Immunosuppressive Effects of Two Probiotics, Lactobacillus paracasei DSM 13434 and Lactobacillus plantarum DSM 15312, on CD4+ T Cells of Multiple Sclerosis Patients.

T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor ß (TGF-ß), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-ß and IFN-γ were not significantly different among any of the study groups.  Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.

The Frequency of CD4+ T Cells in Women with Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disease, and there is no definitive treatment available for this disease. To find the appropriate therapeutic approach, it is necessary to determine the mechanism of this disease. To achieve this purpose, the frequency of CD4+ T cells was evaluated in patients with HT and compared with healthy individuals. METHODS: Twenty-six female patients with HT, aged 20 - 45 years, enrolled in this study. Based on the level of thyroglobulin antibody (anti-TG) and anti-thyroid peroxidase antibody (anti-TPO) in serum of patients with HT, they were divided into two groups. The serum level of anti-TPO was above 100 IU/mL in the group 1 (n = 13), whereas the serum levels of both anti-TPO and anti-TG were above 100 IU/mL in the group 2 (n = 13). Eleven healthy women were considered control group, or group 3. Using flow cytometry, the frequency of T helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), and LT CD4+IL-4+IL-17+ cells and mean fluorescent intensity (MFI) of their related cytokines were evaluated. RESULTS: The frequency of Th2 cells in the groups 1 (anti-TPO > 100) and 2 (anti-TPO > 100 and anti-TG > 100) were more than control group. Only the difference between groups 3 (healthy control) and 2 was significant (P = 0.022). The frequency of LT CD4+IL-4+IL-17+ cells in the group 1 was significantly more than group 3 (P = 0.027); However, the difference between group 2 and 3 was not significant (P = 0.126). The expression of interferon-gamma (IFN-γ) in the group 2 (P = 0.001) and group 1 (P = 0.001) was significantly higher than group 3. The frequency of Th17, Th1, and Tr1 cells and MFI of IL-17 and IL-10 were not significantly different between the study groups. CONCLUSIONS: In the present study, no significant differences were observed in the frequency of Th17 and Tr1 cells and in MFI of IL-17 and IL-10 in comparison to healthy individuals. Therefore, trying to make a change in the population of these cells probably does not have a significant therapeutic effect. Since Th2 cells and the expression of IFN-γ increased in women with HT, reducing the frequency of Th2 cells or the expression of IFN-γ may be effective in controlling the disease progression. It may be helpful for these patients to prevent the progression of the disease.

Effects of vitamin D supplements on frequency of CD4+ T-cell subsets in women with Hashimoto's thyroiditis: a double-blind placebo-controlled study.

BACKGROUND: Vitamin D is a modulator of immune functions. Investigations on the mechanisms of vitamin D action and pathogenesis of Hashimoto's thyroiditis (HT) have revealed that vitamin D can reduce damages to thyroid cells caused by autoreactive immune cells. METHODS: Totally, 48 female patients with HT disease were introduced to the study by endocrinologists. Patients were divided into two major groups of 24 individuals and treated weekly with 50,000 IU of cholecalciferol (vitamin D group) or placebo (placebo group) using oral administration for 3 months. Eventually, 17 of the 24 patients in each group finished the study. Before and after supplementation, frequencies of Th1, Th17, Th2 and Tr1 cells and mean fluorescent intensity (MFI) of the associated cytokines, including IFN-γ, IL-17, IL-4 and IL-10, were assessed using flow cytometry. Furthermore, gene expression of IL-10 was assessed using real-time PCR. RESULTS: Results of this study showed that cholecalciferol supplementation caused a significant decrease in Th17/Tr1 ratio. The proportion and MFI of Th1, Th2, Tr1 and Th17 cells included no significant changes in vitamin D group, compared to those in placebo group. Expression rate and MFI of IL-10 increased in both groups. This increase was higher in vitamin D group than placebo group with no significance. CONCLUSIONS: In this novel preliminary clinical trial study, supplementation with cholecalciferol in HT patients for 3 months changed the balance of CD4+ T-cell subsets to improve the disease control. However, further studies are necessary to investigate effects of vitamin D on immune functions in HT patients.

Investigation of Intertriginous Mycotic and Pseudomycotic (Erythrasma) Infections and Their Causative Agents with Emphasize on Clinical Presentations.

BACKGROUND: Intertrigo is an erythematous inflammatory condition with multiple etiologies including fungi and bacteria. Intertrigo manifests in different clinical forms with various complaints. This study was conducted to evaluate the causative agents of intertriginous infections with emphasize on clinical presentations. METHODS: This descriptive cross-sectional study was carried out in 2015-2016, on 188 patients with clinical suspicion of superficial and cutaneous intertriginous infections in Tehran, Iran. Demographic and additional related data were obtained by questionnaire from all participants. Specimens were collected by gentle scraping of the affected areas. Direct examination and culture were performed for all specimens and grown colonies were identified based on the macroscopic and microscopic features. Supplementary tests were done whenever needed. Data were analyzed in SPSS. RESULTS: Overall, 80 (42.5%) cases with the mean age of 43.5 yr were confirmed for intertrigo. Dermatophytosis was the predominant cause in this study with 36 (45%) cases followed by erythrasma (28 cases, 35%), tinea versicolor (10 cases, 12.5%) and candidiasis (6 cases, 7.5%). Intertrigo lesions with dermatophytic agents significantly were observed in groin in comparison to different infections among body sites (P<0.05). Itching was the most common clinical presentation (57 cases, 71.3%) and also significant association between different infections and clinical manifestations were observed (P<0.05). CONCLUSION: Different clinical manifestations may be observed in infectious intertrigo. Regarding the significant association observed in this study, some clinical features can be used for presumptive diagnosis of diseases but further studies are required to make it clear.

Comparison of three modes of aerobic exercise combined with resistance training on the pain and function of patients with knee osteoarthritis: A randomized controlled trial.

OBJECTIVES: To investigate the effects of three modes of aerobic exercise (lower limbs with and without weight bearing and upper limb) for knee osteoarthritis. DESIGN: Randomized controlled trial. SETTING: Sports medicine clinic. PARTICIPANTS: Seventy-eight patients with knee osteoarthritis were divided into 3 groups of resistance training combined with one of three programs of treadmill, cycle ergometer, or arm ergometer aerobic training. MAIN OUTCOME MEASURES: Pain (VAS), patients' opinion about knee status (KOOS questionnaire), and functional performance [6 min walk test (6MWT), timed up and go test (TUG) and chair stand test]. RESULTS: After 8 weeks, all groups showed significant improvement in the VAS, KOOS and functional tests. After adjusting for baseline characteristics, the change in VAS was significantly higher in arm ergometer than in treadmill group (P = 0.03). Change in TUG was significantly higher in treadmill than arm ergometer group (P = 0.02). Also, the change of function in sport and recreation (a KOOS dimension) was significantly higher in arm ergometer compared to treadmill group (P = 0.04). CONCLUSION: All modes of aerobic exercise combined with resistance training led to reduced pain and improved function. Nevertheless, arm ergometry may provide greater pain relief and sport performance; while treadmill may cause greater improvement in TUG.

Cerebral Oxygenation Under General Anesthesia Can Be Safely Preserved in Patients in Prone Position: A Prospective Observational Study.

BACKGROUND: The effects of prone position (PP) on cerebral tissue metabolism are not well known. The aim of this investigation was to evaluate regional cerebral oxygen desaturation in patients undergoing lumbar spine surgery in PP during routine anesthesia management. MATERIALS AND METHODS: Between July 2013 and October 2013, 50 consecutive patients undergoing lumbar spine surgery under general anesthesia in PP were enrolled. The anesthetic technique was standardized. Using near-infrared spectroscopy, bilateral regional cerebrovascular oxygen saturation was recorded during the surgery. RESULTS: After 30 and 60 minutes of prone repositioning, significant decreases in bilateral regional cerebral oxygen saturation were observed compared with the values in the supine position (from 76.24% to 73.18% at 30 min and 72.76% at 60 min on the right side and from 77.06% to 73.76% at 30 min and 72.92% at 60 min on the left side; P<0.05). These changes were not clinically important and returned to supine values after 90 minutes of prone positioning. Decreases in cerebral oxygen saturation were accompanied by reductions in heart rate and mean arterial pressure (P<0.05). Older age and higher perioperative risk had a significant effect on the reduction of cerebral oxygen values (P<0.05). CONCLUSIONS: The results of our study show that margin of safety against impaired cerebral oxygenation can be maintained in PP. Preventing bradycardia and arterial hypotension is crucial. Older patients and those at higher perioperative risk need more meticulous attention.

A Novel Combination of Docosahexaenoic Acid, All-Trans Retinoic Acid, and 1, 25-Dihydroxyvitamin D3 Reduces T-Bet Gene Expression, Serum Interferon Gamma, and Clinical Scores but Promotes PPARγ Gene Expression in Experimental Autoimmune Encephalomyelitis.

Vitamins are immunologically interesting due to their significant immunomodulatory activities. Experimental autoimmune encephalomyelitis (EAE) is one of the most commonly used experimental models for studying autoimmune disorder in multiple sclerosis (MS). The aim of this study was to evaluate the protective and ameliorative effects of novel combination of all-trans retinoic acid (ATRA), 1,25-dihydroxyvitamin D3 (D3), and docosahexaenoic acid (DHA) on EAE-specific determinants and target gene expressions. Mice were randomly categorized into three groups before EAE induction [non-treated EAE (Group E), treated EAE (Group T), and healthy mice (Group H)]. Encephalomyelitis was induced in female C57BL/6 mice by subcutaneous immunization using commercial kits. Preceding day of EAE induction, combination of ATRA, D3, and DHA was administered with a single IP injection every 48 h and continued until day 26. Findings of present study showed that administration of vitamins A, D, and DHA significantly decreased average clinical scores, cumulative EAE score, and EAE incidence in Group T, compared to Group E (p values <0.001). Interferon γ secretion in serum and T-bet mRNA expression in splenocytes were significantly reduced (p = 0.004, p = 0.029, respectively) while PPARγ mRNA expression was significantly increased in Group T compared to Group E (p = 0.021). These findings highlighted that ATRA, D3, and DHA combination modulated PPARγ and T-bet gene expression and resulted in decrease in Th1 response and lymphocyte invasion into the central nervous system (CNS) and resultant inflammation. In conclusion, the results of this study suggested the potential use of this intervention in treatment and/or prevention of EAE/MS and probably other Th1 cell-mediated autoimmune diseases.