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Background: Multiple sclerosis (MS) is a chronic, typically progressive and most common autoimmune disease which damaged the central nervous system. According to the reports in 2008, this disorder has affected 2 and 2.5 million people globally. While the reason is not clear, proposed causes for this include immunologic, environmental, infectious and genetic factors, and sexuality. MS can cause many symptoms, including blurred vision, loss of balance, poor coordination, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, paralysis, blindness, and more. There are four distinguished illness fields in MS: relapsing-remitting MS (RRMS), primary–progressive MS (PPMS), secondary–progressive MS (SPMS), and progressive–relapsing. MRI is a great tool to identify the asymptomatic distribution of lesions in space and time. Materials and Methods: 32 patients with MS plaques were evaluated by FLAIR and DWI pre- and post-Gadolinium injection compared with 15minutes delay T1w SE. Results: FLAIR post-inject had significantly better detection of the number and signal intensity of active MS lesions. DWI and ADC images detected active plaques different from non-active lesions without contrast. Conclusion: The result of this study showed that FLAIR post-inject had the highest sensitivity in detection of active MS lesions due to the CSF signal suppression in FLAIR, thus offering enough TR time recovery in active enhanced plaques.

Background: Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. This study evaluated the clinical efficacy of immunotherapy with extracts of common aeroallergens North-East of Iran in asthma and allergic rhinitis. Material and Methods: In this prospective study 156 cases were chosen randomley. The mean age of patients was 37 years (range 5-65 years). The patients with mild to moderate asthma and allergic rhinitis and history of atopy were selected for immunotherapy when they showed no effective response to medical treatment.Immunotherapy materials were made from common aeroallergens in north-eastern region of Iran by Dome Hollister US company. Immunotherapy schedule for injection of the extract with vial dilution of 1:10000pg was one injection every week for ten weeks and one injection with dilution of 1:1000pg every other week for the other ten weeks and one injection monthly from dilution of 1:100pg for two years. Results: One hundred twenty (77%) of cases had allergic rhinitis 29(18.5%) cases had allergic asthma and 7(4.5%) cases were mixed. Mean age of patients were 37 years old. 48(30.8%) cases were male. Analysis of efficacy of treatment showed that immunotherapy significantlyimproved the signs and symptoms of all the groups. In allergic rhinitis group 84(70%) cases completely improved, 22(18.4%) patients moderately responded and no response to immunotherapy was observed in 14(11.6%) patients. In allergic asthma group, 22(75%) cases completely improved 4(13.6%) cases moderately responded and no response to immunotherapy was detected in 3(11.4%) cases. In mixed group, 3(42.8%) cases completely improved, 3(42.8%) cases moderately responded and no response was observed in 1(14.4%) case. Conclusion: Specific allergen immunotherapy for patients with allergic persistent mild to moderate asthma and moderate to severe allergic rhinitis without good response to medical treatment is highly recommended. It is recommended as effective treatment in such patients. [ABSTRACT FROM AUTHOR]

Background and the purpose of the study: The use of highly sulfated cyclodextrins (HS-CDs) as chiral selectors in capillary electrophoresis (CE) has been examined for rapid and reproducible enantioseparation of the model drug amlodipine, a calcium channel blocker. Materials and Methods: Fused silica capillaries with an inner diameter of 50 µm, and a total length of 45.5 cm (8.5 cm to the detector) were used. Capillaries were rinsed with polyethylene oxide (PEO) once daily. A systematic method development approach was conducted by modifying selected parameters such as the type and concentration of the chiral selector, the buffer pH and concentration of the background electrolyte. Results: Baseline separation was achieved at low (i.e. 0.05%w/v) concentrations of HS-αCD, but migration time and peak area repeatability were more than 4% and 25% of the relative standard deviation (RSD), respectively. At higher concentrations (>0.3%) of HS-αCD, amlodipine was transported to the anode by the carrier ability of HS-αCD. In carrier mode, the migration order of enantiomers was reversed, the migration time was reduced and the peak area repeatability of analysis was improved. The optimum electrophoretic conditions for the stereoselective analysis of amlodipine were obtained in carrier mode with 25 mM sodium phosphate buffer containing 1.25% w/v of HS-αCD at pH 2.5 with an applied voltage of +15 kV. Under these conditions migration time was less than 3 min and within-day migration time and peak area repeatability, were less than 0.4% and 2.1% RSD, respectively. Conclusions: Rapid enantioseparation was achieved with minimum variation in quantitative analysis. These optimized conditions are appropriate for the enantioselective analysis of amlodipine. [ABSTRACT FROM AUTHOR]

"nBackground: Ekiri syndrome or lethal toxic encephalopathy is a complication of shigellosis with dysentery, hyperpyrexia, seizures, headache and altered level of consiousness, which rapidly progresses to death. These children die at the beginning of the disease (8-48 hours from the beginning of symptoms), from brain edema. However they had no symptoms or signs of sepsis, dehydration, DIC or Hemolytic Uremic Syndrome (HUS). "nMethods: This survey is a case series study of children with Ekiri syndrome in Bahrami hospital from October 1998-2008 presented with loss of consciousness, colitis and high fever shortly after admission. Information about the patients was gathered from the documents according to physical signs and symptoms, lab data of those whom Ekiri syndrome had been diagnosed for them. Studied variables in this assessment were age, sex, fever, convulsions and loss of consciousness. Headache, encephalopathy, dehydration, elevated ICP, colitis, underline disease, stool, blood and CSF cultures. "nResults: The subjects contain 13 cases (10 male, 3 female), averaged 30/5 months of age. All had seizure, elevated ICP, encephalopathy and coma. All of the patients had fever between 39 and 40, averaged 39.5 degree of centigrade. Seven patients had headache and three ones was dehydrated. The first presentation symptom in three patients was gastroenteritis, in 9 was siezure and in 1 patient was headache. Stool culture in all patients was positive, but blood culture was positive in only one of them. CSF culture was negative in all of the patients. Mortality was 100%. "nConclusion: Symptoms, signs and presentation of Ekiri syndrome, a rare complication of infection with shigella, in the patients in Bahrami hospital was similar with the other studies beforehand in other countries. In this study, all the patients were died and supportive treatments were ineffective.

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses., Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings., Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID., Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008)., Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders., Method: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing., Results: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort., Conclusions: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

Background: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders (PID), with a broad spectrum of clinical features ranging from severe and recurrent infections to asymptomatic disease., Objectives: The current study was performed to evaluate and compare demographic and clinical data in the most common types of PAD., Materials and Methods: We performed a retrospective review of the medical records of all PAD patients with a confirmed diagnosis of common variable immunodeficiency (CVID), hyper IgM syndrome (HIgM), selective IgA deficiency (SIgAD), and X-linked agammaglobulinemia (XLA) who were diagnosed during the last 30 years at the Children's Medical Center, Tehran, Iran., Results: A total number of 280 cases of PAD (125 CVID, 32 HIgM, 63 SIgAD, and 60 XLA) were enrolled in the study. The median (range) age at the onset of disease in CVID, HIgM, SIgAD, and XLA was 2 (0-46), 0.91 (0-9), 1 (0-26), and 1 (0-10) years, respectively. Gastrointestinal infections were more prevalent in CVID patients, as were central nervous system infections in XLA patients. Autoimmune complications were more prevalent in HIgM patients, malignancies in CVID patients, and allergies in SIgAD patients. The mortality rate for CVID, HIgM, and XLA was 27.2%, 28.1%, and 25%, respectively. No deaths were reported in SIgAD patients., Conclusions: SIgAD patients had the best prognosis. While all PAD patients should be monitored for infectious complications, special attention should be paid to the finding of malignancy and autoimmune disorders in CVID and HIgM patients, respectively.

Background: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers., Methods: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006., Results: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %)., Conclusions: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.

Every year a large number of new cases of colorectal cancer are diagnosed in the world. Application of Epirubicin (Epi) in treatment of cancer has been limited due to its cardiotoxicity. Specific delivery of chemotherapy drugs is an important factor in reducing the side effects of drugs used in chemotherapy. Enhanced permeability, retention effect and magnetic resonance (MR) traceability of super paramagnetic iron oxide nanoparticles (SPION) make them a great candidate in cancer therapy and imaging. In this study, Epirubicin-5TR1 aptamer-SPION tertiary complex was evaluated for the imaging and treatment of murine colon carcinoma cells (C26 cells, target). For cytotoxic studies (MTT assay), C26 and CHO-K1 (Chinese hamster ovary cells, nontarget) cells were treated with either Epi or Epi-Apt-SPION tertiary complex. Internalization was evaluated by flow cytometry. Finally, Apt-SPION bioconjugate was used for imaging of cancer in vivo. Flow cytometric analysis showed that the tertiary complex was internalized effectively to C26 cells, but not to CHO-K1 cells. Cytotoxicity of Epi-Apt-SPION tertiary complex also confirmed internalization data. The complex was less cytotoxic in CHO-K1 cells when compared to Epi alone. No significant change in viability between Epi- and complex-treated C26 cells was observed. Magnetic resonance imaging (MRI) indicated a high level of accumulation of the nano-magnets within the tumor site. In conclusion Epi-Apt-SPION tertiary complex is introduced as an effective system for targeted delivery of Epi to C26 cells. Moreover this complex could efficiently detect tumors when analyzed by MRI and inhibit tumor growth in vivo., (Copyright © 2013 Elsevier B.V. All rights reserved.)

An important goal for drug development within the pharmaceutical industry is the application of simple methods to determine human pharmacokinetic parameters. Effective computing tools are able to increase scientists' ability to make precise selections of chemical compounds in accordance with desired pharmacokinetic and safety profiles. This work presents a method for making predictions of the clearance, plasma protein binding, and volume of distribution for alkaloid drugs. The tools used in this method were genetic algorithms (GAs) combined with artificial neural networks (ANNs) and these were applied to select the most relevant molecular descriptors and to develop quantitative structure-pharmacokinetic relationship (QSPkR) models. Results showed that three-dimensional structural descriptors had more influence on QSPkR models. The models developed in this study were able to predict systemic clearance, volume of distribution, and plasma protein binding with normalized root mean square error (NRMSE) values of 0.151, 0.263, and 0.423, respectively. These results demonstrate an acceptable level of efficiency of the developed models for the prediction of pharmacokinetic parameters.

Clinical administrations of anthracyclines are limited by cardiotoxicity and myelosuppression. Targeted delivery of anticancer agents is especially important in reducing their side effects. In this work, A10 (Apt), an aptamer for prostate-specific membrane anytigen (PSMA), was applied for targeted delivery of Epirubicin (Epi) to LNCaP cells (PSMA(+)). Flow cytometry analysis showed that PEG-Apt-Epi complex was internalized effectively to LNCaP cells (PSMA(+)), but not to PC3 cells (PSMA(-)). This fact was confirmed by less cytotoxicity of PEG-Apt-Epi complex in PC3 cells in comparison with Epi alone. No significant change in viability between Epi- and complex-treated LNCaP cells was observed. In conclusion, PEG-Apt-Epi complex is an efficient and simple system for specific delivery of drug to PSMA-expressing cell lines.

In chiral and non-chiral electrophoretic resolution of basic drugs, adsorption of analytes to negatively charged capillary wall could lead to poor repeatability of migration time and peak area. In addition, chiral resolutions of basic drugs are commonly performed in low pH buffers. Therefore, longer analysis time due to suppression of electroosmotic flow (EOF) is another dilemma. In this work the improvement effect of polybrene (PB), a cationic polymer, on chiral separation of a model basic drug, amlodipine (AML), was investigated. PB both as a semi-permanent coating agent and as an additive in the running buffer was utilized. Better results were obtained with PB as a buffer additive. Compare to untreated bare silica without using PB in running buffer, addition of 0.0005% PB buffer decreased analysis time downed to 3 folds; efficiency improved up to 5 folds; limit of detection (LOD) and limit of quantification (LOQ) downed to 8 folds and within-day migration time and peak area repeatabilities, in terms of relative standard deviations (RSD) downed to 5 and 20 folds, respectively.