The moderating role of working memory capacity and alcohol-specific rule-setting on the relation between approach tendencies and alcohol use in young adolescents

Background: Dual process models of alcohol addiction propose that the transition from normative alcohol consumption to heavy drinking is the result of an imbalance in interplay between relatively impulsive or automatic and reflective or controlled processes. The current study examines whether impulsive and reflective processes are also detectable in a sample of adolescents with limited alcohol use. Methods: Specifically, we tested the interaction between alcohol approach tendencies and 2 types of reflective processes, working memory capacity (WMC) and alcohol‐specific rule‐setting, on changes in alcohol use of 238 young adolescents (mean age: 13.82 years). Gender differences in these associations were also explored. Results: Results showed that WMC did not moderate the relation between approach tendencies and subsequent alcohol use, whereas rule‐setting did, with stronger associations between approach tendencies and alcohol use for male adolescents reporting more permissive parents than male adolescents with parents enforcing stricter rules involving alcohol use. Associations between approach tendencies and subsequent alcohol use did not emerge for female adolescents. Conclusions: Results indicate that even in a sample of adolescents with limited drinking experience, automatic processes are positively associated with alcohol use for male adolescents that are not motivated by parents to control their drinking.     

The process of cognitive behaviour therapy for chronic fatigue syndrome: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue?

Objective

Cognitive behaviour therapy (CBT) can significantly reduce fatigue in chronic fatigue syndrome (CFS), but little is known about the process of change taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych Res 2012), we examined how (changes in) cognitions and behaviour are related to the decrease in fatigue.

Methods

We included 183 patients meeting the US Centers for Disease Control criteria for CFS, aged 18 to 65 years, starting CBT. We measured fatigue and possible process variables before treatment; after 6, 12 and 18 weeks; and after treatment. Possible process variables were sense of control over fatigue, focusing on symptoms, self-reported physical functioning, perceived physical activity and objective (actigraphic) physical activity. We built multiple regression models, explaining levels of fatigue during therapy by (changes in) proposed process variables.

Results

We observed large individual variation in the patterns of change in fatigue and process variables during CBT for CFS. Increases in the sense of control over fatigue, perceived activity and self-reported physical functioning, and decreases in focusing on symptoms explained 20 to 46% of the variance in fatigue. An increase in objective activity was not a process variable.

Conclusion

A change in cognitive factors seems to be related to the decrease in fatigue during CBT for CFS. The pattern of change varies considerably between patients, but changes in process variables and fatigue occur mostly in the same period.     

Therapeutic Riding or Mindfulness: Comparative Effectiveness of Two Recreational Therapy Interventions for Adolescents with Autism

Journal of Autism and Developmental Disorders - Therapeutic riding (THR) and HeartMath (HM) mindfulness-based interventions have promise for reducing stress in adolescents with autism spectrum...     

Development of a non-denaturing electrophoresis system for characterization of neutralizing epitopes on HPV virus-like particles

The precise structure of the HPV16 major neutralizing epitope recognized by H16.V5 monoclonal antibody is unknown. This paper describes a novel polyacrylamide gel electrophoresis (PAGE) for separation of HPV virus-like particles (VLPs) using cetyltrimethylammonium chloride (CTAC) as a solubilizing agent. CTAC PAGE employs KOH/CH3CO2H (pH 4-5.4) as a buffer system, K+ as the leading ion and 3-aminopropionic acid as a trailing ion. The unique characteristics of a cationic electrophoresis system allow separation of VLPs without heat denaturation. HPV VLP gel migration patterns were dependent on pre-treatment conditions: (1) thiol-agent reduction alone resulted in a 174 kDa band (interpreted as a L1 trimer), a 53 kDa band (size of the L1 monomer), as well as higher Mr aggregates consistent with a pentamer size; (2) both heat denaturation and thiol-agent reduction resulted in a 53 kDa band. Western blot analysis showed that the 174 kDa L1 trimer was strongly immunoreactive with H16.V5 and HPV16 VLP ELISA positive human sera, whereas no reactivity was seen with the monomeric L1 unit. These data suggest that a structure consistent with the migration pattern of a L1 trimer contains the major neutralizing epitope recognized by the H16.V5 MAb and human sera.     

Development of an efficient, scalable, aldolase-catalyzed process for enantioselective synthesis of statin intermediates

A process is reported for efficient, enantioselective production of key intermediates for the common chiral side chain of statin-type cholesterol-lowering drugs such as Lipitor (atorvastatin) and Crestor (rosuvastatin). The process features a one-pot tandem aldol reaction catalyzed by a deoxyribose-5-phosphate aldolase (DERA) to form a 6-carbon intermediate with installation of two stereogenic centers from 2-carbon starting materials. An improvement of almost 400-fold in volumetric productivity relative to the published enzymatic reaction conditions has been achieved, resulting in a commercially attractive process that has been run on up to a 100-g scale in a single batch at a rate of 30.6 g/liter per h. Catalyst load has been improved by 10-fold as well, from 20 to 2.0 wt % DERA. These improvements were achieved by a combination of discovery from environmental DNA of DERAs with improved activity and reaction optimization to overcome substrate inhibition. The two stereogenic centers are set by DERA with enantiomeric excess at >99.9% and diastereomeric excess at 96.6%. In addition, down-stream chemical steps have been developed to convert the enzymatic product efficiently to versatile intermediates applicable to preparation of atorvastatin and rosuvastatin.     

Suppression of lipopolysaccharide-induced inflammatory responses in RAW 264.7 murine macrophages by aqueous extract of Clinopodium vulgare L. (Lamiaceae)

Ethnopharmacological relevance

The wild basil Clinopodium vulgare L. is commonly used in Bulgarian folk medicine for treatment of irritated skin, mastitis- and prostatitis-related swelling, as well as for some disorders accompanied with significant degree of inflammation (e.g. gastric ulcers, diabetes, and cancer).

Aim of study

To determine the effect of aqueous extract of Clinopodium vulgare L. on LPS-induced inflammatory responses of murine RAW 264.7 macrophages.

Materials and methods

Cell cytotoxicity was evaluated by MTT assay. Protein expression levels were monitored by Western blot analysis. Production of NO and PGE₂ was measured by the Griess colorimetric method and enzyme immunoassay, respectively. Activation of MMP-9 was visualized by gelatin zymography. Cytokine levels were determined by BioPlex assay. Intracellular ROS and free radical scavenging potential were measured by DCFH-DA and DPPH method, respectively. Xanthine oxidase activity was evaluated spectrophotometrically.

Results

The extract suppresses NF-κB activation by preventing Iκ-B phosphorylation and inhibits the phosphorylation of p38 and SAPK/JNK MAPKs. It down-regulates iNOS expression which manifests as a drastic decrease of NO production, inhibits MMP-9 activation, but does not affect COX-2 protein levels and reduces only slightly the released PGE₂. Secretion of IL-1β and Il-10 is greatly reduced, whereas suppression of TNF-α and GM-CSF production is less dramatic. The extract has strong free radical scavenging properties and exerts inhibitory effect on xanthine oxidase activity, which lowers the levels of intracellular ROS.

Conclusion

The study provides evidence for the anti-inflammatory potential of Clinopodium vulgare L. aqueous extract.     

Monoclonal antibody-ricin A chain conjugates (immunotoxins): potential therapeutic agents for human colon carcinoma

With the advent of hybridoma technology, monoclonal antibodies (MAbs) can be produced against specific human tumor cell-surface antigens. 44X14, an MAb produced in our laboratory by the immunization of BALB/c mice with colon carcinoma cells, exhibits high affinity for breast, lung, and colon carcinomas. However, this MAb shows little evidence of in vitro cytotoxicity. To enhance the potency of this MAb, it was coupled to the A chain (RTA) of the castor-bean protein ricin. Ricin is composed of two subunits--RTA, which binds to ribosomes and inhibits protein synthesis, and the B chain (RTB), which binds to galactose residues on all human cells and facilitates entry of RTA into the cell. By chemically separating RTA from RTB, RTA can then be coupled to MAb 44X14 so as to redefine its specific toxicity. This immunotoxin 44X14-RTA was assayed for protein-synthesis inhibition in HT-29 colon carcinoma and HT-1080 sarcoma cells by [3H]leucine uptake. Intact ricin (RTA + RTB) inhibited protein synthesis by 50% at concentrations of 0.76 and 4.8 ng/ml in HT-29 and HT-1080 cells, respectively. MAb 44X14 showed the same level of inhibition on HT-29 cells at 6.4 micrograms/ml, whereas the immunotoxin MAb 44X14-RTA showed 50% inhibition at 0.15 micrograms/ml. No effect of either MAb 44X14 or MAb 44X14-RTA at concentrations up to 200 micrograms/ml was seen on HT-1080 cells. Thus, the coupling of RTA to carcinoma-specific MAb 44X14 increased its potency 50-fold without increasing its nonspecific binding to cells that do not contain the appropriate antigen.(ABSTRACT TRUNCATED AT 250 WORDS)