Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: a multicentral-triple blind randomized clinical trial

BackgroundMultiple sclerosis (MS) is a chronic autoimmune disease. Ellagic acid is a natural polyphenol and affects the fate of neurons through its anti-inflammatory and antioxidant properties. The present study aimed to investigate ellagic acid effects on disease severity, the expression of involved genes in the pathogenesis of MS, and the levels of related cytokines.MethodsThe present study was a triple-blind clinical trial. Eligible patients were randomly assigned to two groups: Ellagic acid (25 subjects) for 12 weeks, receiving 180 mg of Ellagic acid (Axenic, Australia) and the control group (25 subjects) receiving a placebo, before the main meals. Before and after the study, the data including general information, foods intake, physical activity, anthropometric data, expanded disability status scale (EDSS), general health questionnaire (GHQ) and pain rating index (PRI), fatigue severity scale (FSS) were assessed, as well as serum levels of interferon-gamma (IFNγ), interleukin-17 (IL-17), interleukin-4 (IL-4) and transforming growth factor-beta (TGF-β), nitric-oxide (NO) using enzyme-linked immunoassay (ELISA) method and expression of T-box transcription factor (Tbet), GATA Binding Protein 3 (GATA3), retinoic acid-related orphan receptor-γt (RORγt) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes were determined using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) method.FindingsEllagic acid supplementation led to a reduction in IFNγ, IL-17, NO and increased IL-4 in the ellagic acid group, however in the placebo group no such changes were observed (−24.52 ± 3.79 vs. -0.05 ± 0.02, p < 0.01; −5.37 ± 0.92 vs. 2.03 ± 1.03, p < 0.01; −18.03 ± 1.02 vs. -0.06 ± 0.05, p < 0.01, 14.69 ± 0.47 vs. -0.09 ± 0.14, p < 0.01, respectively). Ellagic acid supplementation had no effect on TGF-β in any of the study groups (p > 0.05). Also, the Tbet and RORγt genes expression decreased, and the GATA3 gene expression in the group receiving ellagic acid compared to control group significantly increased (0.52 ± 0.29 vs. 1.51 ± 0.18, p < 0.01, 0.49 ± 0.18 vs. 1.38 ± 0.14, p < 0.01, 1.71 ± 0.39 vs. 0.27 ± 0.10, p < 0.01). Also, ellagic acid supplementation led to significant decrease in EDSS, FSS and GHQ scores (p < 0.05), and no significant changes observed in PRI score (p > 0.05).ConclusionEllagic acid supplementation can improve the health status of MS patients by reduction of the inflammatory cytokines and Tbet and RORγt gene expression, and increment of anti-inflammatory cytokines and GATA3 gene expression.Clinical trial registration: (https://en.irct.ir/trial/53020), IRCT20120415009472N22

Iranian clinical practice guideline for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3–5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations

Progressive visual and Hearing Loss As Looming Manifestations of Spinal Meningeal Melanocytoma

Meningeal melanocytoma is a rare tumor of nervous system, which originates from leptomeningeal melanocytes.The locations of melanocytoma in the nervous system are most frequently in the posterior fossa or along the spinal cord, and usually appear as an extra-axial mass.The manifestations of tumor are most often due to its compressing effect on adjacent nervous structures that causes various neurological signs and symptoms depending on its locations. It may also cause superficial siderosis of the central nervous system [1].In this case we describe another manifestation of this tumor which raised intracranial pressure and developed its neurological signs and symptoms. The patient was a 33-year old man with a two-year history of headache and tinnitus, transient diplopia, and had also a three- month history of   progressive bilateral visual and hearing loss. The medical investigations of the patient reveal   raised intracranial pressure (RICP) with a high concentration of protein in the cerebrospinal   fluid, and an extra-axial mass at the T11-12 level in magnetic resonance imaging of the spinal   cord. The patient underwent surgical removal of the tumor, in which the pathological study characterized the tumor as a meningeal melanocytoma. After surgery the CSF pressure returnedto normal state, and its protein level decreased. The patient's hearing loss improved significantly but the visual defect did not change.Base on various causes of the RICP,especially when there is abnormality in CSF protein without any known cause,we must consider melanocytoma as a treatable cause, and thus in such patients, performing spinal cord magnetic resonance imaging (MRI) is a valuble technique for diagnosis as well as investigation.  

Early Outcome of Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) in Advanced Parkinson Disease in First trial of Iranian Patients

Background:To improve the debilitating features of Parkinson disease (PD) different medical and surgical approaches are available. Subthalamic nucleus deep brain stimulation (STN-DBS) was appeared to be a promising method during last two decades. This study aimed to evaluate early motor outcomes of this procedure in first trial of Iranian patients. Methods: Thirty-seven consecutive patients with advanced Parkinson disease with   poor response to common medical agents underwent bilateral STN-DBS. For assessment of motor function parameters Unified Parkinson Disease Rating scale III (UPDRS III) was used. We compared total scores and subscores in three measurements performed as 1) preoperative off-medication, 2) preoperative on-medication and 3) six months postoperative on stimulation and on medication. Reduction in drug consumption was assessed with regard to administered doses of L-Dopa before and after surgery in stable states.Results: 26 men and 10 women with mean age of 50 years were evaluated (one person expired before 6-month follow-up). Mean total scores of UPDRSIII were calculated as 5.2±54.52, 2.88±18.22 and 3±12.8 in three measurements, respectively (p=0.003 ).PostHoc analyses showed significant improvement among all measurements. Analysis of subscores also revealed significant amelioration in rigidity, resting tremor, hand movement, leg agility, finger tap and rapid alternating movement in on-medication phases of pre- and post-operation (all with

Comparison of antibiotic resistance of bacterial agents associated in septicaemia in children and infants

Background: Septicaemia is a leading cause of morbidity and mortality of infant’s and childerens espicially in first week of their life, both in developed and underdeveloped countries.The aim of this research was to study of bacterial agents causing septicaemia and to determine their antibiotic suseptibility patternes. Materials and Methods : This was a descriptive study, it was performed during eight months from October 2011 till May 2011.In total 216 blood culture samples of children suspected of septicaemia in children health centre hospital were send to the laboratory for investigation. The bacterial identification was carried out by culturing and conventional biomedical tests. The antibiotic sensitivity tests were performed by disk diffusion method. These data are analyzed by SPSS and the results Expressed as relative frequencies. Results: Out of 216 tested samples 55(25.6%) were positive and 161 (74.54%) negative. The dominated bacteria was Escherichia coli (31.42%), followed by Staphylococcus aureus (22.86 %), Klebsiella pneumonia (20%)), Staphylococcus epidermidis (14.28%), Streptococcus pneumonia (2.86%), Salmonella typhi (2.86%), Enterobacter cloacae (2.86%) and Stenotrophomonas maltophilia (2.86%). In general gram-negative bacteria were isolated more than gram-positive. Staphylococcus bacteria were more resistant to antibiotics than other isolated bacteria, and were 100% resistant to penicillin. The enterobacteriaceae were more sensitive to norfloxacin, amikacin, tobramycin, and they were 100% resistant to ampicillin. Conclusion: The results obtained in this study showed that gram-negative bacteria are more responsible in septicaemia in children ward, and norfloxacin is the more effective antibiotic in comparison with others

A Mitochondrial Disorder in a Middle Age Iranian Patient: Report of a Rare Case

Introduction: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) can involve multiple systems and cause stroke-like episodes and status epilepticus. Case Presentation: A 48-year-old female with history of early fatigability, migraine-type headaches, and bilateral sensory-neural hearing loss presented 3 episodes of serial seizures. On admission she was affected by Wernicke aphasia and, then, right hemiparesis. Investigations showed elevated arterial lactate and ragged red fibers on muscle biopsy. Conclusion: Though more commonly diagnosed during childhood, some cases of adult-onset MELAS syndrome are reported. This syndrome should be considered in patients with stroke-like events in adults without cerebrovascular risk factors and difficult-to-treat seizures

The value of MUNIX as an objective electrophysiological biomarker of disease progression in chronic inflammatory demyelinating polyneuropathy

Introduction/Aims: Objective outcome measures to monitor treatment response and guide treatment are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we aimed to evaluate the motor unit number index (MUNIX) as an outcome measurement in patients with CIDP and determine the correlation of MUNIX with functional and standard electrodiagnostic tests in a single follow-up study. Methods: We evaluated MUNIX of the abductor pollicis brevis, abductor digiti minimi, and tibialis anterior (TA) muscles bilaterally. Muscle force was assessed by Medical Research Council Sum Score (MRCSS). Functional measures used were the Overall Neuropathy Limitation Score (ONLS) and the Rasch-built Overall Disability Scale (R-ODS) score at baseline and after 6 months of treatment. Standard electrophysiology was evaluated by the Nerve Conduction Study Score (NCSS). Results: Twenty patients were included at baseline, and 16 completed the follow-up study. Significant correlations were found between the MUNIX sum score and both MRCSS and NCSS at baseline, between both the pinch strength and grip and upper limb MUNIX at baseline and follow-up, and between MUNIX of TA and both lower limb MRCSSs with lower limb ONLS at baseline and follow-up. Significant correlations also were found between MUNIX sum score change and MRCSS change, R-ODS change, and ONLS change. Discussion: MUNIX changes correlated with strength and electrophysiological improvements in CIDP patients. This suggests that MUNIX may represent a useful objective biomarker for patient follow-up