Identification of Cytochrome b‐245, beta‐chain gene mutations,and clinical presentations in Iranian patients with X‐linked chronic granulomatous disease

BackgroundX‐linked chronic granulomatous disease (X‐CGD) is an immunodeficiency disorder caused by defects in the gp91^phox subunit that leads to life‐threatening infections. We aimed to identify CYBB gene mutations and study clinical phenotypes in Iranian patients with probable X‐CGD.MethodsWe studied four unrelated Iranian patients with probable X‐CGD and their families recruited in several years. We isolated genomic DNA from whole blood and performed Sanger sequencing in the CYBB gene''s coding and flanking regions. We also performed pathogenicity predictions using in silico tools.ResultsWe detected four different mutations, including a novel insertion mutation in exon 5 (p.Ile117AsnfsX6), in the patient. Bioinformatics analysis confirmed the pathogenic effect of this mutation. We predicted protein modeling and demonstrated lost functional domains. The patient with the insertion mutation presented pneumonia and acute sinusitis during his life. We also detected three other known nonsense mutations (p.Arg157Ter, p.Arg226Ter, and p.Trp424Ter) in the CYBB gene. The patient with p.Arg157Ter developed lymphadenitis and pneumonia. Moreover, the patient with inflammatory bowel disease showed p.Arg226Ter and the patient with tuberculosis presented p.Trp424Ter. We detected different clinical features in the patients compared to other Iranian patients with the same mutations.ConclusionOur results expand the genetic database of patients with X‐CGD from Iran and make it much easier and faster to identify patients with X‐CGD. Our results also help to detect carriers and enable prenatal diagnosis in high‐risk families as a cost‐effective strategy.     

The trend of burn mortality in Iran — A study of fire,heat and hot substance-related fatal injuries from 1990 to 2015

Introduction

Burn injuries are a major cause of preventable mortality worldwide. To implement preventive strategies, a detailed understanding of the rate and trend of fatal burn injuries is needed. The aim of this study was to determine the rate and trend of burn mortality at national and province level in Iran from 1990 to 2015.

Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern

Adenosine deaminase (ADA) plays a crucial role in the development and maintenance of normal immune system. So, any immunological imbalances could associate with its altered activity in serum. This study evaluated the activity of total ADA and its isoenzymes in serum of 45 patients with systemic lupus erythematosus (SLE). Included were 23 patients with active SLE, 22 during the inactive phase of the disease, and 45 healthy subjects. Our results provided evidence that the significantly elevated total ADA activity in serum of SLE patients is correlated mainly with the increased ADA2 level. The highest mean ADA2 activity during the relapse phase of the disease could be an indication to the macrophages, the main source of ADA2. It might be concluded that ADA and its isoenzymes analysis in serum of patients could be used as a useful and non-invasive diagnostic tool in evaluation of SLE active phase and the disease severity.     

Right ventricular myxoma originating from a papillary muscle: a case report

Very few cases of ventricular myxoma originate from a papillary muscle. Patients with a cardiac myxoma and a history of colorectal carcinoma are also rare. Here, we present a case of an extremely large right ventricular myxoma that originated from the posteromedial papillary muscle in a patient with a history of colorectal carcinoma.     

Sub-chronic administration of AM251, CB1 receptor antagonist,within the nucleus accumbens induced sensitization to morphine in the rat

It seems that there is a cross-talk between the cannabinoid CB1 and opioid receptors in the process of sensitization to opiates. In present study, we tried to examine the effect of solely administration of AM251, a CB1 receptor antagonist, on conditioned place preference (CPP) by ineffective dose of morphine in the rat. 102 adult male albino Wistar rats were used in these experiments. Subcutaneous administration of morphine (0.5, 1, 2.5, 5, 7.5 and 10 mg/kg) induced CPP only at the doses of ≥5 mg/kg. The dose of 0.5 mg/kg of morphine was selected as the appropriate (ineffective) dose for induction of CPP in animals which were previously received AM251 (5, 25 and 125 ng/0.5 μl per side) once daily for three days as a sub-chronic administration or those that received a single dose on the test day. Bilateral intra-accumbal sub-chronic but not single administration of AM251 dose-dependently produced sensitization to morphine and induced CPP by ineffective dose of morphine (0.5 mg/kg) in the rat. Bilateral intra-accumbal administration of neither saline nor DMSO (0.5 μl/side) had effects on sensitization to morphine. Our findings indicated that CB1 receptors within the nucleus accumbens are involved in the sensitization to morphine in rats.     

High frequency of de novo DAZ microdeletion in sperm nuclei of subfertile men: possible involvement of genome instability in idiopathic male infertility

The occurrence and diagnosis of Y-chromosome microdeletions, specifically deletions of the DAZ (Deleted in Azoospermia) genes are an important issue in male infertility. Screening Y chromosome microdeletion is mainly done using polymerase chain reaction (PCR) on blood leukocytes. However, there is some evidence indicating that presence of DAZ in somatic cells might not be indicative of its presence in the germ cell lineage. Therefore, a total of 130 men with poor semen quality were examined for presence of DAZ microdeletion in their leukocytes. From these, sperm from 40 randomly selected men with no DAZ microdeletions in their leukocytes (n?=?10 oligozoospermia; n?=?10 asthenozoospermia; n?=?10 oligoasthenozoospermia; and n?=?10 near-azoospermia) were were compared to sperm from men of normal semen quality (n?=?10) using combined primed in situ labelling and fluorescent in situ hybridization (PRINS-FISH) technique as well as screening for sex chromosome aneuploidy. There was an increased frequency of DAZ microdeletion in blood samples from oligozoospermic (5%) (p?p?DAZ microdeletion was observed in the sperm of patients with no DAZ microdeletion in their leukocytes compared to control (p?DAZ microdeletion induction during spermatogenesis.     

Literacy and memory decline among ethnically diverse elders

Literacy may be a more powerful indicator of brain reserve than years of education. Literacy level may be a proxy for native intellectual capacity or life experience that can compensate for brain damage or provide brain reserve. Alternately, the experience of acquiring literacy skills may in itself change the organization of the brain and increase protection against cognitive decline. However, because people with low levels of literacy obtain poor scores on most cognitive measures, only longitudinal studies can elucidate the role of reading ability in reserve. We determined whether literacy skills could predict cognitive change in a sample of 136 English-speaking African American, Caucasian, and Hispanic elders selected from a longitudinal aging study in New York City. According to a physician's independent examination, all participants were nondemented throughout the four longitudinal assessments. Literacy level was assessed using the WRAT-3 reading subtest. After accounting for age at baseline and years of education, GEE analyses showed that elders with low levels of literacy had a steeper decline in both immediate and delayed recall of a word list over time as compared to high literacy elders. Our findings suggest that literacy skills are protective against memory decline among nondemented elders.     

Hematological and Biochemical Profile of Pike Breeders (Esox lucius Linneaus, 1758) from the Anzali Wetland,Caspian Sea

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Pike fish is the most important commercial fish species in the Anzali wetland, Iran. In the present study,...     

Enalapril and losartan affect lipid peroxidation in renal transplant recipients with renin-angiotensin system polymorphisms

OBJECTIVES: In this study, the effect of enalapril (E) and/or losartan (L) on lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with regard to polymorphisms of renin-angiotensin system (RAS). DESIGN AND METHODS: After determination of genotypes of the angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and second (20 patients) groups were treated with enalapril (E(+): 10 mg/day) and losartan (L(+): 50 mg/day) alone for 2 months, respectively. After 2 weeks as washout period, E group changed to L and vice versa as a cross-over design and they were treated for another 2 months. The third group (13 patients) as positive control received enalapril+losartan (E(+)L(+): 10 mg/day+50 mg/day) for 16 weeks, and the forth group (18 patients) as negative control received no medication (E(-)L(-)). Malondialdehyde (MDA) as LPO marker was measured before and after treatment. In this study, P<0.05 was considered significant. RESULTS: After 2 months of treatment, MDA level significantly decreased in all of the groups except the E(-)L(-). MDA level in pre- vs. post-intervention for the E(+)L(+), E(+), L(+) and E(-)L(-) groups were as follows: 5.81+/-2.13 nmol/mL vs. 1.61+/-0.80 nmol/mL (P=0.001), 5.10+/-2.05 nmol/mL vs. 1.68+/-1.01 nmol/mL (P=0.003), 5.20+/-1.61 nmol/mL vs. 1.22+/-0.27 nmol/mL (P=0.000) and 5.27+/-2.12 nmol/mL vs. 5.07+/-2.03 nmol/mL (P=0.52), respectively. Also, the same results were found in the end of 16th week. Although patients with DD genotype of ACE had higher MDA (P=0.01) levels, RAS polymorphisms could not predict the antioxidative response rate to the drugs (P>0.05). CONCLUSIONS: E and/or L reduce MDA regardless of the RAS genotypes.     

Anti-apoptotic effect of sphingosine-1-phosphate and platelet-derived growth factor in human embryonic stem cells

Human embryonic stem (hES) cells hold great promise for use in regenerative medicine. However, technologies first need to be established to maintain hES cells efficiently in vitro. Understanding the signaling networks involved in hES cell maintenance will prove to be essential to the development of such culture systems. Previously, we described a serum-free medium capable of supporting prolonged hES cell maintenance using sphingosine-1-phosphate (S1P) and platelet-derived growth factor (PDGF). Here, we describe an anti-apoptotic effect of S1P and PDGF in hES cells and demonstrate a direct effect of S1P in preventing hES cell apoptosis. Western blot analysis shows that S1P stimulates the phosphorylation of the mitogen-activated protein (MAP) kinases Erk1/2 but not of Akt, whereas PDGF stimulates both Erk1/2 and Akt phosphorylation. Moreover, our study suggests that the Erk1/2 and PI3K/Akt signaling pathways act independently of each other. Furthermore, neither S1P nor PDGF modify intracellular calcium concentration ([Ca(2+)]( i )) and Smad2 phosphorylation. Using pharmacological inhibitors of Erk1/2 and PI3K, our results demonstrate a critical role of the Erk1/2 and PI3K/Akt signaling pathways in mediating the anti-apoptotic effect of S1P and PDGF on hES cells. However, inhibition of the mammalian target of rapamycin (mTOR), a common downstream effector of Erk1/2 and PI3K/Akt, has no effect on hES cell apoptosis.