Effects of Oropharyngeal Exercises on Patients with Moderate Obstructive Sleep Apnea Syndrome

Rationale: Upper airway muscle function plays a major role in maintenance of the upper airway patency and contributes to the genesis of obstructive sleep apnea syndrome (OSAS). Preliminary results suggested that oropharyngeal exercises derived from speech therapy may be an effective treatment option for patients with moderate OSAS. Objectives: To determine the impact of oropharyngeal exercises in patients with moderate OSAS. Methods: Thirty-one patients with moderate OSAS were randomized to 3 months of daily (similar to 30 min) sham therapy (n = 15, control) or a set of oropharyngeal exercises (n = 16), consisting of exercises involving the tongue, soft palate, and lateral pharyngeal wall. Measurements and Main Results: Anthropometric measurements, snoring frequency (range 0-4), intensity (1-3), Epworth daytime sleepiness (0-24) and Pittsburgh sleep quality (0-21) questionnaires, and full polysomnography were performed at baseline and at study conclusion. Body mass index and abdominal circumference of the entire group were 30.3 +/- 3.4 kg/m(2) and 101.4 +/- 9.0 cm, respectively, and did not change significantly over the study period. No significant change occurred in the control group in all variables. In contrast, patients randomized to oropharyngeal exercises had a significant decrease (P < 0.05) in neck circumference (39.6 +/- 3.6 vs. 38.5 +/- 4.0 cm), snoring frequency (4 [4-4] vs. 3 [1.5-3.5]), snoring intensity (3 [3-4] vs. 1 [1-2]), daytime sleepiness (14 +/- 5 vs. 8 +/- 6), sleep quality score (10.2 +/- 3.7vs. 6.9 +/- 2.5), and OSAS severity (apnea-hypopnea index, 22.4 +/- 4.8 vs. 13.7 +/- 8.5 events/h). Changes in neck circumference correlated inversely with changes in apnea-hypopnea index (r = 0.59; P < 0.001). Conclusions: Oropharyngeal exercises significantly reduce OSAS severity and symptoms and represent a promising treatment for moderate OSAS. Clinical trial registered with www.clinicaltrials.gov (NCT 00660777).

A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women

Objective: The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and menopausal symptoms among women who had undergone hysterectomy. Design: A 6-month, randomized, double-blind, placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy. The interventions were physical exercise and hormone therapy (n = 9), being sedentary and hormone therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the Medical Outcome Study Short-Forrn Health Survey and symptoms by Kupperman Index at baseline and after 6 months. Results: There was a decrease in symptoms in all groups, but only groups who performed physical exercise showed an increase in quality of life. Analysis of variance showed that changes in physical functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month period differed significantly between women who exercised and women who were sedentary, regardless of hormone therapy. Hormone therapy had no effect, and there was also no significant association between physical exercise and hormone therapy in HRQOL. Conclusions: Physical exercises can reduce menopausal symptoms and enhance HRQOL, independent of whether hormone therapy is taken.

NEW COUPLING SYSTEM FOR INTERFERENCE SCREWS: BIOMECHANICAL RESISTANCE TO TORSION

Objective: To introduce a new coupling system between screw driver and interference screw, and biomechanical tests that validate the safety of its application. Methods: The new system was submitted to biomechanical torsion assays. Two types of analysis were performed: maximum torque of manual insertion of the screws into bovine bone; destructive assays of torsion of the system using an INSTRON 55MT machine. The same tests were also performed on a control group, using a commercially available interference screw coupling system (Acufex (R)). Results: In the tests on manual insertion of screws in bovine femurs, the average values found with a digital torque meter were 1.958 N/m for Acufex (R) and 2.563 N/m for FMRP. Considering p>0.05, there were no statistical differences between the two groups (p=0.02) in the values for maximum torque of insertion, in the two systems studied. The average values for maximum torque of torsion resisted by the screw were 15N/m for the Acufex (R) screw and 13N/m for the FMRP screw, again with no statistical differences between the two groups (p>0.05). In the evaluation of angular deformation, there was also no significant difference between the two screw types (p=0.15). Conclusion: The new coupling system for interference screws developed at FMRP-USP revealed a torsion resistance that is comparable with the system already available on the market and regulated for international use.

Reliability of electromyographic amplitude values of the upper limb muscles during closed kinetic chain exercises with stable and unstable surfaces

The purpose of the present study was to evaluate the intra and interday reliability of surface electromyographic amplitude values of the scapular girdle muscles and upper limbs during 3 isometric closed kinetic chain exercises, involving upper limbs with the fixed distal segment extremity on stable base of support and on a Swiss ball (relatively unstable). Twenty healthy adults performed the exercises push-up, bench-press and wall-press with different effort levels (80% and 100% maximal load). Subjects performed three maximal voluntary contractions (MVC) in muscular testing position of each muscle to obtain a reference value for root mean square (RMS) normalization. Individuals were instructed to randomly perform three isometric contraction series, in which each exercise lasted 6 s with a 2-min resting-period between series and exercises. Intra and interday reliabilities were calculated through the intraclass correlation coefficient (ICC 2.1), standard error of the measurement (SEM). Results indicated an excellent intraday reliability of electromyographic amplitude values (ICC >= 0.75). The interday reliability of normalized RMS values ranged between good and excellent (ICC 0.52-0.98). Finally, it is suggested that the reliability of normalized electromyographic amplitude values of the analyzed muscles present better values during exercises on a stable surface. However, load levels used during the exercises do not seem to have any influence on variability levels, possibly because the loads were quite similar. (C) 2007 Elsevier Ltd. All rights reserved.

Activation of the shoulder and arm muscles during axial load exercises on a stable base of support and on a medicine ball

The purpose of this study was to compare SEMG activities during axial load exercises on a stable base of support and on a medicine ball (relatively unstable). Twelve healthy male volunteers were tested (x = 23 +/- 7y). Surface EMG was recorded from the biceps brachii, anterior deltoid, clavicular portion of pectoralis major, upper trapezius and serratus anterior using surface differential electrodes. All SEMG data are reported as percentage of RMS mean values obtained in maximal voluntary contractions for each muscle studied. A 3-way within factor repeated measures analysis of variance was performed to compare RMS normalized values. The RMS normalized values of the deltoid were always greater during the exercises performed on a medicine ball in relation to those performed on a stable base of support. The trapezius showed greater mean electric activation amplitude values on the wall-press exercise on a medicine ball, and the pectoralis major on the push-up. The serratus and biceps did not show significant differences of electric activation amplitude in relation to both tested bases of support. Independent of the base of support, none of the studied muscles showed significant differences of electric activation amplitude during the bench-press exercise. The results contribute to the identification of the levels of muscular activation amplitude during exercises that are common in clinical practice of rehabilitation of the shoulder and the differences in terms of type of base of support used. (C) 2006 Elsevier Ltd. All rights reserved.

ELECTROMYOGRAPHIC AMPLITUDE RATIO OF SERRATUS ANTERIOR AND UPPER TRAPEZIUS MUSCLES DURING MODIFIED PUSH-UPS AND BENCH PRESS EXERCISES

Imbalance and weakness of the serratus anterior and upper trapezius force couple have been described in patients with shoulder dysfunction. There is interest in identifying exercises that selectively activate these muscles and including it in rehabilitation protocols. This study aims to verify the UT/SA electromyographic (EMG) amplitude ratio, performed in different upper limb exercises and on two bases of support. Twelve healthy men were tested (average age = 22.8 +/- 3.1 years), and surface EMG was recorded from the upper trapezius and serratus anterior using single differential surface electrodes. Volunteers performed isometric contractions over a stable base of support and on a Swiss ball during the wall push-up (WP), bench press (BP), and push-up (PU) exercises. All SEMG data are reported as a percentage of root mean square or integral of linear envelope from the maximal value obtained in one of three maximal voluntary contractions for each muscle studied. A linear mixed-effect model was performed to compare UT/SA ratio values. The WP, BP, and PU exercises showed UT/SA ratio mean +/- SD values of 0.69 +/- 0.72, 0.14 +/- 0.12, and 0.39 +/- 0.37 for stable surfaces, respectively, whereas for unstable surfaces, the values were 0.73 +/- 0.67, 0.43 +/- 0.39, and 0.32 +/- 0.30. The results demonstrate that UT/SA ratio was influenced by the exercises and by the upper limb base of support. The practical application is to show that BP on a stable surface is the exercise preferred over WP and PU on either surfaces for serratus anterior muscle training in patients with imbalance between the UT/SA force couple or serratus anterior weakness.

Activation of Selected Shoulder Muscles During Unilateral Wall and Bench Press Tasks Under Submaximal Isometric Effort

STUDY DESIGN: Controlled laboratory study. OBJECTIVE: To assess the activation of 7 shoulder muscles under 2 closed kinetic chain (CKC) tasks for the upper extremity using submaximal isometric effort, thus providing relative quantification of muscular isometric effort for these muscles across the CKC exercises, which may be applied to rehabilitation protocols for individuals with shoulder weakness. BACKGROUND: CKC exercises favor joint congruence, reduce shear load, and promote joint dynamic stability. Additionally, knowledge about glenohumeral and periscapular muscle activity elicited during CKC exercises may help clinicians to design protocols for shoulder rehabilitation. METHODS: Using surface electromyography, activation level was measured across 7 shoulder muscles in 20 healthy males, during the performance of a submaximal isometric wall press and bench press. Signals were normalized to the maximal voluntary isometric contraction, and, using paired t tests, data were analyzed between the exercises for each muscle. RESULTS: Compared to the wall press, the bench press elicited higher activity for most muscles, except for the upper trapezius. Levels of activity were usually low but were above 20% maximal voluntary isometric contraction for the serratus anterior on both tasks, and for the long head triceps brachii on the bench press. CONCLUSIONS: Both the bench press and wall press, as performed in this study, led to relatively low EMG activation levels for the muscles measured and may be considered for use in the early phases of rehabilitation. J Ort hop Sports Phys Ther 2011;41(7):520-525, Epub 2 February 2011. doi:10.2519/jospt.2011.3418

Prevalence of Insulin Resistance and Related Risk Factors for Cardiovascular Disease in Patients With Essential Hypertension

BACKGROUND There is evidence that the subgroup of patients with essential hypertension who are also insulin resistant is at increased risk of cardiovascular disease (CVD). We are unaware of the frequency of insulin resistance in patients with essential hypertension as well as the CVD risk in this subgroup of patients. This analysis was aimed at providing the prevalence of insulin resistance and associated CVD risk factors in treated and untreated patients with essential hypertension. METHODS The study population consisted of 126 patients with hypertension: 56 untreated and 70 in a stable treatment program. Body mass index (BMI), blood pressure, plasma glucose and insulin responses to an oral glucose challenge, lipid and lipoprotein concentrations, and steady-state plasma glucose (SSPG) concentration during the insulin suppression test were measured. Insulin resistance was defined operationally as a SSPG concentration >180 mg/dl. RESULTS Demographic characteristics and metabolic CVD risk factors were comparable in both groups, with 30-50% of both treated and untreated patients having abnormalities of all risk factors measured. Approximately 50% of patients met the criteria for insulin resistance in both groups, and the prevalence of abnormal CVD risk factors in this group was increased two to threefold as compared to the other half of the subjects. CONCLUSIONS Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.

THE EFFECT OF DIFFERENT VOLUMES OF ACUTE RESISTANCE EXERCISE ON ELDERLY INDIVIDUALS WITH TREATED HYPERTENSION

Scher, LML, Ferriolli, E, Moriguti, JC, Scher, R, and Lima, NKC. The effect of different volumes of acute resistance exercise on elderly individuals with treated hypertension. J Strength Cond Res 25(4): 1016-1023, 2011-Acute resistance exercise can reduce the blood pressure (BP) of hypertensive subjects. The aim of this study was to evaluate the effect of different volumes of acute low-intensity resistance exercise over the magnitude and the extent of BP changes in treated hypertensive elderly individuals. Sixteen participants (7 men, 9 women), with mean age of 68 6 5 years, performed 3 independent randomized sessions: Control (C: 40 minutes of rest), Exercise 1 (E1: 20 minutes, 1 lap in the circuit), and Exercise 2 (E2: 40 minutes, 2 laps in the circuit) with the intensity of 40% of 1 repetition maximum. Blood pressure was measured before (during 20 minutes) and after each session (every 5 minutes during 60 minutes) using both a mercury sphygmomanometer and a semiautomatic device (Omrom-HEM-431). After that, 24-hour ambulatory blood pressure monitoring was performed (Dyna-MAPA). Blood pressure decreased during the first 60 minutes (systolic: p < 0.01, diastolic: p < 0.05) after all exercise sessions. Only the highest volume session promoted a reduction of mean systolic 24-hour BP and awake BP (p, 0.05) after exercise, with higher diastolic BP during sleep (p, 0.05). Diastolic 24-hour BP and both systolic and diastolic BP during sleep were higher after E1 (p, 0.05). Concluding, acute resistive exercise sessions in a circuit with different volumes reduced BP during the first 60 minutes after exercise in elderly individuals with treated hypertension. However, only the highest volume promoted a reduction of mean 24-hour and awake systolic BP.

Blood and Salivary Oxidative Stress Biomarkers Following an Acute Session of Resistance Exercise in Humans

The aim of the present study was to compare oxidative stress biomarkers determined in blood and saliva before and after acute resistance exercise. 1 week after 1 maximum repetition (1RM) test 11 healthy well-trained males completed a hypertrophy acute session of resistance training including 3 sets of 10 repetitions at 75% of the 1RM, with 90s rest periods between sets. Venous blood and saliva samples were collected before (pre) and 10 min after (post) the resistance training session. A significant (p < 0.05) rise in blood lactate accumulation (pre: 1.6 +/- 0.4 vs. post: 9.5 +/- 2.4) was found post-acute resistance training compared with baseline values. Significant increases (p < 0.05) in TBARS (42%), AOPP (28%), uric acid (27%) and GSH (14%) were detected post-acute resistance training in relation to pre in blood samples. A significant increase (p < 0.05) in uric acid (36%) was found in saliva post-acute resistance training as well as a significant correlation (p < 0.05) between uric acid determined in blood and saliva. Statistical analysis did not reveal any other change in the salivary oxidative stress biomarkers. In conclusion, an acute session of resistance exercise induces oxidative stress in plasma of trained men after acute resistance training, which was not found in saliva samples except for uric acid.

Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis

Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of neutrophil migration. Moreover, TLR2(-/-) mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, neutrophils activated ex vivo by LTA and adoptively transferred into naive WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein-coupled receptor kinases 2 (GRK2) in neutrophils; increased expression of GRK2 was seen in blood neutrophils from WT mice, but not TLR2(-/-) mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.

Leptin resistance and desensitization of hypophagia during prolonged inflammatory challenge

Leptin resistance and desensitization of hypophagia during prolonged inflammatory challenge. Am J Physiol Endocrinol Metab 300: E858-E869, 2011. First published February 22, 2011; doi: 10.1152/ajpendo.00558.2010.-Acute exposure to bacterial lipopolysaccharide (LPS) is a potent inducer of immune response as well as hypophagia. Nevertheless, desensitization of responses to LPS occurs during long-term exposure to endotoxin. We induced endotoxin tolerance, injecting repeated (6LPS) LPS doses compared with single (1LPS) treatment. 1LPS, but not 6LPS group, showed decreased food intake and body weight, which was associated with an increased plasma leptin and higher mRNA expression of OB-Rb, MC4R, and SOCS3 in the hypothalamus. Hypophagia induced by 1LPS was associated with lower levels of 2-arachidonoylglycerol (2-AG), increased number of p-STAT3 neurons, and decreased AMP-activated protein kinase (AMPK) activity. Desensitization of hypophagia in the 6LPS group was related to high 2-AG, with no changes in p-STAT3 or increased p-AMPK. Leptin decreased food intake, body weight, 2-AG levels, and AMPK activity and enhanced p-STAT3 in control rats. However, leptin had no effects on 2-AG, p-STAT3, or p-AMPK in the 1LPS and 6LPS groups. Rats treated with HFD to induce leptin resistance showed neither hypophagia nor changes in p-STAT3 after 1LPS, suggesting that leptin and LPS recruit a common signaling pathway in the hypothalamus to modulate food intake reduction. Desensitization of hypophagia in response to repeated exposure to endotoxin is related to an inability of leptin to inhibit AMPK phosphorylation and 2-AG production and activate STAT3. SOCS3 is unlikely to underlie this resistance to leptin signaling in the endotoxin tolerance. The present model of prolonged inflammatory challenge may contribute to further investigations on mechanisms of leptin resistance.

Heterogeneity in the molecular basis of ACTH resistance syndrome

Objective: ACTH resistance syndromes are rare, autosomal, and genetically heterogeneous diseases that include familial glucocorticoid deficiency (FGD) and triple A syndrome. FGD has been shown to segregate with mutations in the gene coding for ACTH receptor (MC2R) or melanocortin 2 receptor accessory protein (MRAP), whereas mutations in the triple A syndrome (AAAS, Allgrove syndrome) gene have been found in segregation with triple A syndrome. We describe the clinical findings and molecular analysis of MC2R, MRAR and AAAS genes in five Brazilian patients with ACTH resistance syndrome. Design and methods: Genomic DNA from patients and their unaffected relatives was extracted from peripheral blood leucocytes and amplified by PCR, followed by automated sequencing. Functional analysis was carried out using Y6 cells expressing wild-type and mutant MC2R. Results: All five patients showed low cortisol and elevated plasma ACTH levels. One patient had achalasia and alacrima, besides the symptoms of adrenal insufficiency. The molecular analysis of FGD patients revealed a novel p.Gly116Val mutation in the MC2R gene in one patient and p.Met1Ile mutation in the MRAP gene in another patient. Expression of p.Glyll.6Val MC2R mutant in Y6 cells revealed that this variant failed to stimulate cAMP production. The analysis of the AAAS gene in the patient with triple A syndrome showed a novel g.782_783deITG deletion. The molecular analysis of DNA from other two patients showed no mutation in MC2R, MRAP or AAAS gene. Conclusions: In conclusion, the molecular basis of ACTH resistance syndrome is heterogeneous, segregating with genes coding for proteins involved with ACTH receptor signaling/expression or adrenal gland development and other unknown genes.

Antifungal Resistance Mechanisms in Dermatophytes

Although fungi do not cause outbreaks or pandemics, the incidence of severe systemic fungal infections has increased significantly, mainly because of the explosive growth in the number of patients with compromised immune system. Thus, drug resistance in pathogenic fungi, including dermatophytes, is gaining importance. The molecular aspects involved in the resistance of dermatophytes to marketed antifungals and other cytotoxic drugs, such as modifications of target enzymes, over-expression of genes encoding ATP-binding cassette (ABC) transporters and stress-response-related proteins are reviewed. Emphasis is placed on the mechanisms used by dermatophytes to overcome the inhibitory action of terbinafine and survival in the host environment. The relevance of identifying new molecular targets, of expanding the understanding about the molecular mechanisms of resistance and of using this information to design new drugs or to modify those that have become ineffective is also discussed.

A single amino acid substitution in one of the lipases of Aspergillus nidulans confers resistance to the antimycotic drug undecanoic acid

A plausible approach to evaluate the inhibitory action of antifungals is through the investigation of the fungal resistance to these drugs. We describe here the molecular cloning and initial characterization of the A. nidulans lipA gene, where mutation (lipA1) conferred resistance to undecanoic acid, the most fungitoxic fatty acid in the C(7:0)-C(18:0) series. The lipA gene codes for a putative lipase with the sequence consensus GVSIS and WIFGGG as the catalytic signature. Comparison of the wild-type and LIP1 mutant strain nucleotide sequences showed a G -> A change in lipA1 allele, which results in a Glu(214) -> Lys substitution in LipA protein. This ionic charge change in a conserved LipA region, next to its catalytic site, may have altered the catalytic properties of this enzyme resulting in resistance to undecanoic acid.