This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group, in all participants and in overweight children. The Louisiana (LA) Health study utilized a longitudinal, cluster randomized 3-arm controlled design, with 28 months of follow-up. Children (N=2060; M age = 10.5 years, SD = 1.2) from rural communities in Grades 4 to 6 participated in the study. 17 school clusters (M = 123 children/cluster) were randomly assigned to one of three prevention arms: 1) Primary Prevention (PP), an environmental modification program, 2) Primary + Secondary Prevention (PP+SP), the environmental program with an added classroom and internet education component, or 3) Control (C). Primary outcomes were changes in percent body fat and body mass index z scores. Secondary outcomes were changes in behaviors related to energy balance. Comparisons of PP, PP+SP, and C on changes in body fat and BMI z scores found no differences. PP and PP+SP study arms were combined to create an environmental modification arm (EM). Relative to C, EM decreased body fat for boys (−1.7% ± 0.38% versus −0.14% ± 0.69%) and attenuated fat gain for girls (2.9% ± 0.22% versus 3.93% ± 0.37%), but standardized effect sizes were relatively small (< 0.30). In conclusion, this school-based environmental modification programs had modest beneficial effects on changes in percent body fat. Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention, but did impact physical activity and social support in overweight children.

Purpose of review

To understand mechanisms of muscle wasting and how inhibiting myostatin signaling affects them.

Recent findings

Myostatin signaling is critical for understanding the pathogenesis of muscle wasting since blocking it mitigates muscle losses in rodent models of catabolic diseases including cancer, chronic kidney or heart failure.

Summary

Muscle wasting increases the risks of morbidity and mortality. But, the reliability of estimates of the degree of muscle wasting is controversial as are definitions of terms like cachexia. Much has been learned about the pathophysiology of muscle wasting, including the major role of the ubiquitin-proteasome system (UPS) which along with other proteases degrades protein and limits protein synthesis. In contrast, few successful strategies for reversing muscle loss have been tested.

Several catabolic conditions are characterized by inflammation, increased glucocorticoid production and impaired intracellular signaling in response to insulin and IGF-1. These characteristics lead to activation of the UPS and other proteases producing muscle wasting. Another potential initiator of muscle wasting is myostatin and its expression is increased in muscles of animal models and patients with certain catabolic conditions. Myostatin is a member of the TGF-β family; it suppresses muscle growth and its absence stimulates muscle growth substantially. Recently, pharmacologic suppression of myostatin was found to counteract inflammation, increased glucocorticoids and impaired insulin/IGF-1 signaling and most importantly, prevents muscle wasting in rodent models of cancer and kidney failure. Myostatin antagonism as a therapy for patients with muscle wasting should become a topic of clinical investigation.

Background

Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns.

Methods

Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5–91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg−1 was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured.

Results

Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre−1; P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=−0.6; P<0.001). The dibucaine numbers were not different.

Conclusions

The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg−1) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Cross-sectional studies have reported significant temporal increases in prevalence of childhood obesity in both genders and various racial groups, but recently the rise has subsided. Childhood obesity prevention trials suggest that, on average, overweight/obese children lose body weight and non-overweight children gain weight. This investigation tested the hypothesis that overweight children lose body weight/fat and non-overweight children gain body weight/fat using a longitudinal research design that did not include an obesity prevention program. The participants were 451 children in 4th to 6th grades at baseline. Height, weight, and body fat were measured at Month 0 and Month 28. Each child’s body mass index (BMI) percentile score was calculated specific for their age, gender and height. Higher BMI percentile scores and percent body fat at baseline were associated with larger decreases in BMI and percent body fat after 28 months. The BMI percentile mean for African-American girls increased whereas BMI percentile means for white boys and girls and African-American boys were stable over the 28 month study period. Estimates of obesity and overweight prevalence were stable because incidence and remission were similar. These findings support the hypothesis that overweight children tend to lose body weight and non-overweight children tend to gain body weight.

Background

To determine if there are differences in time spent in physical activity and sedentary behavior between African American and Caucasian children.

Methods

Children wore accelerometers for three weekdays. The students were randomly selected from a larger sample of children participating in a weight gain prevention intervention. Usable data was obtained from 272 of the 310 students who agreed to participate. The outcome data included counts per minute (CPM), time spent in moderate to vigorous (MVPA), light (LPA), and sedentary (SED) activity. The equation and cutoff used to analyze national accelerometry data were utilized for the current study.

Results

The sample had an average age of 10.4 (1.1) years and 76% were African American. Lower SES African American boys had more CPM (p = .012) and spent more time in MVPA (p = .008) compared to middle SES African American and lower SES Caucasian children. Lower SES African American children also spent fewer minutes in SED activity (p = .044) compared to middle SES African American children.

Conclusions

These findings support recent results that also used objective activity measures. Children appeared less active and more sedentary than a national sample, warranting interventions in minority and rural populations.

Background

Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation.

Methods

The aim of this investigation was to examine the effect of the soluble receptor antagonist of myostatin (sActRIIB) in cachectic tumor-bearing animals analyzing changes in muscle proteolysis and in quality of life.

Results

Administration of sActRIIB resulted in an improvement in body and muscle weights. Administration of the soluble receptor antagonist of myostatin also resulted in an improvement in the muscle force.

Conclusions

These results suggest that blocking myostatin pathway could be a promising therapeutic strategy for the treatment of cancer cachexia.

Background

Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation.

Methods

The aim of this investigation was to examine the effect of the soluble receptor antagonist of myostatin (sActRIIB) in cachectic tumor-bearing animals analyzing changes in muscle proteolysis and in quality of life.

Results

Administration of sActRIIB resulted in an improvement in body and muscle weights. Administration of the soluble receptor antagonist of myostatin also resulted in an improvement in the muscle force.

Conclusions

These results suggest that blocking myostatin pathway could be a promising therapeutic strategy for the treatment of cancer cachexia.

The study objective was to evaluate the effect of prescribing a low-carbohydrate diet (LCD) and a low-fat diet (LFD) on food cravings, food preferences, and appetite. Obese adults were randomly assigned to a LCD (n=134) or a LFD (n=136) for two years. Cravings for specific types of foods (sweets, high-fats, fast-food fats, carbohydrates/starches); preferences for high-sugar, high-carbohydrate, and low-carbohydrate/high-protein foods; and appetite were measured during the trial and evaluated during this secondary analysis of trial data. Differences between the LCD and LFD on change in outcome variables were examined with mixed linear models. Compared to the LFD, the LCD had significantly larger decreases in cravings for carbohydrates/starches and preferences for high-carbohydrate and high-sugar foods. The LCD group reported being less bothered by hunger compared to the LFD group. Compared to the LCD group, the LFD group had significantly larger decreases in cravings for high-fat foods and preference for low-carbohydrate/high-protein foods. Men had larger decreases in appetite ratings compared to women. Prescription of diets that promoted restriction of specific types of foods resulted in decreased cravings and preferences for the foods that were targeted for restriction. The results also indicate that the LCD group was less bothered by hunger compared to the LFD group and that men had larger reductions in appetite compared to women.

The Cell Imaging and Analysis Network (CIAN) provides services and tools to researchers in the field of cell biology from within or outside Montreal's McGill University community. CIAN is composed of six scientific platforms: Cell Imaging (confocal and fluorescence microscopy; walk-up), Proteomics (2-D, DiGE and fluorescent protein analysis; walk-up), Automation and High throughput screening (Pinning robot and liquid handler; full service), Protein expression and antibody production (in collaboration with local animal facilities; full service), Genomics (real-time PCR; walk-up), and Data storage/analysis (cluster, server and workstations). Users get in-depth consultation for proposed projects, and can obtain training in any of the walk-up aspects of the facility, or take advantage of the full-service platforms. CIAN is designed to facilitate training, enhance interactions, as well as share and maintain resources and expertise.

The primary aim of this study was to test for changes in body image in men and women enrolled in the Look AHEAD trial. Look AHEAD (Action for Health in Diabetes) is a multi-center, randomized controlled trial designed to test whether intentional weight loss reduces cardiovascular morbidity and mortality in overweight individuals with type 2 diabetes. Participants included 157 adults at one site (Pennington Biomedical Research Center) of the Look AHEAD study. At baseline, the mean body mass index (BMI) of the female participants was 36.4, and the mean BMI for males was 33.5. Following baseline assessment, participants were randomly assigned to the Intensive Lifestyle intervention (ILI, n = 81) or Diabetes Support and Education (DSE, n = 76). The Body Morph Assessment version 2.0 (BMA 2.0) was used to assess estimates of perceived current body size, ideal body size, acceptable body size, and body image dissatisfaction at baseline and one year. Over the 1 year, participants in the ILI group had significantly greater reductions in weight (10.1% for men and 8.9% for women) than those in the DSE group (+ 0.8% for men and −0.2%, for women). Perceived current body size was reduced significantly more in both men and women in the ILI group, relative to DSE. There were also significantly greater reductions in body image dissatisfaction in the ILI group, relative to the DSE group for men and women. The results of this study indicate that body image dissatisfaction improved following participation in an intensive behavioral weight loss program.

Oplopanax horridus or devil’s club is a herbal medicine distributed in North America. The constituents and pharmacological activities of O. horridus (OPH) are largely unknown. In this study, we assayed OPH stem and berry extracts using high performance liquid chromatography (HPLC). The anticancer potentials of extracts on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC) were determined by MTS method. The effect of stem extract on cancer cell cycle, expression of cyclin A, and apoptosis were assayed using flow cytometry. HPLC data showed that the composition of OPH stem extract is more complicated than the berry extract. The wavelength of maximum absorption of the major constituent in stem and berry is 196.0 nm and 201.9 nm, respectively. Compared to the berry extract, the stem extract showed significant potent antiproliferative effect on all the studied cell lines. The stem extract at 0.1 mg/ml arrested cancer cells in S- and G2/M-phases, and significantly induced expression of cyclin A. After treatment with 0.1 mg/ml of stem extract for 72 h, apoptotic cells were increased to 45.2%, while control was 9.6%. The cell cycle arrest and induction of apoptosis may play a critical role in cancer chemoprevention by Oplopanax horridus stem extract.

In the current set of experiments, we establish, and explore the consequences of, the imprecision that characterizes the attribute response labels typically employed in the Implicit Association Test (IAT). In Experiment 1, we demonstrate the malleability of the IAT, as conventionally implemented. IAT scores are shown to be influenced by perspective mindsets induced by an unrelated preceding task. Then, we explore how the malleability of the IAT can lead to the inference that attitude change has occurred even when there is very good reason to believe it has not (Experiment 2), and conversely, how it can obscure the detection of attitude change when such change is indeed likely to have occurred (Experiment 3). We provide conceptual explanations for these discrepancies and suggest methodological improvements to enhance the specificity of IAT measures.

Purpose

The pharmacological activities, notably the anticancer properties, of bioactive constituents fromfresh American ginseng berry have not yet been well studied. In this study, we investigated the antiproliferative effects of fresh American ginseng berry extract (AGBE) and its representative triterpenoid glycosides using the human colorectal cancer cell line SW480.

Materials and Methods

Using high performance liquid chromatography (HPLC), the contents of 8 ginsenosides in AGBE were determined. The cell growth inhibitory effects of AGBE and three triterpenoid glycosides (ginsenosides Rb3, Re, and Rg3) were evaluated by proliferation assay and 3H-thymidine incorporation assay. Cell cycle and apoptotic effects were analyzed by using flow cytometry after staining with propidium iodide and annexin V.

Results

HPLC analysis data showed that AGBE has a distinct ginsenoside profile. AGBE inhibited SW480 cell growth significantly in a time-dependent (24-96 hours) and concentration-dependent (0.1-1.0 mg/mL) manner. Ginsenosides Rb3, Re, and Rg3 also possess significant antiproliferative activities on SW480 cells. 3H-thymidine incorporation assay indicated that AGBE and ginsenosides Rb3, Re, and Rg3 might inhibit the transferring and duplication of DNA in SW480 cells. Flow cytometric assay data suggested that AGBE arrested SW480 cells in S and G2/M phases, and significantly induced cell apoptosis.

Conclusion

AGBE and ginsenosides Rb3, Re, and Rg3 possessed significant antiproliferative effects and induced changes of morphological appearance on SW480 cells. The mechanisms of the antiproliferation of AGBE and tested ginsenosides involved could be cell cycle arrest and induction of apoptosis.

Objective

Identifying prognostic factors for work ability in sicklisted employees with myocardial infarction (MI), chronic low back pain (cLBP) and major depressive disorder (MDD) in order to establish an objective basis for work ability evaluation.

Design

Systematic literature search in PubMed database (1 January 1990 to 1 July 2006) with the Yale prognostic research filter. Inclusion criteria were as follows: (1) work-disabled employees; (2) MI, cLBP or MDD patients; (3) longitudinal designs; and (4) return to work or compensation status as outcome measure.

Results

Four studies on MI met the inclusion criteria and described the following prognostic factors for work ability in the acute phase of the disease and disablement: lower age; male gender; no financial basis on which to retire; lower physical job demands; fewer somatic complaints; no anxiety attacks; no diabetes; no heart failure; no atrial fibrillation; no Q waves; and a short time interval between MI and presentation at the occupational medicine clinic. Two studies on cLBP met the inclusion criteria and described the following prognostic factors for work ability after 3 months' work disablement: lower age; male gender; no treatment before sick listing; surgery in the first year of sick listing; being a breadwinner; less pain; better general health; higher job satisfaction; lower physical and/or psychological demands at work; and a higher decision latitude at work. No relevant MDD studies were found.

Conclusion

In the earlier phases of work disablement in MI and cLBP patients, only a few studies describe disease-specific, environmental and personal prognostic factors for return to work. No studies describe prognostic factors for MDD. More evidence is needed on the topic of prognostic factors for return to work in employees with chronic diseases.

We compared the diagnostic performance of non-enhanced MRI and fat-suppressed contrast-enhanced MRI (CEMRI) in diagnosing intravertebral clefts in benign vertebral compression fractures (VCFs). We retrospectively reviewed 99 consecutive patients who had undergone percutaneous vertebroplasty for VCFs. A cleft was defined as a signal void or hyperintense area on non-enhanced MRI (T1 and T2 weighted imaging) or as a hypointense area within a diffusely enhanced vertebra on CEMRI. A cleft was confirmed as a solid opacification on post-procedural radiographs. The interobserver reliability and MRI diagnostic performance were evaluated. The interobserver reliability of non-enhanced MRI was substantial (k _ 0.698) and the interobserver reliability of CEMRI was almost perfect (k _ 0.836). Post-procedural radiographs showed solid cleft opacification in 32 out of the 99 cases. The sensitivity and specificity of non-enhanced MRI were 0.72 and 0.82 (observer 1) and 0.63 and 0.87 (observer 2), respectively. The sensitivity and specificity of CEMRI were 0.94 and 0.63 (observer 1) and 0.85 and 0.60 (observer 2), respectively. The sensitivity of CEMRI was significantly higher than that of non-enhanced MRI, and the specificity of non-enhanced MRI was higher than that of CEMRI. CEMRI was highly reliable and sensitive, and non-enhanced MRI was specific for intravertebral clefts. Therefore, spine MRIs, including CEMRI, could provide useful information about intravertebral clefts before percutaneous vertebroplasty.

Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14+/lowCD16+ monocytes being more susceptible than CD14+CD16− monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14+/lowCD16+ monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14+CD16− monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14+/lowCD16+ monocytes. The apoptosis of CD14+/lowCD16+ monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present.

Background

Low tumour expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) have been linked with improved outcome for colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU). It is unclear whether this occurs because such tumours have better prognosis or they are more sensitive to 5-FU treatment.

Patients and methods

Associations between TS, DPD and TP levels, determined by tissue microarrays and immunohistochemistry, and survival was evaluated in 945 CRC patients according to treatment status.

Results

Low TS and DPD expression associated with worse prognosis in stage II [hazard ratio (HR) = 1.69, 95% confidence interval (CI) (1.09–2.63) and HR = 1.92 (95% CI 1.23–2.94), respectively] and stage III CRC patients treated by surgery alone [HR = 1.39 (95% CI 0.92–2.13) and HR = 1.49 (95% CI 1.02–2.17), respectively]. Low TS, DPD and TP associated with trends for better outcome in stage III patients treated with 5-FU [HR = 0.81 (95% CI 0.49–1.33), HR = 0.70 (95% CI 0.42–1.15) and HR = 0.66 (95% CI 0.39–1.12), respectively].

Conclusion

Low TS and DPD expression are prognostic for worse outcome in CRC patients treated by surgery alone, whereas low TS, DPD and TP expression are prognostic for better outcome in patients treated with 5-FU chemotherapy. These results provide indirect evidence that low TS, DPD and TP protein expression are predictive of good response to 5-FU chemotherapy.

CF-31

The Cell Imaging and Analysis Network (CIAN) provides services and tools to researchers in the field of cell biology from within or outside Montreal's McGill University community. CIAN is composed of six scientific platforms: Cell Imaging (confocal and fluorescence microscopy), Proteomics (2-D protein gel electrophoresis and DiGE, fluorescent protein analysis), Automation and High throughput screening (Pinning robot and liquid handler), Protein Expression for Antibody Production, Genomics (real-time PCR), and Data storage and analysis (cluster, server, and workstations). Users submit project proposals, and can obtain training and consultation in any aspect of the facility, or initiate projects with the full-service platforms. CIAN is designed to facilitate training, enhance interactions, as well as share and maintain resources and expertise.

Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. Survival has not improved dramatically, despite routine use of chemotherapy and radiotherapy; this situation signifies an urgent need for novel therapeutic approaches. Over the past decade, a large number of studies that aimed to target the molecular abnormalities implicated in pancreatic tumor growth, invasion, metastasis, angiogenesis and resistance to apoptosis have been published. This research is of particular importance, as recent data suggest that a large number of genetic alterations affect only a few major signaling pathways and processes involved in pancreatic tumorigenesis. Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth-factor receptor tyrosine kinase inhibitor, has demonstrated modest survival benefit in combination with gemcitabine in a phase III clinical trial. Whilst the failures of targeted therapies in the clinical setting are discouraging, lessons have been learnt and new therapeutic targets that hold promise for the future management of the disease are continuously emerging. This Review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials.

The objective of this study was to identify mechanisms through which valproic acid (VPA) causes weight gain. Healthy participants (N = 52) were randomized to VPA or placebo in a double-blind study. Energy intake (EI) was measured in the laboratory at lunch and dinner, and physical activity (PA) was measured with accelerometry. Glucose levels and hormones [Peptide YY3–36, glucagon-like peptide-1 (GLP-1), leptin, ghrelin, insulin] that regulate EI were measured. Assessments occurred at baseline and week 3. Change from baseline was evaluated with mixed models (α = 0.05). Weight significantly increased in the VPA group (+0.49 kg), but not the placebo group. The VPA group increased fast food fats cravings and decreased glucose levels compared with placebo. Change in weight, EI and PA did not differ by group. Within group analyses indicated that the VPA group increased PA, hunger, binge eating, depression and GLP-1. VPA-associated weight gain is not likely due to changes in PA or the gut hormones studied. Although EI did not increase when measured after 3 weeks of treatment, VPA decreased glucose levels and increased motivation to eat; hence, EI might have increased in the short-term. Research testing VPA on short-term (1 week) EI, metabolism, and substrate partitioning is warranted.

Background: Positron emission tomography (PET) is a powerful predictor of relapse and survival in non-Hodgkin’s lymphomas (NHLs) based on studies carried out in the prerituximab era. Little is known about the predictive power of PET in rituximab-treated patients.

Patients and methods: Patients with aggressive B-cell NHL with baseline and follow-up PET studies were included. Clinical characteristics, PET and computed tomography scans, biopsy results, and outcomes were reviewed. PET was defined as positive if higher than mediastinal or background activity was observed.

Results: In all, 51 patients (diffuse large B cell—38; mantle cell lymphoma—13) treated with rituximab-containing regimens were included. For 13 of 40 patients (32.5%), mid-therapy PET studies were positive and 9 of 48 patients (18.7%) had positive posttherapy PET. The positive predictive value (PPV), negative predictive value (NPV), sensitivity (Se), and specificity (Sp) of the mid-therapy PET for predicting relapse were 33% [95% confidence interval (CI) 19% to 49%], 68% (95% CI 51% to 81%), 33% (95% CI 6% to 76%), and 68% (95% CI 49% to 82%), respectively. For posttherapy PET, the relapse PPV, NPV, Se and Sp were 19% (95% CI 9% to 33%), 81% (95% CI 67% to 91%), 13% (95% CI 0.6% to 53%), and 80%(95% CI 64% to 90%), respectively.

Conclusions: Compared with previous reports in prerituximab era, addition of rituximab resulted in reduced PPV and sensitivity of mid- and posttherapy PET in patients with aggressive B-cell NHL.

Background

Burn injury leads to resistance to the effects of non-depolarizing muscle relaxants. We tested the hypothesis that a larger bolus dose is as effective as priming for rapid onset of paralysis after burns.

Methods

Ninety adults, aged 18–59 yr with 40 (2)% [mean (se)] burn and 30 (2) days after injury, received rocuronium as a priming dose followed by bolus (0.06+0.94 mg kg−1), or single bolus of either 1.0 or 1.5 mg kg−1. Sixty-one non-burned, receiving 1.0 mg kg−1 as a primed (0.06+0.94 mg kg−1) or full bolus dose, served as controls. Acceleromyography measured the onset times.

Results

Priming when compared with 1.0 mg kg−1 bolus in burned patients shortened the time to first appearance of twitch depression (30 vs 45 s, P<0.05) and time to maximum twitch inhibition (135 vs 210 s, P<0.05). The onset times between priming and higher bolus dose (1.5 mg kg−1) were not different (30 vs 30 s for first twitch depression and 135 vs 135 s for maximal depression, respectively). The onset times in controls, however, were significantly (P<0.05) faster than burns both for priming and for full bolus (15 and 15 s, respectively, for first twitch depression and 75 and 75 s for maximal depression). Priming caused respiratory distress in 10% of patients in both groups. Intubating conditions in burns were significantly better with 1.5 mg kg−1 than with priming or full 1.0 mg kg−1 bolus.

Conclusions

A dose of 1.5 mg kg−1 not only produces an initial onset of paralysis as early as 30 s, which we speculate could be a reasonable onset time for relief of laryngospasm, but also has an onset as fast as priming with superior intubating conditions and no respiratory side-effects.

Tocotrienol-rich fraction (TRF) has demonstrated antiproliferative effect on prostate cancer (PCa) cells. To elucidate this anticancer property in PCa cells, this study aimed, first, to identify the most potent isomer for eliminating PCa cells; and second, to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of γ-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of pro-caspases and the presence of sub-G1 cell population. Examination of the pro-survival genes revealed that the γ-tocotrienol-induced cell death was associated with suppression of NF-κB, EGF-R and Id family proteins (Id1 and Id3). Meanwhile, γ-tocotrienol treatment also resulted in the induction of JNK-signalling pathway and inhibition of JNK activity by a specific inhibitor (SP600125) was able to partially block the effect of γ-tocotrienol. Interestingly, γ-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and γ-catenin expression, which was associated with suppression of cell invasion capability. Furthermore, a synergistic effect was observed when cells were co-treated with γ-tocotrienol and Docetaxel. Our results suggested that the antiproliferative effect of γ-tocotrienol act through multiple-signalling pathways, and demonstrated for the first time the anti-invasion and chemosensitisation effect of γ-tocotrienol against PCa cells.

Background

Protease inhibitors such as ritonavir can cause nausea and vomiting which is the most common reason for discontinuation. Rats react to nauseous and emetic stimuli by increasing their oral intake of non-nutritive substances like kaolin, known as pica behavior. In this study, we evaluated the effects of methylnaltrexone, a peripherally acting mu-opioid receptor antagonist that does not affect analgesia, on ritonavir-induced nausea and vomiting in a rat pica model.

Results

We observed that 24 to 48 hr after administration of oral ritonavir 20 mg/kg, kaolin consumption increased significantly in rats (P < 0.01). This increase was attenuated by pretreatment with an intraperitoneal injection of methylnaltrexone (0.3–3.0 mg/kg) in a dose dependent manner (P < 0.01) and also with naloxone (0.1–0.3 mg/kg) (P < 0.01). The areas under the curve for kaolin intake from time 0 to 120 hr were significantly reduced after administration of the opioid antagonists. Food intake was not significantly affected. Plasma naltrexone levels were measured after methylnaltrexone injection, and no detectable levels were found, indicating that methylnaltrexone was not demethylated in our experimental paradigm.

Conclusion

These results suggest that methylnaltrexone may have potential clinical utility in reducing nausea and vomiting in HIV patients who take ritonavir.

Background

Energy or calorie restriction (CR) has consistently been shown to produce weight loss and have beneficial health effects in numerous species, including primates and humans. Most individuals, however, are unable to sustain weight losses induced through reductions in energy intake, potentially due to increased hunger levels. The effects that prolonged CR has on subjective aspects of appetite have not been well studied. Thus, the present study tested the effect of 6 months of caloric restriction on appetite in healthy, overweight men and women.

Methods

Forty-eight overweight men and women with a body mass index (BMI; kg m−2) between 25–29.9 took part in a 6-month study and were randomised into one of four groups: healthy diet (control); 25% CR; 12.5% CR plus exercise (12.5% increased energy expenditure; CR + EX); low-calorie diet [LCD; 3724 kJ day−1 (890 kcal day−1) until 15% of initial body weight was lost, then maintenance]. Appetite markers (i.e. hunger, fullness, desire to eat, etc.) were assessed weekly during a fasting state.

Results

Body weight was significantly reduced in all three energy-restricted groups (CR = −10.4 ± 0.9%; CR + EX = −10.0 ± 0.8%; and LCD = −13.9 ± 0.7%), indicating that participants were adherent to their energy restriction regimen, whereas the healthy diet control group remained weight stable (control = −1.0 ± 1.1%). Despite these significant weight losses, appetite ratings of participants in the three energy-restricted groups at month 6 were similar to the weight stable control group.

Conclusions

CR regimens with low fat diets producing significant weight losses have similar effects on appetite markers over a 6-month time period compared to a weight stable control group.