Beyond pulmonary rehabilitation: can the PICk UP programme fill the gap? A randomised trial in COPD.

INTRODUCTION AND OBJECTIVES: Pulmonary rehabilitation (PR) is a fundamental intervention to manage COPD, however, maintaining its benefits is challenging. Engaging in physical activity might help to prolong PR benefits. This study assessed the efficacy and effectiveness of a personalised community-based physical activity programme to sustain physical activity and other health-related PR benefits, in people with COPD. MATERIALS AND METHODS: This was a multicentre, assessor blinded, randomised controlled trial. Following 12-weeks of PR, people with COPD were assigned to a six-months personalised community-based physical activity programme (experimental group), or to standard care (control group). Physical activity was assessed via: time spent in moderate to vigorous physical activities per day (primary outcome measure), steps/day and the brief physical activity assessment tool. Secondary outcomes included sedentary behaviour, functional status, peripheral muscle strength, balance, symptoms, emotional state, health-related quality of life, exacerbations and healthcare utilization. Assessments were performed immediately post-PR and after three- and six-months. Efficacy and effectiveness were evaluated using intention-to-treat and per-protocol analysis with linear mixed models. RESULTS: Sixty-one participants (experimental group: n = 32; control group: n = 29), with balanced baseline characteristics between groups (69.6 ± 8.5 years old, 84 % male, FEV1 57.1 ± 16.7 %predicted) were included. Changes in all physical activity outcomes and in one-minute sit-to-stand were significantly different (P < 0.05) between groups at the six-month follow-up. In the remaining outcomes there were no differences between groups. CONCLUSIONS: The community-based physical activity programme resulted in better physical activity levels and sit-to-stand performance, six-months after completing PR, in COPD. No additional benefits were observed for other secondary outcomes.

Tearing of free-standing graphene.

We examine the fracture mechanics of tearing graphene. We present a molecular dynamics simulation of the propagation of cracks in clamped, free-standing graphene as a function of the out-of-plane force. The geometry is motivated by experimental configurations that expose graphene sheets to out-of-plane forces, such as back-gate voltage. We establish the geometry and basic energetics of failure and obtain approximate analytical expressions for critical crack lengths and forces. We also propose a method to obtain graphene's toughness. We observe that the cracks' path and the edge structure produced are dependent on the initial crack length. This work may help avoid the tearing of graphene sheets and aid the production of samples with specific edge structures.

Chronic stress, but not hypercaloric diet, impairs vascular function in rats.

The aim of this study was to evaluate vascular and metabolic effects of chronic mild unpredictable stress (CMS) and hypercaloric diet (HD) without carbohydrate supplementation in rats. Male Sprague-Dawley rats were randomly assigned to four groups: Control, HD, CMS, and HD plus CMS. CMS consisted of the application of different stressors for 3 weeks. The rats were killed 15 days after CMS exposure. The HD group presented higher plasma lipid concentrations, without changes in fasting glucose concentration, glucose tolerance test, and vascular function and morphology, in comparison with the control group. Stressed rats presented higher fasting blood concentration of insulin, higher homeostasis model assessment index values and area under the curve in an oral glucose tolerance test, in comparison with non-stressed rats. CMS increased the plasma concentrations of corticosterone and lipids, and the atherogenic index values, without change in high-density lipoprotein level. CMS increased intima-media thickness and induced endothelium-dependent supersensitivity to phenylephrine, and lowered the relaxation response to acetylcholine in the thoracic aorta isolated from rats fed with control or HD, in comparison with non-stressed groups. CMS effects were independent of diet. In non-stressed rats, the HD induced dyslipidemia, but did not change glucose metabolism, vascular function, or morphology. The data from this study indicate that CMS promotes a set of events which together can contribute to impair function of the thoracic aorta.

Proatherosclerotic effects of chronic stress in male rats: altered phenylephrine sensitivity and nitric oxide synthase activity of aorta and circulating lipids.

The aim of this study was to analyze the effects of chronic mild unpredictable stress (CMS) on the vasoconstrictor response and morphology of the thoracic aorta and serum lipid profiles in rats. Male Sprague-Dawley rats were submitted to CMS, which consisted of the application of different stressors for 7 days per week across 3 weeks. The rats were sacrificed 15 days after CMS exposure. CMS induced supersensitivity to the vasoconstrictor effect of phenylephrine in endothelium-intact thoracic aortic rings without changes in aortic rings without endothelium, or pre-incubated with nitric oxide (NO) synthesis inhibitor. Rats submitted to CMS showed hypertrophy of the intima and tunica media of thoracic aorta, increased serum levels of triglycerides, total cholesterol, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and atherogenic index, without changes in high-density lipoprotein cholesterol levels, when compared with control rats. These data indicate that CMS induces physiological and morphological changes that may contribute to the development of atherosclerosis by mechanisms related to deficiency in NO production and dyslipidemia.

Leaching of petroleum refinery ash by acidophilic sulfur-oxidizing microbial cultures.

Sulfur-oxidising acidophilic bacteria were obtained from weathered sulfur piles produced by a petroleum refinery. When grown on commercial sulfur the yield was 10(10)cell/g S. Sulfur conversion to sulfate was about 95% after 17 days. Cultures were also grown together with ash obtained from incinerated refinery sludge, which contained high amounts of iron. Cultures grown in ash plus sulfur gave somewhat higher values for the growth parameters (Y=1.6 x10(10)cell/g S). The sulfur conversion was about 70% (after 17 days) and more than 90% of the iron present in the ash was also leached. The sulfur-reduced compound thiosulfate, determined using ion pair HPLC, was found in the presence and absence of ash although the profile was different in each case. Sulfite was only found in non-ash containing cultures, whereas tetrathionate was only formed in the presence of ash. These results are discussed with reference to the substrates used by the micro-organisms.

Influence of anabolic steroid on anxiety levels in sedentary male rats.

The aim of this study was to evaluate the influence of nandrolone decanoate on anxiety levels in rats. Male Wistar rats were treated with nandrolone decanoate (5mg/kg, two times per week, i.m.) or vehicle (propylene glycol--0.2 ml/kg, two times per week, IM) for 6 weeks. Control rats were subject only to procedures related to their routine husbandry. By the end of 6 weeks, all groups (24-29 rats/group) were submitted to the elevated plus maze test in order to evaluate their anxiety level. Some of these animals (12-14/group) were treated with diazepam (1 mg/kg i.p.) 30 min before the elevated plus maze test. Nandrolone decanoate significantly decreased the percentage of time spent in the open arms (1.46+/-0.49%) compared with control (3.80+/-0.97%) and vehicle (3.96+/-0.85%) groups, with no difference between control and vehicle treatments. The percentage of open arm entries was also reduced in the group treated with nandrolone decanoate in comparison with the vehicle and control. No changes in the number of closed arm entries were detected. Diazepam abolished the effects of nandrolone decanoate on the percentage of time in, and entries into the open arms. The present study showed that chronic treatment with a high dose of nandrolone decanoate increased the anxiety level in male rats.

The influence of core materials and film coating on the drug release from coated pellets.

The objective of this study was to analyse the influence of the composition of the core of the pellets on the in vitro drug release profile. The different materials (drugs and fillers) were chosen according to their relative solubility. Pellets were prepared by a standardised process of extrusion/spheronisation. A selected fraction size (1-1.4 mm diameter) of pellets of each preparation was coated with Surelease (an aqueous dispersion of ethyl cellulose) to give 5% weight gain. The dissolution studies were performed and data analysed in terms of the Area under the Curve (AUC) of the % dissolved as function of time and Mean Dissolution Time (MDT). ANOVA was applied in order to identify the influence factors and the relationship of cross effects. Canonical analysis and multiple regression were employed to quantify these relationships. The film coat was found to be the major factor controlling the drug release. The results however, show that both drug and filler solubility influenced the drug release profile. Some of the unusual results could only be explained if consideration was given to the physical characteristics of both powder and pellets. In particular, the specific surface area of calcium phosphate compared with other fillers played an important role on the release profile of the model drug.

Influence of estradiol and progesterone on the sensitivity of rat thoracic aorta to noradrenaline.

The aim of this study was to investigate the effects of low and high doses of estradiol, and of progesterone on the response to noradrenaline in rat thoracic aorta. Two weeks after bilateral ovariectomy, female rats received a s.c. injection of vehicle (corn oil, 0.1 mL/day), estradiol (10 microg/kg/day or 4 mg/kg/day) and/or progesterone (20 mg/kg/day), for eight days. On the ninth day, the rats were sacrificed and aortic rings, with or without endothelium, were used to generate concentration-response curves to noradrenaline. Aortic rings with intact endothelium from the high-dose (4 mg/kg/day) estradiol group were supersensitive to noradrenaline compared to the vehicle or low-dose (10 microg/kg/day) estradiol groups (pD2 values = 7.86+/-0.09, 7.30+/-0.11 and 7.35+/-0.04, respectively). Endothelium-intact aortic rings from high-estradiol rats were supersensitive to noradrenaline when compared to vehicle-, progesterone- and progesterone + high-estradiol-treated rats (pD2 values = 7.77+/-0.12, 7.21+/-0.13, 6.93+/-0.04 and 7.22+/-0.18, respectively). There were no significant differences among the pD2 values for noradrenaline in aortic rings without endothelium. In conclusion, at high but not low doses, estradiol increased the sensitivity to noradrenaline and this was prevented by progesterone. Both of these effects were endothelium-dependent.

Forced swim stress: supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline and the role of corticosterone.

1. Forced swim (three daily sessions) resulted in an increased plasma corticosterone level and supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline. 2. Bilateral adrenalectomy, performed 2 days before forced swim, abolished the development of pacemaker supersensitivity to isoprenaline. 3. Administration to rats of the antiglucorticoid compound RU-38486 prevented the development of pacemaker supersensitivity to isoprenaline. Pretreatment of rats not submitted to forced swim with the synthetic glucocorticoid RU-28362 causes pacemaker supersensitivity to isoprenaline. 4. Pretreatment of rats with diazepam or imipramine which block the forced swim-induced increase in the plasma level of corticosterone prevented the development of pacemaker supersensitivity to isoprenaline. 5. It is concluded that corticosterone plays a critical role in the modulation of the sensitivity to catecholamines of the pacemaker beta-adrenoceptors during adaptation to repeated stress.

Modeling of immobilized cell reactor for propionic acid fermentation.

A mathematical model of steady state reactor behavior was developed, combining the tanks-in-series model with fermentation kinetic description. The model was tested with experimental data-from an immobilized cell reactor for propionic acid production operated under different residence times. In order to determine the effects of liquid flow rate and gas evolution on the degree of mixing, residence time distribution studies (RTDs) were performed during fermentation. The tanks-in-series model represented adequately the hydrodynamic behavior of the reactor. Association of an intrinsic kinetic model obtained from chemostat studies with the tanks-in-series model allows a "chemostat equivalent" cell concentration profile and a substrate consumption profile to be obtained. The advantage of having a two-level pH adjustment within the reactor is also discussed.