Predictive Ability of Serum Amino Acid Levels to Differentiate Fibromyalgia Patients from Healthy Subjects.

BACKGROUND: Fibromyalgia is a complex illness to diagnose and treat. OBJECTIVES: To evaluate a broad range of circulating free amino acid (AA) levels in fibromyalgia patients as well as the ability of the AAs to differentiate fibromyalgia patients from healthy subjects. DESIGN: We carried out a case-control study to evaluate AA levels in 62 patients with fibromyalgia and 78 healthy subjects. This study adheres to the STROBE guidelines. METHODS: AAs content was assayed by HPLC in serum samples. The predictive value of AA levels in fibromyalgia was determined by receiver operating characteristic (ROC) curve and forward binary logistic regression analyses. RESULTS: Fibromyalgia patients showed higher serum levels of aspartic acid, glutamic acid, aminoadipic acid, asparagine, histidine, 3-methyl-histidine, 5-methyl-histidine, glycine, threonine, taurine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, ornithine, lysine, branched chain AAs (BCAAs), large neutral AAs, essential AAs (EAAs), non-essential AAs (NEAAs), basic AAs, EAAs/NEAAs ratio, phenylalanine/tyrosine ratio, and global arginine bioavailability ratio than the controls. Serum alanine levels were lower in patients than in controls. According to ROC analysis, most of these AAs may be good markers for differentiating individuals with fibromyalgia from healthy subjects. Results of logistic regression showed that the combination of glutamic acid, histidine, and alanine had the greatest predictive ability to diagnose fibromyalgia. CONCLUSIONS: Our results show an imbalance in serum levels of most AAs in patients with fibromyalgia, which suggest a metabolic disturbance. The determination of serum levels of these AAs may aid in the diagnosis of fibromyalgia, in combination with clinical data of the patient.

Serum VEGF and CGRP Biomarkers: Relationships with Pain Intensity, Electric Pain, Pressure Pain Threshold, and Clinical Symptoms in Fibromyalgia-An Observational Study.

Fibromyalgia (FM) is a multifactorial syndrome, mainly characterized by chronic widespread pain, whose physiopathology is yet to be determined. Reliable biomarkers for FM and how they are associated with the symptomatology have not yet been identified. We aimed to examine the relationships among serum vascular endothelial growth factor (VEGF) and calcitonin gene-related peptide (CGRP) levels with clinical manifestations and pain-related variables in women with FM. We conducted an observational case study with forty-seven women diagnosed with FM. Serum VEGF and CGRP levels were spectrophotometrically analyzed. We used questionnaires to measure the impact of FM and the degree of central sensitization, fatigue, and anxiety. We also assessed pain intensity, electric pain threshold and magnitude, and pressure pain threshold (PPT) in tender points. The linear regression analysis adjusting for age, menopause status, and body mass index showed that serum VEGF levels were significantly associated with the PPTs of non-dominant trapezius (ß = 153.418; p = 0.033), non-dominant second metacarpal (ß = 174.676; p = 0.008) and dominant tibialis anterior (ß = 115.080; p = 0.049) in women with FM. We found no association between serum CGRP levels and the variables measured (p ≥ 0.152). Our results suggest that VEGF may be related to pain processing in patients with FM.

Associations among serum VEGF and CGRP levels with the peripheral vascular blood flow of the skin of the hands in women with Fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a long-term condition of unknown physiopathology, whose hallmark symptoms are diffuse musculoskeletal chronic pain and fatigue. OBJECTIVES: We aimed to analyze the associations among serum vascular endothelial growth factor (VEGF) and calcitonin gene-related peptide (CGRP) levels with the peripheral temperature of the skin of both hands and the core body temperature in patients with FM and healthy controls. METHODS: We conducted a case-control observational study with fifty-three women diagnosed with FM and twenty-four healthy women. VEGF and CGRP levels were spectrophotometrically analyzed in serum by enzyme-linked immunosorbent assay. We used an infrared thermography camera to assess the peripheral temperature of the skin of the dorsal thumb, index, middle, ring, and pinkie fingertips and dorsal centre as well as the palm thumb, index, middle, ring, and pinkie fingertips, palm centre and thenar and hypothenar eminences of both hands and an infrared thermographic scanner to record the tympanic membrane and axillary temperature. RESULTS: Linear regression analysis adjusting for age, menopause status, and body mass index showed that serum VEGF levels were positively associated with the maximum (ß = 65.942, 95% CI [4.100,127.784], p = 0.037), minimum (ß = 59.216, 95% CI [1.455,116.976], p = 0.045), and mean (ß = 66.923, 95% CI [3.142,130.705], p = 0.040) temperature of the thenar eminence of the non-dominant hand, as well as with the maximum temperature of the hypothenar eminence of the non-dominant hand (ß = 63.607, 95% CI [3.468,123.747], p = 0.039) in women diagnosed with FM. CONCLUSIONS: Mild associations were observed between serum VEGF levels and the peripheral temperature of the skin in hand areas in patients with FM; therefore, it is not possible to establish a clear relationship between this vasoactive molecule and vasodilation of the hands in these patients.

Do Routine Laboratory Parameters have Predictive Ability to Differentiate Subjects with Fibromyalgia from Healthy Subjects?

The aim of this study was to evaluate laboratory parameters for investigating their potential predictive ability to differentiate patients with fibromyalgia (FM) from healthy subjects. We carried out a case-control study with 79 FM patients and 20 controls to analyze complete blood count, serum chemistry profile, glycosylated hemoglobin (HbA1c), and erythrocyte sedimentation rate (ESR). The predictive value of these parameters was determined by receiver operating characteristic (ROC) analysis. We also examined the relationships with clinical parameters (functional capacity, pain, and physical and mental health status). Results showed significant differences in red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, platelet count, creatinine, HbA1c, and ESR between groups. According to ROC analysis, all these parameters may assist in making FM diagnosis. Hematocrit and ESR values were correlated with FM clinical parameters. The determination of these routine laboratory parameters may be an uncomplicated means of facilitating FM diagnosis, together with the clinical data of the patient.

Calcitonin Gene-Related Peptide, Vascular Endothelial Growth Factor, and Clinical Manifestations in Women With Fibromyalgia.

BACKGROUND: Fibromyalgia is a complex illness to diagnose and treat, which significantly impairs patients' quality of life. OBJECTIVES: The study aims were to compare levels of calcitonin gene-related peptide and vascular endothelial growth factor between patients with fibromyalgia and healthy controls and to examine their relationship with the main clinical manifestations of fibromyalgia. METHODS: This case-control study included 42 women diagnosed with fibromyalgia and 22 healthy women. Serum calcitonin gene-related peptide and vascular endothelial growth factor levels were spectrophotometrically analyzed by enzyme-linked immunosorbent assay. Clinical manifestations were assessed by means of self-administered questionnaires, including functional capacity in daily living activities, musculoskeletal pain, fatigue, anxiety, and sleep quality. The predictive value of these parameters in fibromyalgia was determined by receiver operating characteristic curve analysis. RESULTS: Serum calcitonin gene-related peptide levels significantly increased in the fibromyalgia group in comparison to the control group. However, there were no significant differences in vascular endothelial growth factor levels between patients and controls. No significant correlations were found between calcitonin gene-related peptide and vascular endothelial growth factor and the symptoms analyzed. DISCUSSION: Serum calcitonin gene-related peptide levels were dysregulated in women with fibromyalgia and may be a reliable parameter to help diagnose this complex syndrome.

Associations Among Nitric Oxide and Enkephalinases With Fibromyalgia Symptoms.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome of uncertain etiology, characterized by the presence of widespread pain. Both nitric oxide and enkephalinases modulate pain perception. OBJECTIVES: The aim of this study was to evaluate the relationships among serum nitric oxide levels, oxytocinase activity, and enkephalin-degrading aminopeptidase (EDA) activity with pain-related clinical manifestations in women with FM. METHODS: We performed an observational case study in a population of 58 women diagnosed with FM. Serum nitric oxide levels were analyzed by an ozone chemiluminescence-based assay. Both serum oxytocinase and EDA activities were fluorometrically determined. Pain threshold and pain magnitude were evaluated using the PainMatcher. The pressure pain thresholds were measured using a digital pressure algometer. We used a visual analog scale, the Central Sensitization Inventory, the Revised Fibromyalgia Impact Questionnaire, and the Beck Anxiety Inventory to assess the global level of pain, the symptoms associated with the central sensitization syndrome, the severity of FM, and the anxiety level, respectively. RESULTS: Multiple linear regression analysis adjusted by age, body mass index, and menopause status revealed significant associations between nitric oxide levels and dominant occiput pressure pain thresholds, nondominant occiput pressure pain thresholds, and FM effects. Significant associations of oxytocinase activity with the visual analog scale and dominant knee pressure pain thresholds were also found. Moreover, results showed a significant association between high EDA activity levels and dominant second-rib pressure pain thresholds. DISCUSSION: Our data have shown significant relationships of serum nitric oxide levels and oxytocinase and EDA activities with some body pressure pain thresholds, the daily activity level, and the global intensity of pain in women with FM. These results suggest that pain, which is the main symptom of this syndrome, may be related to alterations in nitric oxide levels and in oxytocinase and EDA activities in patients with FM.

Evaluation of sympathetic adrenergic branch of cutaneous neural control throughout thermography and its relationship to nitric oxide levels in patients with fibromyalgia.

BACKGROUND: Fibromyalgia syndrome is defined as a complex disease, characterized by chronic widespread musculoskeletal pain and other symptoms. The factors underlying physiopathology of fibromyalgia are not well understood, complicating its diagnosis and management. OBJECTIVES: To evaluate the peripheral vascular blood flow of the skin of the hands and the core body temperature as indirect measures of sympathetic adrenergic activity of the nervous system and its relationship to nitric oxide levels (NO) in women with fibromyalgia compared with healthy controls. METHODS: Forty-two women with fibromyalgia and 52 healthy women were enrolled in this observational pilot study. We used infrared thermography of the hands and an infrared dermal thermometer to evaluate the peripheral vascular blood flow and tympanic and axillary core body temperature, respectively. We measured NO levels using the ozone chemiluminescence-based method. RESULTS: Two-way analysis of covariance (ANCOVA) showed that the tympanic (P=0.002) and hand temperatures were significantly higher in the patients with fibromyalgia than in the controls (P≤0.001). Significant associations were also found between serum NO levels and minimum temperatures at the dorsal center of the dominant hand (ß=-3.501; 95% confidence interval [CI] -6.805, ­0.198; P= 0.038), maximum temperature (ß=-5.594; 95% CI ­10.106, ­1.081; P=0.016), minimum temperature (ß=-4.090; 95% CI ­7.905, ­0.275; P=0.036), and mean temperature (ß=-5.519; 95% CI ­9.933, ­1.106; P=0.015) of the center of the palm of the non-dominant hand, maximum temperature at the thenar eminence of the dominant hand (ß=-5.800; 95% CI ­10.508, ­1.092; P=0.017), and tympanic temperature (ß=-9.321; 95% CI ­17.974, ­0.669; P=0.035) in the controls. CONCLUSIONS: Our findings indicate that the women with fibromyalgia showed higher tympanic core body and hand temperature than the healthy controls. Moreover, there were negative associations between hand peripheral vasodilation and NO in the healthy women but not in those with fibromyalgia, suggesting a dysfunction of sympathetic cutaneous neural control.

Influence of Oxidative Stress-Related Genes on Susceptibility to Fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome to diagnose and treat because of its unknown etiology. However, previous studies reported that patients with FM experience oxidative stress. OBJECTIVES: In this study, we investigated single-nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in oxidative stress (superoxide dismutase 1 [SOD1], catalase, and NADPH oxidase [CYBA]) in patients with FM and in healthy subjects, as well as the possible relation with demographic and clinical manifestations of FM. METHODS: A total of 141 patients with FM and 73 healthy subjects participated in this case-control study. For DNA extraction, buccal swabs were collected from patients with FM, and a peripheral blood sample was extracted from controls. We analyzed SNPs in genes related to oxidative stress (rs10432782 in SOD1, rs1001179 in catalase, and rs4673 in CYBA) using TaqMan probes. In patients with FM, severity of FM, fatigue, and pain were assessed by Fibromyalgia Impact Questionnaire, Multidimensional Fatigue Inventory, and Visual Analogue Scale (VAS), respectively. Physical (PCS-12) and mental (MCS-12) health statuses were evaluated by the 12-Item Short-Form Health Survey. RESULTS: The selected SNPs did not show significant differences between patients with FM and controls. The rs10432782 (SOD1) was associated with Fibromyalgia Impact Questionnaire scores in patients with FM, whereas the rs4673 (CYBA) was associated with the Multidimensional Fatigue Inventory score, MCS-12 score, and duration of the disease. DISCUSSION: We have identified significant correlations between SOD1 and CYBA variants with clinical manifestations of FM. These results provide new insights into the pathogenesis of FM that could be useful for guiding future studies along the way to find the cause(s) of this syndrome.

Effects of Olive Oil Consumption on Cardiovascular Risk Factors in Patients with Fibromyalgia.

We have recently reported that patients with fibromyalgia (FM) may be at increased risk for cardiovascular disease. Olive oil reportedly has cardioprotective effects. We examined the influence of olive oil consumption on cardiovascular risk factors in FM. This preliminary study was performed on blood samples of women with FM who consumed 50 mL of organic olive oil daily for 3 weeks. Patients were randomized into two groups: 15 women ingested extra virgin olive oil (EVOO) and 15 refined olive oil (ROO). Cardiovascular risk markers were measured at baseline (pre measure) and after consumption of olive oil (post measure). Red blood cell count and erythrocyte sedimentation rate (ESR; both p < 0.05) declined significantly post-treatment in the EVOO group. Consumption of ROO increased mean platelet volume and reduced platelet distribution width (PDW), neutrophil-to-lymphocyte ratio, ESR and fibrinogen (all p < 0.05). Significant differences were found in pre-post change between the EVOO and ROO groups for cortisol and PDW (both p < 0.05). Our results have shown that consumption of olive oil may have antithrombotic and antiinflammatory properties in patients with FM, thereby improving a number of cardiovascular risk markers. Both EVOO and ROO may be useful as adjuvants for the prevention and/or treatment of cardiovascular disorders in these patients.

Validation of the Spanish version of the migraine disability assessment questionnaire (MIDAS) in university students with migraine.

BACKGROUND: The Migraine Disability Assessment (MIDAS) questionnaire is widely used to determine the degree of migraine-related disability of subjects. So far, and to the best of our knowledge, no Spanish version of this tool has been validated. The questionnaire comprises seven items, with the first five constituting the main scale while the sixth and seventh items referring, respectively, to the frequency and intensity of headache. The present study aims to analyze the clinimetric properties of the Spanish version of the MIDAS questionnaire in a population of university students. METHODS: We performed a cross-sectional study of validation for this measuring instrument. A total of 153 subjects participated in the study. We analyzed construct validity using factor analysis, test-retest reliability by the Intraclass Correlation Coeficient (ICC), internal consistency, and concurrent validity with respect to the 12-Item Short Form Health Survey (SF-12). RESULTS: Factor analysis revealed a two-factor structure. The questionnaire has good reliability for the MIDAS main-scale score ([ICC = 0.81; 95% CI: 0.63-0.90]), excellent reliability for headache frequency (ICC = 0.90; 95%; CI: [0.79-0.95]), and moderately good reliability for headache intensity (ICC = 0.63; 95% CI: [0.34-0.80]). The analysis also yielded good internal consistency results (α Cronbach = 0.797) and a moderate correlation between MIDAS-main scale and the physical component summary of SF-12 (Rho = - 0.326; p <  0.001). CONCLUSIONS: The Spanish version of the MIDAS questionnaire is a valid and reliable tool to measure migraine-related disability in university subjects. The two additional items provide information that could help clinicians in making decisions.

Misperception of the subjective visual vertical in neurological patients with or without stroke: A meta-analysis.

BACKGROUND: The interpretation of the verticality of the environment is crucial for a proper body balance. The subjective visual vertical test (SVV) is a widely used method to determine the visual perception of the verticality, whose alteration has been related with poor functional status. OBJECTIVE: To analyze the visual perception of the verticality in neurological patients in comparison with healthy controls. METHODS: We searched PubMed, Scopus, and Scielo from the start of the databases until October 2017 and manually searched the reference lists of studies comparing SVV values between neurological patients and controls. Standardized mean difference (SMD) and subgroup analysis were used to analyze differences between neurological patients and healthy subjects and between stroke and non-stroke patients, respectively. RESULTS: A total of 1,916 subjects from 31 studies were included. Neurological patients misestimate the true vertical in comparison with controls (SMD = 1.05; 95% CI: 0.81, 1.28). The misperception of the verticality was higher in stroke patients (SMD = 1.35; 95% CI: 1.02, 1.68) than in patients with other neurological conditions (SMD = 0.48; 95% CI: 0.29, 0.68). CONCLUSIONS: Neurological patients showed a misperception of the verticality, estimated using the SVV. The neurological pathology that most alters the SVV is stroke.

Altered Serum Oxytocinase and Enkephalin-Degrading Aminopeptidase Activities in Patients With Fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a chronic pain condition of unclear etiology. We have analyzed, for the first time, the activity of a broad spectrum of aminopeptidases (APs) in patients with FM and controls to investigate whether they are involved in the pathophysiology of this syndrome. METHOD: In this case-control study, we fluorometrically measured specific AP activities in serum samples of 75 patients with FM and 29 healthy controls. The predictive value of AP activities in FM was determined by receiver operating characteristic (ROC) analysis. RESULTS: Oxytocinase activity was higher in patients with FM than in controls (p < .001). A subgroup of patients with FM (n = 18; 24%) showed low levels of enkephalin-degrading aminopeptidase (EDA) activity when compared with the healthy controls (p < .001) and with the rest of FM patients (p < .001). There were no significant differences in the activity levels of aminopeptidase A, aminopeptidase B, aspartyl aminopeptidase, insulin-regulated aminopeptidase, pyroglutamyl aminopeptidase, or aminopeptidase N between FM patients and controls. According to ROC analysis, oxytocinase activity may be a good marker for differentiating individuals with FM from healthy subjects. CONCLUSIONS: Our findings show that serum oxytocinase activity is increased in patients with FM, which could alter the metabolism of peptides with analgesic effects such as oxytocin and enkephalins. The determination of serum oxytocinase activity may aid in FM diagnosis. Additionally, we have identified a subpopulation of FM patients with abnormally low serum EDA activity.

Mediterranean Diet, Body Composition, and Activity Associated With Bone Health in Women With Fibromyalgia Syndrome.

BACKGROUND: There is very little scientific literature on the potential relationships between modifiable factors, including body composition, dietary pattern and physical activity (PA), and bone status in patients with fibromyalgia-a musculoskeletal condition characterized by chronic, widespread pain that is often accompanied by a broad spectrum of symptoms. OBJECTIVES: The aim of the study was to investigate the impact of body composition parameters, adherence to the Mediterranean diet (Med Diet), and PA on bone health in a population of premenopausal and postmenopausal women with fibromyalgia syndrome (FMS). METHODS: Ninety-five women diagnosed with FMS were included in this cross-sectional study. Body composition, including fat mass, percentage of fat mass, and lean mass (LM), were calculated using a body composition analyzer. Adherence to the Med Diet was measured through a validated 14-item questionnaire. The International Physical Activity Questionnaire was used to assess PA. Bone mass at the calcaneus was estimated through quantitative ultrasound. RESULTS: Linear regression analysis revealed that LM had a significant association with broadband ultrasound attenuation (ß = 0.211, 95% CI [0.046, 1.259], p = .035) and stiffness index parameters (ß = 0.201, 95% CI [0.019, 1.654], p = .045) after adjusting for age and menopausal status. The Med Diet was also significantly associated with broadband ultrasound attenuation (ß = 1.693, 95% CI [0.508, 2.879], p = .006). DISCUSSION: LM and the Med Diet were consistently associated with calcaneal quantitative ultrasound parameters, supporting the hypothesis that LM and adherence to the Med Diet play determinant roles in bone health in FMS women. Training programs to maximize LM and strategies for promoting good adherence to the Med Diet should be considered in order to prevent the development of osteoporosis in FMS women. Because nurses are involved in implementing preventive programs, their roles in promoting this adherence to the Med Diet and maximizing LM in patients with FMS should help reduce the impact of osteoporosis.

Are Patients With Fibromyalgia in a Prothrombotic State?

OBJECTIVES: The aim of this study was to investigate thrombosis-related parameters (blood coagulation parameters, platelet indices, red blood cell [RBC] count, and inflammatory markers) in patients with fibromyalgia (FM). METHOD: We carried out a case-control study with 35 women with FM and 12 age-matched healthy volunteers to analyze fibrinogen levels, prothrombin time, cephaline time, platelet count, platelet distribution width (PDW), mean platelet volume (MPV), RBC count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR). RESULTS: The results showed significantly increased fibrinogen levels ( p < .05), platelet count ( p < .05), PDW ( p = .059), RBC count ( p < .05), and PLR ( p < .05) in women with FM versus the healthy volunteers. Prothrombin time ( p < .05) and MPV ( p < .05) were significantly lower in patients with FM than in the controls. CONCLUSIONS: Elevated platelet and RBC counts, PDW values, and fibrinogen levels as well as decreased prothrombin time are all indicative of a prothrombotic state in FM patients, which may be enhanced by an increased inflammatory tone. This prothrombotic state may increase the risk of thrombosis-related cardiovascular disease in patients with FM.

Catecholamine and Indolamine Pathway: A Case-Control Study in Fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a complex syndrome characterized by widespread pain. Its etiology is unclear, and diagnosis is difficult. The aim of this study was to assess plasma levels of monoamine neurotransmitters (catecholamines, indolamines, and intermediate metabolites) in patients with FM and healthy controls to investigate possible alterations in the metabolism of these molecules in FM. We also examined potential relationships between monoamine neurotransmitters and clinical features of FM. The predictive value of these molecules in FM was determined by receiver operating characteristic analysis. METHOD: We measured plasma catecholamines (epinephrine, norepinephrine, and dopamine), as well as indolamines and intermediary metabolites (serotonin or 5-hydroxytryptamine [5-HT], 5-hydroxyindolacetic acid [5-HIAA], 5-hydroxytryptophan [5-HTP], and N-acetyl-5-hydroxytryptamine [Nac-5-HT]) in 35 women with FM and 12 age-matched healthy women. RESULTS: Higher levels of norepinephrine and lower levels of dopamine, 5-HT, 5-HIAA, and 5-HTP were found in women with FM in comparison with controls. Epinephrine and Nac-5-HT levels did not differ significantly between groups. Higher norepinephrine levels were associated with worse physical health status in FM patients. Also, plasma norepinephrine levels > 694.69 pg/ml might be an accurate predictor of FM. CONCLUSIONS: These findings show evidence of the dysregulation of the catecholamine and indolamine pathway in patients with FM, which may contribute to the physiopathology of this syndrome. In addition, the determination of plasma norepinephrine levels could help in the FM diagnosis.

Insight into the biological pathways underlying fibromyalgia by a proteomic approach.

Fibromyalgia (FM) is a form of non-articular rheumatism difficult to diagnose and treat because its etiology remains still elusive. Proteomics makes possible the systematic analysis of hundreds of proteins in clinical samples. Consequently, it has become a key tool for finding altered molecular pathways in different diseases. In this context, the present study analyzes changes in the plasma proteome of patients with FM by nanoscale liquid chromatography coupled to tandem mass spectrometry. Deregulated proteins were studied using Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes. Conventional analytical methods were used to validate selected proteins. We found a total of 33 proteins differentially expressed in patients with FM. Haptoglobin and fibrinogen showed the highest FM/control ratio. IPA analysis revealed that the top enriched canonical pathways were acute-phase response signaling, Liver-X Receptor/Retinoid-X Receptor activation, Farnesoid-X Receptor/Retinoid-X Receptor activation, and coagulation and complement systems. The importance of inflammation in FM was corroborated by the increase in erythrocyte sedimentation rate. In conclusion, our results support the existence of a plasma protein signature of FM that involves different biological pathways all of them related to inflammation, and point to haptoglobin and fibrinogen as plausible biomarker-candidates for future studies. SIGNIFICANCE: The etiology of fibromyalgia (FM) remains elusive making its diagnosis and treatment difficult. The characterization of the proteome signature of this syndrome will improve its understanding. However, to date proteomic analyses in FM are scarce. The goal of the present work is to analyse, for the first time, changes in plasma protein profiles of patients with FM in comparison to control subjects, using label free relative protein quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry. Our data demonstrate the existence of a common protein signature in the plasma of patients with FM that could explain some of the symptoms associated to this syndrome. The analysis of the 33 proteins differentially expressed corroborates the crucial role of inflammation in the pathogenesis of this syndrome. The interplay of the complement and coagulation cascades contributes to the inflammatory process, while the activation of Liver-X Receptor/Retinoid-X Receptor and Farnesoid-X Receptor/Retinoid-X Receptor could attempt to alleviate it. Finally, we have identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of FM for future studies.

Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to acute hypoxia.

Brain hypoxia is involved in many diseases. The activation of angiogenesis is one of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In a previous work, we have shown that the adult rat striatum promotes angiogenesis in response to hypoxia via upregulation of the most important proangiogenic factor, the vascular endothelial growth factor (VEGF). However, the effects of hypoxia on angiogenesis in the aged striatum remain unknown and constitute our aim. Here we show the upregulation of hypoxia-inducible factor-1α in the striatum of aged (24-25 months old) Wistar rats exposed to acute hypoxia and analysed during a reoxygenation period ranging from 0 h to 5 days. While the mRNA expression of the proangiogenic factors VEGF, transforming growth factor-ß1 (TGF-ß1), and adrenomedullin dropped at 0 h post-hypoxia compared to normoxic control, no changes were detected at the protein level, showing an impaired response of these proangiogenic factors to hypoxia in the aged striatum. However, the striatal blood vessel network increased at 24 h of reoxygenation, suggesting that mechanisms independent from these proangiogenic factors may be involved in hypoxia-induced angiogenesis in the striatum of aged rats. A thorough understanding of the factors involved in the response to hypoxia is essential to guide the design of therapies for hypoxia-related diseases in the aged brain.

Effectiveness of Global Postural Re-education for Treatment of Spinal Disorders: A Meta-analysis.

OBJECTIVE: The aim of this study was to investigate the effects of global postural re-education (GPR) on the treatment of spinal disorders by performing a systematic review and a meta-analysis. DESIGN: MEDLINE, Scopus, and PEDro databases were searched without language or publication date restrictions. Data on pain and function were used to evaluate the effectiveness of GPR. Randomized controlled trials and controlled clinical trials analyzing the effectiveness of GPR on spinal disorders were selected. The standardized mean difference (SMD) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis was performed using the Comprehensive Meta-analysis 3.3 software. RESULTS: Seven randomized controlled trials and 4 controlled clinical trials were included in the meta-analysis. The results showed a medium improvement on pain (SMD = -0.63; 95% CI, -0.43 to -0.83) and function (SMD = -0.48; 95% CI, -0.25 to -0.72) after GPR treatment. The positive effect, which was greater in patients with ankylosing spondylitis followed by low back pain and neck pain, was more significant during the intermediate follow-up than immediately after treatment. CONCLUSIONS: This meta-analysis provides reliable evidence that GPR may be an effective method for treating spinal disorders by decreasing pain and improving function.

Response of the Nitric Oxide System to Hypobaric Hypoxia in the Aged Striatum.

BACKGROUND: Nitric oxide (NO) appears to play a key role in the hypoxic injury to the brain. We have previously reported that hypoxia/reoxygenation downregulated NO synthases (NOS) in the adult striatum. Until now, no data were available concerning the influence of aging in conjunction with hypoxia/reoxygenation on the NO system in the striatum. OBJECTIVE: The aim of this study was to assess the role of the NO pathway in the hypoxic aged striatum. METHODS: Wistar rats 24-25 months old were submitted to hypobaric hypoxia (20 min)/reoxygenation (0 h, 24 h, 5 days). Expression (PCR, immunohistochemistry/image analysis) and activity (NADPH-diaphorase/image analysis) of NOS isoforms (neuronal NOS or nNOS, endothelial NOS or eNOS, inducible NOS or iNOS) were analyzed together with nitrated protein expression (immunohistochemistry/image analysis). NO levels were indirectly quantified as nitrates/nitrites (NOx). RESULTS: The mRNA levels of NOS isoforms were undetectable at 0 h after hypoxia in the striatum compared to the control. At later reoxygenation times, nNOS mRNA decreased, while eNOS mRNA augmented. Protein levels of nNOS and eNOS rose at 24 h after hypoxia, and iNOS protein increased at 5 days. NOx levels remained unchanged, whereas in situ NOS activity and protein nitration diminished during reoxygenation in the aged striatum. CONCLUSION: The aged striatum may overexpress NOS isoforms as a neuroprotective-adaptive mechanism to hypoxia. However, this mechanism may not work properly in the aged striatum, since no changes in NO levels were detected after hypoxia. This may be related to the low activity of NOS isoforms in the hypoxic striatum.