Treatment of Dyslipidemia with Statins and Physical Exercises: Recent Findings of Skeletal Muscle Responses

Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords “statin” AND “exercise” AND “muscle”, restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.

Sertraline inhibits formalin-induced nociception and cardiovascular responses

The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg-1·day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors.

The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2

It is currently accepted that superoxide anion (O2•−) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO2), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO2 is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO2. The KO2-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO2 induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO2 also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO2-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO2 is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.

Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses

Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training.

Evaluation of a program to reduce back pain in nursing personnel

OBJECTIVE: To evaluate the effectiveness of a program designed to reduce back pain in nursing aides. METHODS: Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study. Participants were randomly divided into a control group and an intervention group. The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect, administered twice a week during working hours for four months. All subjects answered a structured questionnaire and the intensity of pain was assessed before and after the program using a visual analogue scale (VAS). Student's t-test or the Wilcoxon Rank Sum Test for independent samples, and Chi-square test or the Exact Fisher test for categorical analysis, were used. The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program. RESULTS: There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group. There was also a reduction in cervical pain intensity in the two periods (2 months, 7 days) and lumbar pain intensity in the last 7 days. CONCLUSIONS: The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel.

Clinical and functional aspects of work-related musculoskeletal disorders among active workers

OBJECTIVE: To evaluate musculoskeletal disorders among active industrial workers. METHODS: The study was carried out in São Carlos, Southeastern Brazil, in 2005. One hundred and thirty-four female workers were physically evaluated and answered questions about their physical symptoms, filled out a pain scale and gave responses in the Oswestry Disability Questionnaire, and the Work Ability Index questionnaire. The data were analyzed descriptively, and in correlation tests and through applying logistic regression. The outcome was evaluated in relation to the perceptions of pain, symptoms, physical assessment, ability to work and disability. RESULTS: Clinical evaluations and sick leave presented positive correlations with the subjective variables. The Work Ability Index presented a negative correlation with the physical disability index (r=-0.69). Symptoms reported at the time of the assessment presented a good correlation with the results from the pain scale and the clinical findings. Previous sick leave showed an association with disability (OR=1.13; 95% CI:1.08;1.18). CONCLUSION: Symptom reports and pain scales may be useful for assessing current conditions at the time of evaluating individuals with work-related musculoskeletal disorders, as they are easier to apply. In more severe cases of such injuries, clinical and functional evaluations and questionnaires such as those relating to ability to work and disability are preferable. Precise and specific evaluations of these disorders may contribute towards fairer legal and administrative decisions.

Use of analgesics in adults with pain complaints: prevalence and associated factors, Turkey

OBJECTIVE: Use of analgesics has been increasingly recognized as a major public health issue with important consequences in Turkey. The objective of the study was to determine the prevalence and patterns of analgesics usage and associated factors in adults with pain complaints. METHODS: A cross-sectional study was conducted in 15 cities selected from five demographic regions in Turkey. The study sample population comprised 1.909 adults 18-65 age groups suffering from pain. The sampling method was multi-step stratified weighted quota-adjusted sampling. Data were collected by face-to-face interviews using a semi-structured survey questionnaire consisting of 28 questions. Odds ratios were produced by logistic regression analyses. RESULTS: The prevalence of analgesic use was 73.1%, and it was higher in females (75.7%; p<0.05), in subjects 45-54 years (81.4%; p<0.05), in subjects in rural areas (74.6%; p<0.05), in subjects in northern region (84.3%; p<0.05), in illiterate subjects (79.1%; p>0.05), and in subjects of lower socioeconomic status (74.1%; p>0.05). One in ten of the participants used non-prescription analgesics. Non-prescription analgesics were more prevalent among the 55-65 age groups (18.1%; p<0.05), among female (11.6%; p>0.05), among the urban population (10.7%; p>0.05), and in subjects of lower middle socioeconomic status (13.2%; p<0.05). Logistic regression showed statistically significant ORs only for age groups, duration of education, socioeconomic status, and demographic regions (p<0.05). CONCLUSIONS: The results showed that the prevalence of analgesic use and prescription analgesic use is high in Turkey, and their use is related to sociodemographic characteristics.

Validity of the Brazilian version of WHOQOL-BREF in depressed patients using Rasch modelling

OBJECTIVE: To assess the validity of the Brazilian version of the World Health Organization Quality of Life Instrument - Abbreviated version (WHOQOL-BREF) in adults with major depression, using Rasch modelling. METHODS: Study analyzing data from the baseline sample of the Longitudinal Investigation of Depression Outcomes in Brazil, including a total of 208 patients with major depression recruited in a primary care service in Porto Alegre (Southern Brazil), in 1999. The Center for Epidemiological Studies Depression Scale was used to assess intensity of depression; the WHOQOL-BREF to assess generic quality of life; and the Composite International Diagnostic Interview version 2.1 for the diagnosis of depression. RESULTS: In the Rasch analysis, the four domains of WHOQOL-BREF showed appropriate fit to this model. Some items needed adjustments: four items were rescored (pain, finances, services, and transport); two items (work and activity) were identified as having dependency of responses, and one item was deleted (sleep) due to multidimensionality. CONCLUSIONS: The validation of the WHOQOL-BREF Brazilian version using Rasch analysis complements previous validation studies, evidencing the robustness of this instrument as a generic cross-cultural quality of life measure.

Interactions between physical and psychosocial demands of work associated to low back pain

OBJECTIVE: To examine the interaction between physical and psychosocial demands of work associated to low back pain. METHODS: Cross-sectional study carried out in a stratified proportional random sample of 577 plastic industry workers in the metropolitan area of the city of Salvador, Northeast Brazil in 2002. An anonymous standard questionnaire was administered in the workplace by trained interviewers. Physical demands at work were self-rated on a 6-point numeric scale, with anchors at each end of the scale. Factor analysis was carried out on 11 physical demand variables to identify underlying factors. Psychosocial work demands were measured by demand, control and social support questions. Multivariate analysis was performed using the likelihood ratio test. RESULTS: The factor analysis identified two physical work demand factors: material handling (factor 1) and repetitiveness (factor 2). The multiple logistic regression analysis showed that factor 1 was positively associated with low back pain (OR=2.35, 95% CI 1.50;3.66). No interaction was found between physical and psychosocial work demands but both were independently associated to low back pain. CONCLUSIONS: The study found independent effects of physical and psychosocial work demands on low back pain prevalence and emphasizes the importance of physical demands especially of material handling involving trunk bending forward and trunk rotation regardless of age, gender, and body fitness.

Back pain in adults living in quilombola territories of Bahia, Northeastern Brazil

OBJECTIVE To analyze the factors associated with back pain in adults who live in quilombola territories. METHODS A population-based survey was performed on quilombola communities of Vitória da Conquista, state of Bahia, Northeastern Brazil. The sample (n = 750) was established via a raffle of residences. Semi-structured interviews were conducted to investigate sociodemographics and employment characteristics, lifestyle, and health conditions. The outcome was analyzed as a dichotomous variable (Poisson regression). RESULTS The prevalence of back pain was of 39.3%. Age ≥ 30 years and being a smoker were associated with the outcome. The employment status was not related to back pain. CONCLUSIONS The survey identified a high prevalence of back pain in adults. It is suggested to support the restructuring of the local public service in order to outline programs and access to healthy practices, assistance, diagnosis, and treatment of spine problems.

Prevalence of chronic low back pain: systematic review

OBJECTIVE To estimate worldwide prevalence of chronic low back pain according to age and sex. METHODS We consulted Medline (PubMed), LILACS and EMBASE electronic databases. The search strategy used the following descriptors and combinations: back pain, prevalence, musculoskeletal diseases, chronic musculoskeletal pain, rheumatic, low back pain, musculoskeletal disorders and chronic low back pain. We selected cross-sectional population-based or cohort studies that assessed chronic low back pain as an outcome. We also assessed the quality of the selected studies as well as the chronic low back pain prevalence according to age and sex. RESULTS The review included 28 studies. Based on our qualitative evaluation, around one third of the studies had low scores, mainly due to high non-response rates. Chronic low back pain prevalence was 4.2% in individuals aged between 24 and 39 years old and 19.6% in those aged between 20 and 59. Of nine studies with individuals aged 18 and above, six reported chronic low back pain between 3.9% and 10.2% and three, prevalence between 13.1% and 20.3%. In the Brazilian older population, chronic low back pain prevalence was 25.4%. CONCLUSIONS Chronic low back pain prevalence increases linearly from the third decade of life on, until the 60 years of age, being more prevalent in women. Methodological approaches aiming to reduce high heterogeneity in case definitions of chronic low back pain are essential to consistency and comparative analysis between studies. A standard chronic low back pain definition should include the precise description of the anatomical area, pain duration and limitation level.

Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats

The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10-3M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10-8 to 10-3M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.

Immune responses induced by a Leishmania (Leishmania) amazonensis recombinant antigen in mice and lymphocytes from vaccinated subjects

In the search for Leishmania recombinant antigens that can be used as a vaccine against American Cutaneous Leishmaniasis, we identified a Leishmania (Leishmania) amazonensis recombinant protein of 33 kD (Larp33) which is recognized by antibodies and peripheral blood leukocytes (PBL) from subjects vaccinated with Leishvacin ®, Larp33 was expressed in Escherichia coli after cloning of a 2,2 kb Sau3A digested genomic fragment of L. (L.) amazonensis into the pDS56-6 His vector. Immunoblotting analysis indicated that Larp33 corresponds to an approximately 40-kD native protein expressed in promastigotes of L.(L.) amazonensis and L. (Viannia) braziliensis. Northern blots of total RNA also demonstrated that the gene coding for this protein is expressed in promastigotes of the major lineages of Leishmania causing American Cutaneous Leishmaniasis. Larp33 induced partial protection in susceptible mouse strains (BALB/c and C57BL/10) against L. (L.) amazonensis after vaccination using Bacille Calmette-Guerin (BCG) as adjuvant. In vitro stimulation of splenocytes from BALB/c protected mice with Larp33 elicited the secretion of IL-2 and IFN-g, suggesting that a Th1 cell-mediated protective response is associated with the resistance observed in these mice. As revealed by its immunogenic and antigenic properties, this novel recombinant antigen is a suitable candidate to compose a vaccine against cutaneous leishmaniasis

IgM and IgA Antibody Responses in 12 Cases of Human Acquired Toxoplasmosis

The persistence, in some subjects, of specific IgM antibodies to Toxoplasma gondii for several months after the acute phase of infection has complicated the interpretation of serological test results for toxoplasmosis. Several reports have emphasized the value of the detection of Toxoplasma-specific IgA antibodies for the diagnosis of acute toxoplasmosis. In this article, we report the follow-up profiles of Toxoplasma-specific IgM and IgA antibodies in serum samples obtained from 12 patients at various intervals after the onset of the clinical manifestations of infection. IgM antibodies were detected by the indirect immunofluorescence (IIF) test, antibody capture enzyme-linked immunosorbent assay (cELISA) and enzyme-mediated chemilluminescent technique (CmL). IgA antibodies were quantified by the direct ELISA (dELISA) and cELISA procedures. As defined by the manufacturer of the cELISA test for IgA used, most patients with acute toxoplasmosis have antibody levels > 40 arbritary units per ml (AU/ml). At values > 40 AU/ml, the cELISA for IgA detected significant antibody levels for a shorter time than the other techniques used for IgM and IgA detection. However, IgA levels £ 40 AU/ml do not exclude the possibility of acute toxoplasmosis since such levels can be reached very soon after infection with T. gondii. The results obtained in the present study show that the serological diagnosis of acute toxoplasmosis may not be such an easy task. Our data suggest that use of the IgA-cELISA concomitantly with IgM antibody screening could permit, in some circumstances, a more efficient diagnosis of acute acquired toxoplasmosis