A randomized double-blind placebo-controlled trial to increase feasibility of dobutamine stress echocardiography in patients with hypertension

Objective: To increase dobutamine stress echocardiography feasibility in patients with uncontrolled hypertension, we studied 729 consecutive patients referred for ischemia assessment. Methods: Patients with blood pressure ( BP) levels above 160/ 110 mm Hg were randomized to sublingual placebo or captopril ( 25 mg), and dobutamine stress echocardiography undertaken if BP decreased below 160/ 110 mm Hg after 15 minutes. Results: Of 149 patients ( 20%) with high BP levels, 104 ( 63 +/- 11 years, 51 male) were randomized. Baseline BP levels were similar for captopril ( 178 +/- 15/ 103 +/- 15 mm Hg) and placebo ( 181 +/- 17/ 103 +/- 15 mm Hg) groups. After intervention, 15 patients from captopril and 17 from placebo group had decreased BP ( 11% and 12% for systolic and 13% and 13% for diastolic BP, respectively). Five patients from placebo group ( P =.007) had to prematurely terminate the test because of hypertension ( BP > 220/ 120 mm Hg). Feasibility was similar for captopril and placebo groups ( 35% vs 25%, respectively, P = not significant). Conclusion: Although both captopril and placebo are effective in increasing dobutamine stress echocardiography feasibility in patients with uncontrolled BP, test interruption because of hypertension is less likely to occur after captopril administration.

Age-related increase of reactive oxygen species in neat semen in healthy fertile men

OBJECTIVES The effects of advancing paternal age on the male reproductive system are well known, but its effects on fecundity remain controversial. Although oxidative stress is associated with poor semen quality and function, a relationship with advancing male age has not been established. The objective of this study was to analyze the relationship between male age and seminal reactive oxygen species (ROS) levels in men presenting for voluntary sterilization. METHODS We prospectively evaluated 98 fertile men who were candidates for vasectomy. These were divided into 2 age groups: less than 40 years (n = 78) and 40 or more years (n = 20). We used 46 infertile patients as positive controls. Standard semen analysis, seminal leukocyte count and ROS levels were measured in all samples. Fertile men with leukocytospermia were excluded. RESULTS The mean age of the men was 35.1 +/- 5.6 years. Men 40 years and older had significantly higher ROS levels compared with younger men (P < 0.001). We observed a positive correlation between seminal ROS levels and age (r = 0.20; P = 0.040). In addition, ROS was negatively correlated with sperm concentration (r = -0-48; P < 0.001) and motility (r = -0.21; P = 0.030). CONCLUSIONS Reactive oxygen species levels are significant higher in seminal ejaculates of healthy fertile men older than 40 years. ROS levels in whole ejaculate are significantly correlated to age among fertile men. Because ROS are clearly implicated in the pathogenesis of male infertility, these data suggest that delayed fatherhood may reduce the chances of pregnancy as men become progressively less fertile with age.

THERAPEUTIC ULTRASOUND DID NOT INCREASE THE MECHANICAL PROPERTIES OF FLEXOR TENDONS AFTER THEIR REPAIR

Objective: Experimental study idealized to investigate the mechanical properties of deep flexor tendons of rabbits that underwent the tenotomy followed by tenorrhaphy and early application of therapeutic ultrasound with different intensities, in comparison to tendons submitted to tenorrhaphy only. Material and Method: Forty-four rabbits were divided into four experimental groups according to the ultrasound application. They were all submitted to a section of deep flexor tendon in zone 2 and immobilized with an orthosis maintained throughout the experiment. Group A received ultrasonic treatment with an intensity of 1.4 W/cm(2), group B with 0.6 W/cm(2), both in continuous mode, group C with 0.6 W/cm(2) SATA, in pulsated mode at 50% and group D did not receive any ultrasonic treatment. The ultrasonic frequency employed was 1 MHz. After euthanasia, the tendons were dissected and submitted to the mechanical test of traction and qualitative histological analysis. The evaluated mechanical properties were: maximum force, deformation in maximum force and stiffness. Results: There were no statistically significant differences among the experimental groups. Conclusion: Therapeutic ultrasound did not improve the mechanical properties of the flexor tendons after repair.

Electrical Stimulation During Gait Promotes Increase of Muscle Cross-sectional Area in Quadriplegics: A Preliminary Study

Increases in muscular cross-sectional area (CSA) occur in quadriplegics after training, but the effects of neuromuscular electrical stimulation (NMES) along with training are unknown. Thus, we addressed two questions: (1) Does NMES during treadmill gait training increase the quadriceps CSA in complete quadriplegics?; and (2) Is treadmill gait training alone enough to observe an increase in CSA? Fifteen quadriplegics were divided into gait (n = 8) and control (n = 7) groups. The gait group performed training with NMES for 6 months twice a week for 20 minutes each time. After 6 months of traditional therapy, the control group received the same gait training protocol but without NMES for an additional 6 months. Axial images of the thigh were acquired at the beginning of the study, at 6 months (for both groups), and at 12 months for the control group to determine the average quadriceps CSA. After 6 months, there was an increase of CSA in the gait group (from 49.8 +/- A 9.4 cm(2) to 57.3 +/- A 10.3 cm(2)), but not in the control group (from 43.6 +/- A 7.6 cm(2) to 41.8 +/- A 8.4 cm(2)). After another 6 months of gait without NMES in the control group, the CSA did not change (from 41.8 +/- A 8.4 cm(2) to 41.7 +/- A 7.9 cm(2)). The increase in quadriceps CSA after gait training in patients with chronic complete quadriplegia appears associated with NMES.

Benefits of sunlight: Vitamin D deficiency might increase the risk of sudden unexpected death in epilepsy

Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. In parallel, studies have shown a link between vitamin D dysfunction and epilepsy. Moreover, several evidences in the literature suggest an association between low vitamin D and seizures, indicating the possibility of anticonvulsant properties of this hormone. Quite interesting, a growing body of data suggests that low vitamin D levels may adversely affect cardiovascular health, directly associated with death from heart failure and sudden cardiac death. In view of the above findings, our research group focused in this review article that SUDEP, at least in some cases, could be related with low vitamin D levels. (C) 2009 Elsevier Ltd. All rights reserved.

Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes

Mesenchymal stromal cells (MSCs) suppress T cell responses through mechanisms not completely understood. Adenosine is a strong immunosuppressant that acts mainly through its receptor A(2a) (ADORA2A). Extracellular adenosine levels are a net result of its production (mediated by CD39 and CD73), and of its conversion into inosine by Adenosine Deaminase (ADA). Here we investigated the involvement of ADO in the immunomodulation promoted by MSCs. Human T lymphocytes were activated and cultured with or without MSCs. Compared to lymphocytes cultured without MSCs, co-cultured lymphocytes were suppressed and expressed higher levels of ADORA2A and lower levels of ADA. In co-cultures, the percentage of MSCs expressing CD39, and of T lymphocytes expressing CD73, increased significantly and adenosine levels were higher. Incubation of MSCs with media conditioned by activated T lymphocytes induced the production of adenosine to levels similar to those observed in co-cultures, indicating that adenosine production was mainly derived from MSCs. Finally, blocking ADORA2A signaling raised lymphocyte proliferation significantly. Our results suggest that some of the immunomodulatory properties of MSCs may, in part, be mediated through the modulation of components related to adenosine signaling. These findings may open new avenues for the development of new treatments for GVHD and other inflammatory diseases. (C) 2011 Elsevier B.V. All rights reserved.

NO in the caudal NTS modulates the increase in respiratory frequency in response to chemoreflex activation in awake rats

The role of nitric oxide (NO) in the caudal NTS (cNTS) on baseline cardiovascular and respiratory parameters and on changes in respiratory frequency (fR) and cardiovascular responses to chemoreflex activation was evaluated in awake rats. Bilateral microinjections of L-NAME (200 nmoles/50 nL), a non-selective NO synthase (NOS) inhibitor, into the cNTS increased baseline arterial pressure, while microinjections of NPLA (3 pmoles/50 nL), a selective neuronal NOS (nNOS) inhibitor, did not. L-NAME or N-PLA microinjected into the cNTS reduced the increase in fR in response to chemoreflex activation but not cardiovascular responses. These data show that (a) NO produced by non-nNOS in the cNTS is involved in the baseline autonomic control and (b) NO produced by nNOS in the cNTS is involved in modulation of the increase in fR in response to chemoreflex activation but not in the cardiovascular responses. We conclude that NO produced by the neuronal and endothelial NOS play a different role in the cNTS neurons integral to autonomic and respiratory pathways. (C) 2009 Elsevier B.V. All rights reserved.

Does rapid maxillary expansion increase nasopharyngeal space and improve nasal airway resistance?

Objective: To evaluate the effect of rapid maxillary expansion (RME) on the dimension of the nasopharyngeal space and its relation to nasal airway resistance. Methods: Twenty-five school-age children (from 7 to 10 year-old) with mouth and/or mixed breathing, with mixed dentition and uni- or bilateral posterior crossbite involving the deciduous canines and the first permanent molars, were evaluated. RME was placed and remained during 90 days. Rhinomanometry and orthodontic documentation were performed at four different times, i.e., before (T(1)), immediately after (T(2)), 90 days (T(3)) and 30 months (T(4)) after RME. Results: Differences in nasopharyngeal area and in nasal airway resistance were observed only 30 months after RME, and could be explained by facial growth, and not because of the orthodontic procedure. Conclusion: RME does not influence on nasopharyngeal area or nasal airway resistance in long-term evaluation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Plasticity of Opioid Receptors in the Female Periaqueductal Gray: Multiparity-Induced Increase in the Activity of Genes Encoding for Mu and Kappa Receptors and a Post-Translational Decrease in Delta Receptor Expression

The periaqueductal gray (PAG) has been reported as a potential site for opioid regulation of behavioral selection. Opioid-mediated behavioral and physiological responses differ between nulliparous and multiparous females. This study addresses the effects of multiple reproductive experiences on mu-, kappa- and delta-opioid receptor (Oprm1, Oprk1, and Oprd1 respectively) gene activity and mu, kappa and delta protein expression (MOR, KOR and DOR respectively) in the PAG of the female rats. This was done by evaluating the opioid gene expression using real-time (RT-PCR) and quantification of each protein receptor by Western blot analysis. The RT-PCR results show that multiple reproductive experiences increase Oprm1 and Oprk1 gene expression. Western blot analysis revealed increased MOR and KOR while DOR protein was decreased in multiparous animals. Taken together, these data suggest that multiple reproductive experiences influence both gene activity and opioid receptor expression in the PAG. Post-translational mechanisms seem particularly relevant for DOR expression. Thus, opioid transmission in the PAG might be modulated by different mechanisms of multiparity-induced plasticity according to the opioid receptor type.

Pfaffia paniculata (Brazilian ginseng) roots decrease proliferation and increase apoptosis but do not affect cell communication in murine hepatocarcinogenesis

Pfaffia paniculata (Brazilian ginseng) roots and/or its extracts have shown anti-neoplastic, chemopreventive, and anti-angiogenic properties. The aim of this work was to investigate the chemopreventive mechanisms of this root in Mice Submitted to the infant model of hepatocarcinogenesis, evaluating the effects oil cellular proliferation, apoptosis. and intercellular communication. Fifteen-day-old BALB/c male mice were given, i.p., 10 mu g/g of the carcinogen N-nitrosodiethylamine (DEN). Animals were separated into three groups at weaning and were given different concentrations of powdered P. paniculata root (0%, 2%, or 10%) added to commercial food for 27 weeks. Control group (CT) was not exposed to the carcinogen and was given ration without the root. After euthanasia, the animals` liver and body weight were measured. Liver fragments were sampled to Study intercellular communication, molecular biology, and histopathological analysis. Cellular proliferation was evaluated by immunohistochemistry for PCNA, apoptosis was evaluated by apoptotic bodies count and alkaline cornet technique, and inter-cellular communication by diffusion of lucifer yellow dye, immunofluorescence, western blot and real-time PCR for connexins 26 and 32. Chronic treatment with powdered P. paniculata root reduced cellular proliferation and increased apoptosis in the 2%, group. Animals in the 10% group had an increase in apoptosis with chronic inflammatory process. Intercellular communication showed no alterations in any of the groups analyzed. These results Indicate that chemopreventive effects of P. paniculata are related to the control of cellular proliferation and apoptosis, but not to cell communication and/or connexin expression, and are directly Influenced by the root concentration. (C) 2009 Elsevier GmbH. All rights reserved.

Can Fiber Posts Increase Root Stresses and Reduce Fracture?

The clinical success of fiber posts has been attributed to their lower elastic modulus. The tested hypothesis was that fiber posts could lead to lower risk of post debonding and lower risk of root fracture, despite an increase in root stresses. Stress analyses were carried out with a 3D finite element model of a premolar restored with a metallic or a fiber post. Bonded and non-bonded post/cement interface conditions were simulated. We calculated risk-of-fracture indices by determining the highest principal stress values divided by the tensile strength. Shear stresses along the post/cement interface were analyzed for the bonded models. Compared with the premolar restored with a metallic post, the fiber post generated lower stresses along the interface and higher stresses in the root. However, with the fiber post, fracture was less likely to occur in the root, since its core and post fracture indices were higher.

Root Canal Area Increase Promoted by the EndoSequence and ProTaper Systems: Comparison by Computed Tomography

Introduction: The aim of this study was to compare the increase of the root canal area after instrumentation with EndoSequence or ProTaper rotary systems. Methods: Twenty-two mesial root canals from mandibular molars were instrumented. Teeth were mounted on a base, numbered, and divided into 2 groups; teeth from 1-11 (PT group) were instrumented by using the ProTaper system, and teeth from 12-22 (ES group) were instrumented by using the EndoSequence system. Cone beam computed tomography was performed on all teeth before and after instrumentation. Measurements at 3,5, and 7 mm as well as differences in instrument performance were statistically compared by the Student t test at 5% significance level. Results: Both systems increased significantly the root canal area (P < .05) at all levels. Comparison between the rotary systems showed significantly greater increase (P < .05) for EndoSequence at 3 mm, with no statistically significant difference (P < .05) at the other levels. Conclusions: Both rotary systems increased significantly the root canal area. (J Endod 2010;36:1179-1182)

Circulating cell-free DNA levels in plasma increase with severity in experimental acute pulmonary thromboembolism

Background: The diagnosis of acute pulmonary thromboembolism (APT) and its severity is challenging. No previous study has examined whether there is a linear relation between plasma DNA concentrations and the severity of APT. We examined this hypothesis in anesthetized dogs. We also examined the changes in plasma DNA concentrations in microspheres lung embolization and whether the therapy of APT with nitrite could modify APT-induced changes in plasma DNA concentrations. In vitro DNA release from blood clots was also studied. Methods: APT was induced with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into the right atrium. A group of dogs received 300 pm microspheres into the inferior vena cava to produce similar pulmonary hypertension. Another group of dogs received 6.75 mu mol/kg nitrite after APT with blood clots of 5 ml/kg. Hemodynamic evaluations were carried out for 120 min. DNA was extracted from plasma samples using QIAamp DNA Blood Mini Kit and quantified using Quant-iT (TM) PicoGreen (R) dsDNA detection kit at baseline and 120 min after APT. Results: APT produced dose-dependent increases in plasma DNA concentrations. which correlated positively with pulmonary vascular resistance (P=0.002, r=0.897) and with mean pulmonary arterial pressure (P=0.006, r=0.856). Conversely, lung embolization with microspheres produced no significant changes in plasma DNA concentrations. While nitrite attenuated APT-induced pulmonary hypertension, it produced no changes in plasma DNA concentrations. Blood clots released dose-dependent amounts of DNA in vitro. Conclusions: Cell-free DNA concentrations increase in proportion to the severity of APT, probably as a result of increasing amounts of thrombi obstructing the pulmonary vessels. (C) 2009 Elsevier B.V. All rights reserved.

Influence of the irradiation distance and the use of cooling to increase enamel-acid resistance with Er:YAG laser

Objectives: The aim of this study was to assess the influence of irradiation distance and the use of cooling in the Er:YAG laser efficacy in preventing enamel demineralization. Methods: 84 enamel blocks were randomly assigned to seven groups (n = 12): G1: control group - no treatment, G2-G7: experimental groups treated with Er:YAG laser (80 mJ/2 Hz) at different irradiation distances with or without cooling: G2: 4 mm/2 mL; G3: 4 mm/no cooling; G4: 8 mm/2 mL; G5: 8 mm/no cooling; G6: 16 mm/2 mL; G7: 16 mm/no cooling. The samples were submitted to an in vitro pH cycles for 14 days. Next, the specimens were sectioned in sections of 80-100 mu m in thickness and the demineralization patterns of prepared slices were assessed using a polarized light microscope. Three samples from each group were analyzed with scanning electronic microscopy. Analysis of variance and the Fisher test were performed for the statistical analysis of the data obtained from the caries-lesion-depth measurements (CLDM) (alpha = 5%). Results: The control group (CLDM = 0.67 mm) was statistically different from group 2 (CLDM = 0.42 mm), which presented a smaller lesion depth, and group 6 (0.91 mm), which presented a greater lesion depth. The results of groups 3 (CLDM = 0.74 mm), 4 (CLDM = 0.70 mm), 5 (CLDM = 0.67 mm) and 7 (CLDM = 0.89 mm) presented statistical similarity. The scanning electronic microscopy analysis showed ablation areas in the samples from groups 4, 5, 6 and 7, and a slightly demineralized area in group 2. Conclusions: It was possible to conclude that Er:YAG laser was efficient in preventing enamel demineralization at a 4-mm irradiation distance using cooling. (C) 2010 Elsevier Ltd. All rights reserved.

Stromal-derived factor-1 alpha (CXCL12) levels increase in periodontal disease

Background: The CXC chemokine receptor 4 (CXCR4) and its ligand, stromal cell-derived factor-1 (SDF-1 alpha or CXC chemokine ligand 12) are involved in the trafficking of leukocytes into and out of extravascular tissues. The purpose of this study was to determine whether SDF-1 alpha secreted by host cells plays a role in recruiting inflammatory cells into the periodontia during local inflammation. Methods: SDF-1 alpha levels were determined by enzyme-linked immunosorbent assay in gingival crevicular fluid (GCF) of 24 individuals with periodontitis versus healthy individuals in tissue biopsies and in a preclinical rat model of Porphyromonas gingivalis lipopolysaccharide-induced experimental bone loss. Neutrophil chemotaxis assays were also used to evaluate whether SDF-1 alpha plays a role in the recruitment of host cells at periodontal lesions. Results: Subjects with periodontal disease had higher levels of SDF-1 alpha in their GCF compared to healthy subjects. Subjects with periodontal disease who underwent mechanical therapy demonstrated decreased levels of SDF-1 alpha. Immunohistologic staining showed that SDF-1 alpha and CXCR4 levels were elevated in samples obtained from periodontally compromised individuals. Similar results were observed in the rodent model. Neutrophil migration was enhanced in the presence of SDF-1 alpha, mimicking immune cell migration in periodontal lesions. Conclusions: SDF-1 alpha may be involved in the immune defense pathway activated during periodontal disease. Upon the development of diseased tissues, SDF-1 alpha levels increase and may recruit host defensive cells into sites of inflammation. These studies suggest that SDF-1 alpha may be a useful biomarker for the identification of periodontal disease progression.