ABSTRACT
Background: Sulfite oxidase deficiency [SOD] is a rare neurometabolic inherited disorder causing severe delay in developmental stages and premature death. The disease follows an autosomal recessive pattern of inheritance and causes deficiency in the activity of sulfite oxidase, an enzyme that normally catalyzes conversion of sulfite to sulfate
Aim of the study: SOD is an underdiagnosed disorder and its diagnosis can be difficult in young infants as early clinical features and neuroimaging changes may imitate some common diseases. Since the prognosis of the disease is poor, using exome sequencing as a powerful and efficient strategy for identifying the genes underlying rare mendelian disorders can provide important knowledge about early diagnosis, disease mechanisms, biological pathways, and potential therapeutic targets
Patients and methods: In this study, a case who was a newborn infant boy with suspected SOD and his healthy parents were recruited for exome sequencing. The first laboratory reports of the patient were positive urine sulfite, elevated urinary thiosulfate, and high levels of plasma lactate and pyruvate. The patient also presented some symptoms such as intractable seizures, abnormal tone, feeding difficulties, profound mental retardation, abnormal respiratory drive, aspiration pneumonia, microcephaly, and dislocated ocular lenses. The genomic DNA of the patient and his parents was extracted from peripheral blood lymphocytes as targets for exome sequencing, performed by Axeq Technologies [Amsterdam, the Netherlands]
Results: The results showed no single predominate mutation in the SUOX gene as one of the candidate genes involved in the catabolism of sulfur-containing amino acids. The same results obtained in the molybdenum cofactor biosynthetic genes [MOCS1, MOCS2, and GEPH genes]. Instead, the results revealed that causal variations are present in genes underlying in different biochemical pathways among which the sulfur metabolism, signaling and signal transduction, and transcription pathways are of higher importance
Conclusion: In this study, several classes of genes were introduced as candidate genes involved in SOD. However, further studies are necessary to examine the reported genes in more details on how these genes may relate to each other and contribute to the pathology of SOD disease
Subject(s)
Humans , Male , Infant , Sulfite Oxidase/deficiency , Exome , Sequence Analysis , MutationABSTRACT
Background: Migraine consisting of migraine with aura [MA] and migraine without aura [MO] is a painful neurovascular disorder affecting approximately 16% of the general population. A combination of genetic and environmental factors is involved in the pathogenesis of migraine. The MTHFR enzyme is involved in homocysteine [Hcy] metabolism and it has been reported that 1298 A to C and 677 C to T mutations in the MTHFR gene are associated with an increased in plasma Hcy levels. Hcy is a highly reactive amino acid and causes endothelial injury. Because a plausible theory about vascular impairment in migraine, it is considered that mutations in MTHFR gene and folate metabolism are associated with migraine
Materials and Methods: in total, 75 patients with migraine [24 with MA and 51with MO] in accordance with the IHS criteria participated in this case-control study. Control group were 128 normal matched healthy subjecys who selected from same region without history of migraine or other neurologic disorder after interviewing and examining by a physician. Mean age at entry was 36.42+/-9.6 and 31.64+/-8.9 years old in migraine and control group respectively. MTHFR polymorphisms were investigated by PCR-RFLP
Results: genotypic results indicated that the prevalence of the MTHFR 677TT genotype in migraine subjects was higher than control [17.3% and 3.1% respectively, P<0.001]. Interestingly the risk of migraine was 6-fold higher in subjects possessing the MTHFR 677T homozygous variant [OR=6.5; CI95%: 2.03-20.76]. No significant difference in the prevalence of MTHFR A1298C genotypes was observed in migraine group when compared to controls [P>0.001]
Conclusion: it seems that MTHFR C677T is a potential genetic risk factor for migraine attacks, both in MA and MO subclasses in Iranian population. C677T and A1298C joint effect could amplify the potential influence of each SNPs
ABSTRACT
Molecular imprinting is a method for synthesizing polymers with structure-selective adsorption properties with applications such as, selectivity binding, drug delivery systems and anti-bodies. The present study aims at optimizing the preparation of molecularly imprinted polymer [MIP] against 1-phenylalanine, in order to increase phenylalanine-binding in Enzymatic Intestinal Simulated Fluid [ESIF]. The MIP for 1-phenylalanine, as a water-soluble template, was successfully synthesized without derivatization. Synthesization was done by a UV polymerization method in which methacrylic acid [MAA], as a functional monomer, and ethylene glycol dimethacrylate [EGDMA], as a cross-linker, were used in the presence of five different porogenic solvents including; acetonitrile, tetrahydrofuran [THF], chloroform, toluene and dimethyl sulfoxide [DMSO]. The selectivity of the MIP was examined using 19 different amino acids in human serum and was evaluated by HPLC. In addition, morphological studies were conducted using SEM. The results showed that the obtained MIP with acetonitrile had the highest capacity and selectivity compared with other solvents. The data indicated that Phe-binding to MYS was significantly more than the former binding to NIP in EIS1 [p<0.05]. Moreover, in comparison wthNIP and control grouf MIP showed abetter selectivity and binding for Phe. This could be used for the reduction of Phe in human serum samples of Phenylketonuria. Our findings suggest that the MIP against PI prepared with acetonitrile, showed a good selectivity ai binding, which caused a reduction of blood Phe concentrati in enzymatic simulated intestinal fluid and human serum sam] of Phenylketonuria
ABSTRACT
Increased vascular stiffness is a marker of atherosclerosis, which is diagnosed in the early stages of diabetes II. Matrix metalloproteinases [MMPs] and their tissue inhibitors [TIMPs] are a family of proteolytic enzymes necessary for structure and function of great vessels. This study examined the effects of 8 weeks of aerobic exercise on MMP9 and TIMP-1 levels in type II diabetic women. This is a quasi-experimental study which included 20 in type II diabetic women with mean age of 53.2 +/- 2.5 years, body mass index [BMI] of 28.73 +/- 2.27 and fat percentage of 30.6 +/- 2.05, who were randomly divided into two groups: aerobic exercise group [8 weeks, 3 sessions per week for 50 minutes] and control group. To examine changes in MMP[9] and TIMP-1, 5 ml of blood was taken from the brachial vein of patients before and 48 hours after completion of exercise period and after 12 hours of fasting at rest. Data analysis was performed using SPSS-16 software with the independent and paired t-tests. A significant decrease was observed in body mass index and body fat percentage in the experimental group [p<0.05]. Compared with the control group, the aerobic exercise group showed a significant decrease in MMP[9] [p=0.01] and a significant increase in TIMP-1 levels [p=0.02] after 8 weeks of aerobic exercise. The results showed that aerobic exercise as a stimulus can change the levels of matrix metalloproteinases and their tissue inhibitors in order to prevent cardiovascular diseases in diabetics
ABSTRACT
Oligodendrocytes, the myelinating glial cells of central nervous system, are highly vulnerable to ischemic-induced excitotoxic insult, a phenomenon in which calcium overload triggers cell death. Berberine is an alkaloid extracted from medicinal herbs as Coptidis Rhizoma with several pharmacological effects like inhibition of neuronal apoptosis in cerebral ischemia. We examined the effects of berberine [0.5-4 microM] and glutamate receptors antagonists [MK-801 [10 microM] and NBQX [30 microM] on OLN-93 cell line [a permanent immature rat Oligodendrocyte] during [30, 60, 240 min] oxygen-glucose deprivation [OGD]/24 h reperfusion. The cells were cultured in 12-well plates. The cells were exposed to glucose-free medium and hypoxia in a small anaerobic chamber. Cell viability was evaluated by MTT [3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide] assay. The intracellular calcium levels also were evaluated by Ca[2+]-sensitive indicator Fura-2/AM in presence or absence of berberine [2 microM] during 30 min chemical OGD by NaN3 [20 mM]. Student's t-test and AN OVA were used for statistical analysis. Berberine, MK-801 and NBQX significantly increased Oligodendrocyte viability in all 3 time-scheduled oxygen-glucose deprivation/reperfusion. Berberine at 2 microM produced peak of protection, and increased cell viability to 83%, 77%, and 79% during 30, 60, 240 min ischemic experiments, respectively [P < 0.001]. Berberine significantly attenuated intracellular Ca[2+] rise induced by chemical ischemia, and this effect of berberine was significantly stronger than MK-801 and NBQX [P < 0.001]. We concluded that berberine protected OLN-93 Oligodendrocyte against ischemic induced excitotoxic injury. Attenuation of intracellular Ca[2+] overload by berberine may be the key mechanism that saved OLN-93 from excitotoxicity damage
ABSTRACT
Ankle sprain is one of the most common injuries among athletes and Instability and injury to this joint is responsible for long time loss of physical and recreational activity. Also it can impose high cost to sport teams. Prevention of this injury is an important concern of practice and rehabilitation. One way of reducing the possibility of ankle joint injury is using ankle orthosis. The present study aimed at inspecting the effects of two ankle orthoses on dynamic and semi-dynamic postural stability in athletes with chronic ankle instability. [CAI] Twenty basketball players with CAI and fifteen non-injured athletes volunteered to participate in this study. Biodex Balance System was used to assess the participants' postural stability in bilateral position at level 8 and level 2. Repeated measures analyses variance [ANOVA] was performed in order to examine the effects of ankle orthoses. Statistical significance level was determined at P< 0.05. Statistical analyses revealed the significant effect of ankle supports on dynamic and semi-dynamic postural stability in the two groups and results indicated there wasn't significant difference between groups. According to our results the orthoses improved both dynamic and semi-dynamic postural stability. Therefore orthoses can prevent of injury and its reoccurrence
ABSTRACT
According to some studies, fetal wound in contrast with adult wound heals without scar formation which is probably due to amniotic fluid around the fetus, unique extracellular matrix and the fetal immature immunity. It is supposed that biochemical and physical characteristics of amniotic fluid prepares the conditions for wound healing without scar formation. The goal of this study was to compare the scar diameter of uncomplicated appendectomy by Rocky-Davis incision with scar diameter of cesarean section by Pfanneistiel incision in order to evaluate the effect of amniotic fluid on scar diameter. In this analytic within-patient study all women with uncomplicated appendectomy by Rocky-Davis incision who were pregnant or had history of cesarean in the last 18 months were included [2007-2009]. After 18 months of operation [appendectomy and cesarean], scar diameters were measured in three points [first, middle and end of scar] and the mean was calculated. Then the mean scar diameter of appendectomy was compared with the mean scar diameter of cesarean in each patient. For data analysis we used T-test, Paired T-test, correlation coefficient and regression tests. In this study the effect of weight and height on scar diameter was evaluated. Mean scar diameter of appendectomy was 2.09 +/- 0.677 millimeter and the mean scar diameter of cesarean was 0.467 +/- 0.633 millimeter which was significantly less than appendectomy scar diameter [p=0.008]. It seems that the presence of amniotic fluid in the first hours of healing decreases the future scar diameter
ABSTRACT
Oxidative stress and neuroinflammation are involved in neurodegeneration procedure in Parkinson's disease. Recently, neuroprotective potential of Boswellia resin has been demonstrated. Therefore, this study examined whether administration of Boswellia resin would attenuate MPP+- induced neuronal death in SK-N-SH- cell line, a human dopaminergic neurons- in vitro. Boswellia resin extract was added to culture medium [10microg/ml] before and after exposure of SK-N-SH cell line to MPP+ [1000microM]. Cell viability and apoptosis features were assessed using MTT and Hoechst staining, respectively. Treatment with Boswellia resin 2 and 3h prior to MPP ° exposure and up to 60 minutes after MPP ° exposure significantly increased cell viability compare to untreated cells. Apoptotic features were also reduced significantly by Boswellia resin [10 microg/ml] compare to that of control untreated cells. Boswellia resin has neuroprotective effects on dopaminergic neurons which can be applicable in Parkinson's disease
Subject(s)
Parkinson Disease/therapy , Oxidative Stress , Antioxidants , Plants, Medicinal , Plant Extracts , Dopamine , Neurotoxicity Syndromes/prevention & control , Nerve Degeneration/prevention & control , Dopaminergic Neurons , Neuroprotective AgentsABSTRACT
The aim of the present study was to examine the effects of a course of aerobic exercise on pulmonary function and tolerance of activity in asthmatic patients. Among the asthmatic patients, 36 patients [M= 16, F= 20] were chosen after clinical examinations, pulmonary function test, skin prick test [SPT] for aeroallergen and a six minute walk test [6MWT] on their own free will. A patient was said to have Exercise Induced Asthma [EIA] when he/she fulfilled the following criteria; [1] FEV[1] < 80%, [2] 12% increase or more in FEV[1] or PEF after short-acting [beta][2] agonist prescription and [3] 15% decrease in FEV[1] or PEF after 6MWT with 70% or 80% of maximum heart rate. The patients were randomly put into two groups of case [M=8, F=10, Mean age=27] and control [M=8, F=10, Mean age=29]. Case group participated in eight week aerobic exercise plan, while control group had no plan of exercise. Pulmonary function tests were done before and after the course of exercise. There were significant changes in FEV1, FVC, PEF, FEF[25-75%], MVV, RF and 6MWT between asthmatic patients of the two groups [P