Anxiety-induced antinociception in mice: effects of systemic and intra-amygdala administration of 8-OH-DPAT and midazolam

Rationale: Mice exhibit antinociception after a single experience in the elevated plus maze (EPM), an animal model of anxiety. Objective: This study investigated the mechanisms involved in this form of anxiety-induced antinociception. Methods: Nociception was evaluated by means of the writhing test in mice confined either to the open or enclosed arms of the EPM. The effects of systemic (naloxone, midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT. NAN-190 and midazolam) drug infusions were investigated in mice previously treated i.p. with 0.6% acetic acid, an algic stimulus that induces abdominal contortions. The effects of these drugs on conventional measures of anxiety (% entries and % time in open arms) in a standard EPM test were also independently investigated. Results: Open-arm confinement resulted in a high-magnitude antinociception (minimum 85%, maximum 450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1 mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA) nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg, s.c.) increased OAIA and produced antinociception in enclosed confined animals, as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response at the lowest dose and intensifying it at the highest dose. In addition, low doses of this agent reduced anxiety in the EPM. Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 mu l) or NAN-190 (5.6 nmol and 10 nmol/0.4 mu l) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4 mu l) blocked both OAIA and anxiety. Conclusions: These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are recruited during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.

Chromosome polymorphism of heterochromatin and nucleolar regions in two populations of the fish Astyanax bockmanni (Teleostei: Characiformes)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gender and Health Status Response to Long-Term Oxygen Therapy in COPD Patients

Introduction: The association of gender with health status (HS) response to long-term oxygen therapy (LTOT) in very severe COPD is unclear. The aims of this study were: (1) to compare dyspnea perception and HS between male and female with very severe COPD at baseline and (2) to provide a prospective assessment of HS response to LTOT, according to gender.Patients and methods: Hypoxemic COPD (n =97, age: 65.5 +/- 9.6 years, 53% males) were enrolled in a prospective longitudinal study over 12 months or until death. St. George's Respiratory Questionnaire (SGRQ) and baseline dyspnea index (BDI) were assessed.Results: At baseline, HS impairment and dyspnea sensation were similar between genders. After 12 months of LTOT, women presented improvement in symptom (64.1 +/- 120.6 versus 40.6 +/- 122.9; P < 0.0001) and total SGRQ scores. Men also showed improvement in symptoms after 12 months (62.7 +/- 23.3 versus 49.6 +/- 22.8; P < 0.0005); however, they presented deterioration of activity, impact and total scores during the study period, with markedly decline of activity domain (68.5 +/- 20.0 versus 75.9 +/- 16.9; P = 0.008). BDI did not show significant difference by gender over the study period.Conclusions: Our results show that the HS course in very severe COPD patients differs according to gender, as females show greater response longitudinally to LTOT. (C) 2010 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

Long-term effects of insulin therapy, islet transplantation, and pancreas transplantation in the prevention of glomerular changes in kidneys of alloxan-induced diabetic rats

Groups of inbred alloxan-induced diabetic rats were treated with insulin (I), islets (IT), or pancreas transplantation (PT). Nondiabetic (N) and untreated diabetic (D) control groups were concurrently included. Each group was divided into five subgroups of 10 rats and killed after follow-up of 1, 3, 6, 9, and 12 months. Clinical and laboratory parameters were recorded, and kidney ultrastructural and morphometric analyses performed in each 12-month subgroup, namely glomerular basement membrane (GM) thickening, podocyte number, and number/extension of slit diaphragms (S). Rats from the I group showed poor metabolic control of diabetes compared with N group control rats. However, successfully transplanted rats (IT and PT) had complete restoration to normal levels for all metabolic parameters. GM thickening was significantly higher in diabetic compared with control rats. In contrast, the numbers of podocytes and slits as well as slit extensions were significantly decreased. Insulin therapy did not prevent any alterations upon comparison of diabetic vs control rats. Despite good metabolic control in IT rats, the degree of kidney lesion control never compared with that achieved in PT rats. In this group all glomerular changes were similar to the age-dependent lesions observed in control rats. We conclude that either IT or PT may be a good option for diabetes treatment, although pancreas transplantation seems to be the most effective treatment to control chronic complications.

Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis

Objective: In an attempt to clarify the clonality and genetic relationships that are involved in the tumorigenesis of uterine leiomyomas, we used a total of 43 multiple leiomyomas from 14 patients and analyzed the allelic status with 15 microsatellite markers and X chromosome inactivation analysis.Study design: We have used a set of 15 microsatellite polymorphism markers mapped on 3q, 7p, 11, and 15q by automated analysis. The X chromosome inactivation was evaluated by the methylation status of the X-linked androgen receptor gene.Results: Loss of heterozygosity analysis showed a different pattern in 7 of the 8 cases with allelic loss for at least 1 of 15 microsatellite markers that were analyzed. A similar loss of heterozygosity findings at 7p22-15 was detected in 3 samples from the same patient. X chromosome inactivation analysis demonstrated the same inactivated allele in all tumors of the 9 of 12 informative patients;. different inactivation patterns were observed in 3 cases.Conclusion: Our data support the concept that uterine leiomyomas are derived from a single cell but are generated independently in the uterus. Loss of heterozygosity findings at 7p22-15 are consistent with previous data that suggested the relevance of chromosomal aberrations at 7p that were involved in individual uterine leiomyomas. (C) 2005 Mosby, Inc. All rights reserved.

Comparison of decompressive surgery, electroacupuncture, and decompressive surgery followed by electroacupuncture for the treatment of dogs with intervertebral disk disease with long-standing severe neurologic deficits

Objective To compare the effects of decompressive surgery (DSX), electroacupuncture (EAP), and DSX followed by EAP (DSX + EAP) for the treatment of thoracolumbar intervertebral disk disease (IVDD) in dogs with severe neurologic deficits of > 48 hours' duration.Design Retrospective case series and prospective clinical trial.Animals-40 dogs between 3 and 6 yEAPs old and weighing between 10 and 20 kg (22 and 44 lb) with long-standing (>48 hours) clinical signs of severe neurologic disease attributable to thoracolumbar IVDD.Procedures Thoracolumbar medullar injury was classified on the basis of neurologic signs by use of a scale ranging from 1 (least severe) to 5 (most severe). The DSX dogs (n = 10) were retrospectively selected from those that underwent DSX for the treatment of thoracolumbar IVDD. In addition, 19 dogs received EAP alone and 11 dogs underwent DSX followed by EAP (DSX + EAP). Outcome was considered a clinical success when a dog initially classified as grade 4 or 5 was classified as grade 1 or 2 within 6 months after the end of treatment.Results The proportion of dogs with clinical success was significantly higher for dogs that underwent EAP (15/19) than for dogs that underwent DSX (4/10); the proportion of dogs with clinical success for dogs that underwent DSX + EAP was intermediate (8/11).Conclusions and Clinical Relevance EAP was more effective than DSX for recovery of ambulation and improvement in neurologic deficits in dogs with long-standing severe deficits attributable to thoracolumbar IVDD. (J Am Vet Med Assoc 2010;236:1225-1229)

Selection of X chromosome of buffaloes sperm with Percoll gradients

The aim of the present study was to evaluate the selection of X chromosome of buffaloes sperm with Percoll gradients. The stock solution of Percoll was prepared in the proportion of 1:11 (1 part of Percoll:11 parts of a solution containing KCl 1M, NaH(2)PO(4) 0.1M, NaCl 1.5M and sodium HEPES 23.8 g/ml). In order to prepare 9 different gradients were added to the stocked Percoll the A solution (glicine-yolk extender) in the following proportions: 90, 80, 72, 65, 57, 49, 34 and 25%. A sample of 0.7 ml of the fresh semen was deposited at 2 ml of Percoll 80% for the sperm wash. The precipitate was put in tube with 0.7 ml of each gradient. Then, the precipitated was washed in TES solution by centrifugation (500xg for 10 minutes), and collected again and diluted in TES solution to be freeze. The presence of the F body in the spermatozoa was observed in 58.7 +/- 5.4% of the control group and in 41.2 +/- 5.4% of the treated group (p<0.01). This result showed an increment of 17.55 of male sperm in the Percoll's group. The reduction of the centrifugation force did not improve the percentage of X sperm.

Myostatin (GDF8) single nucleotide polymorphisms in Nellore cattle

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Long-term treatment with alendronate increases the surgical difficulty during simple exodontias - an in vivo observation in Holtzman rats

Background: Atraumatic teeth extractions protocols are highly encouraged in patients taking bisphosphonates (Bps) to reduce surgical trauma and, consequently, the risk of jaws osteonecrosis development. In this way, this paper aims to report the findings of increased surgical difficulty during simple exodontias in animals treated with bisphosphonates.Methods: Sixty male Holtzman rats were randomly distributed into three groups of 20 animals and received daily subcutaneous administration of 1 mg/kg (AL1) or 3 mg/kg (AL3) of alendronate or saline solution (CTL). After 60 days of drug therapy all animals were submitted to first lower molars extractions under general anesthesia. Operatory surgical time and the frequency of teeth fractures were measured as principal outcomes and indicators of surgical difficulty degree.Results: Animals treated with alendronate (AL1 and AL3) were associated to higher operatory times and increased frequency of teeth fractures compared to match controls.Conclusions: The bisphosphonate therapy may be associated with an increased surgical difficulty and trauma following simple exodontias protocols, which is considered a critical issue when it comes to osteonecrosis development.

Hardness of heat-polymerized acrylic resins after disinfection and long-term water immersion

Statement of the problem. In selecting a disinfectant for dental prostheses, compatibility between the disinfectant and the type of denture base material must be considered to avoid adverse effects on the hardness of the acrylic resin.Purpose. This study investigated the hardness of 2 denture base resins after disinfection and long-term water immersion.Material and methods. Thirty-two disk-shaped specimens (13 mm in diameter and 8 mm thick) were fabricated from each resin (Lucitone 550 and QC-20), polished, stored in water at 37degreesC for 48 hours, and submitted to hardness tests (Vickers hardness number [VHN]) before disinfection. Disinfection methods included scrubbing with 4% chlorhexidine gluconate for 1 minute, immersion for 10 minutes in I of the tested disinfectant Solutions (n=8) (3.78% sodium perborate, 4% chlorhexidine gluconate, or 1% sodium hypochorite), and immersion in water for 3 minutes. The disinfection procedures were repeated 4 times, and 12 hardness measurements were made on each specimen. Control specimens (not disinfected) were stored in water for 56 minutes. Hardness tests (VHN) were also performed after 15, 30, 60, 90, and 120 days of storage in water. Statistical analyses of data were conducted with a repeated measures 3-way analysis of variance (ANOVA) and Tukey post-hoc test (alpha=.05).Results. Mean values +/- SD for Lucitone 550 (16.52 +/- 0.94 VHN) and QC-20 (9.61 +/- 0.62 VHN) demonstrated a significant (P<.05) decrease in hardness after disinfection, regardless of material and disinfectant solutions used (Lucitone 550: 15.25 +/- 0.74; QC-20: 8.09 +/- 0.39). However, this effect was reversed after 15 days of storage in water. Both materials exhibited a continuous increase (P<.05) in hardness values for up to 60 days of water storage, after which no significant change was observed.Conclusion. Within the limitations of this in vitro study, QC-20 and Lucitone 550 specimens exhibited significantly lower hardness values after disinfection regardless of the disinfectant solution used.

Effect of long-term water immersion on the fracture toughness of denture base and reline resins

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Long-Term Exogenous Melatonin Treatment Modulates Overall Feed Efficiency and Protects Ovarian Tissue Against Injuries Caused by Ethanol-Induced Oxidative Stress in Adult UChB Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

B lineage acute lymphoblastic leukemia transformation in a child with juvenile myelomonocytic leukemia, type 1 neurofibromatosis and monosomy of chromosome 7 - Possible implications in the leukemogenesis

This report describes the case of an 8-month-old infant with a diagnosis of juvenile myelomonocytic leukemia (JMML) and type I neurofibromatosis that presented progression to B lineage acute lymphoid leukemia (ALL). The same rearrangement of gene T-cell receptor gamma (TCRgamma) was detected upon diagnosis of JMML and ALL, suggesting that both neoplasias may have evolved from the same clone. Our results support the theory that JMML may derive from pluripotential cells and that the occurrence of monosomy of chromosome 7 within a clone of cells having an aberrant neurofibromatosis type 1 (NFI) gene may be the cause of JMML and acute leukemia. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

X-chromosome inactivation patterns in monozygotic twins and sib pairs discordant for nonsyndromic cleft lip and/or palate

Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X chromosome inactivation (XCI) in orofacial clefts. Our samples consisted of female monozygotic (MZ) twins (n = 8) and sister pairs (n = 152) discordant for nonsyndromic clefting. We measured the XCI pattern in peripheral blood lymphocyte DNA using a methylation based androgen receptor gene assay. Skewing of XCI was defined as the deviation in inactivation pattern from a 50:50 ratio. Our analysis revealed no significant difference in the degree of skewing between twin pairs (P = 0.3). However, borderline significant differences were observed in the sister pairs (P = 0.02), with the cleft lip with cleft palate group showing the most significant result (P=0.01). We did not find evidence for involvement of skewed XCI in the discordance for clefting in our sample of female MZ twins. However, results from the paired sister study suggest the potential contribution of skewed XCI to orofacial clefting, particularly cleft lip and palate. (C) 2007 Wiley-Liss, Inc.