Implication of intestinal microbiota in the etiopathogenesis of fibromyalgia: A systematic review.

Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide range of physical and psychological symptoms. The etiopathogenesis of this disease is multifactorial, which makes its diagnosis and treatment challenging. Recently, the increase in the number of studies on microbiota has provided new data that can help to understand the onset and development of FM. An updated systematic review of the causes of FM has been carried out in this work. Particularly in the last decade, research has focused on the gut-brain axis, which has emerged as a crucial mechanism for microbiota-host crosstalk. In FM patients, quantitative imbalances of the intestinal microbiota (dysbiosis) and bacterial metabolites with differential relative abundance have been found, especially short-chain fatty acids and lipopolysaccharides. Furthermore, the microbiota has been found to indirectly influence host neurotransmitter mechanisms, mainly through the serotonin precursor, glutamate, and gamma-aminobutyric acid. Thus, all these mechanisms and their influence on the etiopathogenesis of FM are discussed in this review.

Mitochondrial Imbalance as a New Approach to the Study of Fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a common chronic pain disease, whose pathogenic mechanism still remains elusive. Oxidative stress markers and impaired bioenergetics homeostasis have been proposed as relevant events in the pathogenesis of the disease. Hence, the aim of the study is to analyse the potential biomarkers of mitochondrial imbalance in FM patients along with coenzyme Q10 (CoQ10) as a possible treatment. METHODS: The symptomatology of patients was recorded with an adaption of the Fibromyalgia Impact Questionnaire (FIQ). Mitochondrial imbalance was tested from blood extraction and serum isolation in 33 patients diagnosed with FM and 30 healthy controls. Western blot and HPLC techniques were performed to study the different parameters. Finally, bioinformatic analysis of machine learning was performed to predict possible associations of results. RESULTS: CoQ10 parameter did not show evidence to be a good marker of the disease, as the values are not significantly different between control and patient groups (Student's t-test, CI 95%). For this reason, the focus of the study changed into the ratio between mitochondrial mass and autophagy levels. The bioinformatics analysis showed a possible association between this ratio and patients' symptomatology. Finally, the effects of coenzyme Q10 as a potential treatment for the disease were different within patients, and its efficacy may be related to the initial mitochondrial status. However, there is no statistical significance due to limitations within the sample size. CONCLUSION: Our study supports the hypothesis that an imbalance in mitochondrial homeostasis is involved in the FM pathogenesis. However, whether the increase in oxidative stress is the result of mitochondrial imbalance or the cause of this disease remains an open question. The measurement of this imbalance might be used as a preliminary biomarker for the diagnosis and follow-up of patients with FM, and even for the evaluation of the effects of the different antioxidants therapies.

Autohemotherapy with ozone as a possible effective treatment for Fibromyalgia.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of autohemotherapy with ozone in the management of fibromyalgia (FM). DESIGN: 20 FM patients (according to the criteria of the American College of Rheumatology), were treated with 10 sessions of ozone hemotherapy (2 sessions per week) with a concentration of 30-60 mcgr/ml. The health condition of the patients was evaluated before and after treatment, through the Fibromyalgia Impact Questionnaire (FIQ). Blood samples were obtained from all patients by venous puncture for biochemical routine analysis and serotonin levels in serum and the following peripheral blood mononuclear cells (BMCs) were isolated for oxidative stress quantification: reactive oxygen species (ROS) generation, and lipid peroxidation (LP) and protein carbonyl (PC) content, as these are signs of oxidative cell damage. RESULTS: All patients treated with ozone reported an improvement in sleep and mental alertness, a marked decrease of asthenia accompanied by a decrease of FIQ as well as tender points, and a moderate increase of serotonin levels. Also, an important decrease of LP and PC was observed; ROS also decreased, although less obvious, which indicates a reduction in oxidative stress levels. CONCLUSIONS: The autohemotherapy with ozone in patients with FM showed an important decline of tender points and FIQ score, as well as a decrease of oxidative stress levels. This treatment allows patients to face life with greater vitality and less drug use, diminishing harmful side effects. Further investigation should be carried out, including groups with more patients and clinical trials, to elucidate the effect of ozone therapy in patients suffering from FM.

Increased salivary oxidative stress parameters in patients with type 2 diabetes: Relation with periodontal disease. / Incremento de los parámetros de estrés oxidativo salival en pacientes con diabetes tipo 2: relación con la enfermedad periodontal.

OBJECTIVE: The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. MATERIAL AND METHODS: This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c<7%), and 27 patients DM2 with poor metabolic control (HbA1c>7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. RESULTS: The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (P<.001). The activity of the enzymes measured was significantly less in patients with poor metabolic control in comparison with the control group and well-controlled diabetic groups (P<.001). Both diabetic groups showed higher GSSG/GSH quotients and CPI in comparison with the control group, and both parameters were significantly higher in diabetic patients with poor metabolic control in comparison with well-controlled diabetic patients. CONCLUSIONS: Poor metabolic control in DM2 patients is associated with higher levels of salivary oxidative stress and worse periodontal health.

Incremento de los parámetros de estrés oxidativo salival en pacientes con diabetes tipo 2: relación con la enfermedad periodontal / Increased salivary oxidative stress parameters in patients with type 2 diabetes: Relation with periodontal disease

Objetivo: Nuestro objetivo fue analizar si existen diferencias en los niveles de estrés oxidativo salival de pacientes con DM2 en comparación con sujetos sanos no diabéticos, y si dicho estrés oxidativo se puede asociar a la presencia de enfermedad periodontal en pacientes con diabetes. Material y métodos: Se realizó un estudio observacional que incluyó 70 pacientes, estableciéndose 3 grupos de estudio en función del control metabólico: 19 pacientes sin diabetes (grupo control); 24 pacientes DM2 con buen control metabólico (HbA1c<7%), y 27 pacientes DM2 con mal control metabólico (HbA1c>7%). En todos ellos se midieron los siguientes parámetros de estrés oxidativo salival: glutatión peroxidasa (GPx), glutatión reductasa (GRd), glutatión reducido (GSH) y glutatión oxidado (GSSG). El estado de salud periodontal se determinó mediante el índice periodontal comunitario (CPI), recomendado por la OMS. Resultados: El grupo de diabetes con buen control metabólico mostró un incremento significativo en la actividad de GPx y GRd con respecto al grupo control (p<0,001). La actividad de dichas enzimas fue significativamente menor en los pacientes con diabetes con mal control metabólico en comparación con el grupo control y de diabéticos bien controlados (p<0,001). Los 2 grupos de pacientes con diabetes mostraron mayor cociente GSSG/GSH e índice CPI con respecto al grupo control, resultando también ambos parámetros significativamente aumentados en el grupo de diabetes con mal control metabólico respecto a los bien controlados. Conclusiones: Un peor control metabólico se asocia a mayores niveles de estrés oxidativo en saliva de pacientes con DM2, así como a un peor estado de salud periodontal (AU)

Objective: The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. Material and methods: This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c<7%), and 27 patients DM2 with poor metabolic control (HbA1c>7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. Results: The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (P<.001). The activity of the enzymes measured was significantly less in patients with poor metabolic control in comparison with the control group and well-controlled diabetic groups (P<.001). Both diabetic groups showed higher GSSG/GSH quotients and CPI in comparison with the control group, and both parameters were significantly higher in diabetic patients with poor metabolic control in comparison with well-controlled diabetic patients. Conclusions: Poor metabolic control in DM2 patients is associated with higher levels of salivary oxidative stress and worse periodontal health (AU)

Fibromyalgia syndrome and temporomandibular disorders with muscular pain. A review.

OBJECTIVES: Temporomandibular disorders (TMD) refer to a group of clinical picture affecting the masticatory muscles and temporomandibular joint that are characterized by muscular or joint pain, dysfunction (limited or altered functions) and joint noises, as well as other associated symptoms, such as tension headaches, otalgia, dizziness, tinnitus, and others. Fibromyalgia (FM) is a syndrome of unknown etiology involving generalized chronic pain accompanied, in a high percentage of cases, by other symptoms such as asthenia, anxiety, depression, sleep disturbances, and other less frequent symptoms, such as temporomandibular disorders (TMD). DATA: Data were compiled by two experienced examiners following a specific form. SOURCES: An electronic search was carried out in the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and SCOPUS electronic databases (up to April 2016, unrestricted by date or language). STUDY SELECTION: Comparative clinical studies with patients with both clinical pictures involving the study of pathogenic processes. CONCLUSIONS: Fibromyalgia and temporomandibular disorders with muscle pain both have profiles that affect the muscular system and therefore share many epidemiological, clinical, and physiopathological symptoms. Because of this, we are led to think that there is, if not a common etiology, at least a common pathogenesis. This article revises the physiopathological processes of both clinical pictures in an attempt to determine their similarities and likenesses. This would undoubtedly help in providing a better therapeutic approach.

Concrescencia clínica pero no histológica: presentación de un caso clínico / Fused roots does not imply concrescence: a case report with histological analysis

La concrescencia es una anomalía dentaria poco frecuente que se define como la unión de las raíces de dos dientes adyacentes a través del cemento. Aunque en la práctica clínica el término "concrescencia" es utilizado para referirse a todos los casos de unión entre las raíces de dos dientes adyacentes, para confirmar el diagnóstico de concrescencia es necesario un estudio histológico que demuestre la unión a nivel del cemento. Esta anomalía se ha identificado en el 0,8% de los casos de exodoncia de dientes permanentes, siendo su incidencia mayor en la región posterior del maxilar superior. La detección previa de la concrescencia mediante la exploración clínica y radiográfica es, la mayoría de las ocasiones, casi imposible, por lo que el diagnostico suele hacerse después de la extracción. No obstante, es conveniente que el clínico evalúe cada paciente y cada diente de forma exhaustiva para poder planificar, caso de que exista concrescencia, la técnica quirúrgica adecuada para la extracción. Por lo tanto, deben conocerse la incidencia e implicaciones de esta anomalía para llevar a cabo un diagnóstico y plan de tratamiento correcto. En este artículo se presenta un caso clínico de aparente concrescencia diagnosticado post-extracción y cuyo estudio histológico no mostró unión de cemento entre ambas raíces. Por lo tanto, en la práctica clínica es más conveniente utilizar el término "raíces fusionadas" que "concrescencia", el cual sólo debería ser utilizado después del examen histológico de la pieza extraída

Concrescence is a rare dental anomaly defined as the cemental union of two adjacent teeth. Concrescence diagnosis requires histological confirmation, but in the clinical practice the term "concrescence" is used to refer to all the cases of union of the roots of two adjacent teeth. The anomaly has been reported in extraction cases with an incidence of 0.8% in the permanent dentition. Also has been reported a higher incidence of concrescence in the posterior maxilla. It is prudent for the clinician to evaluate carefully each patient and each tooth to be removed for the possibility and desirability of a surgical extraction technique. Therefore, consideration should be given to the possible occurrence, recognition, and implications of this anomaly in diagnosis and treatment planning. Clinically and radiographically is nearly impossible to detect concrescent teeth, and most of these cases are diagnosed post extraction. The purpose of this article is to report a case of clinical concrescence between a retained third molar and an erupted second molar identified during the extraction, which histological study did not show cementum union between both roots. Thus, in the clinical practice is better to use the term "fused roots" than "concrescence", which would be used only after the histological examination of the specimen

Clinical symptoms in fibromyalgia are associated to overweight and lipid profile.

In order to analyze the association between body mass index (BMI), lipid profile and clinical symptoms in patients with fibromyalgia, we assessed BMI levels, lipid profile and its association with clinical symptoms in 183 patients with fibromyalgia. The patients were evaluated using tender points, FIQ and Visual Analogue Scales of pain (VAS). Serum lipid profile analysis (total cholesterol, triglyceride, HDL, LDL and VLDL), and biochemical parameters were measured in the biochemistry laboratory. The BMI distribution of the nonobese, overweight and obese patients' groups were relatively even with 37.7, 35.5 and 26.8%, respectively, with a mean BMI of 27.3 ± 4.9. The number of tender points showed significantly positive correlation with higher BMI (P < 0.05). A total of 57.9% of patients showed increased levels of total cholesterol, 63.4 % increased levels of LDL cholesterol and 19.9% high levels of triglycerides. BMI, total cholesterol and triglycerides showed high association with some clinical parameters. Overweight and lipid profile could be associated with fibromyalgia symptoms. A treatment program with weight loss strategies, and control in diet and increased physical activity is advised to patients.

Interleukin 1 receptor antagonist (IL1RN) genetic variations condition post-orthodontic external root resorption in endodontically-treated teeth.

External apical root resorption (EARR) is a frequent iatrogenic problem following orthodontic treatment in endodontically-treated teeth, about which the literature reports substantial variability in post-orthodontic treatment EARR responses. The main focus of the present study is to clarify whether variants in the interleukin-1 receptor antagonist gene coding for the IL-1ra protein have a positive/negative influence on EARR of endodontically-treated teeth. Ninety-three orthodontic patients were genetically screened for a single nucleotide polymorphism (SNP:rs419598) in the IL1 cluster. The sample was classified into 2 groups: group 1 (affected-group) showed radiographic EARR of more than 2mm; group 2 (control-group), had no EARR or EARR ≤ to 2mm following orthodontic treatment on root-filled teeth. Logistic regression analysis was performed to obtain an adjusted estimate between the SNPs studied and EARR. Genotype distributions, allelic frequencies, adjusted odds ratios (OR) and 95% confidence intervals were also calculated. We found that subjects homozygous [1/1(TT)] for the IL1RN gene [OR:10.85; p=0.001;CI:95%] were at risk of EARR in root-filled teeth. Genetic variants in the antagonist axis balance of the IL1RN (rs419598) have a direct repercussion on the predisposition to post-orthodontic EARR in root-filled teeth. Variants in allele 1 of the interleukin-1 receptor antagonist gene(rs419598) are associated(p=0.001**) with an increased risk of suffering post-orthodontic EARR in root-filled teeth.

Stem cells in current paediatric dentistry practice.

New protocols for regenerative endodontic treatment along with the parallel development of tissue engineering technologies are changing traditional knowledge and treatment possibilities for young patients with pulp-affected permanent immature teeth. The regeneration and completion of apical root development in pathological situations such as these is a clinical challenge that traditional treatments have not so far been able to resolve with complete success. In clinical terms, the decision of whether to perform apexogenesis or apexification on an immature tooth is determined by whether the pulp tissue is vital or non-vital. Recent evidence and reports in the literature have questioned the old dogmas. In this respect, the ever growing scientific literature in this field makes it essential to compile a critical reflection and summary of everything that has been written to date, in order to understand the biological basis of current clinical advances and ensuing lines of future therapy. In this paper, we wish to give scientific coverage and background to more recent clinical and molecular advances described in the field of apical regeneration using stem cell therapy and their potentially key role in the future clinical success of new pulp regenerative protocols.

Corticotomy-assisted orthodontic enhancement by bone morphogenetic protein-2 administration.

PURPOSE: To determine the possibility of synergistically enhancing orthodontic tooth movement (OTM) and bone formation in vivo by administering bone morphogenetic protein type 2 (BMP-2) on the tension side or in combination with corticotomy on the pressure side. MATERIALS AND METHODS: The sample consisted of 56 Wistar rats that were subjected to experimental OTM for 32 days using a split-mouth design. The sample was divided into 4 groups: a control group, a corticotomy group, a BMP-2 group, and a corticotomy plus BMP-2 group. An OTM force of 10 cN was applied to each group. BMP-2 18 µL was administered locally on the tension side alone or in conjunction with corticotomy and then compared with the controls using fluorescence-based tartrate-resistant acid phosphatase staining for osteoclast counts, histologic bone resorption, and clinical OTM results. RESULTS: Corticotomy surgery increased the OTM rate (P < .05) by more than 20%. The injection of BMP-2 alone on the tension side did not induce significant changes in the degree of OTM compared with the vehicle-treated or control group (P > .05). When BMP-2 was combined with corticotomy on the tension and pressure sides (corticotomy plus BMP-2 group), respectively, nonsignificant OTM rates were observed (P > .05) compared with the controls; however, decreased osteoclast counts, bone resorption, and clinical results were observed in the corticotomy plus BMP-2 group. CONCLUSIONS: In contrast to reports published to date, the present preliminary study suggests that there are limits to OTM acceleration by bone formation on the tension side and agrees with the idea that there is a single continuous periodontal compartment in OTM, rather than a pressure side and a tension side.

Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients.

Amitriptyline is a commonly prescribed tricyclic antidepressant, which has been shown to impair mitochondrial function and increase oxidative stress in a variety of in vitro assays. Coenzyme Q(10) (CoQ(10)), an essential component of the mitochondrial respiratory chain and a potent antioxidant, has been proposed as a mitochondrial dysfunction marker. In order to evaluate the putative mitochondrial toxicity of amitriptyline, we have analyzed CoQ(10) and ATP levels, oxidative damage and mitochondrial mass in peripheral blood cells from control healthy volunteers and psychiatric patients with depressive episodes treated or non-treated with amitriptyline. In patients not following amitriptyline treatment, CoQ(10) and ATP levels and mitochondrial mass were reduced when compared to normal individuals while lipid peroxidation was clearly increased. All these alterations were aggravated in patients following oral amitriptyline therapy. These results suggest that mitochondrial dysfunction could be involved in the pathophysiology of depression and may be worsened by amitriptyline treatment. CoQ(10) supplementation is postulated to counteract the adverse effects of amitriptyline treatment in psychiatric patients.

Common standards in facial esthetics: craniofacial analysis of most attractive black and white subjects according to People magazine during previous 10 years.

PURPOSE: The aim of the present case-control study was to determine--using the 10 most recent annual listings of the most beautiful black and white people--whether any common, measurable esthetic parameter could be extracted from both groups. MATERIALS AND METHODS: A total of 80 women (40 white and 40 black), who had been included in the list of People magazine's 100 most beautiful people during the previous 10 years, were selected. Lateral photographs of all 80 subjects were obtained from Internet databases, oriented, and sized. A modified photogrammetric analysis was performed on the lateral view of each subject to obtain the angle and proportion measurements. Differences between the 2 groups were compared with 95% significance using the Student t test for independent samples. RESULTS: Facial similarities in the 2 ethnic groups were observed for the angle of the inferior facial third, labiomental angle, angle of facial convexity, and cervicomental angle. These results point to a similar conformation of the lower part of the face in relation to the neck that was shared by both groups of beautiful women. Additionally, both groups showed similar results for the lower lip projection. Likewise, similar proportional measurements were found for the upper lip proportion, notwithstanding differences in protrusion. CONCLUSIONS: Modern society is changing the classic concept of facial beauty because of globalization and the prevalence of multiethnic communities in the developed world. Independently of ethnic origin, beautiful women tend to have similar facial features that are a mixture of both black and white features.

La disfunción mitocondrial en la fibromialgia y su implicación en la patogénesis de la enfermedad / Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease

La fibromialgia (FM) es un síndrome de dolor crónico generalizado de etiología desconocida. Recientes estudios han mostrado evidencias sobre el papel que podría tener el estrés oxidativo en la fisiopatología de la FM, pero aún no está claro si es la causa o el efecto de las anormalidades observadas en esta. Además, se desconoce la función de la mitocondria en la fisiopatología de la enfermedad, sin embargo, se han observado signos de alteración mitocondrial en esta. Se sabe que la mitocondria es una importante productora de especies reactivas de oxígeno, por lo que se la ha relacionado con el mecanismo patogénico de numerosas enfermedades, incluida la FM. A este respecto, se ha observado que los tratamientos con antioxidantes podrían ser beneficiosos para mejorar el funcionamiento mitocondrial. Por tanto, la disfunción mitocondrial abre un gran campo de investigación terapéutica, por lo que se debería empezar a considerar en la medicina clínica el abordaje de la FM mediante tratamiento con antioxidantes y fármacos relacionados con la biogénesis mitocondrial (AU)

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Recent studies have shown evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM, however it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in FM. Furthermore, it is also controversial the role of mitochondria in the pathophysiology of FM, however signs associated with mitochondrial dysfunction have been observed in FM. Mitochondria are also known to be strong producers of ROS, so have been related with the pathogenic mechanism of numerous diseases including FM. To this respect, it has been observed antioxidants therapies might be beneficial to improve the mitochondrial performance. Therefore, the dysfunction mitochondrial opens a great field of therapeutic research, for what it should start considering in the clinical medicine the boarding of the FM by means of therapy with antioxidant and drugs related to the mitochondrial biogenesis (AU)

[Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease]. / La disfunción mitocondrial en la fibromialgia y su implicación en la patogénesis de la enfermedad.

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Recent studies have shown evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM, however it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in FM. Furthermore, it is also controversial the role of mitochondria in the pathophysiology of FM, however signs associated with mitochondrial dysfunction have been observed in FM. Mitochondria are also known to be strong producers of ROS, so have been related with the pathogenic mechanism of numerous diseases including FM. To this respect, it has been observed antioxidants therapies might be beneficial to improve the mitochondrial performance. Therefore, the dysfunction mitochondrial opens a great field of therapeutic research, for what it should start considering in the clinical medicine the boarding of the FM by means of therapy with antioxidant and drugs related to the mitochondrial biogenesis.

Bajos valores de serotonina en suero se correlacionan con la gravedad de los síntomas de la fibromialgia / Low levels of serotonin in serum correlates with severity of fibromyalgia

Objetivo: La fibromialgia es un síndrome de dolor crónico generalizado de etiología desconocida, que afecta predominantemente a mujeres. Dentro de las hipótesis que se han descrito como posibles mecanismos etiopatogénicos destaca la alteración de los valores y metabolismo de la serotonina y su relación con los síntomas en la fibromialgia. El objetivo del presente estudio fue demostrar si existía una correlación entre valores bajos de serotonina y los síntomas de la fibromialgia. Pacientes y método: Se determinó la concentración de serotonina sérica mediante enzimoinmunoensayo en una muestra de 38 pacientes y 25 sujetos sanos. Se correlacionaron los resultados con los síntomas relacionados con el dolor, la depresión, el impacto de la enfermedad (mediante el test Fibromyalgia Impact Questionnaire [FIQ]) y la edad de las pacientes. Resultados: Las pacientes presentaban un descenso de los valores de serotonina de un 45% respecto a los sujetos sanos. Se observó correlación con los parámetros predeterminados de dolor, depresión, FIQ y edad.Conclusión: Los valores de serotonina correlacionan con la gravedad de la fibromialgia. Además, existe una relación entre la edad y el descenso de la serotonina (AU)

Objetive: Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology, which affects predominantly women. Among the alterations that have been implicated in the pathophysiology of FM, there have been postulated disturbances in serotonin levels and metabolism, and their implication in symptoms. The aim of the present study was to assess the correlation levels between low levels of serotonin and severity of symptoms in FM. Patients and methods: We determined serotonin levels using an ELISA kit in serum from 38 FM patients and 25 healthy individual. Results were correlated with symptoms regarding pain, depression, impact of disease (FIQ) and age. Results: Serotonin levels were decreased by 45% compared to healthy individual. An important correlation was observed between serotonin levels and predetermined parameters of pain, depression, FIQ and age. Conclusion: Serotonin levels are correlated with severity of FM. In addition, there is an interesting correlation between serotonin levels and age of patients (AU)

Mitochondrial dysfunction in skin biopsies and blood mononuclear cells from two cases of fibromyalgia patients.

OBJECTIVES: Coenzyme Q(10) (CoQ(10)) is an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant. Signs associated with skin alteration and mitochondrial dysfunction have been observed in patients with fibromyalgia (FM). The aim of this study was to analyze CoQ(10) levels, mitochondrial dysfunction, and oxidative stress in plasma, blood mononuclear cells, and skin biopsies from FM patients. METHODS: We studied CoQ(10) level by HPLC in plasma, blood mononuclear cells, and skin obtained from patients with FM and healthy control subjects. Oxidative stress markers and mitochondrial respiratory chain enzyme activities were analysed in both plasma, blood mononuclear cells, and skin biopsies from FM patients. RESULTS: Oxidative stress, mitochondrial dysfunction, and CoQ(10) deficiency have been observed in blood mononuclear cells and skin biopsies. CONCLUSIONS: In our patients, mitochondrial dysfunction and CoQ(10) deficiency are present in several tissues. These results may contribute to the understanding of the pathophysiology of FM, and, moreover, CoQ(10) deficiency could represent a good marker for the diagnosis of FM.

[Low levels of serotonin in serum correlates with severity of fibromyalgia]. / Bajos valores de serotonina en suero se correlacionan con la gravedad de los síntomas de la fibromialgia.

OBJECTIVE: Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology, which affects predominantly women. Among the alterations that have been implicated in the pathophysiology of FM, there have been postulated disturbances in serotonin levels and metabolism, and their implication in symptoms. The aim of the present study was to assess the correlation levels between low levels of serotonin and severity of symptoms in FM. PATIENTS AND METHODS: We determined serotonin levels using an ELISA kit in serum from 38 FM patients and 25 healthy individual. Results were correlated with symptoms regarding pain, depression, impact of disease (FIQ) and age. RESULTS: Serotonin levels were decreased by 45% compared to healthy individual. An important correlation was observed between serotonin levels and predetermined parameters of pain, depression, FIQ and age. CONCLUSION: Serotonin levels are correlated with severity of FM. In addition, there is an interesting correlation between serotonin levels and age of patients.

Oxidative stress and mitochondrial dysfunction in fibromyalgia.

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and pathophysiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM. Furthermore, it is controversial the role of mitochondria in the oxidant imbalance documented in FM. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with FM. To this respect, Coenzyme Q10 (CoQ10) deficiency, an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant, alters mitochondria function and mitochondrial respiratory complexes organization and leading to increased ROS generation. Recently have been showed CoQ10 deficiency in blood mononuclear cells in FM patients, so if the hypothesis that mitochondrial dysfunction is the origin of oxidative stress in FM patients is demonstrated, could help to understand the complex pathophysiology of this disorder and may lead to development of new therapeutic strategies for prevention and treatment of this disease.

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease.

INTRODUCTION: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia. METHODS: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells. RESULTS: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy. CONCLUSIONS: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.