Placebo Response of Non-Pharmacological and Pharmacological Trials in Major Depression: A Systematic Review and Meta-Analysis

Background: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device-rTMS) trials. Methodology/Principal Findings: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria-29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d-random-effects model-1.48; 95% C.I. 1.26 to 1.6) and rTMS studies (0.82; 95% C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. Conclusions/Significance: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself.

KeaA, a Dictyostelium kelch-domain protein that regulates the response to stress and development

Background: The protein kinase YakA is responsible for the growth arrest and induction of developmental processes that occur upon starvation of Dictyostelium cells. yakA-cells are aggregation deficient, have a faster cell cycle and are hypersensitive to oxidative and nitrosoative stress. With the aim of isolating members of the YakA pathway, suppressors of the death induced by nitrosoative stress in the yakA-cells were identified. One of the suppressor mutations occurred in keaA, a gene identical to DG1106 and similar to Keap1 from mice and the Kelch protein from Drosophila, among others that contain Kelch domains. Results: A mutation in keaA suppresses the hypersensitivity to oxidative and nitrosoative stresses but not the faster growth phenotype of yakA-cells. The growth profile of keaA deficient cells indicates that this gene is necessary for growth. keaA deficient cells are more resistant to nitrosoative and oxidative stress and keaA is necessary for the production and detection of cAMP. A morphological analysis of keaA deficient cells during multicellular development indicated that, although the mutant is not absolutely deficient in aggregation, cells do not efficiently participate in the process. Gene expression analysis using cDNA microarrays of wild-type and keaA deficient cells indicated a role for KeaA in the regulation of the cell cycle and pre-starvation responses. Conclusions: KeaA is required for cAMP signaling following stress. Our studies indicate a role for kelch proteins in the signaling that regulates the cell cycle and development in response to changes in the environmental conditions.

Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

Background: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate. Methods and Findings: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. Conclusion: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

Complex Oscillatory Response of a PEM Fuel Cell Fed with H(2)/CO and Oxygen

Oscillatory kinetics is commonly observed in the electrocatalytic oxidation of most species that can be used in fuel cell devices. Examples include formic acid, methanol, ethanol, ethylene glycol, and hydrogen/carbon monoxide mixtures, and most papers refer to half-cell experiments. We report in this paper the experimental investigation of the oscillatory dynamics in a proton exchange membrane (PEM) fuel cell at 30 degrees C. The system consists of a Pt/C cathode fed with oxygen and a PtRu (1:1)/C anode fed with H(2) mixed with 100 ppm of CO, and was studied at different cell currents and anode flow rates. Many different states including periodic and nonperiodic series were observed as a function of the cell current and the H(2)/CO flow rate. In general, aperiodic/chaotic states were favored at high currents and low flow rates. The dynamics was further characterized in terms of the relationship between the oscillation amplitude and the subsequent time required for the anode to get poisoned by carbon monoxide. Results are discussed in terms of the mechanistic aspects of the carbon monoxide adsorption and oxidation. (C) 2010 The Electrochemical Society. [DOI: 10.1149/1.3463725] All rights reserved.

Response of oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae), eggs to gamma radiation

As insects increase in radiotolerance as they develop and usually several developmental stages of the pest may be present in the fresh shipped commodity, it is important to know the radiation susceptibility of the stages of the target insect before the establishment of ionizing radiation quarantine treatments. This study was performed to determine the radiotolerance of eggs of the oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae), to gamma radiation. This species is considered as one of the most serious worldwide pests for temperate fruits, especially peaches. Eggs (12 h old) were exposed to 0 (control), 25, 35, 50, 75, 100, 125 and 150 Gy of gamma radiation. Surviving larvae were allowed to feed on an artificial diet. Three days after irradiation, it was verified that larvae`s cephalic capsules were significantly affected by gamma radiation, and the estimated mean LD(90) and LD(99) were 66.3 Gy and 125.8 Gy, respectively. Oriental fruit moth eggs revealed to be quite radiosensitive and very low doses as 50 Gy were sufficient to disrupt G. molesta embryogenesis. At 25 Gy, only male adults originated from the surviving larvae and, after mating with untreated fertile females, shown to be sterile. (C) 2010 Elsevier Ltd. All rights reserved.

Cardiovascular response during trigeminal ganglion compression for trigeminal neuralgia according to the use of local anesthetics

There are controversies about the use of local anesthetics during balloon compression for trigeminal neuralgia (TN) as a protective factor for cardiovascular events. The objective of this study was to investigate cardiovascular parameters (blood pressure and heart rate [HR]) of patients that underwent trigeminal balloon compression with local anesthetics compared to a control group (placebo). This is a randomized controlled study; 55 patients were randomized into two groups: study (deep sedation and trigeminal block with 0.8-mL lidocaine 2%) and control group (deep sedation and trigeminal injection of 0.8-mL saline). Blood pressure and HR were measured in five distinct moments: preoperative, during puncture for local anesthesia/placebo, during puncture with the catheter, during balloon compression, and final evaluation. Statistical analysis was performed with Pearson`s chi (2) and McNemar tests and the analysis of variance for repetitive measures. The means of systolic and diastolic blood pressures (SBP and DBP, respectively) were higher in the control group when compared to the study group at the evaluation during puncture with the catheter (p < 0.001) and balloon compression (p < 0.001 and p = 0.018 for DBP and SBP, respectively). There was an increase in the HR in the control group during the procedure (p = 0.017). The use of local anesthetics during the trigeminal balloon compression for TN can have a preventive role for the risk of cardiovascular events.

Post-eccentric exercise blunted hGH response

The purpose of the present study was to test if a previous acute concentric exercise bout blunts hGH response after an eccentric exercise bout. Nine healthy untrained male university students (25.4 +/- 0.5 yr, 176.5 +/- 1.2 cm, and 79.4 +/- 2.0 kg) performed a concentric exercise bout followed by an eccentric exercise bout one week later. Serum human growth hormone (hGH), creatine kinase (CK), and lactate were measured before, immediately and up to 32 h after both exercise bouts. Higher lactate values were observed immediately, 5 and 10 min after the concentric bout (70%, 119%, and 142%, respectively, p < 0.05) than the eccentric bout. There was a CK main time effect at 8 and 32 h after the exercise bouts compared to baseline values (p < 0.002). However, peak serum CK effect size was higher after the concentric than the eccentric exercise bout, 1.3 and 0.9, respectively. hGH increased after both exercise bouts, however it reached significance only at immediately (207%), 5 min (256%), 10 min (276%), 20 min (300%), and 40 min (168%) after the concentric exercise bout (p < 0.05). Our findings suggest that a previous concentric exercise bout may blunt the anabolic response expected after an eccentric exercise bout.

Salivary immunoglobulin a response to a match in top-level Brazilian soccer players

Moreira, A, Arsati, F, Cury, PR, Franciscon, C, Oliveira, PR, and Araujo, VC. Salivary immunoglobulin a response to a match in top-level brazilian soccer players. J Strength Cond Res 23(7): 1968-1973, 2009-It has been suggested that several parameters of mucosal immunity, including salivary immunoglobulin A (s-IgA), are affected by heavy exercise either in field sports or in the laboratory environment. Few observations have been made during a true sporting environment, particularly in professional soccer. We tested the hypothesis that salivary IgA levels will be decreased after a 70-minute regulation in a top-level professional soccer friendly match. Saliva samples from 24 male professional soccer players collected before and after the match were analyzed. Salivary immunoglobulin A concentration was measured by enzyme-linked immunosorbent assay and expressed as the absolute concentration (s-IgAabs), s-IgA relative to total protein concentration (IgA-Pro), and the secretion rate of IgA (s-IgArate). Rate of perceived exertion (RPE) was used to monitor the exercise intensity. The paired t-test showed no significant changes in s-IgAabs and s-IgArate (p > 0.05) from PRE to POST match. However, a significant (p < 0.05) increase in total protein concentration (1.46 +/- 0.4 to 2.00 +/- 07) and a decrease in IgA-Pro were observed. The best and most significant correlation was obtained with the RPE and changes in IgA-Pro (rs = -0.43) and could indicate that this expression may be an interesting marker of intensity in a soccer match. However, further investigation regarding exercise intensity, protein concentration, and immune suppression, particularly in team sports, is warranted. From a practical application, the variability of the responses among the players leads us to suggest that there is a need to individually analyze the results with team sports. Some athletes showed a decrease in s-IgA expressions, suggesting the need for taking protective actions to minimize contact with cold viruses or even reducing the training load.

Influence of strength training background on postactivation potentiation response

Batista, MAB, Roschel, H, Barroso, R, Ugrinowitsch, C, and Tricoli, V. Influence of strength training background on postactivation potentiation response. J Strength Cond Res 25(9): 2496-2502, 2011-The aim of this study was to evaluate the influence of the subjects` level of maximal dynamic strength and training background on postactivation potentiation (PAP). A group of 23 subjects, composed of power track-and-field athletes (PT = 8), bodybuilders (BB = 7), and physically active subjects (PA = 8), participated in the study. Maximal dynamic strength (1 repetition maximum test) was assessed in the leg press exercise for subjects` characterization. Their countermovement vertical jump (CMJ) performance was assessed before and after 2 different conditioning activity (CA) protocols (1 or 3 maximum voluntary isometric contractions [MVICs] of 5-second duration in the leg press exercise) or after control (no CA), performed on separate days. No significant differences among groups were found for CMJ height or take-off velocity after any of the CA protocols (p <= 0.05). However, individual analysis showed that some subjects increased performance in response to the CA, despite their previous training history. We concluded that subjects` level of maximal dynamic strength and training background have no influence on PAP manifestation. Our data suggest that coaches should individually identify the athletes that are PAP responders before introducing MVICs as part of their warm-up routines.

Response surface methodology as an approach to determine optimal activities of lipase entrapped in sol-gel matrix using different vegetable oils

The conditions for maximization of the enzymatic activity of lipase entrapped in sol-gel matrix were determined for different vegetable oils using an experimental design. The effects of pH, temperature, and biocatalyst loading on lipase activity were verified using a central composite experimental design leading to a set of 13 assays and the surface response analysis. For canola oil and entrapped lipase, statistical analyses showed significant effects for pH and temperature and also the interactions between pH and temperature and temperature and biocatalyst loading. For the olive oil and entrapped lipase, it was verified that the pH was the only variable statistically significant. This study demonstrated that response surface analysis is a methodology appropriate for the maximization of the percentage of hydrolysis, as a function of pH, temperature, and lipase loading.

Response of Wolfiporia cocos to iron availability: alterations in growth, expression of cellular proteins, Fe3+-reducing activity and Fe3+-chelators production

Aims: The main objective of this study was to evaluate the behaviour of the brown-rot fungus Wolfiporia cocos under differential iron availability. Methods and Results: W. cocos was grown under three differential iron conditions. Growth, catecholate and hydroxamate production, and mycelial and extracellular Fe3+-reducing activities were determined. Iron starvation slowed fungal growth and accelerated pH decline. Some mycelial proteins of low molecular weight were repressed under iron restriction, whereas others of high molecular weight showed positive iron regulation. Mycelial ferrireductase activity decreased as culture aged, while Fe3+-reducing activity of low molecular reductants constantly increased. Hydroxamates production suffered only limited iron repression, whereas catecholates production showed to be more iron repressible. Conclusions: W. cocos seems to possess more than one type of iron acquisition mechanism; one involving secretion of organic acids and ferrireductases and/or extracellular reductants, and another relying on secretion of catecholates and hydroxamates chelators. Significance and Impact of the Study: This paper is the first to report the kinetic study of brown-rot fungus grown under differential iron availability, and the information provided here contributes to address more traditional problems in protecting wood from brown decay, and also makes a contribution in the general area of the physiology of brown-rot fungi.

Improved xylitol production in media containing phenolic aldehydes: application of response surface methodology for optimization and modeling of bioprocess

BACKGROUND: The combined effects of vanillin and syringaldehyde on xylitol production by Candida guilliermondii using response surface methodology (RSM) have been studied. A 2(2) full-factorial central composite design was employed for experimental design and analysis of the results. RESULTS: Maximum xylitol productivities (Q(p) = 0.74 g L(-1) h(-1)) and yields (Y(P/S) = 0.81 g g(-1)) can be attained by adding only vanillin at 2.0 g L(-1) to the fermentation medium. These data were closely correlated with the experimental results obtained (0.69 +/- 0.04 g L(-1) h(-1) and 0.77 +/- 0.01 g g(-1)) indicating a good agreement with the predicted value. C. guilliermondii was able to convert vanillin completely after 24 h of fermentation with 94% yield of vanillyl alcohol. CONCLUSIONS: The bioconversion of xylose into xylitol by C. guilliermondii is strongly dependent on the combination of aldehydes and phenolics in the fermentation medium. Vanillin is a source of phenolic compound able to improve xylitol production by yeast. The conversion of vanillin to alcohol vanilyl reveals the potential of this yeast for medium detoxification. (C) 2009 Society of Chemical Industry

Simultaneous saccharification and ethanol fermentation of oxalic acid pretreated corncob assessed with response surface methodology

Response surface methodology was used to evaluate optimal time, temperature and oxalic acid concentration for simultaneous saccharification and fermentation (SSF) of corncob particles by Pichia stipitis CBS 6054. Fifteen different conditions for pretreatment were examined in a 2(3) full factorial design with six axial points. Temperatures ranged from 132 to 180 degrees C, time from 10 to 90 min and oxalic acid loadings from 0.01 to 0.038 g/g solids. Separate maxima were found for enzymatic saccharification and hemicellulose fermentation, respectively, with the condition for maximum saccharification being significantly more severe. Ethanol production was affected by reaction temperature more than by oxalic acid and reaction time over the ranges examined. The effect of reaction temperature was significant at a 95% confidence level in its effect on ethanol production. Oxalic acid and reaction time were statistically significant at the 90% level. The highest ethanol concentration (20 g/l) was obtained after 48 h with an ethanol volumetric production rate of 0.42 g ethanol l(-1) h(-1). The ethanol yield after SSF with P. stipitis was significantly higher than predicted by sequential saccharification and fermentation of substrate pretreated under the same condition. This was attributed to the secretion of beta-glucosidase by P. stipitis. During SSF, free extracellular beta-glucosidase activity was 1.30 pNPG U/g with P. stipitis, while saccharification without the yeast was 0.66 pNPG U/g. Published by Elsevier Ltd.

Effect of Amblyomma cajennense Ticks on the Immune Response of BALB/c Mice and Horses

This work evaluated the effect of the Amblyomma cajennense tick on the immune response of BALB/c mice and on horse lymph node cell proliferation. We observed that mice do not develop resistance to nymphs of this tick species and that lymphocyte proliferation of this host is inhibited by tick saliva, nymphal extract, or infestations. Horse lymph node cell proliferation is inhibited by tick saliva as well. Mice lymphocytes under the effect of tick saliva, nymphal extract, or infestations display a predominantly. p Th-2 cytokine production pattern. Observed results partially explain this tick`s disease vectoring capacity and broad host range.

LOW-INTENSITY PULSED ULTRASOUND PRODUCED AN INCREASE OF OSTEOGENIC GENES EXPRESSION DURING THE PROCESS OF BONE HEALING IN RATS

The aim of this study was to measure the temporal expression of osteogenic genes during the process of bone healing in low-intensity pulsed ultrasound (LIPUS) treated bone defects by means of histopathologic and real-time polymerase chain reaction (PCR) analysis. Animals were randomly distributed into two groups (n = 30): control group (bone defect without treatment) and LIPUS treated (bone defect treated with LIPUS). On days 7, 13 and 25 postinjury, 10 rats per group were sacrificed. Rats were treated with a 30 mW/cm(2) LIPUS. The results pointed out intense new bone formation surrounded by highly vascularized connective tissue presenting a slight osteogenic activity, with primary bone deposition was observed in the group exposed to LIPUS in the intermediary (13 days) and late stages of repair (25 days) in the treated animals. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) showed an upregulation of bone morphogenetic protein 4 (BMP4), osteocalcin and Runx2 genes 7 days after the surgery. In the intermediary period, there was no increase in the expression. The expression of alkaline phosphatase, BMP4 and Runx2 was significantly increased at the last period. Our results indicate that LIPUS therapy improves bone repair in rats and upregulated osteogenic genes, mainly at the late stages of recovery. (E-mail: a.renno@unifesp.br) (C) 2010 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.