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@#Objective: Multiple sclerosis (MS) is a chronic neuroinflammatory disease, characterizes by demyelination in the central nervous system (CNS). Co-stimulatory molecules such as CD137 (4-1 BB) play a major role in the activation of lymphocytes in CNS. The exact immunopathogenesis of MS is unknown. Hence, detection of specific biomarkers in the process of MS disease can lead to new therapeutic approaches. This study aimed to compare plasma sCD137 levels in relapsing-remitting multiple sclerosis (RRMS) patients with healthy controls in Isfahan province. Methods: Plasma sCD137 level was measured by enzyme-linked immune sorbent assays (ELISA) in 36 RRMS patients as well as 52 (age and sex-matched) healthy controls and the results were compared. Results: The plasma sCD137 level in studied RRMS patients was significantly higher in the patient group compared to the healthy controls (P- value=0.027). In addition, there was no significant association between age, sex, job and education level, with plasma sCD137 level in both the control and the case groups (P value>0.05). There was no correlation between mean of sCD137 and EDSS score, age of onset, duration of disease as well as serum 25 (OH) D concentrations of the patients. Conclusion: High plasma sCD137 level was detected in RRMS patients when compared with the controls, which may indicate the possible role of this biomarker in the immunopathogenesis of MS. Since CD137 can affect T lymphocytes activation and apoptosis, further studies are needed to elucidate its exact role in the pathogenesis of MS.
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Objective: Semaphorin-3A [SEMA3A] and its receptors are found on some immune cells and act as suppressors of immune cells over-activation. Considering the role of SEMA3A and its down-regulation in some autoimmune diseases, as well as our bioinformatics predictions, we assumed that miR-145-5p might affect SEMA3A expression. So, we aimed to determine the effect of miR-145-5p on SEMA3A gene expression level
Materials and Methods: In this experimental study, we evaluated the effect of miR-145-5p transfection on SEMA3A expression in peripheral blood mononuclear cells [PBMCs] using ELISA and quantitative real-time polymerase chain reaction [PCR] methods
Results: Our results showed that miR-145-5p is able to decrease SEMA3A expression at both protein and mRNA levels. These data confirmed our previous bioinformatic prediction about the inhibitory effect of miR-145-5p on SEMA3A expression
Conclusion: These results enlightened us about an unknown aspect of SEMA3A role in some autoimmune disorders like multiple sclerosis [MS] and rheumatoid arthritis [RA] and also proposed SEMA3A as a potential therapeutic approach
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Objective: MicroRNAs [miRNA] are a class of non-coding RNAs which play key roles in post-transcriptional gene regulation. Previous studies indicate that miRNAs are dysregulated in patients with multiple sclerosis [MS]. Th17 and regulatory T [Treg] cells are two subsets of CD4[+] T-cells which have critical functions in the onset and progression of MS. The current study seeks to distinguish fluctuations in expression of CD4[+] T-cell derived miR-223 during the relapsing-remitting [RR] phase of MS [RR-MS], as well as the expressions of Th17 and Treg cell markers
Materials and Methods: this experimental study used real-time quantitative polymerase chain reaction [qRT-PCR] to evaluate CD4[+] T cell derived miR-223 expression patterns in patients that experienced either of the RR-MS phases [n=40] compared to healthy controls [n=12], along with RNA markers for Th17 and Treg cells. We conducted flow cytometry analyses of forkhead box P3 [FOXP3] and RAR-related orphan receptor ?t [ROR?t] in CD4[+] T-cells. Putative and validated targets of miR-223 were investigated in the miRWalk and miRTarBase databases, respectively
Results: miR-223 significantly upregulated in CD4[+] T-cells during the relapsing phase of RR-MS compared to the remitting phase [P=0.000] and healthy individuals [P=0.036]. Expression of ROR?t, a master transcription factor of Th17, upregulated in the relapsing phase, whereas FOXP3 upregulated in the remitting phase. Additionally, potential targets of miR-223, STAT1, FORKHEAD BOX O [FOXO1] and FOXO3 were predicted by in silico studies
Conclusion: miR-223 may have a potential role in MS progression. Therefore, suppression of miR-223 can be proposed as an appropriate approach to control progression of the relapsing phase of MS
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Background & Objective: Resistance training is deemed to be beneficial for multiple sclerosis patients. The aim of this study was to determine whether a program of RT and whole body vibration has any effect on the pattern of hormonal changes in female MS patients. Methods: Twenty-four female MS patients were enrolled in this study. They were aged between 20-40 years and ranged from 2-4 on the Expanded Disability Status Scale (EDSS). Twelve patients took part in this protocole. The duration of the program was eight weeks, each sessions were held three times per week. The twelve controls did not take part in this program. Serum levels of follicle-stimulating hormone, luteinizing-hormone, estradiol, progesterone, testosterone, prolactin and cortisol were measured before and after the protocole between the 8th and 10th day of the follicular phase of the patients’ menstrual cycle. Descriptive statistics and co-variance analysis were adapted for evaluating the data. Results: Significant increases in levels of testosterone and prolaction, whereas a significant decrease in levels of cortisol were detected. Conclusion: The results provide clues as to the involvement of testosterone, prolactin and cortisol as possible mediators of the beneficial effects of resistance training and whole body vibration in multiple sclerosis.
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Background & Objectives:Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system. The disease occurs with higher frequency among families. This study aimed to investigate the frequency and type of familial MS among patients with definite MS registered in the Isfahan Society for MS. Methods: A cross sectional study was performed on 3911 MS patients in Isfahan. All patients had a diagnosis of definite MS. Demographic characteristics, medical history, signs and symptoms at onset, course of disease, having a relative with MS, degree and type of relationship were recorded. Results: Familial MS was found in 11% of patients, with 57. 7% having a first degree relative with MS. Mean age of patients with familial MS was 36.9±10.4 years, with higher rates among women (female to male ratio 2.6). Highest rate for familial MS was observed in sister-sister relations, and brother-sister relation. Lowest rate was observed in father-son relation. Conclusions: Familial MS is more common among sisters while father-son relationship has the lowest association. Female to male ratio is 2.6 in familial MS which shows higher rates of males relative to general population.
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The aim of this study was to estimate the conversion rate from radiologically isolated syndrome [RIS] to definite multiple sclerosis [MS]. During a mean [standard deviation [SD]] follow-up period of 17.4 [5.4] [range 8-29] months, 25 subjects with RIS and without neurological symptom aged 22-45 year from a single-center have been examined for the occurrence of definite MS. The mean [SD] age of participants was 35.1 [6.2] years at first brain magnetic resonance imaging [MRI]. The definite MS were assessed using the revised McDonald's criteria [2010]. Six of 25 patients developed clinical symptom consistent with criteria for definite MS. The conversion rate from RIS to definite MS was 1.5 [95% confidence interval [CI] 0.54, 3.17] per 100 person-months based on 480 person-months of follow-up. Multivariate analysis revealed that presence of contrast-enhancing lesions on the initial MRI was marginally significantly associated with MS [hazard ratio 1.83, 95% CI 0.98, 3.45, P = 0.060]. This is the first estimate of conversion rate from RIS to definite MS in Iran. The conversion rates from RIS to definite MS in these participants are high and intensive follow-up and intervention strategies are recommended for these high-risk individuals. A larger study is warranted to assess this risk in greater detail
ABSTRACT
Multiple sclerosis [MS] is an autoimmune disease of central nerves system, in which neurological disabilities occur in young adults. Despite increasing number of studies on MS, some aspects of this disorder are still unclear. In the previous studies, it has been proven that there is direct relation between MS incidence and vitamin D deficiency. Thereby, strong evidence in MS pathogenesis suggests that endothelial cells [EC] could be harmed in MS. In addition, functional changes in EC and macrovascular injuries lead blood-brain barrier disruption in MS. Current study is the first investigation to elucidate positive influences of vitamin D against EC apoptosis in MS. Human umbilical vein endothelial cells [HUVECs] were cultured and then treated with sera from patients with active MS [in relapse] and sera from healthy volunteer participants as control group [each group n=15]. 3-[4,5-dimethylthiazol-2-yl]-5- [3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt [MTS] assay for cell surveillance and cell-death detection kit for evaluating apoptosis were used in this study. There was a significant decrease in apoptosis rate by the serum of patients, just when 1,25[OH][2]D[3] applied before treating HUVECs with sera from active MS [in relapse]. Furthermore, the cells surveillance increased markedly with the presence of 1,25[OH][2]D[3] in culture, too. With regard to increment in EC apoptosis rate, which treated by the sera from MS patients and decrement in apoptosis rate by the presence of vitamin D in culture media, it could be proposed that vitamin D pre-treatment can be used for MS patients, due to its beneficial effects on protecting EC apoptosis
Subject(s)
Humans , Female , Male , Apoptosis , Vitamin D/pharmacology , Vitamin D Deficiency , Endothelial Cells , Umbilical VeinsABSTRACT
The purpose of this study was to evaluate the effect of an eight-week progressive resistance training and vibration program on strength and ambulatory function in multiple sclerosis [MS] patients. Twenty-Four female MS patients with the following demographics: age 27-45 years, and expanded disability status scale [EDSS] 2-4, participated in this study. The subjects were randomly allocated to one of two groups. The exercise group [n=12] trained according to a progressive program, mainly consisting of resistance training and vibration, three times a week for eight weeks and compared with subjects in the control group [n=12] that received no intervention. Subjects completed one set of 5-12 reps at%50-70 maximal voluntary contraction [MVC]. After 5-10 minutes rest, six postures on plate vibration were done. Isotonic MVC of knee extensors, abduction of the scapula and downward rotation of the scapular girdle muscle groups were predicted by using the Brzycki formula. Right leg balance [RLB], left leg balance [LLB], and walking speed [10-Meter Walk Test] were assessed before and after the training program. Descriptive statistics and Co-variance were used for analyzing data. After eight weeks of training the exercise group showed significant increase in MVC of Knee extensors [32.3%], Abduction of the scapula [24.7%] and Downward Rotation Scapular [39.1%] muscle groups, RLB [33.5%], LLB [9.5%], and decrease in 10-Meter Walk Test [10MWT] [9.3%], [P<0.05]. The results of this study indicated this type of training can cause improvements in muscle strength and functional capacity in patients with multiple sclerosis
ABSTRACT
Multiple sclerosis [MS] typically affects young adults; however, the first symptoms can occur after age 50 and is classified as late-onset MS [LOMS]. In this retrospective study, we extracted the records of 3522 MS patients [2716 females and 806 males] registered in the Isfahan MS Society [IMSS] from 2003 to 2010. Next, we searched for LOMS cases. We aimed to compare these cases with 1698 non-LOMS subjects also extracted from the IMSS database. We found 48 LOMS patients [28 females and 20 males], which gave a crude frequency of 1.36%. The frequency by sex of LOMS in males [2.4%] was significantly greater than in females [1.0%, P = 0.002]. The mean age at onset was 55.1 +/- 4.3 years. The female to male ratio of 1.4:1 in these patients was significantly lower than in non-LOMS subjects [3.37:1, P= 0.003]. The leading pattern of MS was relapsing-remitting [RR] in 62.5%, followed by primary progressive [PP] in 27.1%, and secondary progressive [SP] in 10.4%. Predominant presenting symptoms and signs were motor disturbances [35.4%], followed by brainstem [25%], optic neuritis [22.9%], and sensory related deficits [18.7%]. The mean progression index [PI] in LOMS patients [0.88 +/- 0.48] was significantly higher than in non-LOMS cases, 0.37 +/- 0.17 [P< 0.0001]. In comparing LOMS patients with the non-LOMS cohort, there was a higher frequency of the PP pattern and a higher PI in the LOMS group. In comparing other high-risk populations with the Isfahan cohort, LOMS formed a lower percentage of the total Isfahan MS population
Subject(s)
Humans , Male , Female , Age of Onset , Retrospective StudiesABSTRACT
Early-onset multiple sclerosis [EOMS] is defined as the first presentation of symptoms in childhood [before the age of 16 years]. EOMS occurs in about 0.4% to 10.5% of multiple sclerosis [MS] patients. In this retrospective population-based study we aimed to describe the clinical/paraclinical details and frequency of epileptic seizures in Iranian EOMS patients registered with the Isfahan Multiple Sclerosis Society [IMSS] from April 2003 to July 2010. EOMS cases were extracted from the Isfahan total MS cohort and included 3522 patients. A total of 117 EOMS patients [19 males and 98 females] with a mean age at onset of 14.2 +/- 2.0 years [range: 7-16 years] were extracted from our database [3.3% of the total cohort]. Of cases, ten [one male and nine females] had experienced at least two epileptic seizures, providing a crude prevalence of 8.5%. The frequency of epilepsy in EOMS patients [3.3%, 10/117] was significantly greater [P < 0.001] than that of non-EOMS cohort [2.0%, 71/3405]. Epileptic seizures occurred before MS onset in two patients, after MS onset in seven, and at MS onset in one as the presenting symptom of the disease. Our findings mostly indicate an excessive prevalence of epileptic seizures in Iranian EOMS patients [8.5%], which is higher than any other report concerning seizures or epileptic seizures in a large MS series. These findings might be supportive of increased prevalence of epileptic seizures in EOMS
Subject(s)
Humans , Male , Female , Seizures , Epilepsy , Retrospective StudiesSubject(s)
Humans , Young Adult , Adult , Prevalence , Incidence , Multiple Sclerosis/etiology , Multiple Sclerosis/prevention & control , Age DistributionABSTRACT
The onset of multiple sclerosis in the majority of the cases occurs as a clinically isolated syndrome [CIS]. We sought to assess serum levels of 25-hydroxyvitamin D [25-OHD] in CIS patients and healthy controls. In this cross-sectional study 40 patients [36 women and 4 men] with CIS manifesting as a single isolated optic neuritis and 40 Age- and sex-matched healthy controls [35 women and 5 men] were enrolled between late October 2010 and early March 2011. General vitamin D deficiency was defined as serum 25-OHD levels of lower than 20 ng/ml and was classified as mild [15 < 25-OHD <20 ng/ml], moderate [8 < 25-OHD <15 ng/ml], and severe [25- OHD <8 ng/ml]. We found no difference in the median interquartile range [IQR] between CIS patients and controls [17.95 [10.40- 29.13] vs. 17.00 [12.25-31.00]; P=0.57]. However, when stratified by the levels of deficiency, among CIS patients a significantly higher proportion had severe vitamin D deficiency in comparison to healthy controls [20% vs. 2.5%; P=0.034]. Nevertheless, the frequency of general [62.5% vs. 60%, P=0.82], mild [25% vs. 30%, P=0.80], and moderate [17.5% vs. 27.5%, P=0.42] vitamin D deficiency were not different between the two groups. Our findings do not indicate any significant difference of serum 25-OHD between CIS patients and healthy controls. However, in our series severe vitamin D deficiency was more frequent among CIS patients.
Subject(s)
Humans , Male , Female , Adult , Vitamin D/blood , Vitamin D Deficiency , Optic Neuritis/blood , Multiple Sclerosis , Demyelinating Diseases/blood , Cross-Sectional StudiesABSTRACT
Optic neuritis [ON] can be the first presentation of multiple sclerosis [MS] or neuromyelitis optica [NMO]. Anti-aquaporin-4 IgG [AQP4 IgG] is a highly specific and moderately sensitive biomarker for NMO. This study was designed to assess the rate of seropositivity for AQP4 IgG, and the short-term outcome of patients presenting with single isolated ON [SION]. A cohort of 41 consecutive patients experiencing severe [< 20 / 200] SION [not fulfilling the diagnostic criteria for MS or NMO], was prospectively recruited. Blood sampling was carried out immediately after the diagnosis of ON, and AQP4 IgG was tested qualitatively, using an indirect immunofluorescence kit. After clinical and paraclinical investigations, all the patients were followed up for a short-term period of at least 18 months. The seroprevalence among the initial ON patients was 9.7% [4 / 41]. The short-term conversion rate to MS and NMO was estimated to be about 7.3 and 4.9%, respectively. The conversion rate to NMO in initially seropositive patients was greater than that for the whole cohort [2/4 [50%] vs. 2/41 [4.9%]; P = 0.035; Odds ratio: 19.5, 95% confidence interval: 1.73 to 219.50]. AQP4 IgG seropositive SION patients were more likely to develop NMO in comparison to the total SION population. Further studies, with a longer follow-up period and larger sample sizes are warranted to assess the clinical and prognostic value of assessing AQP4 IgG in SION
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To prospectively investigate the prevalence and clinical relevance of orthostatic hypotension [OH] in Parkinson"s disease [PD] in Isfahan, Iran. We investigated 150 consecutive patients with PD [42 women, 108 men] in Al-Zahra Hospital, Isfahan, Iran from January 2002 to January 2004. Blood pressure was measured first in a supine position following a rest of at least 10 minutes, and then after 3 minutes of active standing. Data concerning the age, gender, duration of disease, and drug consumption were recorded in a questionnaire. Orthostatic hypotension in PD is more frequent in women, patients taking a higher dose of levodopa, in higher age groups, and patients with longer duration of the disease, however, a statistically significant difference was seen in the female group and patients taking a higher dose of levodopa. Orthostatic hypotension is mainly related to PD pathology and the clinical relevance of OH to gender, age, and disease duration may be due to the natural course for progression of human autonomic dysfunction during life. Higher doses of levodopa may increase the risk of OH