 15q25 in the survival of patients with early-stage non–small-cell lung cancer (NSCLC).Methods:Five hundred and eighty-three consecutive patients with surgically resected NSCLC were enrolled. The rs6495309C > T polymorphism in the promoter of the CHRNA3 gene was investigated. The association between genotype and overall survival (OS) and disease-free survival (DFS) was analyzed.Results:Patients with the rs6495309 CT or TT genotype had a significantly better OS and DFS than the rs6495309 CC genotype (adjusted hazard ratio for OS = 0.56, 95% confidence interval = 0.41–0.75, p = 0.0001; and adjusted hazard ratio for DFS = 0.61, 95% confidence interval = 0.48–0.79, p = 0.0001). An association between the rs6495309C > T polymorphism and survival outcome was demonstrated in smokers and never-smokers, and in squamous-cell carcinomas and adenocarcinomas.Conclusion:The CHRNA3 rs6495309C > T polymorphism may affect survival in patients with early-stage NSCLC. Analysis of the rs6495309C > T polymorphism can help identify patients at high risk of a poor disease outcome

Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration.</p> <p>Methods</p> <p>We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored.</p> <p>Results</p> <p>The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004); fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p < 0.001, p < 0.001, respectively). When data analysis was refined by dividing each group into high-baseline and low-baseline subgroups, it was observed that fatigue was reduced in the lower baseline vitamin C level group after two hours and after one day (p = 0.004). The same did not hold for the higher baseline group (p = 0.206).</p> <p>Conclusion</p> <p>Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study.</p> <p>Trial Registration</p> <p>The clinical trial registration of this trial is <url>http://ClinicalTrials.gov</url><a href="http://www.clinicaltrials.gov/ct2/show/NCT00633581">NCT00633581</a>.</p

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity