Change in health-related quality of life and social cognitive outcomes in obese,older adults in a randomized controlled weight loss trial: Does physical activity behavior matter?

This article compared the effect of dietary weight loss administered alone (WL) or in combination with aerobic training (WL + AT) or resistance training (WL + RT) on health related quality of life, walking self-efficacy, stair climb self-efficacy, and satisfaction with physical function in older adults with cardiovascular disease or the metabolic syndrome. Participants (N = 249; M _age = 66.9) engaged in baseline assessments and were randomly assigned to one of three interventions, each including a 6-month intensive phase and a 12-month follow-up. Those in WL + AT and WL + RT engaged in 4 days of exercise training weekly. All participants engaged in weekly group behavioral weight loss sessions with a goal of 7–10% reduction in body weight. Participants in WL + AT and WL + RT reported better quality of life and satisfaction with physical function at 6- and 18-months relative to WL. At month 6, WL + AT reported greater walking self-efficacy relative to WL + RT and WL, and maintained higher scores compared to WL at month 18. WL + AT and WL + RT reported greater stair climbing efficacy at month 6, and WL + RT remained significantly greater than WL at month 18. The addition of either AT or RT to WL differentially improved HRQOL and key psychosocial outcomes associated with maintenance of physical activity and weight loss. This underscores the important role of exercise in WL for older adults, and suggests health care providers should give careful consideration to exercise mode when designing interventions.     

Is weight loss a realistic goal of treatment in type 2 diabetes? The implications of restraint theory

Obesity is a two-fold problem affecting both physical health and psychological well-being and one of the biggest obstacles to the management of type 2 diabetes because the most effective treatments frequently lead to weight gain. Recent studies have shown that addressing the problem of obesity first can lead to an improvement in blood glucose control, accompanied by favourable changes in physiological profiles. With the exception of surgical treatments, all obesity treatment programmes involve recommending dieting in one form or another, in order that individuals lose weight. However, all reviews document the failure of all obesity treatment approaches, behavioural, dietetic or pharmacological, to achieve significant and long-lasting weight loss. Research further suggests that dietary restraint may have many negative consequences and weight fluctuation may also have profound effects on psychological and physical health. The present paper highlights the need to reappraise the management of obesity in type 2 diabetes in light of these research findings and suggests an approach to treatment, which would help patients to limit the associated physical and psychological costs and importantly ensure that the treatment itself does not compound their difficulties.     

What predicts weight regain in a group of successful weight losers?

This study identified predictors of weight gain versus continued maintenance among individuals already successful at long-term weight loss. Weight, behavior, and psychological information was collected on entry into the study and 1 year later. Thirty-five percent gained weight over the year of follow-up, and 59% maintained their weight losses. Risk factors for weight regain included more recent weight losses (less than 2 years vs. 2 years or more), larger weight losses (greater than 30% of maximum weight vs. less than 30%), and higher levels of depression, dietary disinhibition, and binge eating levels at entry into the registry. Over the year of follow-up, gainers reported greater decreases in energy expenditure and greater increases in percentage of calories from fat. Gainers also reported greater decreases in restraint and increases in hunger, dietary disinhibition, and binge eating. This study suggests that several years of successful weight maintenance increase the probability of future weight maintenance and that weight regain is due at least in part to failure to maintain behavior changes.     

“Memory bias” for recall of experiences during initial weight loss is affected by subsequent weight loss outcome

Research has suggested that memories of mood, emotions, and behaviors are not purely unbiased retrieval, but more similar to reconstructions based on current opinions, positive or negative experiences associated with the memory, and how a person believes they would have felt, thought, or acted. We investigated this memory bias in 66 adult participants with overweight/obesity who rated their mood, emotions, and behaviors during a 12-week, Internet-based behavioral weight loss program and later recalled these ratings at Month 3 (immediate post-test) and Month 12 (follow-up). At Month 3, participants recalled the intervention more positively than reported previously, p = .010, but reported remembering the intervention more negatively at the Month 12 follow-up, p = .004. Memory bias was associated with initial weight loss and regain, ps < .05, such that participants who lost more weight at Month 3 remembered their mood, emotions, and behaviors during intervention more positively, and those who regained more weight at Month 12, more negatively. Future research should investigate whether this bias is associated with willingness to re-engage with intervention.     

Ontogeny of spatial navigation in rats: a role for response requirements?

Three experiments investigated the role of response requirements in the Morris water maze for pre- and postweanling rats. Fischer-344N pups were required to locate a hidden platform using extramaze cues in a tank modified for the pups' immature response repertoire. Weanlings (20-22 days) displayed spatial learning in a pool 1/2 the size of the adults' (Experiment 1); by 26-28 days of age, probe performance was comparable to adults' on quadrant preference and platform-crossing measures. Preweanlings (17 days), in a pool 1/3 the original size, significantly reduced escape latencies and displayed quadrant preference and platform-crossing scores indicative of spatial navigation. These results suggest that despite its protracted postnatal development, the preweanling hippocampus allows neural integration of visual-spatial information; however, the capacity to demonstrate such learning is dependent on task parameters and the pup's response repertoire.     

Angiomotin p80/p130 ratio: a new indicator of exercise-induced angiogenic activity in skeletal muscles from obese and non-obese rats?

Skeletal muscle capillarisation responds to physiological and pathological conditions with a remarkable plasticity. Angiomotin was recently identified as a new pro-angiogenic molecule. Angiomotin is expressed as two protein isoforms, p80 and p130. Whereas p80 stimulates endothelial cell migration and angiogenesis, p130 is rather characteristic of stabilized and matured vessels. To date, how angiomotin expression is physiologically regulated in vivo remains largely unknown. We thus investigated (1) whether angiomotin was physiologically expressed in skeletal muscle; (2) whether exercise training, known to stimulate muscle angiogenesis, affected angiomotin expression; and (3) whether such regulation was altered in obesity, a pathological situation often associated with an impaired angiogenic activity and some capillary rarefaction in skeletal muscle. Two models of obesity were used: a high fat diet regime and Zucker Diabetic Fatty rats (ZDF). Our results provide evidence that angiomotin was expressed both in capillaries and myofibres. In non-obese rats, the p80 isoform was increased in plantaris muscle in response to endurance training whereas p130 was unaffected. In obese animals, no change was observed for p80 whereas training significantly decreased p130 expression. Exercise training induced angiogenesis in plantaris from both obese and non-obese rats, possibly through the modulation of angiomotin level and its consequences on RhoA–ROCK signalling. In conclusion, any increase in p80 or decrease in p130, as respectively observed in non-obese and obese animals, led to an increased ratio between p80 and p130 isoforms. This increased angiomotin p80/p130 ratio might then directly reflect the enhanced angiogenic ability of skeletal muscle in response to exercise training.     

Hydrogen sulfide: Therapeutic or injurious in ischemic stroke?

Hydrogen sulfide (H₂S) has been identified as a vasodilatory, neuromodulatory, and anti-inflammatory gasotransmitter with antioxidant properties. Studies focused in cardiac tissue suggest H₂S functions as a protective agent; however in the central nervous system (CNS) the effects of H₂S during states of stress or injury, such as stroke, remain controversial. Currently, the application of H₂S donors and modulators in stroke depends on the type of H₂S donor and the timing of the therapy.     

Cannabis and Δ-tetrahydrocannabinol (THC) for weight loss?

Obesity is one of the highest preventable causes of morbidity and mortality in the developed world [1]. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the ‘munchies’). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB₁ receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile [2]. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ⁹-tetrahydrocannabinol (THC) present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.     

Therapeutic blockade of TNF in patients with SLE-promising or crazy?

TNF is an important mediator of inflammation, but is also involved in the control of autoimmunity. The latter has been demonstrated in a murine model of SLE (NZB/W) and by the occurrence of autoantibodies to nuclear antigens as well as occasional, transient lupus-like syndromes in patients under TNF blockade. In contrast, data on increased TNF levels in serum, kidney and skin samples of SLE patients as well as results in other mouse models of the disease point to an inflammatory role of TNF in SLE organ disease. Despite all due caution, given these two sides of the cytokine, TNF blockade has by now been employed for several years in single cases and open label studies; data on more than fifty patients have meanwhile been published, for the vast majority of which infliximab was employed. These clinical data have to be very cautiously interpreted, as always with data on single cases or open label trials. However, some consistent pieces of information emerge and may inform controlled clinical trials: (i) While antibodies to double-stranded DNA commonly showed transient increases, lupus flares have not been seen so far and thus apparently are at least not the rule; (ii) in contrast, increases in anti-phospholipid antibodies may be associated with vascular adverse events; (iii) bacterial infections, pneumonia and urinary tract infections in particular, have been observed; (iv) short term induction therapy appears relatively safe, while long-term TNF blockade may confer significant risks in SLE; (v) TNF blocker induction therapy may lead to long-term remission in patients with lupus nephritis, hemophagocytic syndrome, and interstitial lung disease; (vi) patients with lupus arthritis often respond to TNF-blockade but symptoms recur after cessation of therapy, necessitating longer term therapy, which is more risky than short term treatment.     

Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: A new therapeutic target?

ObjectivePancreatic renin-angiotensin system has been implied to play a role in the regulation of pancreatic functions and could be a new therapeutic target in acute pancreatitis. The aim of this study was to evaluate the therapeutic potential of angiotensin-converting-enzyme inhibition by captopril and angiotensin II type1 receptor inhibition by L-158809 and losartan experimentally in acute pancreatitis.DesignRats were randomly divided into 15 groups. Acute edematous pancreatitis was induced by injection of cerulein 20 μg/kg SC four times at hourly intervals. Severe necrotizing pancreatitis was induced by retrograde injection of 3% taurocholate into the biliary-pancreatic duct.InterventionsCaptopril, L-158809 and losartan were given intraperitoneally. Main outcome features: pancreatic pathology, pancreatic myeloperoxidase activity and serum amylase activity were assessed.ResultsCaptopril decreased serum amylase (10,809±1867 vs. 4085±1028 U/L, p<0.01), myeloperoxidase activity (3.5±0.5 vs. 1.5±0.1, p<0.05) and histopathological score (5.0±0.4 vs. 1.1±0.5, p<0.01) in acute edematous pancreatitis. In taurocholate induced severe necrotizing pancreatitis captopril ameliorated histopathological score (10.1±1.2 vs. 3.4±0.5, p<0.01), pancreatic parenchymal necrosis (4.5±0.6 vs. 0.0±0.0, p<0.001), fatty necrosis (2.8±0.9 vs. 0.1±0.1, p<0.01) and edema (2.1±0.3 vs. 1.4±0.3, p<0.05). However, L-158809 did not have similar beneficial effects on acute pancreatitis in rats while losartan decreased pancreatic parenchymal necrosis and neutrophil infiltration.ConclusionsThis study not only demonstrated the differential effects of captopril, losartan and L-158809 in acute pancreatitis but also showed that there is still much to investigate about pancreatic renin-angiotensin system. Inhibition of angiotensin-converting enzyme should be evaluated carefully as a potential new therapeutic target in acute pancreatitis.     

Augmented β cell loss and mitochondrial abnormalities in sucrose-fed GK rats

Progressive decline of islet β cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model. Six-week-old male GK rats were given 30% sucrose orally for 2 weeks. Normal Wistar rats fed with sucrose served as controls. Compared to untreated GK rats, sucrose-fed GK rats showed severe degeneration and death of β cells with disrupted and swollen mitochondria and a greater β cell loss. Submicroscopic analysis disclosed a smaller mean volume and a greater number of mitochondria in β cells in GK rats compared to those in Wistar rats. Mitochondria in sucrose-fed GK rats were 2.4-fold greater in mean volume than those in untreated state. Without sucrose feeding, there was no significant difference in mitochondrial membrane potentials (MmPs) of isolated islets between Wistar and GK rats. MmPs were reduced by 44% in sucrose-fed GK rats but not influenced in sucrose-fed Wistar rats. Current results suggest that nutritional insults like sucrose feeding may exert deleterious effects on mitochondria, resulting in augmented β cell loss in type 2 diabetes.     

Role of Theoretical Bias in Therapeutic Interventions: To See or Not to See?

Considering the role of theory in child psychosocial treatment, it is important to acknowledge some of its associated problems. Among the shortcomings of theory discussed in this article are its potential for biasing what we see and do clinically, the arbitrary nature of some theoretical explanations, and the way that theory-based jargon can interfere with communication. A bottom-up approach to the development of clinical principles is advocated instead, especially when these principles are derived from the convergence of clinical observation and research findings.     

The monosodium iodoacetate model of osteoarthritis: a model of chronic nociceptive pain in rats?

Osteoarthritis (OA) is a widespread condition affecting the elderly population. One of the most prominent features but least studied symptoms is chronic pain associated with OA. The study objective was to determine pain endpoints in rats with monosodium iodoacetate (MIA) induced OA, and to investigate the efficacy of common nociceptive agents. Sprague–Dawley rats received an intraarticular injection of either 25 μl 80 mg/ml MIA or 25 μl 0.9% sterile saline into the right knee joint. Changes in von Frey thresholds and latencies to stroking with a cotton bud (punctate and dynamic allodynia, respectively) were measured pre- and for up to 10 weeks post-intraarticular injection. Changes in hind paw weight distribution were also determined. Both punctate allodynia and a weight bearing deficit were observed in MIA-treated rats for up to 10 weeks. Interestingly, dynamic allodynia was not detected at any time point tested. Morphine (0.3–3 mg/kg, s.c.) and tramadol (3–100 mg/kg, p.o.) dose-dependently inhibited punctate allodynia and partially reversed weight bearing deficit. In conclusion, the MIA model of OA is reproducible and mimics OA pain in humans. Analgesic drug studies indicate this model may be useful for investigating chronic nociceptive pain.     

Pentylenetetrazol kindling in rats: Is neurodegeneration associated with manifestations of convulsive activity?

Structural changes in neurons and measures of oxidative stress were studied in the hippocampus of rats tolerant (ST) and sensitive (SS) to developing clonic-tonic seizures in conditions of pentylenetetrazol kindling. Sequences of 11 injections of pentylenetetrazol significantly decreased the number of normal neurons in hippocampal field CA1 in SS rats, this effect being seen in both hippocampal field CA1 and the dentate fascia in ST rats. Decreases in the numbers of normal neurons were accompanied by increases in the numbers of damaged cells in field CA4 in rats of both groups. After 21 injections, decreases in the numbers of normal neurons were seen in field CA1 in both SS and ST rats, while the numbers of damaged neurons were significantly greater than control only in ST rats in fields CA1 and CA4. The glutathione level was significantly lower in the hippocampus in both groups of rats than in controls. Thus, rats “ tolerant” to developing convulsions show signs of oxidative stress and neurodegenerative changes in the hippocampus. This suggests that oxidative neuron damage leading to neurodegeneration in the pentylenetetrazol kindling model is not directly associated with convulsive activity. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 7, pp. 764–775, July, 2005.