Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.

Syndrome of chronic fatigue / myalgic encephalomyelitis (CFS / ME) is a complex multifactorial disease of unknown cause with multi-system events. Although the etiology of CFS / ME remains elusive, immunological dysfunction and specifically low cytotoxic activity in natural killer (NK) cells is the result of more consistent laboratory.

The transient receptor potential (TRP) superfamily of cation channels play a central role in the pathophysiology of immune diseases and are therefore potential therapeutic targets. We have already identified single nucleotide polymorphisms in the genes of the TRP in NK peripheral cells of patients of CFS / ME.

We also described the changes in biochemical and signaling pathways calcium disturbances in NK cells of patients with CFS / ME. In particular, we have previously reported a decrease in the cation channel TRP function subfamily member melastatin 3 (TRPM3) in isolated NK cells from patients CFS / ME compared to healthy controls after modulation with pregnenolone sulfate and ononetin using a patch-clamp technique.

In this study, we aim to confirm the previous results describing a TRPM3 activity with disabilities in a new cohort of patients with CFS / ME using a technical whole cell patch clamp after modulation by agonists TRPM3 reversible, the pregnenolone sulfate and nifedipine, and an effective antagonist TRPM3, ononetin. Indeed, no formal research has commented on the use of pregnenolone sulfate or nifedipine to treat CFS / ME patients when there is evidence that clinicians prescribe calcium channel blockers to improve different techniques of cell patch clamp symptoms.

Whole was used to measure activity in TRPM3 isolated NK cells from twelve healthy controls age and sex and CFS patients / ME, after activation with pregnenolone sulfate and nifedipine and inhibition ononetin .

We have confirmed a significant reduction in the amplitude of currents after TRPM3 sulfate stimulation pregnenolone in isolated NK cells from another cohort of patients with CFS / ME compared to healthy controls.

The ionic currents evoked by pregnenolone sulphate TRPM3 way were again modulated significantly by ononetin in isolated NK cells from healthy controls compared to patients CFS / ME. In addition, we used nifedipine, another agonist reversible TRPM3 to support the previous results and found similar results confirming a significant loss of activity TRPM3 channel activity CFS / ME was patients.

Impaired TRPM3 validated in isolated NK cells from patients with CFS / mE using different techniques of whole-cell patch clamp pharmacological tools and as the gold standard for ion channel research. This survey also establish channels TRPM3 as prognostic marker and / or a potential therapeutic target for CFS / ME.

Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.
Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.

Evaluation of four clinical laboratory parameters for the diagnosis of myalgic encephalomyelitis.

CONTEXT
myalgic encephalomyelitis (ME) is a complex and debilitating disease that often present initially with flu-like symptoms, accompanied by debilitating fatigue. Currently, there are no biomarkers objectives or laboratory tests that can be used for diagnosis unequivocally ME; Therefore, a diagnosis is made when a patient encounters a series of criteria for inclusion and exclusion of costly and subjective. The purpose of this study was to evaluate the utility of four clinical parameters in the diagnosis ME.


METHODS
In this study, we used logistic regression and classification and regression tree analysis to conduct a retrospective survey of four clinical laboratories in ME 140 cases and 140 healthy controls.


RESULTS
The correlations between covariates were between [- 0.26, 0.61]. The best model included serum levels of the soluble form of CD14 (sCD14), serum levels of prostaglandin E2 (PGE2) and serum levels of interleukin-8, with coefficients of 0.002, 0.249 and 0.005, respectively, and p-values ​​of 3 × 10-7 1 × 10-5 and 3 x 10-3, respectively.


CONCLUSIONS
Our results show that these parameters may help doctors in their diagnosis of ME and may shed more light on the pathophysiology of this disease.

Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test.

Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test.

The mitochondrial energy score (TSS) protocol developed by the group Myhill, is marketed as a diagnostic test for chronic fatigue syndrome / myalgic encephalomyelitis (CFS / ME). This study evaluated the reliability and reproducibility of the test, currently provided by private clinics, to assess its potential to be developed as an NHS accredited laboratory test.

We reproduced the ESM protocol using neutrophils and peripheral blood mononuclear cells (PBMC) of patients with CFS / ME (10) and healthy controls (13). The protocol was then repeated in PBMCs and neutrophils from healthy controls to investigate the effect of the delayed sample processing time used by the group Myhill.

Experiments using the established protocol showed no difference between patients CFS / ME and healthy controls in one of the components of the MES (p ≥ 0.059). Delaying treatment blood samples within 24 hours (and in the period of 72 hours cited by Myhill group) significantly altered number of parameters used to calculate the MES in both neutrophils and PBMCs.

The MES test was not required reliability and reproducibility of a diagnostic test and should therefore not be proposed as a diagnostic test for CFS / ME. The differences observed by Myhill group may be reduced to differences in processing time between sample cohorts.

Advances in ME/CFS: Past, Present, and Future.

The precursor of what is now known as myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS) has been described by the Public Health Service of the United States in 1934. At present, we do not yet know the cause and / or how to detect by routine clinical laboratory tests.

Accordingly, the nature of the disease ME / CFS has been overlooked and the disease was wrongly stigmatized by such a psychosomatic or somatoform illness. These misperceptions of the disease have led to the exploration of insufficient research of the disease and a minimum of care for patients absent.

A report by the Institute of Medicine in 2015 declared the disease ME / CFS a disease that affects up to 2.5 million Americans and rebuked the US government for doing little to research the disease and support patients .

Clinicians currently treating the disease state be more devastating than HIV / AIDS. A comparison of the stories of the two diseases, a review of the current status of the two diseases, and a list of accomplishments that would be required for ME / CFS to achieve the same level of treatment and currently care of patients with HIV / AIDS is provided.

Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study.

Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study.

The present study discusses the effects of a combination of probiotics can stimulate the immune system of patients with chronic fatigue syndrome / myalgic encephalomyelitis (CFS / ME). For this purpose, patients diagnosed according to the criteria of Fukuda and treated with probiotics were analyzed by clinical and laboratory evaluations, before and after probiotic administration.

Probiotics have been chosen taking into account the possible pathogenic mechanisms of ME / CFS syndrome, which was associated with an impaired immune response, dysregulation of Th1 / Th2 ratio, and high oxidative stress with exhausted antioxidant reserves due to severe mitochondrial dysfunction. And a oxidative immune dysfunction may be related to inflammation of low grade chronic gastrointestinal (GI) in the lamina propria and surface of the intestinal mucosa associated with dysbiosis, intestinal permeability, bacterial translocation, and immune dysfunction and oxidative.

Literature data show that bacterial species are capable of modulating immune system function and oxidative and that certain probiotics administration can improve the mucosal barrier function, modulation of cytokine release proinflammatory in patients SFC / ME. This study is a preliminary investigation to verify the safety and efficacy of a certain combination of probiotics in patients CFS / ME.

The results suggest that probiotics can alter the state of well-being as well as inflammatory and oxidative indexes in patients CFS / ME. No adverse effects were observed except for one patient who shows a surge in symptoms, although all inflammatory parameters (ie, cytokines, fecal calprotectin, ESR and immunoglobulins) have been reduced after taking probiotics.

The reactivation of the symptoms of fatigue in this patient, whose clinical history reported the onset of CFS / ME following mononucleosis, may be linked to an abnormal stimulation of the immune system as suggested by a recent study describing an exaggerated immune activation associated to chronic fatigue.

Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study.
Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study.

Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity.

biomarker discovery applied to myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS), a debilitating disease inconclusive etiologies identified several cytokines potentially to fill a role as a marker quantitative blood / serum for laboratory diagnostics, activin B with a recent addition.

We further explored the potential serum activin B as ME / CFS biomarker, alone and in combination with a series of routine tests results obtained by pathology laboratories. Previous results from the pilot study showed that activin B was significantly higher for ME / CFS participants compared with healthy participants (controls). All participants were recruited by CSA Discovery and ranked by the criteria of Canada / international consensus. for ME / CFS cohort A significant difference in serum activin B was also detected for ME / CFS and control cohorts recruited for the study, but the median levels were significantly lower.

Random Forest (RF) modeling identified five markers blood test routine pathology that collectively predicted ME / CFS in ≥62% compared with rest time weighted (WST) severity classes. Further analysis revealed that the inclusion of activin B Pathology marker panel has improved the forecast slight to moderate ME / CFS cases.

The correct application prediction WST class modeling FRG, new reference intervals were calculated for activin B and markers associated pathologies where clearance urinary creatinine 24, urea serum and serum activin B showed the best potential as diagnostic markers. While serum activin B results remained statistically significant for new cohorts of participants, activin B was also found useful in improving the prediction of the severity of symptoms, as shown by WST class.