Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Methods. We studied participants with acute and/or early HIV infection and TDR in 2 cohorts (San Francisco, California, and Sao Paulo, Brazil). We followed baseline mutations longitudinally and compared replacement rates between mutation classes with use of a parametric proportional hazards model. Results. Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval [CI], 14.7-408.2; P < .0001), while protease inhibitor and NNRTI replacement rates were similar. Higher plasma HIV-1 RNA level predicted faster mutation replacement, but this was not statistically significant (hazard ratio, 1.71 log(10) copies/mL; 95% CI, .90-3.25 log(10) copies/mL; P = .11). We found substantial person-to-person variability in mutation replacement rates not accounted for by viral load or mutation class (P < .0001). Conclusions. The rapid replacement of M184V/I mutations is consistent with known fitness costs. The long-term persistence of NNRTI and protease inhibitor mutations suggests a risk for person-to-person propagation. Host and/or viral factors not accounted for by viral load or mutation class are likely influencing mutation replacement and warrant further study.

Obstructive Sleep Apnea An Emerging Risk Factor for Atherosclerosis

Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area. CHEST 2011; 140(2):534-542

Role of p21 and oxidative stress on renal tubular resistance after acute ischaemic injury

Background. Subsequent ischaemic episodes may induce renal resistance. P21 is a cell cycle inhibitor that may be induced by oxygen-free radicals and may have a protective effect in ischaemic acute kidney injury (AKI). This study aimed at evaluating the role of oxidative stress and p21 on tubular resistance in a model of acquired resistance after renal ischaemia and in isolated renal tubules. Methods. Wistar rats were divided into: Group 1-sham; Group 2-sham operated and after 2 days submitted to 45-min ischaemia; and Group 3-45-min ischaemia followed after 2 days by a second 45-min ischaemia. Plasma urea was evaluated on Days 0, 2 and 4. Serum creatinine, creatinine clearance and oxidants (thiobarbituric acid-reactive substances) were determined 48 h after the second procedure (Day 4). Histology, immunohistochemistry for lymphocytes (CD3), macrophages (ED1), proliferation (PCNA) and apoptosis (TUNEL) were also evaluated. Rat proximal tubules (PTs) were isolated by collagenase digestion and Percoll gradient from control rats and rats previously subjected to 35 min of ischaemia. PTs were submitted to 15-min hypoxia followed by 45-min reoxygenation. Cell injury was assessed by lactate dehydrogenase release and hydroperoxide production (xylenol orange). Results. Ischaemia induced AKI in Group 2 and 3 rats. Subsequent ischaemia did not aggravate renal injury, demonstrating renal resistance (Group 3). Renal function recovery was similar in Group 2 and 3. Plasma and urine oxidants were similar among in Group 2 and 3. Histology disclosed acute tubular necrosis in Group 2 and 3. Lymphocyte infiltrates were similar among all groups whereas macrophages infiltrate was greater in Group 3. Cell proliferation was greater in Group 2 compared with Group 3. Apoptosis was similar in groups 2 and 3. The p21 expression was increased only in Group 3 whereas it was similar in groups 1 and 2. PTs from the ischaemia group were sensitive to hypoxia but resistant to reoxygenation injury which was followed by lower hydroperoxide production compared to control PT. Conclusion. Renal resistance induced by ischaemia was associated with cell mechanism mediators involving oxidative stress and increased p21 expression.

Changes in Perfusion-Weighted Magnetic Resonance Imaging after Carotid Angioplasty with Stent

Carotid artery stenosis due to arteriosclerosis increases the risk of cerebral ischemia via embolic phenomena or reduced blood flow. The changes in cerebral perfusion that may occur after treatment are not clearly understood. This study evaluated the changes in cerebral microcirculation following carotid angioplasty with stenting (CAS) under cerebral protection with filters using ultrafast gradient echo (GRE) perfusion weighted imaging (PWI) with magnetic resonance imaging (MRI). Prospectively, 21 cervical carotid stenosis patients, mean age 69.95 years, underwent MRI 12 h before and 72 h after CAS. PWI parameters were collected for statistical analysis: cerebral blood volume (CB V), mean transit time (MTT) and time to peak (TTP). Statistical analysis was applied to absolute parameters and to values normalized against those from the contralateral parenchyma. The main finding of this study was improved hemodynamics for the normalized data after CAS, shown by reduced MTT (p<0.001) and TTP (p=0.019) in the territory fed by the middle cerebral artery ipsilateral to the CAS. Absolute data showed increased blood volume in the cerebral hemispheres after CAS, which was more accentuated on the stent side (p=0.016) than the contralateral side (p=0.029). Early improvements in cerebral perfusion, mainly seen in the normalized data, were clearly demonstrated in the timing parameters - TTP & MTT - after CAS.

Additive Effects of Obstructive Sleep Apnea and Hypertension on Early Markers of Carotid Atherosclerosis

Obstructive sleep apnea (OSA) has emerged as an independent risk factor for atherosclerosis. However, OSA is frequently associated with several risk factors for atherosclerosis, including hypertension (HTN). The impact of OSA and HTN alone compared with the association of both conditions on carotid atherosclerosis is not understood. We studied 94 middle-aged participants free of smoking and diabetes mellitus who were divided into 4 groups: controls (n = 22), OSA (n = 25), HTN (n = 20), and OSA + HTN (n = 27). All of the participants underwent polysomnography and carotid measurements of intima-media thickness, diameter, and distensibility with an echo-tracking device. Compared with controls, intima-media thickness and carotid diameter were similarly higher in OSA (713 +/- 117 and 7117 +/- 805 mu m), and HTN groups (713 +/- 182 and 7191 +/- 818 mu m), with a further significant increase in OSA + HTN patients (837 +/- 181 and 7927 +/- 821 mu m, respectively; P < 0.01). Carotid distensibility was significantly lower in HTN (P < 0.05) and OSA + HTN subjects (P < 0.001) compared with controls. In the OSA + HTN group, carotid distensibility was significantly lower than in the OSA group and controls (P < 0.05 for each comparison). Multivariate analysis showed that intima-media thickness was positively related to systolic blood pressure and apnea-hypopnea index. Apnea-hypopnea index was the only factor related to carotid diameter. Age and systolic blood pressure were independently related to carotid distensibility. In conclusion, the association of OSA and HTN has additive effects on markers of carotid atherosclerosis. Because early markers of carotid atherosclerosis predict future cardiovascular events, including not only stroke but also myocardial infarction, these findings may help to explain the increased risk of cardiovascular disease in patients with OSA. (Hypertension. 2009; 53: 64-69.)

Effects of sinoaortic Denervation on Hemodynamic parameters during natural sleep in rats

Study Objectives: To analyze the role of arterial baroreflex on hemodynamic changes during synchronized and desynchronized sleep phases of natural sleep in rats. Design: Experimental study. Setting: Laboratory. Participants: Seventeen male Wistar rats. Interventions: No intervention (control, n = 8) or sinoaortic denervation (SAD, n = 9). Measurements and Results: Sleep phases were monitored by electrocorticogram, and blood pressure was measured directly by a catheter in the carotid artery. Cardiac output, as well as total and regional vascular resistances, were determined by measuring the subdiaphragmatic aorta and iliac artery flows with Doppler flow probes, respectively. In contrast to the control group, the SAD group had a strong reduction in blood pressure (-19.9% +/- 2.6% vs -0.7% +/- 2.1%) during desynchronized sleep, and cardiac output showed an exacerbated reduction (-10.4% +/- 3.5% vs 1.1% +/- 1.7%). In SAD rats, total vascular resistance decreased during desynchronized sleep (-10.1% +/- 3.5% vs -1.0% +/- 1.7%), and the increase in regional vascular resistance observed in the control group was abolished (27.5% +/- 8.3% vs -0.8% +/- 9.4%). Conclusions: SAD caused profound changes in blood pressure, cardiac output, and total vascular resistance, with a significant increase in muscle vascular resistance during synchronized sleep. Our results suggest that baroreflex plays an important role in maintaining the normal balance of cardiac output and total vascular resistance during sleep.

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.

Effects of progressive resistance strength training on knee biomechanics during single leg step-up in persons with mild knee osteoarthritis

Background: The goal of this study was to determine if increasing strength in primary knee extensors and flexors would directly affect net knee joint moments during a common functional task in persons with knee osteoarthritis. Methods: An exploratory single sample clinical trial with pre-post treatment measures was used to study volunteers with clinical diagnosis of mild knee osteoarthritis (OA) in one knee. Subjects participated in an individually supervised training program 3 times a week for eight weeks consisting of progressive resistive exercises for knee extensors and knee flexors. Pre and post training outcome assessments included: 1. Net internal knee joint moments, 2. Electromyography of primary knee extensors and flexors, and 3. Self-report measures of knee pain and function. The distribution of lower extremity joint moments as a percent of the total support moment was also investigated. Findings: Pain, symptoms, activities of daily life, quality of life, stiffness, and function scores showed significant improvement following strength training. Knee internal valgus and hip internal rotation moments showed increasing but non-statistically significant changes post-training. There were no significant differences in muscle co-contraction activation of the Quadriceps and Hamstrings. Interpretation: While exercise continues to be an important element of OA management, the results of this study suggest improvements in function, pain, and other symptoms, as a result of strength training may not be causally related to specific biomechanical changes in net joint moments. (C) 2011 Elsevier Ltd. All rights reserved.

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.

Muscle mass gain observed in patients with short bowel syndrome subjected to resistance training

Few studies are available about the evaluation of resistance training in patients with protein-energy malnutrition. To assess the effects of resistance training on the recovery of nutritional status of patients with short bowel syndrome, with a small bowel remnant of less than 100 cm, 9 patients of both sexes with protein-energy malnutrition after extensive resection of the small bowel were submitted to resistance training of progressive intensity consisting of concentric and eccentric work exercises for the upper limbs, trunk, and lower limbs, with the individuality and limitations of each patients being respected. Food consumption was monitored by 24-hour food recall performed during the initial phase of the study, before and 7 and 14 weeks after physical training, and by a dietary record for a period of 3 days of oral feeding. The nutrients administered by the enteral and parenteral route were recorded. A significant increase in total arm area (P <= .01) and fat-free mass (P <= .01) was observed as determined by computed tomography. An increase in total energy ingestion and carbohydrate consumption (P <= .01) was also observed. In addition, the activity of the enzyme carnosinase was increased after resistance training (P <= .01). The present results show that resistance training in patients with short bowel syndrome and protein-energy malnutrition can be considered to be a part of the nonmedicamentous treatment of these patients, leading to better nutrient use and to a gain of lean mass. (c) 2008 Elsevier Inc. All rights reserved.

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.

OXIDATIVE STRESS BIOMARKER RESPONSES TO AN ACUTE SESSION OF HYPERTROPHY-RESISTANCE TRADITIONAL INTERVAL TRAINING AND CIRCUIT TRAINING

Deminice, R, Sicchieri, T, Mialich, MS, Milani, F, Ovidio, PP, and Jordao, AA. Oxidative stress biomarker responses to an acute session of hypertrophy-resistance traditional interval training and circuit training. J Strength Cond Res 25(3): 798-804, 2011-We have studied circuit resistance schemes with high loads as a time-effective alternative to hypertrophy-traditional resistance training. However, the oxidative stress biomarker responses to high-load circuit training are unknown. The aim of the present study was to compare oxidative stress biomarker response with an acute session of hypertrophy-resistance circuit training and traditional interval training. A week after the 1 repetition maximum (1RM) test, 11 healthy and well-trained male participants completed hypertrophy-resistance acute sessions of traditional interval training (3 x 10 repetitions at 75% of the 1RM, with 90-second passive rest) and circuit training (3 x 10 repetitions at 75% of the 1RM, in alternating performance of 2 exercises with different muscle groups) in a randomized and cross-over design. Venous blood samples were collected before (pre) and 10 minutes after (post) the resistance training sessions for oxidative stress biomarker assays. As expected, the time used to complete the circuit training (20.2 +/- 1.6) was half of that needed to complete the traditional interval training (40.3 +/- 1.8). Significant increases (p < 0.05) in thiobarbituric acid reactive substances (40%), creatine kinase (CK) (67%), glutathione (14%), and uric acid (25%) were detected posttraditional interval training session in relation to pre. In relation to circuit training, a significant increase in CK (33%) activity postsession in relation to pre was observed. Statistical analysis did not reveal any other change in the oxidative stress biomarker after circuit training. In conclusion, circuit resistance-hypertrophy training scheme proposed in the current study promoted lower oxidative stress biomarkers and antioxidant modulations compared with resistance traditional interval training.

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.