Erectile Dysfunction in Young Non-Obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased eNOS Phosphorylation at Ser1177

Introduction. Diabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90-95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED. Aim. Goto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability. Methods. Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured. Main Outcome Measure. GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein. Results. GK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages. Conclusion. Although GK rats display ED, they exhibit changes in cavernosal reactivity that would facilitate erectile responses. These results are in contrast to those described in other experimental diabetes models. This may be due to compensatory mechanisms in cavernosal tissue to overcome restricted pre-penile arterial blood supply or impaired veno-occlusive mechanisms. Carneiro FS, Giachini FRC, Carneiro ZN, Lima VV, Ergul A, Webb RC, and Tostes RC. Erectile dysfunction in young non-obese type II diabetic Goto-Kakizaki rats is associated with decreased eNOS phosphorylation at Ser1177. J Sex Med 2010;7:3620-3634.

The bed nucleus of the stria terminalis modulates exercise-evoked cardiovascular responses in rats

Dynamic exercise evokes sustained cardiovascular changes, which are characterized by blood pressure and heart rate (HR) increases. Although it is well accepted that there is a central nervous system (CNS) mediation of cardiovascular adjustments during dynamic exercise, information on the role of specific CNS structures is limited. The bed nucleus of the stria terminalis (BST) is a forebrain structure known to be involved in central cardiovascular control. Based on this, we tested the hypothesis that BST modulates HR and mean arterial pressure (MAP) responses evoked when rats are submitted to dynamic exercise. Male Wistar rats were tested at three levels of exercise (0.4, 0.8 and 1 km h-1) on a rodent treadmill before and after BST treatment with CoCl(2), a non-selective neurotransmission blocker. Bilateral microinjection of CoCl(2) (1 nmol in 100 nl artificial cerebrospinal fluid) into the BST reduced the pressor response to exercise at 0.4 km h-1 as well as the tachycardic responses evoked by exercise at 0.4, 0.8 and 1 km h-1. The BST treatment with CoCl(2) did not affect baseline MAP or HR, suggesting a lack of tonic BST influence on cardiovascular parameters at rest. Moreover, BST treatment with CoCl(2) did not affect motor performance in the open-field test, which indicates that effects of BST inhibition on cardiovascular responses to dynamic exercise are not due to changes in motor activity. The present results suggest that local neurotransmission in the BST modulates exercise-related cardiovascular adjustments. Data indicate that BST facilitates pressor and tachycardic responses evoked by dynamic exercise in rats.

PYK2/PDZ-RhoGEF Links Ca(2+) Signaling to RhoA

Objective-Ras homolog gene family member A (RhoA)/Rho-kinase-mediated Ca(2+) sensitization is a critical component of constrictor responses. The present study investigates how angiotensin II activates RhoA. Methods and Results-Adenoviral vectors were used to manipulate the expression of regulator of G protein signaling (RGS) domain containing Rho-specific guanine exchange factors (RhoGEFs) and proline-rich tyrosine kinase 2 (PYK2), a nonreceptor tyrosine kinase, in primary rat vascular smooth muscle cells. As an evidence of RhoA activation, RhoA translocation and MYPT1 (the regulatory subunit of myosin light chain phosphatase) phosphorylation were analyzed by Western blot. Results showed that overexpression of PDZ-RhoGEF, but not p115-RhoGEF or leukemia-associated RhoGEF (LARG), enhanced RhoA activation by angiotensin II. Knockdown of PDZ-RhoGEF decreased RhoA activation by angiotensin II. PDZ-RhoGEF was phosphorylated and activated by PYK2 in vitro, and knockdown of PDZ-RhoGEF reduced RhoA activation by constitutively active PYK2, indicating that PDZ-RhoGEF links PYK2 to RhoA. Knockdown of PYK2 or PDZ-RhoGEF markedly decreased RhoA activation by A23187, a Ca(2+) ionophore, demonstrating that PYK2/PDZ-RhoGEF couples RhoA activation to Ca(2+). Conclusions-PYK2 and PDZ-RhoGEF are necessary for angiotensin II-induced RhoA activation and for Ca(2+) signaling to RhoA. (Arterioscler Thromb Vasc Biol. 2009;29:1657-1663.)

LONGITUDINAL REFERENCE VALUES FOR DUCTUS VENOSUS DOPPLER IN LOW-RISK PREGNANCIES

The aim of this study was to establish normal ranges of blood flow velocities and indices in the fetal ductus venosus (DV) during the second half of normal pregnancy. A Doppler study of 60 healthy pregnant women without fetal pathologies was performed during the second half of pregnancy. The peak systolic velocity (PSV), peak diastolic velocity (PDV), maximum velocity during atrial contraction (VAC), peak systolic velocity/maximum velocity during atrial contraction (S/A ratio), pulsatility index for the vein (PIV), preload index (PLI) and velocity index for the vein (VIV) were calculated from the DV at 4-week intervals. A significant increase in PSV, PDV and VAC was observed from the 20-23(6/7) to the 28-31(6/7) weeks, with stabilization of values until the end of the pregnancy. On the other hand, the study showed a significant decrease for the S/A ratio, PIV, PLI and VIV from the 20-23(6/7) to the 28-31(6/7) weeks and remaining stable from then until term. (E-mail:dralemar@uol.com.br) (C) 2010 World Federation for Ultrasound in Medicine & Biology.

Age and gender influence on maximal bite force and masticatory muscles thickness

The present study aimed investigate the age and gender influence on maximal molar bite force and at outlining the criteria for normal masticatory muscle development in a sample of 177 Brazilian Caucasian dentate individuals aged 7-80 years divided into five age groups: I(7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years), and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided in respect to gender (20 M/20 F). Bite force was recorded with a mouth-adapted 1000 N dynamometer and the highest out of three records was regarded as the maximal bite force. The data were submitted to multivariate statistical analysis (SPSS 17.0 p < 0.05). Effects of group and gender were found, but no interactions between them. The ANOVA showed significant differences between groups bilaterally. Bonferroni`s test showed that group I had significantly lower bite force means at both sides as compared to all groups, except group V. No differences were found between the left and right sides. In all the groups, gender was found to be a significant factor associated with maximal bite force. A global comparison including all the subjects and measures showed that the means of men were approximately 30% higher than those of women, within-group comparisons yielded similar results in all groups. Muscle thickness was measured with a SonoSite Titan ultrasound tool using a high-resolution real-time 56 mm/10 MHz linear-array transducer. Three ultrasound images were obtained from the bilateral masseter and temporal muscles at rest and at maximal voluntary contraction. The means of the three measures in each clinical condition were analyzed with multivariate statistical analysis (SPSS 17.0 p < 0.05). A gradual increase in thickness of the masseter and temporal muscles was found both at rest and maximal voluntary contraction for groups I to IV, whereas a decrease in muscle thickness was observed in group V. Multivariate analysis showed that in both conditions there was an effect of group and gender. The study of the development of the stomatognathic system in relation to age and gender can provide useful data for the identification of normal and impaired functioning patterns. The results of this study indicate that age and gender are associated with structural and functional alterations in the muscles of the stomatognathic system. (C) 2010 Elsevier Ltd. All rights reserved.

Ageing and surface EMG activity patterns of masticatory muscles

P>The purpose of this study was to evaluate the influence of age on the electromyographic activity of masticatory muscles. All volunteers were Brazilian, fully dentate (except for Group I - mixed dentition), Caucasian, aged 7-80, and divided into five groups: I (7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years) and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided with respect to gender (20 M/20 F). Surface electromyographic records of masticatory muscles were obtained at rest and during maximal voluntary contraction, right and left laterality, maximal jaw protrusion and maximal clenching in the intercuspal position. Statistically significant differences (P < 0 center dot 05) were found in all clinical conditions among the different age groups. Considerably different patterns of muscle activation were found across ages, with greater electromyographic activity in children and youth, and decreasing from adults to aged people.

The relationship between two types of upper eyelid movements: Saccades and pursuit

PURPOSE. To establish the relationship between upper eyelid saccades and upper eyelid pursuit movements. METHODS. Upper eyelid saccades and periodic sinusoidal upper eyelid pursuit movements were recorded in a sample of controls and patients with Graves upper eyelid retraction. A video-computerized system was used to register both types of movements that accompanied 60 of eye rotation across the upper and lower hemifields. The forced harmonic oscillator model was used to fit saccadic and pursuit movements. RESULTS. Mean mid-pupil eyelid distance for the Graves patients (6.6 +/- 1.1 mm) was significantly higher than for the controls (4.6 +/- 0.8 mm; t = 7.18; P < 0.00001). Despite the difference in the upper eyelid resting position, saccades and pursuit eyelid movements of both groups were extremely well fitted by underdamped solutions and steady forced solutions of the harmonic oscillator model, respectively. For the controls, the amplitude of the pursuit movements was well correlated with the upward and downward saccades. The amplitude of the eyelid movements of the Graves patients (saccades and pursuit) was significantly reduced compared with that of the controls. CONCLUSIONS. Saccadic and pursuit movements of the upper eyelid can be described by the harmonic oscillator model. In healthy subjects and Graves patients, the amplitude of pursuit lid movements is correlated to the saccade amplitude. Pursuit eyelid movements are more difficult to register than saccades, and their measurements do not allow clear separation of the relaxation and contraction properties of the upper eyelid retractors.

Chronic Ethanol Consumption Induces Cavernosal Smooth Muscle Dysfunction in Rats

OBJECTIVES To investigate the effects of chronic ethanol consumption on nitric oxide (NO)-mediated relaxation in rat cavernosal smooth muscle (CSM). METHODS Male wistar rats were divided into 2 groups: control and ethanol. CSM obtained from both groups were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hertz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (0.01-1000 mu mol L(-1)), sodium nitroprusside (SNP, 0.01-1000 mu mol L(-1)), or EFS (1-32 Hz) in strips precontracted with phenylephrine (10 mu mol L(-1)). Blood ethanol, serum testosterone levels, and basal nitrate generation were determined. Immunoexpression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was also accessed. RESULTS Ethanol intake for 4 weeks significantly increased noradrenergic nerve-mediated contractions of CSM in response to EFS. The endothelium-dependent relaxation induced by acetylcholine decreased after the ethanol treatment. Ethanol consumption decreased serum testosterone levels but did not affect the nitrate levels on rat CSM. The mRNA and protein levels for eNOS and iNOS receptors were increased in CSM from ethanol-treated rats. CONCLUSIONS Ethanol consumption reduces endothelium-dependent relaxation induced by acetylcholine, but does not affect SNP or EFS-induced relaxation, suggesting that ethanol disrupts the endothelial function. Despite the overexpression of eNOS and iNOS in ethanol-treated rats, the impaired relaxation induced by acetylcholine may suggest that chronic ethanol consumption induces endothelial dysfunction. UROLOGY 74: 1250-1256, 2009. (C) 2009 Published by Elsevier Inc.

Comparisons of the release of vasodilator substances from left and right cardiac chambers of the isolated perfused rabbit heart: Implications for intraventricular thrombus formation

Prostacyclin (PgI(2)) and endothelium-derived nitric oxide (EDNO) are produced by the arterial and venous endothelium. In addition to their vasodilator action on vascular smooth muscle, both act together to inhibit platelet aggregation and promote platelet disaggregation. EDNO also inhibits platelet adhesion to the endothelium. EDNO and PgI(2) have been shown to be released from the cultured endocardial cells. In this study, we examined the release of vasoactive substances from the intact endocardium by using isolated rabbit hearts perfused with physiological salt solution (95% O(2)/5% CO(2), T = 37 degrees C). The right and left cardiac chambers were perfused through separate constant-flow perfusion loops (physiological salt solution, 8 ml min(-1)). Effluent from left and right cardiac, separately, was bioassayed on canine coronary artery smooth muscle, which had been contracted with prostaglandin F(2 alpha_)(2 x 10(-6) M) and no change in tension was exhibit. However, addition of calcium ionophore A23187 (10(-6) M) to the cardiac chambers` perfusion line induced vasodilation of the bioassay coronary ring, 61.4 +/- 7.4% versus 70.49 +/- 6.1% of initial prostaglandin F(2 alpha) contraction for the left and right cardiac chambers perfusate, respectively (mean +/- SEM, n = 10, p > 0.05). Production of vasodilator was blocked totally in the left heart but, only partially blocked in the right heart by adding indomethacin (10(-5) M) to the perfusate, respectively, 95.2 +/- 2.2% versus 41.5 +/- 4.8% (mean +/- SEM, n = 10, p < 0.05). 6-Keto prostaglandin F(1 alpha), measured in the endocardial superfusion effluent was also higher for the left cardiac chambers than for the right at the time of stimulation with the A23187, respectively, 25385.88 +/- 5495 pg/ml (n = 8) versus 13,132.45 +/- 1839.82 pg/ml (n = 8), (p < 0.05). These results showed that cyclooxygenase pathway plays major role in generating vasoactive substances for the left cardiac chamber endocardium; while it is not the main pathway for the right ventricular endocardium at which EDNO and PgI(2) Could act together and potentiate their antithrombogenic activities in isolated perfused rabbit heart. This may be an explanation for the intraventricular thrombus mostly seen in left ventricle rather than in right ventricle as a complication of myocardial infarction. (C) 2009 Elsevier Inc. All rights reserved.

Inter-rater reliability study of the modified Oxford Grading Scale and the Peritron manometer

Objective To evaluate the inter-rater reliability of the modified Oxford Grading Scale and the Peritron manometer. Design All participants were evaluated twice, first by one examiner and 30 days later by a second examiner. Measurements of vaginal squeeze pressure were compared with the results from the palpation test. Participants Nineteen women with a mean age of 23.7 years (range 21 to 28 years). Results Inter-rater reliability for vaginal palpation was fair (kappa = 0.33, 95% confidence interval 0.09 to 0.57). Using the Peritron manometer, the difference between examiners was less than 10 cmH(2)O in 11 of the 19 (58%) cases. The palpation test did not differentiate between weak, moderate, good and strong muscle contractions. This study found fair inter-rater reliability for the modified Oxford Grading Scale and moderate inter-rater reliability for the Peritron manometer. Conclusions The inter-rater reliability of vaginal squeeze pressure measurement using the Peritron manometer is acceptable and can be used in re-evaluations performed by different examiners in clinical practice. However, for research purposes, the ideal situation would be for a single examiner to assess and re-assess the subject. Vaginal palpation is important in the clinical assessment of correctness of a pelvic floor muscle contraction, but this study does not support the use of the modified Oxford Grading Scale as a reliable and valid method to measure and differentiate pelvic floor muscle strength. (C) 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Effect of bolus volume on proximal esophageal contractions of patients with Chagas` disease and patients with idiopathic achalasia

Chagas` disease and idiopathic achalasia patients have similar impairment of distal esophageal motility. In Chagas` disease, the contractions occurring in the distal esophageal body are similar after wet or dry swallows. Our aim in this investigation was to evaluate the effect of wet swallows and dry swallows on proximal esophageal contractions of patients with Chagas` disease and with idiopathic achalasia. We studied 49 patients with Chagas` disease, 25 patients with idiopathic achalasia, and 33 normal volunteers. We recorded by the manometric method with continuous water perfusion the pharyngeal contractions 1 cm above the upper esophageal sphincter and the proximal esophageal contractions 5 cm from the pharyngeal recording point. Each subject performed in duplicate swallows of 3-mL and 6-mL boluses of water and dry swallows. We measured the time between the onset of pharyngeal contractions and the onset of proximal esophageal contractions (pharyngeal-esophageal time [ PET]), and the amplitude, duration, and area under the curve (AUC) of proximal esophageal contractions. Patients with Chagas` disease and with achalasia had longer PET, lower esophageal proximal contraction amplitude, and lower AUC than controls (P <= 0.02). In Chagas` disease, wet swallows caused shorter PET, higher amplitude, and higher AUC than dry swallows (P <= 0.03). There was no difference between swallows of 3- or 6-mL boluses. There was no difference between patients with Chagas` disease and with idiopathic achalasia. We conclude that patients with Chagas` disease and with idiopathic achalasia have a delay in the proximal esophageal response and lower amplitude of the proximal esophageal contractions.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early after Tetralogy of Fallot Repair

Background: Twenty-three patients (median age 23 months) who underwent Fallot`s tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction. Methods: Intraoperatively resected infundibular bands and subendocardial biopsy samples from the right ventricle (RV) and left ventricle were obtained for histopathologic evaluation. Tissue Doppler echocardiographic interrogation of the ventricles was performed before surgery and in the postoperative period. Results: Histopathologic data revealed hypertrophy of the RV cardiomyocytes and increased interstitial collagen in both ventricles. Mean values of RV isovolumic acceleration decreased significantly at the third evaluation compared with the preoperative values (P = .006). RV myocardial fibrosis greater than 8.3% was associated with a probability of altered E` of at least 0.7 (odds ratio = 2.31). Conclusion: Preoperative histologic myocardial remodeling influenced the postoperative RV function in this group of patients with late repair. Further studies are necessary to evaluate the myocardium in younger patients and to define its influence in the long-term follow-up. (J Am Soc Echocardiogr 2010;23:912-8.)

Chronic alcoholism associated with diabetes impairs erectile function in rats

OBJECTIVE To investigate the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)-mediated relaxation of cavernosal smooth muscle (CSM). MATERIAL AND METHODS Male Wistar rats were divided into four groups: control, isocaloric, diabetic and ethanol-diabetic. The CSMs were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (ACh; 0.01-1000 mu mol/L), sodium nitroprusside (SNP, 0.01-1000 mu mol/L) or EFS (1-32 Hz) in strips pre-contracted with phenylephrine (10 mu mol/L). Immunoexpression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was also accessed. RESULTS The endothelium-dependent relaxation induced by ACh was decreased in CSM from ethanol-diabetic rats when compared with the controls, with a mean (sem) of 21 (4) vs 37 (2)%. Similarly, the potency and maximal responses induced by SNP were reduced in the ethanol-diabetic [3.97 (0.38) and 85 (1)%, respectively] and diabetic groups [3.78 (0.56) and 81 (2)%, respectively] when compared with the controls [5.3 (0.22) and 90 (3)%, respectively] and isocaloric [5.3 (0.19) and 92 (1)%, respectively] groups. Noradrenergic nerve-mediated contractions of CSM in response to EFS were increased in rats from ethanol-diabetic and diabetic groups when compared with the control and isocaloric groups. Conversely, there were no differences in EFS-induced relaxation among the groups. The immunostaining assays showed overexpression of eNOS and iNOS in the CSM from diabetic and ethanol-diabetic rats when compared with the control and isocaloric rats. CONCLUSION There was an impairment of relaxation of CSM from ethanol-diabetic and diabetic rats that involved a decrease in the NO-cyclic guanosine monophosphate signalling pathway by endothelium-dependent mechanisms accompanied by a change in the CSM contractile sensitivity.

Implant-supported prosthesis following Branemark protocol on electromyography of masticatory muscles

This research evaluated the effects of Branemark protocol on electromyography of the masseter and temporal muscles. The patients were divided into two groups: Group 1: patients who wore an implant-supported prosthesis in the mandibular arch following Branemark protocol, and maxillary removable complete dentures; Group II: dentate individuals (control). Electromyography was carried out at rest, right (RL) and left (LL) laterality, protrusion and maximum voluntary contraction (MVC). Data were compared by t-test. At rest, a higher electromyographic (EMG) activity was observed in Group I, and the values were significant in the right masseter and left temporal muscles. In RL, there were statistically significant differences for right masseter (P < 0.01), left masseter and temporal muscles and for the left temporal muscle in LL (P < 0.05). In protrusion, Group I presented a higher EMG activity, and there was a statistically significant difference for the right masseter muscle (RM) (P < 0.05). In MVC, the EMG values were higher in Group II (control), but significant just for the right temporal muscle (P < 0.05). In conclusion, individuals with mandibular fixed dentures supported according to the Branemark protocol and maxillary removable complete dentures showed a higher activity of masticatory muscles during the mandibular postural clinical conditions examined; however, in the MVC, Group I presented lower values when compared to dentate group. Despite presenting different EMG values in all of the clinical conditions, both groups showed similar EMG patterns of muscle activation which demonstrates that the proposed treatment can be considered as a good option for oral rehabilitation.

Do Low-shrink Composites Reduce Polymerization Shrinkage Effects?

Progress in polymer science has led to continuous reduction of polymerization shrinkage, exemplified by a new generation of ""low-shrink composites"". The common inference that shrinkage stress effects will be reduced in teeth restored with such restoratives with lower shrinkage was tested in extracted human premolars. Mesio-occluso-distal slot-shaped cavities were cut and restored with a conventional (SupremePlus) or low-shrink (RefleXions, Premise, Kalore, and LS) composite (N = 5). We digitized the coronal surfaces before and 10 min after restoration to determine cuspal deflection from the buccal and lingual volume change/area. We also determined the main properties involved (total shrinkage, post-gel shrinkage, degree of conversion, and elastic modulus), as well as microleakage, to verify adequate bonding. It was shown that, due to shrinkage stresses, buccal and lingual surfaces pulled inward after restoration (9-14 microns). Only Kalore and LS resulted in significantly lower tooth deformation (ANOVA/Student-Newman-Keuls post hoc, p = 0.05). The other two low-shrink composites, despite having the lowest and highest total shrinkage values, did not cause significant differences in cuspal deflection. Deflection seemed most related to the combination of post-gel shrinkage and elastic modulus. Therefore, even for significantly lower total shrinkage values, shrinkage stress is not necessarily reduced.