In vivo effects of chicken interferon-gamma during infection with Eimeria

Newly hatched chickens are highly susceptible to infection by opportunistic pathogens during the first 1 or 2 weeks of life, The use of cytokines as therapeutic agents has been studied in animal models as well as in immunosuppressed patients, This approach has become more feasible in livestock animals, in particular poultry, with the recent cloning of cytokine genes and the development of new technologies, such as live delivery vectors, We have recently cloned the gene for chicken interferon-gamma (Ch-IFN-gamma), Poly-HIS-tagged recombinant Ch-IFN-gamma was expressed in Escherichia coil, was purified by Ni chromatography, and was found to be stable at 4 degrees C and an ambient temperature for at least several months and Several weeks, respectively, Ch-IFN-gamma was capable of protecting chick fibroblasts from undergoing virus-mediated lysis, induced nitrite secretion from chicken macrophages in vitro, and enhanced MHC class II expression on macrophages, Administration of recombinant Ch-IFN-gamma to chickens resulted in enhanced weight gain over a 12-day period, Furthermore, the therapeutic potential of Ch-IFN-gamma was assessed using a coccidial challenge model, Birds were treated with Ch-IFN-gamma or a diluent control and then infected with Eimeria acervulina. Infected birds treated with Ch-IFN-gamma showed improved weight gain relative to noninfected birds, The ability of Ch-IFN-gamma to enhance weight gain in the face of coccidial infection makes it an excellent candidate as a therapeutic agent.

Effects of oxide promoters on metal dispersion and metal-support interactions in Ni catalysts supported on activated carbon

Various oxide-promoted Ni catalysts supported on activated carbon were prepared, and the effect of promoters on the surface structure and properties of Ni catalysts was studied. Physical adsorption (Na adsorption), thermogravimetric analysis (TGA), temperature-programmed desorption (TPD), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to characterize the catalysts. It is found that nickel is fairly uniformly distributed in the pores of the carbon support. Addition of promoters produces a more homogeneous distribution of nickel ion in carbon. However, distributions of promoters in the pores are varying. Addition of promoters increases the dispersion of nickel in carbon. Promoters also change the interaction between the carbon and Ni, resulting in significantly different behaviors of catalysts under various environments. CaO and MgO promoters improve the reactivity of nickel catalysts with O-2 but retard the interaction between nickel oxide and carbon. La2O3 shows some inhibiting effect on the interactions between nickel oxide and oxygen as well as carbon.

The intrinsic antinociceptive effects of oxycodone appear to be kappa-opioid receptor mediated

Our previous studies in the Sprague-Dawley rat showed that the intrinsic antinociceptive effects of oxycodone are naloxone reversible in a manner analogous to morphine but that in contrast to morphine, oxycodone's antinociceptive effects have a rapid onset of maximum effect (approximate to 5-7 min compared to 30-45 min for morphine), comprise one antinociceptive phase (compared to two phases) and are of relatively short duration (approximate to 90 min compared to approximate to 180 min). In the present study, administration of a range of selective opioid receptor antagonists has shown that the intrinsic antinociceptive effects of oxycodone (171 nmol) are not attenuated by i.c.v. administration of (i) naloxonazine, a mu(1)-selective opioid receptor antagonist, or (ii) naltrindole, a delta-selective opioid receptor antagonist, in doses that completely attenuated the intrinsic antinociceptive effects of equipotent doses of the respective mu- and delta-opioid agonists, morphine and enkephalin-[D-Pen(2,5)] (DPDPE). Although beta-funaltrexamine (beta-FNA) attenuated the antinociceptive effects of oxycodone (171 nmol i.c.v.), it also attenuated the antinociceptive effects of morphine and bremazocine (kappa-opioid agonist) indicative of non-selective antagonism. Importantly, the antinociceptive effects of oxycodone (171 nmol i.c.v.) were markedly attenuated by the prior i.c.v. administration of the selective kappa-opioid receptor antagonist, norbinaltorphimine (nor-BNI), in a dose (0.3 nmol) that did not attenuate the antinociceptive effects of an equipotent dose of i.c.v. morphine (78 nmol). Taken together, these data strongly suggest that the intrinsic antinociceptive effects of oxycodone are mediated by K-opioid receptors, in contrast to morphine which interacts primarily with mu-opioid receptors. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.

Effects of Somatosensory Stimulation on Motor Function After Subacute Stroke

Background. Previous works showed potentially beneficial effects of a single session of peripheral nerve sensory stimulation (PSS) on motor function of a paretic hand in patients with subacute and chronic stroke. Objective. To investigate the influence of the use of different stimulus intensities over multiple sessions (repetitive PSS [RPSS]) paired with motor training. Methods. To address this question, 22 patients were randomized within the second month after a single hemispheric stroke in a parallel design to application of 2-hour RPSS at 1 of 2 stimulus intensities immediately preceding motor training, 3 times a week, for 1 month. Jebsen-Taylor test (JTT, primary endpoint measure), pinch force, Functional Independence Measure (FIM), and corticomotor excitability to transcranial magnetic stimulation were measured before and after the end of the treatment month. JTT, FIM scores, and pinch force were reevaluated 2 to 3 months after the end of the treatment. Results. Baseline motor function tests were comparable across the 2 RPSS intensity groups. JTT improved significantly in the lower intensity RPSS group but not in the higher intensity RPSS group at month 1. This difference between the 2 groups reduced by months 2 to 3. Conclusions. These results indicate that multiple sessions of RPSS could facilitate training effects on motor function after subacute stroke depending on the intensity of stimulation. It is proposed that careful dose-response studies are needed to optimize parameters of RPSS stimulation before designing costly, larger, double-blind, multicenter clinical trials.

Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia

We assessed for the first time the long-term maintenance of repetitive transcranial magnetic stimulation (rTMS)-induced analgesia in patients with chronic widespread pain due to fibromyalgia. Forty consecutive patients were randomly assigned, in a double-blind fashion, to 2 groups: one receiving active rTMS (n = 20) and the other, sham stimulation (n = 20), applied to the left primary motor cortex. The stimulation protocol consisted of 14 sessions: an ""induction phase"" of 5 daily sessions followed by a ""maintenance phase"" of 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions a month apart. The primary outcome was average pain intensity over the last 24 hours, measured before each stimulation from day 1 to week 21 and at week 25 (1 month after the last stimulation). Other outcomes measured included quality of life, mood and anxiety, and several parameters of motor cortical excitability. Thirty patients completed the study (14 in the sham stimulation group and 16 in the active stimulation group). Active rTMS significantly reduced pain intensity from day 5 to week 25. These analgesic effects were associated with a long-term improvement in items related to quality of life (including fatigue, morning tiredness, general activity, walking, and sleep) and were directly correlated with changes in intracortical inhibition. In conclusion, these results suggest that TMS may be a valuable and safe new therapeutic option in patients with fibromyalgia. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Neuropeptide Y in Rat Spiral Ganglion Neurons and Inner Hair Cells of Organ of Corti and Effects of a Nontraumatic Acoustic Stimulation

Neuropeptide Y (NPY) is an important neuromodulator found in central and peripheral neurons. NPY was investigated in the peripheral auditory pathway of conventional housed rats and after nontraumatic sound stimulation in order to localize the molecule and also to describe its response to sound stimulus. Rats from the stimulation experiment were housed in monitored sound-proofed rooms. Stimulated animals received sound stimuli (pure tone bursts of 8 kHz, 50 ms duration presented at a rate of 2 per second) at an intensity of 80 dB sound pressure level for 1 hr per day during 7 days. After euthanizing, rat cochleae were processed for one-color immunohistochemistry. The NPY immunoreactivity was detected in inner hair cells (IHC) and also in pillar and Deiters` cells of organ of Corti, and in the spiral ganglion putative type I (1,009 m3) and type II (225 m3) neurons. Outer hair cells (OHC) showed light immunoreaction product. Quantitative microdensitometry showed strong and moderate immunoreactions in IHC and spiral ganglion neurons, respectively, without differences among cochlear turns. One week of acoustic stimulation was not able to induce changes in the NPY immunoreactivity intensity in the IHC of cochlea. However, stimulated rats showed an overall increase in the number of putative type I and type II NPY immunoreactive spiral ganglion neurons with strong, moderate, and weak immunolabeling. Localization and responses of NPY to acoustic stimulus suggest an involvement of the neuropeptide in the neuromodulation of afferent transmission in the rat peripheral auditory pathway.

Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study

Objective: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17 beta estradiol. Methods: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the a angle), clot tensile strength (MA and G), global index of coagulation (Cl) and fibrinolysis (LY30) and fibrinogen levels. Results: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. Conclusions: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in FIT women.

Effects of metoclopramide-induced hyperprolactinemia on the prolactin receptor of murine endometrium

Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia, on the prolactin receptor of murine endometrium. Design: Experimental study using the RNA extraction to detect tissue prolactin recepter isoforms by reverse-transcriptase polymerase chain reaction (RT-PCR). Setting: University-based laboratory. Animal(s): Seventy-two female swiss albino mice (Mus musculus), approximately 100 days old, were divided into six 12-animal groups: (Cl) nonoophorectomized mice given vehicle; (GII) nonoophorectomized mice treated with metoclopramide; (Gill) oophorectomized mice treated with metoclopramide; (GIV)oophorectomized mice treated with metoclopramide and 17 beta-estradiol; (GV) oophorectomized mice treated with metoclopramide and micronized progesterone; (GVI) oophorectomized mice treated with metoclopramide and a solution of 17 beta-estradiol and micronized progesterone. Intervention(s): Drugs were administered for 50 days. Following euthanasia, the middle portions of the uterine horns were removed, sectioned, and immediately frozen for RT-PCR procedures. Blood was collected for the dosage of prolactin and serum estrogen and progesterone using radioimmune assay. Main Outcome Measure(s): Identification of uterine prolactin receptor isoforms: Result(s): The PRL receptor and its isoform L were identified only in GI (control group) and GII (metoclopramide), the two groups with nonoophorectomized animals. The amount of PRL receptor mRNA and that of its isoform L from GII were the largest. No other isoforms of the prolactin receptor were identified in any of the groups. Conclusion(s): Our results suggest that replacement of estrogen and progestin may not increase the mRNA of endometrial PRL receptor in metoclopromide-induced hyperprolactinemia in rats after castration. (Fertil Steril (R) 2010;93:1643-9. (C)2010 by American Society for Reproductive Medicine.)

The effects of topical isoflavones on postmenopausal skin: Double-blind and randomized clinical trial of efficacy

Objective: The aim of this study was to evaluate the effects of estrogen and isoflavones on postmenopausal skin morphological parameters. Study design: A randomized, double-blind, estrogen-controlled trial was performed on postmenopausal women treated in the Gynecology Department of the Federal University of Sao Paulo. This study was designed to analyze the effects of topical administration of estradiol and isoflavones on facial skin for 24 weeks. The participants were divided into two groups: G1-17-betaestradiol 0.01% (n = 18) and G2-isoflavones 40% (genistein 4%, n = 18). Skin biopsies were performed on each patient before and after the treatment. The skin samples were processed for histological analysis, stained with haematoxylin and eosin, and examined using light microscopy. Results: After 24 weeks of treatment, the estradiol group had a significant increase in skin parameters analyzed compared to the isoflavone group and to the baseline measurements: epidermal thickness (a 75% increase in the estrogen group and 20% in the isoflavone group), number of dermal papillae (a rise of 125% with estrogen, no significant gain with isoflavones), fibroblasts (a 123% accretion with estradiol, no significant gain with isoflavones), and vessels (a 77% increase with estrogen and 36% with isoflavones). Conclusion: Our data suggest that estrogens may have a stronger effect on histomorphometrical parameters than isoflavones. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Estrogen effects on pilocarpine-induced temporal lobe epilepsy in rats

Objetive: To evaluate the effects of conjugated equine estrogens (CEE) on the pilocarpine-induced epilepsy in rats. Study design: 40 female rats were divided into: GPC (positive control) presented ""status epilepticus"" (SE) induced by pilocarpine; GOC(ovariectomized control) only castrated; GNC (negative control) received only saline solution; GPE received pilocarpine, presented SE, castrated and received 50 mu g/kg CEE treatment; GPV received pilocarpine, castrated and received propylene glycol (vehicle). The animals were monitored by a video system. At the end of observation, the brains removed for later histologic analysis using Neo-Timm and Nissl methods. Results: The GPE presented a reduction in number of seizures compared to GPV. The Neo-Timm analysis showed that GPV had greater sprouting of mossy fibers, with a denser band in the area of the dentate gyrus hilum compared to GPE. On Nissl staining, GPE showed evident neuronal loss in the CA3 area. GPV presented loss in CA1 and dentate gyrus. Conclusion: Estrogen may have a protecting effect on the central nervous system. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Effects of melatonin on the endometrial morphology and embryo implantation in rats

Objective: To determine the effects of melatonin on rat endometrium morphology and embryo implantation. Design: Experimental study. Setting: Federal University of Sao Paulo, Brazil. Animal(s): Forty female rats. Intervention(s): GI: control, GII: sham-operated, GIII: pinealectomized, and GIV: pinealectomized rats that received melatonin during 3 months. The GI, GII, and Gin groups received the vehicle of melatonin (NaCl + ethanol). At the end of the treatment, the animals were killed during the estrous phase; the uterus was removed for morphometric analysis. Urine was collected for 6-sulfatoxymelatonin. Blood was collected for estrogen (E) and progesterone (P) level determinations. In a second experiment, female rats were used to evaluate the endometrial embryo implantation. Main Outcome Measure(s): Endometrial morphology and embryo implantation. Result(s): Gin presented the highest values for endometrial area and thickness index, number of endometrial glands, and eosinophils. The number of vessels of groups I, II, and IV was fewer than that of Gin. The highest number of eosinophils was detected in Gin in comparison to other groups. The implantation rate in Gin was the lowest of all groups. This implantation rate was significantly increased and restored toward normal in GIV. Conclusion(s): Our data suggested that, in nonphotoperiodic animals such as rats, melatonin may positively affect the endometrial morphology and improve embryo implantation.

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow

Objectives: To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy. Methods: A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2 mg oral micronized estradiol (E(2)) (n = 25); (B) 2 mg oral E(2) + 1 mg oral norethisterone acetate (NETA) (n = 28); or Q placebo (n = 24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography. Results: Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E(2), E(2) + NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E(2), E(2) + NETA and placebo groups, respectively (p < 0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E2 group and increased 12.9% and 16.0% in the E(2) + NETA group (p < 0.05), respectively. Carotid PI following treatment was 1.18 +/- 0.23, 1.38 +/- 0.20 and 1.41 +/- 0.21 for the E(2), E(2) + NETA and placebo groups, respectively (p = 0.0006). Conclusions: Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Ultrastructural evaluation of gingival glycosaminoglycans in ovariectomized rats: Effects of steroid hormone therapy

Background/Aims: To evaluate the behavior of glycosaminoglycans (GAGs) in rat gingiva and the effects of lack of sexual steroids and the hormonal therapy with estrogen and dexamethasone (DEX). Methods: 40 female rats were divided into four groups: GI: animals in permanent estrus; GII: ovariectomized (OVX) animals + vehicle; GIII: OVX animals treated with 17 beta-estradiol benzoate (10 mu g/kg), and GIV: OVX animals treated with 17 beta-estradiol benzoate (10 mu g/kg) + DEX (3 mg/kg). After treatment, the gingiva was removed and its GAGs content was evaluated by electronic microscopy after stained by cuprolinic blue technique. Results: The electron-microscopic data showed that low values of chondroitin sulfate were found in castrated animals (35.05 +/- 3.58%) compared to other groups (GI: 41.17 +/- 1.13; GIII: 48.04 +/- 2.60; GIV: 49.09 +/- 2.68%). In contrast, the amount of dermatan sulfate in GII (57.70 +/- 2.50%) was higher than in the other groups (GI: 46.12 +/- 1.30; GIII: 42.65 +/- 2.98; GIV: 42.68 +/- 5.43%). Conclusions: GAGs may be influenced by estradiol, and DEX did not seem to antagonize the role of estradiol in the GAGs of gingiva. The histotypical structure of gingiva is related to the amount of chondroitin sulfate. Consequently, the estrogen therapy may be important for gingival health. Copyright (C) 2007 S. Karger AG, Basel.

The effects of cinnarizine on menopausal symptoms in women

Objective To evaluate the effectiveness and safety of cinnarizine in the treatment of menopausal symptoms. Design A total of 100 climacteric and symptomatic women participated in a double-blind, placebo-controlled study. They were divided into two groups of the same size: Gcin, intake of 25 mg of cinnarizine every 12 h for 6 months (n = 50); and Gpla, placebo intake every 12 hours for 6 months (n = 50). Menopausal symptoms were evaluated according to the Kupperman menopausal index on the first visit and at 6 months of treatment. A total of 62 women completed the study: 27 from the Gcin group and 35 from the Gpla group. Results Based on the Kupperman menopausal index, there were no statistically significant differences between the two groups before and after the treatment. Conclusion Our data suggest cinnarizine is not effective on menopausal symptoms because it had no more efficacy than placebo.