Mechanisms of potentiation of the mammalian GABAA receptor by the marine cembranoid eupalmerin acetate.

Background And Purpose: Eupalmerin acetate (EPA) is a marine diterpene compound isolated from the gorgonian octocorals Eunicea succinea and Eunicea mammosa. The compound has been previously shown to modulate muscle-type and neuronal nicotinic acetylcholine receptors, which are inhibited in the presence of low micromolar concentrations of EPA. In this study, we examined the effect of EPA on another transmitter-gated ion channel, the GABA(A) receptor.

The role of fear-avoidance and helplessness in explaining functional disability in chronic pain: a prospective study.

Objective: Based on the fear-avoidance and helplessness models, the relative contribution of fear of pain, avoidance behavior, worrying, and helplessness were examined in relation to fluctuations in functional disability in chronic-pain patients.

Methods: A cohort of 181 chronic-pain patients first completed various questionnaires and kept a 7-day pain journal during a standard 3-month waiting-list period prior to their scheduled treatment at an Interdisciplinary Pain Centre and did so again immediately preceding the intervention.

Results: At baseline, fear of pain, avoidance behavior, and helplessness all predicted functional disability after 3 months.

The Impact of Chronic Skin Disease on Daily Life (ISDL): a generic and dermatology-specific health instrument.

Background: In dermatological research and clinical practice, there is a need for comprehensive self-report instruments that assess a broad spectrum of health implications of chronic skin diseases, including generic and skin-specific aspects of disease-related quality of life. The advantages of dermatology-specific, multidimensional instruments over generic instruments or single-dimensional quality-of-life measures are in the detailed and specific information they provide about health areas that are affected by the skin condition and that may change through therapeutic intervention.

Objectives: The development of a multidimensional health status inventory for chronic skin diseases (Impact of Chronic Skin Disease on Daily Life, ISDL) is described.

DairyWise, a whole-farm dairy model.

A whole-farm dairy model was developed and evaluated. The DairyWise model is an empirical model that simulated technical, environmental, and financial processes on a dairy farm. The central component is the FeedSupply model that balanced the herd requirements, as generated by the DairyHerd model, and the supply of homegrown feeds, as generated by the crop models for grassland and corn silage.

Physical activity and adherence to compression therapy in patients with venous leg ulcers.

Objective: To assess levels of physical activity, particularly walking and leg exercises, among patients with venous leg ulcers and the extent to which patients adhere to compression therapy.

Design: Descriptive cross-sectional study.

Setting: Patients from 12 outpatient dermatology clinics were invited to participate in this study.

Generalized and symptom-specific sensitization of chronic itch and pain.

Background: Physicians are frequently confronted with patients reporting severe itch and pain. Particularly in patients suffering from persistent itch and pain, central and peripheral sensitization processes are assumed to be involved in the long-term maintenance and aggravation of the symptoms. The present study explores generalized and symptom-specific sensitization processes in patients suffering from persistent itch and pain.

Sedentary patients with venous or mixed leg ulcers: determinants of physical activity.

Aim: This paper is a report of a study to identify the determinants of physical activity (PA) in patients with venous leg ulcers to develop recommendations for behavioural interventions aimed at enhancing physical activity.

Background: Physical activity promotes wound healing and prevents the recurrence of wounds in venous patients with leg ulcers. Many patients with leg ulcers, however, have a sedentary lifestyle.

Prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases in general practice.

Background: Physical symptoms of skin diseases have been shown to negatively affect patients' wellbeing. Although insight into physical symptoms accompanying skin diseases is relevant for the management and treatment of skin diseases, the prevalence of physical symptoms among patients with skin diseases is a rather unexplored territory.

Objectives: The goal of the present study was to examine the prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases.

Mechanisms of neurosteroid interactions with GABA(A) receptors.

Neuroactive steroids have some of their most potent actions by augmenting the function of GABA(A) receptors. Endogenous steroid actions on GABA(A) receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants.

Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS.

Cross-cultural inequivalence of dermatology-specific health-related quality of life instruments in psoriasis patients.

The dermatology life questionnaire index (DLQI) and the Skindex are the most commonly used dermatology-specific health-related quality of life (HRQOL) instruments. Although these tools are used in international surveys and clinical trials, the cross-cultural equivalence of their items has not been documented. We used differential item functioning (DIF), which is part of the Rasch model, to assess the impact of cultural background on the items of the DLQI and Skindex-29 and-17.

Psychosocial well-being of patients with skin diseases in general practice.

Background: Skin diseases are a substantial part of the problems dealt with by general practitioners. Although the psychosocial consequences of skin diseases in secondary care has been extensively studied, little is known about the psychosocial well-being of patients with skin diseases in primary care.

Objective: To investigate the psychosocial well-being of patients with skin diseases in primary care.

Neurosteroid analogues. 12. Potent enhancement of GABA-mediated chloride currents at GABAA receptors by ent-androgens.

Allopregnanolone (1) and pregnanolone (2), steroids containing a 17beta-acetyl group, are potent enhancers of GABA (gamma-aminobutyric acid) action at GABAA receptors. Their effects are enantioselective with the non-naturally occurring enantiomers (ent-1 and ent-2) being less potent. Androsterone (3) and etiocholanolone (4), steroids with a C-17 carbonyl group, are weak enhancers of GABA action at GABAA receptors.

Anticonvulsant and anesthetic effects of a fluorescent neurosteroid analog activated by visible light.

Most photoactivatable compounds suffer from the limitations of the ultraviolet wavelengths that are required for activation. We synthesized a neuroactive steroid analog with a fluorescent (7-nitro-2,1,3-benzoxadiazol-4-yl) amino (NBD) group in the beta configuration at the C2 position of (3alpha,5alpha)-3-hydroxypregnan-20-one (allopregnanolone, 3alpha5alphaP). Light wavelengths (480 nm) that excite compound fluorescence strongly potentiate GABAA receptor function.

Understanding oligomerization in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni: an in silico approach and evidence for an active protein.

3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from Comamonas testosteroni belongs to the short chain dehydrogenase/reductase (SDR) protein superfamily and catalyzes the oxidoreduction of a variety of steroid substrates, including the steroid antibiotic fusidic acid. The enzyme also mediates the carbonyl reduction of non-steroidal aldehydes and ketones such as a novel insecticide. It is suggested that 3alpha-HSD/CR contributes to the bioremediation of natural and synthetic toxicants by C.

Ethanol modulates the interaction of the endogenous neurosteroid allopregnanolone with the alpha1beta2gamma2L GABAA receptor.

We have examined alpha1beta2gamma2L GABAA receptor modulation by the endogenous steroids allopregnanolone (3alpha5alphaP), pregnenolone sulfate, and beta-estradiol in the absence and presence of ethanol. Coapplication of 0.1 to 1% (17-170 mM) ethanol influenced receptor modulation by 3alpha5alphaP but not that by pregnenolone sulfate or beta-estradiol.

Cognitive, behavioral, and physiological reactivity to chronic itching: analogies to chronic pain.

It is well-known that cognitive, behavioral, and physiological reactivity to pain, such as catastrophizing, avoidance of activity, and increased physiological responses, can unfavorably affect long-term outcomes in patients with chronic pain. In line with similarities between the psychophysiology of pain and itching, corresponding mechanisms may be relevant for the maintenance of chronic itching. The goal of this study was to examine the role of self-reported cognitive, behavioral, and physiological reactivity factors on itching-related outcomes in 235 patients with chronic skin diseases suffering from chronic itching.

Women's emotional adjustment to IVF: a systematic review of 25 years of research.

This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF treatment of which 27 investigated the women's emotional adjustment with standardized measures in relation to norm or control groups. Most studies involved concurrent comparisons between women in different treatment phases and different types of control groups.

Cognitive-behavioural therapies and exercise programmes for patients with fibromyalgia: state of the art and future directions.

This review provides an overview of the effects of non-pharmacological treatments for patients with fibromyalgia (FM), including cognitive-behavioural therapy, exercise training programmes, or a combination of the two. After summarising and discussing preliminary evidence of the rationale of non-pharmacological treatment in patients with FM, we reviewed randomised, controlled trials for possible predictors of the success of treatment such as patient and treatment characteristics. In spite of support for their suitability in FM, the effects of non-pharmacological interventions are limited and positive outcomes largely disappear in the long term.

The potential of P1 site alterations in peptidomimetic protease inhibitors as suggested by virtual screening and explored by the use of C-C-coupling reagents.

A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer-supported C-acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C-acylation can be conducted without racemization. Diastereoselective reduction was effected with L-selectride.

Neurosteroid analogues. 11. Alternative ring system scaffolds: gamma-aminobutyric acid receptor modulation and anesthetic actions of benz[f]indenes.

Benz[f]indenes are tricyclic compounds with a linear 6-6-5 fused carbocyclic ring system. When properly substituted, benz[f]indenes can satisfy the pharmacophore requirements of the critical hydrogen-bond donor and acceptor groups found in neuroactive steroids that modulate gamma-aminobutyric acidA (GABAA) receptor function. Thus, the benz[f]indene ring system provides an opportunity to extend the previously well-studied GABAA receptor structure-activity relationships (SAR) of neuroactive steroids to a different ring system.

Reduced work capacity after lumbar disc surgery: the role of cognitive-behavioral and work-related risk factors.

A significant number of patients who have had surgery for lumbosacral radicular syndrome still have a reduced work capacity several months later. In a prospective cohort study of 182 people who underwent lumbar disc surgery, we determined the predictive value of preoperatively measured cognitive-behavioral and work-related factors on work capacity 6 months after surgery. Logistic regression analyses indicated that these factors independently predicted work capacity 6 months after surgery.

Continued disability and pain after lumbar disc surgery: the role of cognitive-behavioral factors.

Cognitive-behavioral factors are considered important in the development of chronic disability and pain in patients with low back pain. In a prospective cohort study of 277 patients undergoing surgery for lumbosacral radicular syndrome, the predictive value of preoperatively measured cognitive-behavioral factors (fear of movement/(re)injury, passive pain coping, and negative outcome expectancies) for disability and pain intensity at 6 weeks and 6 months after surgery was investigated, taking into account the effect of possible confounding variables. Higher levels of cognitive-behavioral factors were found to be associated with a worse outcome at both 6 weeks and 6 months.

The role of helplessness, fear of pain, and passive pain-coping in chronic pain patients.

Objectives: The goal of this study was to examine the relative contribution of helplessness, fear of pain, and passive pain-coping to pain level, disability, and depression in chronic pain patients attending an interdisciplinary pain center.

Methods: One hundred sixty-nine chronic pain patients who had entered treatment at an interdisciplinary pain center completed various questionnaires and a pain diary.

Results: Helplessness, fear of pain, and passive pain-coping strategies were all related to the pain level, disability, and depression.