Mixtures of four organochlorines enhance human breast cancer cell proliferation.

In view of the large differences between the concentrations of estrogenic chemicals needed to elicit effects in in vitro assays and their levels in human tissues, it is hard to explain possible health risks in terms of exposure to individual compounds. Human populations, however, are exposed to mixtures of estrogenic and estrogen-like agents and it is necessary to consider the impact of combined effects. We assessed the combined effects of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (p,p'-DDT) on the induction of cell proliferation in MCF-7 cells. All four compounds are persistent organochlorines that can be found in human tissues. We performed extensive concentration-response analyses with the single agents to predict the effects of two mixtures of all four compounds with different mixture ratios. We calculated the predictions by using the pharmacologically well-founded models of concentration addition and independent action and then tested them experimentally. o,p'-DDT, p,p'-DDE, beta-HCH, and p,p'-DDT acted together to produce proliferative effects in MCF-7 cells. The combined effect of the four agents could be predicted on the basis of data about single agent concentration-response relationships. Regression analysis demonstrated that there were combination effects even when each mixture component was present at levels at or below its individual no-observed-effect-concentration. We assessed combination effects in two ways: First, evaluations in relation to the proliferative responses induced by single mixture components revealed that the combination effects were stronger than the effects of the most potent constituent. Thus, according to this method of evaluation, the combined effects may be termed synergistic. Second, comparisons with the expected effects, as predicted by concentration addition and independent action, showed excellent agreement between prediction and observation. With this approach, the combined effect of all four compounds can be termed additive

Escitalopram—translating molecular properties into clinical benefit: reviewing the evidence in major depression

The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents

A COMPARISON OF CHOLINESTERASE DISTRIBUTION IN THE CEREBELLUM OF SEVERAL SPECIES *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65142/1/j.1471-4159.1964.tb06717.x.pd

Loss of Productivity Due to Neck/Shoulder Symptoms and Hand/Arm Symptoms: Results from the PROMO-Study

Introduction: The objective of the present study is to describe the extent of productivity loss among computer workers with neck/shoulder symptoms and hand/arm symptoms, and to examine associations between pain intensity, various physical and psychosocial factors and productivity loss in computer workers with neck/shoulder and hand/arm symptoms. Methods: A cross-sectional design was used. The study population consisted of 654 computer workers with neck/shoulder or hand/arm symptoms from five different companies. Descriptive statistics were used to describe the occurrence of self-reported productivity loss. Logistic regression analyses were used to examine the associations. Results: In 26% of all the cases reporting symptoms, productivity loss was involved, the most often in cases reporting both symptoms (36%). Productivity loss involved sickness absence in 11% of the arm/hand cases, 32% of the neck/shoulder cases and 43% of the cases reporting both symptoms. The multivariate analyses showed statistically significant odds ratios for pain intensity (OR: 1.26; CI: 1.12-1.41), for high effort/no low reward (OR: 2.26; CI: 1.24-4.12), for high effort/low reward (OR: 1.95; CI: 1.09-3.50), and for low job satisfaction (OR: 3.10; CI: 1.44-6.67). Physical activity in leisure time, full-time work and overcommitment were not associated with productivity loss. Conclusion: In most computer workers with neck/shoulder symptoms or hand/arm symptoms productivity loss derives from a decreased performance at work and not from sickness absence. Favorable psychosocial work characteristics might prevent productivity loss in symptomatic workers. © 2007 Springer Science+Business Media, LLC

Neuromusculoskeletal disorders in the neck and upper extremities among drivers of all-terrain vehicles – a case series

BACKGROUND: The purpose of this study was to investigate whether professional drivers of all-terrain vehicles (ATVs) with neck pain have a different array of neuromusculoskeletal disorders in the neck and upper extremities than a referent group with neck pain from the general population. It is hypothesized that exposure to shock-type vibration and unfavorable working postures in ATVs have the capacity to cause peripheral nervous lesions. METHODS: This study was based on a case series analyzed according to a case-case comparison design. The study population consisted of 60 male subjects, including professional drivers of forest machines (n = 15), snowmobiles (n = 15), snowgroomers (n = 15) and referents from the general population (n = 15) all of whom had reported neck pain in a questionnaire and underwent an extensive physical examination of the neck and upper extremities. Based on symptom history, symptoms and signs, and in some cases chemical, electroneurographical and radiological findings, subjects were classified as having a nociceptive or neuropathic disorder or a mix of these types. RESULTS: The occurrence of asymmetrical and focal neuropathies (peripheral nervous lesion), pure or in a mix with a nociceptive disorder was common among cases in the ATV driver groups (47%–79%). This contrasted with the referents that were less often classified as having asymmetrical and focal neuropathy (27%), but instead had more nociceptive disorders. The difference was most pronounced among drivers of snowgroomers, while drivers of forest machines were more frequently classified as having a nociceptive disorder originating in the muscles. CONCLUSION: This study found a high prevalence of assymetrical and focal neuropathies among drivers with pain in the neck, operating various ATVs. It seems as if exposure to shock-type whole-body vibration (WBV) and appurtenant unfavorable postures in ATVs may be associated to peripheral nervous lesions

Pharmacogenomic and structural analysis of constitutive G-protein coupled receptor activity

Premi a l'excel·lència investigadora. Àmbit de les Ciències de la Salut. 2008G-protein coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i.e. in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. With the recognition of constitutive GPCR activity and the fact that GPCR binding and signaling can be strongly affected by a single point mutation, GPCR pharmacogenomics obtained a lot of attention. For a variety of GPCRs, point mutations have been convincingly linked to human disease. Mutations within conserved motifs, known to be involved in GPCR activation, might explain the properties of some naturally occurring constitutively active GPCR variants linked to disease. A brief history historical introduction to the present concept of constitutive receptor activity is given and the pharmacogenomic and the structural aspects of constitutive receptor activity are described

Prognostic factors for disability claim duration due to musculoskeletal symptoms among self-employed persons

<p>Abstract</p> <p>Background</p> <p>Employees and self-employed persons have, among others, different personal characteristics and different working conditions, which may influence the prognosis of sick leave and the duration of a disability claim. The purpose of the current study is to identify prognostic factors for the duration of a disability claim due to non-specific musculoskeletal disorders (MSD) among self-employed persons in the Netherlands.</p> <p>Methods</p> <p>The study population consisted of 276 self-employed persons, who all had a disability claim episode due to MSD with at least 75% work disability. The study was a cohort study with a follow-up period of 12 months. At baseline, participants filled in a questionnaire with possible individual, work-related and disease-related prognostic factors.</p> <p>Results</p> <p>The following prognostic factors significantly increased claim duration: age > 40 years (Hazard Ratio 0.54), no similar symptoms in the past (HR 0.46), having long-lasting symptoms of more than six months (HR 0.60), self-predicted return to work within more than one month or never (HR 0.24) and job dissatisfaction (HR 0.54).</p> <p>Conclusions</p> <p>The prognostic factors we found indicate that for self-employed persons, the duration of a disability claim not only depends on the (history of) impairment of the insured, but also on age, self-predicted return to work and job satisfaction.</p

Associations between neck musculoskeletal complaints and work related factors among public service computer workers in Kaunas

Objectives:Information technologies have been developing very rapidly, also in the case of occupational activities. Epidemiological studies have shown that employees, who work with computers, are more likely to complain of musculoskeletal disorders (MSD). The aim of this study was to evaluate associations between neck MSD and individual and work related factors. Materials and Methods: The investigation which consisted of two parts - a questionnaire study (using Nordic Musculoskeletal questionnaire and Copenhagen Psychosocial Questionnaire) and a direct observation (to evaluate ergonomic work environment using RULA method) was carried out in three randomly selected public sector companies of Kaunas. The study population consisted of 513 public service office workers. Results: The survey showed that neck MSDs were very common in the investigated population. The prevalence rate amounted to 65.7%. According to our survey neck MSDs were significantly associated with older age, bigger work experience, high quantitative and cognitive job demands, working for longer than 2 h without taking a break as well as with higher ergonomic risk score. The fully adjusted model working for longer than 2 h without taking a break had the strongest associations with neck complaints. Conclusion: It was confirmed, that neck MSDs were significantly associated with individual factors as well as conditions of work, therefore, preventive acions against neck complaints should be oriented at psychosocial and ergonomic work environment as well as at individual factors

Work related complaints of neck, shoulder and arm among computer office workers: a cross-sectional evaluation of prevalence and risk factors in a developing country

<p>Abstract</p> <p>Background</p> <p>Complaints of arms, neck and shoulders (CANS) is common among computer office workers. We evaluated an aetiological model with physical/psychosocial risk-factors.</p> <p>Methods</p> <p>We invited 2,500 computer office workers for the study. Data on prevalence and risk-factors of CANS were collected by validated Maastricht-Upper-extremity-Questionnaire. Workstations were evaluated by Occupational Safety and Health Administration (OSHA) Visual-Display-Terminal workstation-checklist. Participants' knowledge and awareness was evaluated by a set of expert-validated questions. A binary logistic regression analysis investigated relationships/correlations between risk-factors and symptoms.</p> <p>Results</p> <p>Sample size was 2,210. Mean age 30.8 ± 8.1 years, 50.8% were males. The 1-year prevalence of CANS was 56.9%, commonest region of complaint was forearm/hand (42.6%), followed by neck (36.7%) and shoulder/arm (32.0%). In those with CANS, 22.7% had taken treatment from a health care professional, only in 1.1% seeking medical advice an occupation-related injury had been suspected/diagnosed. In addition 9.3% reported CANS-related absenteeism from work, while 15.4% reported CANS causing disruption of normal activities. A majority of evaluated workstations in all participants (88.4%,) and in those with CANS (91.9%) had OSHA non-compliant workstations. In the binary logistic regression analyses female gender, daily computer usage, incorrect body posture, bad work-habits, work overload, poor social support and poor ergonomic knowledge were associated with CANS and its' severity In a multiple logistic regression analysis controlling for age, gender and duration of occupation, incorrect body posture, bad work-habits and daily computer usage were significant independent predictors of CANS</p> <p>Conclusions</p> <p>The prevalence of work-related CANS among computer office workers in Sri Lanka, a developing, South Asian country is high and comparable to prevalence in developed countries. Work-related physical factors, psychosocial factors and lack of awareness were all important associations of CANS and effective preventive strategies need to address all three areas.</p