Interferon beta-1a and atorvastatin in the treatment of multiple sclerosis

Background: statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects

Objective: to evaluate the effects of atorvastatin in combination with Interferon-[beta] in the treatment of multiple sclerosis [MS] in a randomized controlled clinical trial

Methods: multiple sclerosis patients were randomized independently, in a double blind design, into one of two treatment groups. Control group [n=45] received 30 [micro]g/week interferon [beta]-1a via intra-muscular injection. Atorvastatin-treated group [n=50] received interferon [beta]-1a similar to control group in addition to atorvastatin [40 mg/day] for 18-months. All clinical and immunological variables were measured at the baseline and at the end of the study

Results: there was no significant difference between the two groups in the expanded disability status scale scores and the number of gadolinium-enhancing lesions during the 18-month treatment period. After 18 months, the levels of interleukin [IL]-4, IL-10, transforming growth factor-[beta] and serum ferric reducing antioxidant power in the atorvastatin treatment group were significantly higher than the control group. Levels of IL-17, TNF-[alpha] and lymphocyte proliferation in the atorvastatin treatment group were significantly lower than the control group

Conclusion: although combined atorvastatin and interferon-[beta] do not change the clinical course of MS, atorvastatin might have beneficial effects in MS treatment possibly through inducing anti-inflammatory responses

Changes in Synaptic Transmission and Long-term Potentiation Induction as a Possible Mechanism for Learning Disability in an Animal Model of Multiple Sclerosis / 대한배뇨장애요실금학회지

PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It has been shown that memory deficits is common in patients with MS. Recent studies using experimental autoimmune encephalomyelitis (EAE) as an animal model of MS have shown that indicated that EAE causes hippocampal-dependent impairment in learning and memory. Thus far, there have been no in vivo electrophysiological reports describing synaptic transmission in EAE animals. The aim of the present work is to evaluate the synaptic changes in the CA1 region of the hippocampus of EAE rats. METHODS: To evaluate changes in synaptic transmission in the CA1 region of the hippocampus of EAE rats, field excitatory postsynaptic potentials (fEPSPs) from the stratum radiatum of CA1 neurons, were recorded following Schaffer collateral stimulation. RESULTS: The results showed that EAE causes deficits in synaptic transmission and long-term potentiation (LTP) in the hippocampus. In addition, paired-pulse index with a 120 msec interstimulus interval was decreased in the EAE group. These findings indicate that EAE might induce suppression in synaptic transmission and LTP by increasing the inhibitory effect of GABAB receptors on the glutamate-mediated EPSP. CONCLUSIONS: In conclusion, influence of inflammation-triggered mechanisms on synaptic transmission may explain the negative effect of EAE on learning abilities in rats.

diagnostic value of surface markers in acute appendicitis; a diagnostic accuracy study

Objective: To determine the diagnostic value of blood cells surface markers in patients with acute appendicitis

Methods: In this cross-sectional study, 71 patients who underwent appendectomy following a diagnosis of appendicitis were recruited during a one-year period. The patients were divided into two groups: patients with histopathologically confirmed acute appendicitis and subjects with normal appendix. Blood cell surface markers of all patients were measured. Univariate and multivariate analytical methods were applied to identify the most useful markers. Receiver operating characteristics [ROC] curves were also used to find the best cut-off point, sensitivity, and specificity

Results: Overall we included 71 patients with mean age of 22.6 +/- 10.7 years. Of the 71 cases, 45 [63.4%] had acute appendicitis while 26 [36.6%] were normal. There was no significant difference between two study groups regarding the age [p=0.151] and sex [p=0.142]. The initial WBC count was significantly higher in those with acute appendicitis [p=0.033]. Maximum and minimum area under the ROC curve in univariate analysis was reported for CD3/RA [0.71] and CD38 [0.533], respectively. Multivariate regression models revealed the percentage of accurate diagnoses based on the combination of gamma/delta TCR, CD3/RO, and CD3/RA markers to be 74.65%. Maximum area under the ROC curve [0.79] was also obtained for the same combination

Conclusion: the best blood cell surface markers in the prediction of acute appendicitis were HLA-DR+CD19, alpha/beta TCR, and CD3/RA. The simultaneous use of gamma/delta TCR, CD3/RA, and CD3/RO showed the highest diagnostic value in acute appendicitis

inhibitory effect of satureja khozestanica essential oil and carvacrol on nitric oxide production in macrophage cell line

Satureja Khozestanica is among the native Iranian plants which grow mostly in Lorestan and Khozestan. A number of reports show that Satureja plant possesses anti-inflammatory effects. The aim of this study is to determine the effects of Satureja Khozestanica essential oil on nitric oxide in the presence or absence of lipopolysaccharide in J774A.1 macrophage-like cell line. J774A.1 cells are cultured at a concentration of 10[6] cells per ml in RPMI 1640 medium with 10% fetal Bovin serum. Then, the cells were treated in the presence of lipopolysaccharide [1micro g/ml] containing 0.004%, 0.008%, and 0.016% doses of Satureja essential oil and 0.004, 0.008, and 0.016 macromolar of carvacrol over 12, 24, and 48 hours. Next, the level of nitric oxide in the cell culture supernatant was measured using Griess's technique. The results showed that Satureja Khozestanica extract significantly decreased the production of nitric oxide in J774A.1 macrophage cell line, dependent on dose and time. In addition, in the presence of lipopolysaccharide, Satureja Khozestanica extract inhibited the production of nitric oxide more effectively than carvacrol. The results demonstrate that Satureja Khozestanica essential oil is effective in lowering inflammation through inhibition of nitric oxide production. Therefore, this extract may be effectual in treatment of inflammatory diseases

Is CD19 an immunological diagnostic marker for acute appendicitis?

The appendix is considered as part of the gut-associated lymphoid tissue; however, lymphocyte subsets in this tissue are not fully defined. To investigate and compare the function and phenotype of lymphocyte subsets in peripheral blood and appendix of patients with normal and inflamed appendix tissues. Peripheral blood samples and appendiceal mononuclear cells were obtained from 81 patients [mean age; 23 +/- 10.5 years], clinically suspected of having appendicitis. The phenotypic characteristics of lymphocyte subsets in peripheral blood [before and 48-72 hrs after appendectomy] and in appendix tissue were analyzed by three color-flow cytometry. The proliferative response of mononuclear cells was assessed by MTT method. The frequency of CD19+DR+, HLA-DR+ and CD19+ cells in the appendix tissue were significantly higher than that of the peripheral blood in all the groups [p<0.001]. The percentage of CD19+ cells and HLA-DR+CD19+ cells significantly decreased after appendectomy in the peripheral blood of the patients with acute appendicitis [p=0.047 and p=0.03, respectively]. CD19 and HLA-DR plus CD19 had better diagnostic efficiency compared with T cell markers [area under the ROC curve [AUC]= 0.76 and 0.73, respectively]. These results indicate a significant difference in CD19+ and HLA-DR+ lymphocytes between peripheral blood and the appendix tissue.

effect of opium dependency on testis volume: a case-control study

Given the paucity of data on possible testis changes in opioid dependents, we sought to compare the testis volumes between a group of opium dependents and a group of healthy controls. Comparison of testis volume between opium dependents and healthy controls. This case-control study recruited 100 men with opium dependency [cases] and 100 healthy men [controls] in Iran, in 2008. A checklist containing questions about age, height, weight, daily amount of cigarette use, and duration of cigarette use for all the participants as well as daily amount of opium use [grams] and duration of opium use [years] for the case group was completed. Additionally, the dimensions of each testis were measured by a single person using calipers, and the mean of the left and right testes volume was compared between these two groups. The mean of the testis volumes in the case group was significantly lower than that of the case group [11.2 +/- 2.2 and 25.1 +/- 2.7cm[3], p<0.001]. The results of the ANCOVA test showed that even after the omission of the cigarette smoking effect [p=0.454], the testis volume remained lower in the opium dependents [R[2]=0.884, p<0.001]. In the case group, there were significant reverse correlations between testis volume and age [r=-0.404, p<0.001], daily amount of opium use [r=-0/207, p=0.039] and duration of opium use [r=-0.421, p<0.001]. We found that the testis volume in the male opium dependents was lower than that of the healthy controls. We would recommend that future studies into the impact of drugs on the testis dimensions pay heed to possible histological changes in the testes owing to opium dependency

Therapeutic effects of all-trans retinoic acid on experimental autoimmune encephalomyelitis and its role in T-helper lymphocyte responses

Recent studies have demonstrated an essential role for IL-17 in the pathogenesis of experimental autoimmune encephalomyelitis [EAE]. Furthermore, it has been shown that FoxP3+Treg cells play an important role in the suppression of auto inflammatory reactions. Although, previous studies have determined the immunomodulatory potentials of all-trans-retinoic acid [ATRA], but these immunomodulations have been mostly justified by alteration in Thl/Th2 cytokines. The present study was carried out to investigate the therapeutic effects of ATRA on EAE and its effects on T-helper cells responses. EAE was induced by MOG[35-55] peptide and complete Freund's adjuvant in female C57BL/6 mice. The mice were allocated to two therapeutic groups [n=7 per group]. Treatment with ATRA [500 microg/mouse; every other day] was initiated in treatment group on day 12 when they developed a disability score. EAE controls received vehicle alone with the same schedule. Signs of disease were recorded daily until day 33 when the mice were sacrificed. Splenocytes were tested for proliferation by MTT test, cytokine production by ELISA and FoxP3[+] reg cell frequency by flowcytometry. ATRA significantly reduced the clinical signs of established EAE. Aside from decreasing lymphocytic proliferation [P<0.05], ATRA significantly inhibited the production of pro-inflammatory IL-17 [P<0.005] as well as IFN-gamma [P<0.0005] upon antigen-specific restimulation of splenocytes. FoxP3+Treg cell frequency and IL-10 levels were not altered significantly. However, IFN-gamma to IL-10 and IL-17 to IL-10 ratios decreased significantly [P<0.0005]. Parallel to reducing autoreactive lymphocyte proliferation and cytokine production in favor of pro-inflammatory cytokines, all-trans-retinoic acid ameliorated established experimental autoimmune encephalomyelitis

[Design of enzyme-linked immunosorbent assay method for detection of anti-streptolysin-O antibodies on base of recombinant streptolysin-O]

Group A, beta hemolytic streptococci are among the major causative agents of otorhinolaryngology infections. Inadequate treatment of disease may lead to serious disorders such as acute rheumatic fever and glomerulonephritis. Anti-streptolysin-O [ASO] is commonly used as a marker in the diagnosis of infection. Purification of native streptolysin-O has several difficulties and its industrial production process is time consuming with very low yield and the risk of biological contamination. In this study, we used a recombinant streptolysin-O protein as an antigen to detect ASO antibodies in enzymes-linked immunosorbent assay [ELISA]. We amplified streptolysin-O gene by polymerase chain reaction [PCR] method and subcloned in prokaryotic expression vector PET28a. E.coli. BL21-DE3-plySs strain was transformed with PET28a-streptolysin-O and gene expression was induced by IPTG. ELISA microplates were coated with different concentration of streptolysin-O protein. Level of ASO antibodies were detected by ELISA method. The results obtained from ELISA method were compared with inhibition of hemolysis assay as a standard method. The results showed that there is a positive significant correlation between the ELISA and inhibition of hemolysis method[r=0.97, p=0.0001]. The sensitivity and specificity of ELISA for detection of ASO anti bodies were 100% and 83%, respectively. ELISA developed with recombinant streptolysine O showed a good sensitivity for detection of ASO antibodies. It is suggested that this method could be suitable for immunoassays

Spleen and liver dendritic cells differ in their tolerogenic and cytokine induction potential

Dendritic cells [DCs] play an important role in induction of cellular immune responses. It seems that DCs that reside in different organs may be distinct in their ability to induce immune responses. This study was done to address the differences between spleen and liver DCs in induction of immune response and/or tolerance. CD11c+ DCs were separated from the liver and spleen of C57BL/6 mice and pulsed with myelin oligodendrocyte glycoprotein [MOG] peptide 35-55. 6[5]105 MOG35-55 pulsed spleen or liver DCs were injected in foot pad of different groups of mice. Control groups received unpulsed DCs. After 5 days, the mononuclear cells [MNCs] of the regional lymph nodes were isolated from immunized mice for cytokine assays and lymphocyte transformation test. To study the immunologic or tolerogenic effects of DCs, three weeks after immunization of mice with MOG pulsed liver or spleen DCs, experimental autoimmune encephalomyelitis [EAE] was induced in DC-immunized mice by injection of MOG along with complete Freund's adjuvant. Our results showed that spleen DCs were more potent in stimulating lymph node T cells as illustrated in lymphocyte transformation test. Moreover IL-10 production was higher in mice immunized with liver DCs compared with those immunized with splenic DCs [p=0.017]. However, no significant difference in IFN-8 production was observed between two groups. We also found that liver DCs+MOG immunized mice displayed a significantly delayed disease onset compared with spleen DCs+MOG immunized mice and the control groups. The disease score was also milder in liver DCs immunized mice compared with other groups. It seems that the higher IL-10 production induced by the liver DCs may be one of the main factors in down regulation of immune responses in this organ. It can be concluded also that the liver DCs may inhibit the progress of EAE by shifting the cytokines profile