Effects of muscle composition and architecture on specific strength in obese older women.

NEW FINDINGS: What is the central question of this study? Do obesity-specific factors affect skeletal muscle performance in older individuals? What is the main finding and its importance? Older obese women have a larger quadriceps femoris size but develop lower tension per unit of skeletal muscle than their normal-weight counterparts. Muscle impairment and excess body mass are very common among older people. Given that the effect of obesity on strength production has scarcely been studied in older individuals, we analysed functional and structural characteristics of quadriceps femoris (QF) in obese (OB) and normal-weight (NW) older women with comparable habitual physical activity. In five OB (body mass index 36.8 ± 1.9 kg m(-2), age 72.4 ± 2.3 years) and six NW well-functioning older women (body mass index 24.3 ± 1.8 kg m(-2), age 72.7 ± 1.9 years), peak knee-extension torque (KET) was measured in isometric (90 deg knee flexion) and isokinetic conditions (240, 180, 120 and 60 deg s(-1)). Mid-thigh QF cross-sectional area (CSA) and muscle tissue fat content (MF%) were determined with magnetic resonance imaging (Dixon sequence). Muscle fascicle length and pennation angle (PA) were assessed with ultrasonography for each muscle belly of the QF (vastus lateralis, vastus intermedius, rectus femoris and vastus intermedius). Despite similar values of KET, CSA was 17.0% larger in OB than in NW women (P < 0.05), so that KET/CSA was significantly lower (P < 0.05) in OB women. Compared with NW women, OB women had 28.7% higher MF% (P < 0.05) and 24.9% higher average PA (P < 0.05), while fascicle length was similar. Overall, isometric KET/CSA was negatively affected by both MF% (P < 0.05) and PA (P < 0.05), while isokinetic KET/CSA was negatively affected only by MF% (P < 0.01). Muscle composition and architecture seem to be important determinants of KET/CSA in elderly women. In fact, owing to the effect of obesity overload, OB women have a larger QF size than NW women, but unfavourable muscle composition and architecture. The higher MF% and steeper PA observed in OB women are associated with reduced levels of muscle specific strength.

Effect of mechanical and metabolic factors on motor function and fatigue in obese men and women: a cross-sectional study.

BACKGROUND: Mechanical overload and poor quality of contractile elements related to metabolic abnormalities concur to motor disability of obesity. The independent contribution of these factors to motor dysfunction in obese individuals is scarcely defined. AIM: Aim of the study is to test the hypothesis that metabolic factors may independently affect motor function in obesity. METHODS: Leg maximum power output per unit body mass (W Mb), per unit fat-free mas (W FFM) and fatigue in daily functioning were assessed in 635 obese [body mass index (BMI)≥ 35 kg/m(2)] individuals (286 men, 349 women) aged 19-78 yr. The independent effects of age, BMI, insulin resistance and the five components of the metabolic syndrome on W Mb, W FFM and fatigue were evaluated by multivariate analysis. RESULTS: A multiple regression analysis revealed that in both genders W Mb (denoting the individual's performance capability during anaerobic tasks) was independently reduced by age (p<0.001), BMI (p<0.05-0.001) and abnormalities of glucose metabolism (p<0.06-0.01), while W FFM (representing the muscle intrinsic anaerobic capability) was affected only by age (p<0.001) and glucose metabolism impairment (p<0.06-0.01). In both genders fatigue was increased by age (p<0.001) and BMI (p<0.05-0.01), but augmented by low levels of HDL-cholesterol in men only (p<0.05). CONCLUSIONS: Besides depending on mechanical overload and age, low muscle power output in obese individuals was independently associated also with metabolic abnormalities related to impaired glucose homeostasis. Fatigue and performance, although similarly influenced by age and body mass excess, are affected by different metabolic factors.

Effects of low- and high-intensity exercise training on body composition and substrate metabolism in obese adolescents.

The objective was to investigate the effects of a 3- week weight-management program including moderate energy restriction and exercise training at 2 intensities [low intensity (LI): 40% and high intensity (HI): 70% maximal oxygen uptake (V'O(2)max)] on body composition, energy expenditure, and fat oxidation rate in severely obese adolescents. Twenty obese adolescents, aged 15-17 yr (body mass index: 37.5 kg/m(2); 38.2% fat mass) participated in this study. Before starting (week 0, W0) and at the end of the weight-management period (week 3,W3), body composition was assessed by a multifrequency tetrapolar impedancemeter; basal metabolic rate (BMR), energy expenditure, and substrate oxidation rate during exercise and post-exercise recovery by indirect calorimetry. At W3, body mass and fat mass decreased significantly (p<0.005) in all groups, and the decreases were significantly greater in the LI than in the HI group (-8.1±1.6 vs -5.9±1.6 kg and -4.2±1.9 vs -2.3±1.7 kg, p<0.05, respectively). Predicted V'O(2)max, expressed in relative values, changed significantly only in the HI group by +0.010±0.006 l/(kg fat-free mass × min) (p=0.010). By contrast, no significant changes were observed at W3 in BMR, energy expenditure, and substrate oxidation rate during exercise and post-exercise recovery. In conclusion, LI (40% of V'O(2)max) physical activity favors fat oxidation and it seems advisable to encourage obese adolescents to perform LI physical activity which is more feasible and acceptable than intense exercise.

Energy cost and cardiovascular response to upper and lower limb rhythmic exercise with different equipments in normal-weight and severely obese individuals.

AIMS: The purpose of the study was to assess energy expenditure and cardiovascular response to rhythmic activity with 6 machines exercising different arm and leg muscle groups in normal-weight (NW) and obese (OB) individuals. METHODS: In 16 extremely OB subjects and 15 NW controls, oxygen uptake (VO2), heart rate (HR), blood lactate (LA) concentration and ratings of perceived exertion (RPE) were determined during submaximal rhythmic exercise at different intensities obtained by increasing the frequency of the movement (FOM) with each machine. Peak VO2 (VO2p) for each equipment was determined with incremental tests up to exhaustion, whereas maximal VO2 was estimated at cycle ergometer. RESULTS: Net energy cost (Enet) of exercise increased (p<0.001) for effect of FOM, in both NW and OB with all equipments. Enet was higher in OB than NW during submaximal exercise with Chest/Back, Shoulder Press/Lat Pull, and Leg Press. Higher VO2p were attained with lower limbs than with upper limbs, in both NW (p<0.001) and OB (p<0.001). At the same VO2 (relative to maximal), HR, LA, and RPE were similar in NW and OB but higher during arm than leg activity (p<0.001), while at the same VO2 (relative to VO2p) no difference was detected. CONCLUSION: Enet of rhythmic exercise is higher in OB than NW with machines requiring wide displacement of large body segments. For both NW and OB, physiological responses and RPE are importantly affected by the relative activation of involved muscles. LA concentration is an important determinant of RPE, independent of the limb in activity.

Growth hormone and lactate responses induced by maximal isometric voluntary contractions and whole-body vibrations in healthy subjects.

BACKGROUND: In contrast with maximal voluntary resistance exercise, which is allegedly considered a potent GH stimulus in young subjects, evaluation of GH response to whole-body vibrations (WBV) has yielded conflicting results. METHODS: The acute effects of WBV alone (test A), maximal voluntary isometric contractions (MVC) (test B), and combination of WBV and MVC (test C) on serum GH and blood lactate (LA) levels were studied in 9 healthy adult males. Muscle soreness was assessed 24 and 48 h after exercise by a visual analogue scale. RESULTS: GH responses were significantly higher after tests B and C than after test A (GH peaks: 18.8 ± 9.5 ng/ml or 20.8 ± 13.7 ng/ml, respectively, vs 4.3 ± 3.5 ng/ml; p<0.05), with no difference between tests B and C. LA concentrations significantly increased after tests A, B, and C, being significantly higher after tests B and C than after test A (LA peaks: 2.0 ± 0.5 mmol/l or 6.7 ± 2.3 mmol/l, respectively, vs 7.6 ± 0.9 mmol/l; p<0.05). Peak LA values were significantly correlated to GH peaks in the 3 tests (r=0.48; p<0.05). Muscle soreness was significantly higher 24-48 h after tests B and C than after test A, no significant differences being present between tests B and C. CONCLUSIONS: WBV stimulates GH secretion and LA production, with no additive effect when combined with repeated isometric voluntary contractions. Optimization of protocols based on WBV seems important to maximize the positive effects of this intervention on the somatotropic function.

Changes in plasma levels of ghrelin, leptin, and other hormonal and metabolic parameters following standardized breakfast, lunch, and physical exercise before and after a multidisciplinary weight-reduction intervention in obese adolescents.

OBJECTIVE: To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of some hormonal and metabolic parameters to meals and exercise. DESIGN: Clinical longitudinal study on inpatients in a specialised institution. SUBJECTS: A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg]. MEASUREMENTS: The changes in plasma concentration of leptin, ghrelin, GH, IGF-I, insulin, glucose, and non-esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale. RESULTS: At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (p<0.05), without any significant fat-free mass loss (in % terms). In response to both meals and exercise, after the 3-week intervention, plasma leptin concentration decreased significantly (p<0.05), whereas the other hormones (insulin, ghrelin, GH, and IGF-I) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention. CONCLUSION: This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.

Metabolic responses to submaximal treadmill walking and cycle ergometer pedalling in obese adolescents.

Physical activity is essential in obesity management because of the impact of exercise-related energy expenditure (EE) and fat oxidation (Fox) rate on a daily balance, but the specific physiological effects of different exercise modalities are scarcely known in obese individuals. The objective of the study was to compare the metabolic responses to treadmill (TM) and cycle ergometer (CE) exercise in obese adolescents. Gas exchange, heart rate (HR), blood lactate (LA) concentration, EE and Fox were determined at different intensity levels (up to about 85% of maximal oxygen uptake) during TM and CE in 14 pubertal (Tanner stage: >3) obese (BMI SDS: 2.15-3.86) male adolescents (age: 13-18 years). At comparable HR, oxygen uptake, EE and Fox were higher, and LA lower, during TM than CE (P<0.05-0.001), suggesting that cycling imposes a metabolic involvement at the level of the single active muscles greater than walking. Therefore, due to different physiological responses to TM and CE, walking was more convenient than cycling in obese adolescents, permitting to attain the same EE at lower HR, with lower blood LA concentration and with greater Fox. These conclusions seem clinically relevant when using exercise as a part of multidisciplinary treatment for juvenile obesity and amelioration of related metabolic disturbances.

Physical activity ratios for various commonly performed sedentary and physical activities in obese adolescents.

The physical activity ratio (PAR) values are commonly used to convert subjects' physical activity recalls into estimates of daily energy expenditure (DEE). A PAR is defined as the ratio between energy expenditure corresponding to a sedentary or a physical activity (kJ/min) and basal metabolic rate [(BMR) kJ/min]. The objective of the present study was to determine the PAR for different sedentary and physical activities in obese adolescents. Thirty-three obese adolescents [mean body mass index: 35.1 kg/m2; 40.3 % fat mass] aged 11 to 17 yr participated in this study. BMR was assessed by indirect calorimetry after an overnight fast by means of an open-circuit, indirect computerised calorimetry with a rigid, transparent, ventilated canopy. Energy expenditures corresponding to various sedentary and physical activities in free-living conditions were determined using a portable metabolic unit, and body composition by bioelectrical impedance analysis (BIA). The PAR of each activity was obtained by dividing the assessed energy expenditure by BMR. In this study, the PAR of various sedentary and physical activities did not vary significantly with sex, age, and body mass. Thus, the data for boys and girls were combined and the PAR for 27 sedentary and physical activities were determined. The PAR values can be applied to determine the mean DEE (kJ) using the specific equation considering BMR (kJ/min), PAR, and duration (min) of each activity performed by the subject during the 24 h. This information will be useful to health-care professionals because estimation of DEE in obese adolescents is necessary in order to prescribe an adequate dietary therapy to induce a desired level of energy deficit.

The energy cost of cycling and aerobic performance of obese adolescent girls.

In order to assess the energy cost of cycling and aerobic capacity in juvenile obesity, responses to cycle ergometer exercise were studied in 10 pubertal obese (OB) [body mass index (BMI) SD score (SDS): 3.40+/-0.58 SD] adolescent girls (age: 16.0+/-1.2 yr) and in 10 normal-weight (NW, BMI SDS: -0.30+/-0.54) girls of the same age (15.1+/-1.9). To this aim, gas exchange, heart rate (HR), and energy expenditure (EE) were studied during graded cycle ergometer test at 40, 60, 80, 100, and 120 W. The energy cost of cycling was higher in OB, being oxygen uptake (VO2) higher (about 20%) in OB than in NW girls at all workloads (p<0.01-0.001). Estimated maximal VO2 and VO2 at anaerobic threshold were significantly (p<0.05) higher in OB girls [although lower per unit body mass (p<0.01) and similar for unit fat-free mass], and explained the higher oxygen pulse and lower HR for any EE observed during submaximal exercise in OB. While net mechanical efficiency (ME) was significantly lower in OB (p<0.01), delta ME was similar in both groups, indicating no substantial derangement of muscle intrinsic efficiency. It is concluded that, despite a higher cost of cycling, OB girls can rely on a larger aerobic capacity which makes them able to sustain this kind of exercise within a wide range of work loads, with relevant implications when planning protocols of physical activity in the context of interventions for the reduction of juvenile obesity.

Factor analysis of metabolic syndrome components in severely obese girls and boys.

AIMS AND METHODS: Factor analysis is a multivariate correlation technique frequently employed to characterise the aggregation of abnormalities underlying the metabolic syndrome (MS), but scarcely used in obese adolescents. Aim of the study was to investigate the clustering of anthropometric and metabolic variables related to the MS in 487 obese pubertal adolescents (140 boys, 347 girls) in the range of age 11-18 yr employing the factor analysis with exploratory approach. RESULTS: Principal component analysis reduced 11 correlated physiological variables to 4 uncorrelated factors that explained 68.7% of the variance in the original parameters in boys, and 68.4% in girls. In boys, these factors were: obesity/ hypertension, insulin resistance, dyslipidemia, and hyperglycemia, with elements related to obesity and fat distribution loaded also in dyslipidemia and insulin resistance. In girls no commonalities were detected, but elements of dyslipidemia and insulin resistance were loaded in a single factor, whereas elements of obesity and hypertension were loaded in separate factors. CONCLUSIONS: The identification of 4 independent factors suggests a multiple physiological origin of the MS also in youngsters. The measures of adiposity were correlated with development of hypertension, insulin resistance, and dyslipidemic phenomena in boys only, whereas in girls anthropometric measures were not correlated with any tested component of the MS, possibly disclosing the protective effect of female sex hormones in the juvenile age span.

The combined effect of adiposity, fat distribution and age on cardiovascular risk factors and motor disability in a cohort of obese women (aged 18-83).

Obesity is associated with a number of serious diseases and with a degree of motor disability, but the extent of the risk and functional derangement within the obese population is not yet completely defined. The study aims to evaluate the combined effect of degree of adiposity, body fat distribution and age on selected cardiovascular risk factors and functional motor disability in a cohort of obese women. A multivariate analysis of variance (MANOVA) is employed to show the combined impact of body mass index (BMI), waist-to-hip ratio (WHR) and age on systolic and diastolic blood pressure (SBP and DBP), total and HDL cholesterol (T-CH and HDL-CH), coronary heart disease (CHD) risk, leg power output (W, assessed with a Margaria test for stair climbing) and subjective general fatigue in a cohort of 463 obese women (BMI range 30.2-66.7 kg/m2; age range 18-83 yr). High WHR and older age, but not BMI, are to a variable degree related to unfavorable values of parameters which contribute to the cardiovascular risk. WHR in the high range is associated with significantly higher values of SBP (p<0.001), CHD risk scores (p<0.001) as well as lower levels of HDL-CH (p=0.01), while older age is significantly associated with higher SBP (p<0.001), T-CH (p<0.001) and CHD risk scores (p<0.001). A significant interaction between age and WHR was detected in the effect on DBP (p=0.01), the negative role of high WHR values being apparent in older women (age > or = 51 yr) but not in younger ones (age < 51 yr). Although not significantly related to CHD risk scores, BMI interacted significantly with WHR in determining high risk score values (p=0.01), the negative effect of a high WHR being apparent in women with a high degree of obesity (BMI > or = 40 kg/m2) but not in those with a low one (BMI < 40 kg/m2). In contrast, WHR did not significantly affect W, which appeared to be mainly dependent on age (p<0.001) and BMI (p<0.001), when considered in terms of unit body mass (BM). Subjective global fatigue, however, was unaffected by any of the factors considered. In the present cohort of obese women, older age and excessive abdominal fat distribution (as assessed by WHR) appear to be significant factors in relation to increased cardiovascular disease risk, irrespective of BMI, while older age and higher levels of overall adiposity are associated with functional motor derangement irrespective of body fat distribution. This suggests that obesity increases metabolic risk and induces motor dysfunction by means of different biological mechanisms and with a different impact within the obese female population.

Changes in body composition, physical performance and cardiovascular risk factors after a 3-week integrated body weight reduction program and after 1-y follow-up in severely obese men and women.

OBJECTIVE: To investigate the short- and medium-term (ie, at 1-y follow-up) effects of a hospital-based body weight reduction (BWR) program lasting 3 weeks in severely obese individuals. DESIGN: Longitudinal, clinical intervention study entailing energy-restricted diet, tailored aerobic-strength exercise, psychological counselling and nutritional education during a 3-week period followed by 49 weeks of indirect supervision at home. SUBJECTS: In all, 45 women and 19 men aged 30.2 +/- 7.2 y (mean +/- s.d.) with severe obesity (BMI: 41.3 +/- 4.3 kg/m(2)), classified as weight losers (final < initial weight) and regainers (final> or =initial weight). INTERVENTIONS: Body composition, physical performance and cardiovascular risk factors before and after the BWR program and at follow-up. RESULTS: The large majority of the experimental subjects obtained a clinical success after the 1-y period, and the rate was higher in females (n = 37/45, ie, 82.2%) than in males (n = 11/19, ie, 57.9%). At follow-up, weight losers had higher percent fat-free mass, muscle strength, HDL-cholesterol and self-reported physical activity level and lower total cholesterol and glucose levels than weight regainers (P < 0.05-0.01). Males displayed significantly larger fat-free mass losses than females at post-BWR and at follow-up. CONCLUSIONS A 3-week hospital-based integrated BWR program resulted in a high rate of clinical success in severely obese individuals at 1-y follow-up (particularly in females), that was associated with increased levels of self-reported physical activity and improved muscle strength and lipid profile. Further research is needed to establish the long-term effects (ie, at 2-5 y) associated to this treatment.

Effect of inhaled salbutamol on mucociliary clearance in patients with chronic bronchitis.

We investigated, in a double blind fashion, the acute effect of an inhaled beta 2-agonist drug (salbutamol) on mucociliary clearance in 20 patients with chronic bronchitis: ten treated with the drug and the remaining ten with placebo. Following inhalation of pre-sized human albumin microspheres with a mass median diameter of 1.5 micrometers, radioactivity was recorded for one hour (control period) with the patient in the supine posture with a large field computerized gamma camera collimated over the chest. At the end of the first hour, without moving the patient, either salbutamol (500 micrograms) or placebo was nebulized from a commercial canister and recording carried out for another two hours. At the end of the recording period areas of interest were selected and time activity curves generated, from which the percentage activity cleared in the first, second and third hour was calculated. Whereas no significant differences in clearance between the two groups were found in the control period, inhaled salbutamol significantly increased mucociliary clearance rate; particle removal in the second hour (test period) was 36.42 +/- 5.61 (SD) percent for the group treated with salbutamol, and 10.87 +/- 2.47 (SD) percent for the group receiving placebo.

Effect of NO synthase inhibition on cardiovascular and pulmonary dysfunction in a porcine short-term model of endotoxic shock.

In a porcine model of endotoxic shock, we evaluated the circulatory and respiratory effects of NO synthase (NOS) blockade. Twenty anaesthetised pigs were divided into three groups and studied for 240 min after induction of endotoxic shock with lipopolysaccharides of Escherichia coli (LPS). After 180 min of endotoxic shock, one group (n = 6) received aminoguanidine, another group (n = 6) received N(G)-nitro-L -arginine methyl ester (L -NAME) and a third group (n = 8) received only LPS. A sham group (n = 3) was also studied. LPS decreased systemic arterial pressure and cardiac output (CO) and increased mean pulmonary arterial pressure (MPAP), pulmonary vascular resistance (PVR) and heart rate. Significant changes were also observed in compliance (-18.4%) and resistance (+33.6%) of the respiratory system. Aminoguanidine did not modify LPS-dependent effects, while, after L -NAME, a significant increase in MPAP, PVR and SVR and a decrease in CO were observed. In conclusion, aminoguanidine does not play a significant cardiocirculatory and pulmonary role in the short-term dysfunction of endotoxic shock, while L -NAME has a detrimental effect on haemodynamics, suggesting a protective role of constitutive NO production at vascular level during the early stages of endotoxaemia.

Endothelin involvement in respiratory centre activity.

To evaluate the role of endothelin (ET) in respiratory homeostasis we studied the effects of the ET(A) and ET(B) receptor blocking agent bosentan on respiratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The results show that the block of ET receptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, without affecting the centroid frequency of the power spectrum. Bosentan administration induced a significant increase in tidal volume (V(T)), accompanied by a significant decrease in respiratory frequency, without any significant change in pulmonary ventilation, CO(2) arterial blood gas pressure or pH. Since the relationship between V(T) and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch threshold. Both inspiratory and expiratory times during occluded breathing were increased by block of ET receptors, suggesting also a central respiratory neuromodulator effect of ET. In conclusion the present results suggest that the block of ET receptors in spontaneously breathing pigs exerts a role on mechanical properties of the respiratory system as well as on peripheral and central mechanisms of breathing control.

Short-term changes of cardiovascular risk factors after a non-pharmacological body weight reduction program.

OBJECTIVE: To test the short-term effectiveness of a 3 week hospital-based body weight reduction (BWR) program on selected coronary heart disease (CHD) risk factors in obese subjects. DESIGN: Intervention study to assess the modifications in CHD risk factor scores estimated according to Framingham risk factor categories (age, total cholesterol, high density lipoprotein (HDL) cholesterol, blood pressure, diabetes and smoking). SETTING: 3rd Division of Metabolic Diseases, Italian Institute for Auxology, Piancavallo (VB), Italy. SUBJECTS: Two-hundred and sixty-eight obese patients (43 men, 225 women, age range 19-81 y; body mass index (BMI) range 30-67). INTERVENTION: The BWR program consisted of a 3 week integrated energy-restricted diet (1200-1800 kcal/day), associated with moderate aerobic exercise, psychological counselling and educational lectures. RESULTS: Substantial reductions of total cholesterol (16.7%), HDL cholesterol (14.8%), systolic (11.2%) and diastolic blood pressure (8.7%) were observed at the end of the intervention, even with relatively moderate decrease in weight (4.1%) and in persistence of elevated BMI (over 40 kg/m2). The mean CHD Framingham score decreased by 16.1%, from 7.8 to 6.2. The BWR-induced changes were similar in both sexes, and across strata of age and BMI. CONCLUSIONS: The full-time participation of the patients in the hospital-based, integrated BWR program may explain the positive clinical outcome in all the subgroups considered, although the long-term results need to be quantified. SPONSORSHIPS: Partially supported by Progetti di Ricerca Corrente, Istituto Auxologico Italiano, IRCCS, Milan, Italy.

Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs.

PURPOSE: To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs. MATERIALS AND METHODS: Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals. RESULTS: LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance. CONCLUSIONS: We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.

Rationale for hospital-based rehabilitation in obesity with comorbidities.

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to-date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.