Metabolic disorders across the body mass index spectrum in a Colombian population with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: The relationship between obesity and nonalcoholic fatty liver disease (NAFLD) has long been established, and the prevalence of both conditions has grown together. Recent interest in NAFLD in nonobese individuals has led to an increasing number of studies, especially in Asia. Despite the fact that the prevalence of NAFLD in Latin America is one of the highest in the world, there is a lack of information on lean NAFLD populations from the region. The aim of the present study was to assess the risk of metabolic comorbidities across the whole body mass index spectrum when nonalcoholic steatohepatitis (NASH) was first diagnosed in a Latin American population. METHODS: A single-center, cross-sectional study on Colombian patients newly diagnosed with NAFLD, within the time frame of 2010-2020, compared their metabolic biochemical profile, liver enzymes, risk of prevalent metabolic abnormalities, and liver disease. RESULTS: Data from 300 patients were collected. Ninety-two percent of the patients were men and the median patient age was 47 (IQR 20) years. We found no significant differences in the biochemical, metabolic profile, or liver enzyme plasma concentration between lean, overweight, and obese individuals. Obese patients had significantly higher LDL cholesterol, and a higher risk of dyslipidemia (OR 1.86, 95% CI 1.14-3.05). Every 1kg increase in body weight increased the risk of having NASH by 2% (95% CI 2-4). CONCLUSIONS: We evaluated the metabolic risk across the entire body mass index spectrum in a Colombian cohort with NAFLD and presented the characteristics of what we believe is the first Latin American lean NAFLD population to be described.

A rationally designed self-immolative linker enhances the synergism between a polymer-rock inhibitor conjugate and neural progenitor cells in the treatment of spinal cord injury.

Rho/ROCK signaling induced after spinal cord injury (SCI) contributes to secondary damage by promoting apoptosis, inflammation, and axon growth inhibition. The specific Rho-kinase inhibitor fasudil can contribute to functional regeneration after SCI, although inherent low stability has hampered its use. To improve the therapeutic potential of fasudil, we now describe a family of rationally-designed bioresponsive polymer-fasudil conjugates based on an understanding of the conditions after SCI, such as low pH, enhanced expression of specific proteases, and a reductive environment. Fasudil conjugated to poly-l-glutamate via a self-immolative redox-sensitive linker (PGA-SS-F) displays optimal release kinetics and, consequently, treatment with PGA-SS-F significantly induces neurite elongation and axon growth in dorsal root ganglia explants, spinal cord organotypic cultures, and neural precursor cells (NPCs). The intrathecal administration of PGA-SS-F after SCI in a rat model prevents early apoptosis and induces the expression of axonal growth- and neuroplasticity-associated markers to a higher extent than the free form of fasudil. Moreover, a combination treatment comprising the acute transplantation of NPCs pre-treated with PGA-SS-F leads to enhanced cell engraftment and reduced cyst formation after SCI. In chronic SCI, combinatory treatment increases the preservation of neuronal fibers. Overall, this synergistic combinatorial strategy may represent a potentially efficient clinical approach to SCI treatment.

Evaluation of Swallowing Related Muscle Activity by Means of Concentric Ring Electrodes.

Surface electromyography (sEMG) can be helpful for evaluating swallowing related muscle activity. Conventional recordings with disc electrodes suffer from significant crosstalk from adjacent muscles and electrode-to-muscle fiber orientation problems, while concentric ring electrodes (CREs) offer enhanced spatial selectivity and axial isotropy. The aim of this work was to evaluate CRE performance in sEMG recordings of the swallowing muscles. Bipolar recordings were taken from 21 healthy young volunteers when swallowing saliva, water and yogurt, first with a conventional disc and then with a CRE. The signals were characterized by the root-mean-square amplitude, signal-to-noise ratio, myopulse, zero-crossings, median frequency, bandwidth and bilateral muscle cross-correlations. The results showed that CREs have advantages in the sEMG analysis of swallowing muscles, including enhanced spatial selectivity and the associated reduction in crosstalk, the ability to pick up a wider range of EMG frequency components and easier electrode placement thanks to its radial symmetry. However, technical changes are recommended in the future to ensure that the lower CRE signal amplitude does not significantly affect its quality. CREs show great potential for improving the clinical monitoring and evaluation of swallowing muscle activity. Future work on pathological subjects will assess the possible advantages of CREs in dysphagia monitoring and diagnosis.

Tablet-based electroencephalography diagnostics for patients with epilepsy in the West African Republic of Guinea.

BACKGROUND AND PURPOSE: Epilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established. METHODS: Tablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility. RESULTS: There were 149 participants (41% female; median age 17.9 years; 66.6% ≤21 years of age; mean seizures per month 5.7 ± SD 15.5). The mean duration of EEG1 was 53 ± 12.3 min and that of EEG2 was 29.6 ± 12.8 min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n = 53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n = 23, 24.2%), 12 (52.1%) did not have EDs at EEG2. CONCLUSIONS: Tablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.

Aß Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival.

The E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aß), a peptide related to Alzheimer's disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca(2+) dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxicity and apoptosis in Aß treated neurons. Furthermore, glutamate also decreases cdh1 and leads to accumulation of glutaminase, suggesting that there may be a positive feedback loop of cdh1 inactivation. We confirmed the main findings in vivo using microinjection of either Aß or glutamate in the CA1 region of the rat hippocampus. We show here for the first time in vivo that both Aß and glutamate cause nuclear exclusion of cdh1 and an increase in glutaminase. These results show that maintaining normal APC/C-Cdh1 activity may be a useful target in Alzheimer's disease treatment.

Reductive Stress: A New Concept in Alzheimer's Disease.

Reactive oxygen species play a physiological role in cell signaling and also a pathological role in diseases, when antioxidant defenses are overwhelmed causing oxidative stress. However, in this review we will focus on reductive stress that may be defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. This may occur in hypoxia and also in several diseases in which a small but persistent generation of oxidants results in a hormetic overexpression of antioxidant enzymes that leads to a reduction in cell compartments. This is the case of Alzheimer's disease. Individuals at high risk of Alzheimer's (because they carry the ApoE4 allele) suffer reductive stress long before the onset of the disease and even before the occurrence of mild cognitive impairment. Reductive stress can also be found in animal models of Alzheimer's disease (APP/PS1 transgenic mice), when their redox state is determined at a young age, i.e. before the onset of the disease. Later in their lives they develop oxidative stress. The importance of understanding the occurrence of reductive stress before any signs or symptoms of Alzheimer's has theoretical and also practical importance as it may be a very early marker of the disease.

Molecular mechanisms linking amyloid ß toxicity and Tau hyperphosphorylation in Alzheimer׳s disease.

Neurofibrillary tangles (aggregates of cytoskeletal Tau protein) and senile plaques (aggregates mainly formed by amyloid ß peptide) are two landmark lesions in Alzheimer׳s disease. Some researchers have proposed tangles, whereas others have proposed plaques, as primary lesions. For a long time, these were thought of as independent mechanisms. However, experimental evidence suggests that both lesions are intimately related. We review here some molecular pathways linking amyloid ß and Tau toxicities involving, among others, glycogen synthase kinase 3ß, p38, Pin1, cyclin-dependent kinase 5, and regulator of calcineurin 1. Understanding amyloid ß and Tau toxicities as part of a common pathophysiological mechanism may help to find molecular targets to prevent or even treat the disease.

Aß and tau toxicities in Alzheimer's are linked via oxidative stress-induced p38 activation: protective role of vitamin E.

Oxidative stress is a hallmark of Alzheimer's disease (AD). We propose that rather than causing damage because of the action of free radicals, oxidative stress deranges signaling pathways leading to tau hyperphosphorylation, a hallmark of the disease. Indeed, incubation of neurons in culture with 5 µM beta-amyloid peptide (Aß) causes an activation of p38 MAPK (p38) that leads to tau hyperphosphorylation. Inhibition of p38 prevents Aß-induced tau phosphorylation. Aß-induced effects are prevented when neurons are co-incubated with trolox (the water-soluble analog of vitamin E). We have confirmed these results in vivo, in APP/PS1 double transgenic mice of AD. We have found that APP/PS1 transgenic mice exhibit a high level of P-p38 in the hippocampus but not in cortex and this is prevented by feeding animals with a diet supplemented with vitamin E. Our results underpin the role of oxidative stress in the altered cell signaling in AD pathology and suggest that antioxidant prevention may be useful in AD therapeutics.

Applicability of 2-DE to assess differences in the protein profile between cold storage and not cold storage in nectarine fruits.

Cold storage is being used to increase nectarine fruits' postharvest life. However, low temperatures lead to chilling injury and limit their commercial quality and value. In this study a proteomic approach was used to compare the protein profile between control and cold storage nectarine fruits. Protein extracted from tissue was resolved by two-dimensional gel electrophoresis (2-DE) in the 4-7 pH and 10-200 kDa Mr range. Around 350 spots were well determined, and 11 from 17 spots that showed significant differences were identified by peptide mass fingerprinting (PMF) using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS). Four differentially expressed proteins were characterized as allergens and were further assessed at the transcription level using quantitative real time-RT-PCR (qRT-PCR).

Uso de la actividad colinesterasa para el diagnóstico de intoxicaciones por insecticidas organofosforados y carbamatos / Use of cholinesterase activity in the diagnosis of acute intoxications by organophosphorus and carbamate insecticides

Objetivo. La medición de la actividad colinesterasa (ChE) es una prueba rápida y económica que se emplea en el diagnóstico de intoxicaciones por insecticidas organofosforados y carbamatos. Como la interpretación por el laboratorio requiere valores de referencia para cada especie, en este estudio se establecieron las actividades de ChE normales en sangre, cerebro y retina de varias especies de animales domésticos mediante el método de Ellman. Materiales y métodos. Se obtuvieron encéfalos y globos oculares en el matadero central de Medellín, mientras que las muestras de sangre procedieron de animales remitidos al laboratorio de diagnóstico clínico de la Universidad de Antioquia. Resultados. Las medias (±D.E.) de actividad ChE sanguínea, expresada en µmoles de acetiltiocolina iodada hidrolizada/min/mL, fueron de 2.4± 0.2, 1.5±0.3, 1.9±0.3 y 2.5±0.2 para caninos, felinos, equinos y bovinos, respectivamente. En el encéfalo, la actividad ChE (µmol/min/g peso fresco), fue de 4.0±0.4, 5.4 ±0.3 y 4.9±0.3, en bovinos, porcinos y caninos, respectivamente. La retina bovina mostró una actividad de 21.7±2.45 µmol/min/g. Conclusiones. Los valores obtenidos coinciden ampliamente con los reportados por laboratorios certificados por la Asociación Americana de Laboratorios de Diagnostico Veterinarios (AAVLD), corroborando la buena reproducibilidad de la técnica y validando su uso como apoyo al diagnóstico de intoxicaciones por insecticidas inhibidores de la colinesterasa.

Objective. The measurement of cholinesterase activity (ChE) is a rapid and inexpensive test used in the diagnosis of intoxications by organophosphorus and carbamate insecticides. As the interpretation by laboratories entails reference values for each species, the present study was aimed to establish normal ChE activities in blood, brain and retina of several species of domestic animals by the use of the Ellman method. Materials and methods. Brains and eyeballs were obtained from Medellin's central slaughterhouse, while blood samples came from animals referred to the clinical diagnostic laboratory from the University of Antioquia. Results. The mean (± SD) of blood ChE activity, expressed as µmoles of iodide hydrolyzed acetylthiocholine/min/mL, were 2.4±0.2, 1.5±0.3, 1.9±0.3 and 2.5±0.2 for canines, felines, equines and bovines, respectively. In the brain, ChE activity (µmol/min/g wet weight) was 4.0±0.4, 5.4±0.3 and 4.9±0.3, in bovines, porcine, and canines, respectively. The bovine retina showed an activity of 21.7±2.45 µmol/min/g. Conclusions. The values obtained coincide with those reported by laboratories accredited by the American Association of Veterinary Diagnostic Laboratories (AAVLD), confirming its ease to reproduce the technique and validating its use to support the diagnosis of intoxications by cholinesterase inhibitors.

Aquatic exercise improves the monocyte pro- and anti-inflammatory cytokine production balance in fibromyalgia patients.

Current hypotheses of the etiology of fibromyalgia (FM) include inflammatory disorders. We evaluated the effect of a pool-aquatic exercise program (8 months, two weekly 60-min sessions) on the inflammatory cytokine production by isolated monocytes, and on the serum concentration of C-reactive protein (CRP), in a group of female FM patients. Monocytes from FM patients released more IL-1ß, TNFα, IL-6, and IL-10 than those from an age-matched control group of healthy women (HW). This inflammatory disorder in FM women was also manifested by high circulating concentrations of CRP. Increased IL-6 with a concomitant decreased TNFα spontaneous release was found after 4 months (midway through) of the exercise program. At the end of the program (8 months), monocytes from FM patients showed diminished spontaneous production of pro-/anti-inflammatory cytokines, with a similar spontaneous release of IL-1ß and IL-6 to that of HW, but a lower production of TNFα and higher of IL-10. Lipopolysaccharide-induced production of IL-1ß, TNFα, IL-6, and IL-10 also decreased at the end of the exercise program, although IL-10 remained higher than HW. The anti-inflammatory effect of the exercise program was also corroborated by a decrease in the circulating CRP concentration. Exercise also improved the health-related quality of life of FM patients.

Antioxidant pathways in Alzheimer's disease: possibilities of intervention.

Alzheimer's disease (AD) is closely related to the occurrence of oxidative stress. It was claimed that all pathophysiological mechanisms involved in the onset and progression of AD are related to oxidative stress. Thus, it is important to evaluate if there is oxidative stress as well as the mechanism by which this happens in AD patients as well as in animal models of AD. Extracellular plaques of amyloid b peptides (Aß), a hallmark of the disease, have been postulated to be more protective than damaging in terms of oxidative stress because they may be chemical sinks in which heavy metals are placed. More than a decade ago we reasoned that damage due to Ab might be caused not by extracellular, but rather intracellular Ab peptide interacting with normal cell metabolism. Ab binds to mitochondrial membranes, interacts with heme and thus interferes with the normal electron flow through the respiratory chain. This results in a faulty mitochondrial energy metabolism and in an increased production of reactive oxygen species (ROS). The low mitochondrial energy metabolism may important to explain the hypo metabolism observed in AD patients in vivo (measured by positron emission tomography) and in isolated neurons incubated in the presence of Ab peptide. The increased ROS production results in oxidative stress. The occurrence of such stress provides the basis for a putative treatment of AD with antioxidants. Major efforts have been made to determine whether antioxidant supplementation could be a means of preventing, or even treating AD, but this idea is far from being well- established. We found that even though there is oxidative stress in AD, the administration of antioxidant vitamins, particularly vitamin E, is not effective in preventing the progression of the disease in all patients. We termed this the vitamin E paradox in AD. The paradox is the fact that for some patients, vitamin E could even be detrimental whereas for others vitamin E treatment partially prevents the loss memory associated with the progression of the disease. It is clear, however, that increasing the intake of fruits and vegetables rich in antioxidant vitamins, prevents or retards the onset of AD. Thus, the issue of whether antioxidant treatment is of use in AD is not settled and more research is warranted to clarify this point.

EEG source localization based on multivariate autoregressive models using Kalman filtering.

The estimation of current distributions from electroencephalographic recordings poses an inverse problem, which can approximately be solved by including dynamical models as spatio-temporal constraints onto the solution. In this paper, we consider the electrocardiography source localization task, where a specific structure for the dynamical model of current distribution is directly obtained from the data by fitting multivariate autoregressive models to electroencephalographic time series. Whereas previous approaches consider an approximation of the internal connectivity of the sources, the proposed methodology takes into account a realistic structure of the model estimated from the data, such that it becomes possible to obtain improved inverse solutions. The performance of the new method is demonstrated by application to simulated electroencephalographic data over several signal to noise ratios, where the source localization task is evaluated by using the localization error and the data fit error. Finally, it is shown that estimating MVAR models makes possible to obtain inverse solutions of considerably improved quality, as compared to the usual instantaneous inverse solutions, even if the regularized inverse of Tikhonov is used.

Reduction of irrelevant and redundant data from TFRs for EEG signal classification.

Time-frequency representations (TFR) are one of the most popular characterization methods for non-stationary biosignals. Despite of their potential advantages, these representations suffer of large quantity of redundant and irrelevant data which makes them difficult to use for classification purposes. In this work, a methodology for reduction of irrelevant and redundant data is explored. This approach consists on removing irrelevant data, applying a relevance measure on the t-f plane that measures the dependence of each t-f point with the class labels. Then, principal component analysis (PCA) and partial least squares (PLS) are used as non-supervised and supervised linear decomposition approaches to reduce redundancy of remaining t-f points. Results show that the proposed methodology improves the performance of classifier up to 3% when no relevance and redundancy on TFRs is reduced.

Estimation of dynamic neural activity using a Kalman filter approach based on physiological models.

This paper presents a new method to estimate dynamic neural activity from EEG signals. The method is based on a Kalman filter approach, using physiological models that take both spatial and temporal dynamics into account. The filter's performance (in terms of estimation error) is analyzed for the cases of linear and nonlinear models having either time invariant or time varying parameters. The best performance is achieved with a nonlinear model with time-varying parameters.

Seroprevalencia de Brucella canis en perroscallejeros del Centro de Bienestar Animal La Perla,Medellín (Colombia), 2008 / Seroprevalência da Brucelose canis em cachorros de rua do Centro de Bem-estarAnimal La Perla, Medellín (Colômbia), 2008 / Brucella canis seroprevalence in stray dogs from “Centro de Bienestar Animal La Perla, Medellín (Colombia), 2008

Brucella canis es el principal agente causal de enfermedad reproductiva en caninos. Por su potencialzoonótico y su distribución mundial, esta infección tiene una gran importancia. En Colombia, la bacteriase ha aislado de mascotas caninas, de perros de criadero, y de humanos. Este estudio se realizó con elobjetivo de determinar la frecuencia de esta infección en perros callejeros, alojados en el Centro deBienestar Animal “La Perla” (Medellín, Colombia). En junio de 2008 se muestrearon 221 caninos y serealizó prueba de aglutinación rápida en placa. Se encontró una seroprevalencia del 6.78%, y no hubodiferencia por grupos de edad o sexo. Los resultados alertan sobre la población de perros callejeros comoun factor de riesgo para la transmisión de la enfermedad.

Brucella canis is the main causal agent of reproductive illness in dogs. The disease has a zoonoticpotential and is distributed worldwide, hence his great importance. In Colombia, the bacterium has been isolated from pet dogs, kennel dogs, and also from human beings. The objective of this study was to takea look at the frequency of B. canis infection in street dogs sheltered in the Center for Animal Welfare “LaPerla” (Medellín, Colombia). In June 2008, 221 dogs were sampled and their sera were tested by the rapidslide agglutination test. Seroprevalence was 6.78%,and no difference was found between different age orsex groups. The results alert about the street dogs population as a risk factor for the transmission of theBrucella canis.

Brucella canis é o principal agente causador da doença reprodutiva em cães. Por seu potencial zoonóticoe sua distribuição global, esta infecção é de grande importância. Na Colômbia, a bactéria foi isolada decães, canil, e os seres humanos. Este estudo foi conduzido com o objetivo de fazer uma abordagem àfreqüência desta infecção em cães de rua, alojados no Centro de Bem-Estar Animal "Pearl" (Medellín,Colômbia). Em junho de 2008, foram amostrados 221 cães e foi feito o teste rápido de aglutinação. Foiencontrada uma soroprevalência de 6.78%, e não houve diferença de idade e do sexo. Os resultados alertampara a população de cães de rua como um fator de risco para transmissão da doença.

Noradrenaline increases the expression and release of Hsp72 by human neutrophils.

UNLABELLED: The blood concentration of extracellular 72kDa heat shock protein (eHsp72) increases under conditions of stress, including intense exercise. However, the signal(s), source(s), and secretory pathways in its release into the bloodstream have yet to be clarified. The aim of the present study was to evaluate the role of noradrenaline (NA) as a stress signal on the expression and release of Hsp72 by circulating neutrophils (as a source), all within a context of the immunophysiological regulation during exercise-induced stress in sedentary and healthy young (21-26years) women. The expression of Hsp72 on the surface of isolated neutrophils was determined by flow cytometry, and its release by cultured isolated neutrophils was determined by ELISA. Incubation with cmHsp70-FITC showed that neutrophils express Hsp72 on their surface under basal conditions. In addition, cultured isolated neutrophils (37 degrees C and 5% CO(2)) also released Hsp72 under basal conditions, with this release increasing from 10min to 24h in the absence of cell damage. NA at 10(-9)-10(-5)M doubled the percentage of neutrophils expressing Hsp72 after 60min and 24h incubation. NA also stimulated (by about 20%) the release of Hsp72 after 10min of incubation. IN CONCLUSION: (1) Hsp72 is expressed on the surface of isolated neutrophils under basal conditions, and this expression is augmented by NA. (2) Isolated neutrophils can also release Hsp72 under cultured basal conditions in the absence of cell death, and NA can increase this release. These results may contribute to confirming the hypothesis that NA can act as a "stress signal" for the increased eHsp72 in the context of exercise stress, with a role for neutrophils as a source for the expression and, to a lesser degree, the release of Hsp72 after activation by NA.

Role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK) and nuclear transcription factor kappa beta (NF-k beta) on neutrophil phagocytic process of Candida albicans.

In humans, Candida albicans is the microorganism most frequently associated with fungal infections. Alterations in the balance between the host and this commensal pathogen, turns into a parasitic relationship which results in the development of invasive infections. Neutrophils via chemotaxis, phagocytosis, and microbicide capacity can eradicate this pathogen. Taken together, the aim of this work was to study the possible role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK) and the nuclear transcription factor kappa beta (NF-k beta) on the phagocytic process of neutrophils. The chemotactic capacity of neutrophils and their ability to phagocytose and to destroy C. albicans in absence and presence of 1, 10, or 100 microM of wortmannin (a PI3K inhibitor); 10, 25, or 50 microM of Bay 11-7082 (a NF-k beta inhibitor) or 1, 5 or 10 microM of PD 98,059 (an ERK inhibitor) were determined. Our results show that fMLP-induced chemotaxis needs the participation of PI3K and NF-k beta. In contrast, ERK seems not to be involved. On the other hand, the inhibition of NF-kappa beta and ERK decreased neutrophil phagocytosis and microbicide capacity against C. albicans. However, both the phagocytic and candicide capacities were PI3K independent.

Exercise in fibromyalgia and related inflammatory disorders: known effects and unknown chances.

Fibromyalgia (FM) is characterised by chronic widespread pain and allodynia (pain from stimuli which are not normally painful with pain that may occur other than in the area stimulated) of more than 3 months duration. The current hypothesis of the aetiology of FM includes inflammatory and neuroendocrine disorders. The biophysiology of this syndrome, however; remains still widely elusive, and there are no formally approved therapies. Non-pharmacological interventions in FM patients include habitual exercise programs which improve physical function and quality of life of patients and may even reduce pain. However the mechanisms through which exercise benefits FM symptoms needs to be elucidated. In this article we firstly review the main topics and characteristics of the FM syndrome, while focusing our attention on the inflammatory hypothesis of FM, as well as on the beneficial effects of habitual exercise as a co-therapy for FM patients. In this context, the latest developments in research on anti-inflammatory effects of exercise are also reviewed and discussed. To find out what is known about the connection between benefits of exercise for FM and anti-inflammatory effects of exercise, we carried out a PubMed search using the term "fibromyalgia" and "exercise" together with "inflammation", and no more than ten published articles were found (six of them reviews), which are also discussed. In the second part of the article we present a pilot investigation on a group of 14 female FM patients with a diagnosis of FM by a rheumatologist. They took part in a pool-aquatic program in warm water over a period of fourth months (three weekly 60-min sessions). Circulating inflammatory (IL-1beta, IL-2, IFNgamma, TNFalpha, IL-8, IL-6, IL-4, IL-10 and CRP) and neuroendocrine (NA and cortisol) markers were determined. FM patients showed higher circulating levels of IL-8, IFNgamma and CRP as well as cortisol and NA than age-matched healthy control women. After the exercise program, a significant decrease in IL-8, IFNgamma, and CRP were found, in parallel with a decrease in circulating concentrations of cortisol and increased levels of NA. The results confirm an elevated "inflammatory status" in the FM syndrome and strengthen the hypothesis that the benefits of exercise in FM patients are mediated, at least in part, by its anti-inflammatory effects. A better regulation of the cytokine-HPA axis feedback may be also involved.

Influence of exercise on the circulating levels and macrophage production of IL-1beta and IFNgamma affected by metabolic syndrome: an obese Zucker rat experimental animal model.

Regular physical activity is recognized as a non-pharmacological treatment of genetic obesity and type-II diabetes, and based on the "anti-inflammatory" effects of exercise, it has been also proposed for improving the "chronic low-grade inflammation" in metabolic syndrome (MS). The aim of the present work was to evaluate the effects of an habitual exercise program (running, 5 days/week for 35 min at 35 cm/s for 14 weeks) and of a bout of acute exercise (running, for 35 min at 35 cm/s) on MS-associated disorders in the pro-inflammatory cytokines IL-1beta and IFNgamma. The study was carried out on obese Zucker rats (fa/fa). The obese rats presented higher circulating concentrations and constitutive macrophage production (in the absence of antigenic stimulus) of IL-1beta (but not of IFNgamma). But their production of both IL-1beta and IFNgamma by lipopolysaccharide (LPS)-stimulated macrophages was lower than that of the control lean rats. Our protocol of exercise training did not modify the circulating concentration and constitutive macrophage release of either IL-1beta or IFNgamma in the obese rats, but increased the production of both cytokines by LPS-stimulated macrophages. The single bout of acute exercise only increased the release of IL-1beta by the LPS-stimulated macrophages from obese rats, in both sedentary and trained animals. The results indicated that: (1) circulating levels and constitutive production of IL-1beta by macrophages are deregulated in rats with MS, and (2) IL-1beta and IFNgamma production by macrophages in response to antigenic stimulus (LPS) is impaired in the obese animals, and this MS-associated disorder is improved by the program of habitual exercise training.