Protection effect of cerium oxide nanoparticles against radiation-induced acute lung injuries in rats.

INTRODUCTION: Radiation therapy is one of the most common tools for treating cancer. The aim is to deliver adequate doses of radiation to kill cancer cells and the most challenging part during this procedure is to protect normal cells from radiation. One strategy is to use a radioprotector to spare normal tissues from ionizing radiation effects. Researchers have pursued cerium oxide nanoparticles as a therapeutic agent, due to its diverse characteristics, which include antioxidant properties, making it a potential radioprotector. MATERIALS AND METHODS: One hundred rats were divided into five groups of A) control group, intraperitoneal (IP) saline injection was done twice a week; B) bi-weekly IP injection of 14.5 nM (0.00001 mg/kg) CNP for two weeks; C) a single whole thorax radiation dose of 18 Gy; D) a single whole thorax radiation dose of 18 Gy + bi-weekly injection of 14.5 nM CNP for two weeks after radiation; E) bi-weekly IP injection of 14.5 nM CNP for two weeks prior to radiation + a single whole thorax radiation dose of 18 Gy. Thirty days after irradiation, 7 rats from each group were anesthetized and their lungs extracted for histopathological examination. RESULTS: Statistical analyses revealed that CNP significantly decreased the incidence of tissue collapse and neutrophile aggregation in rats receiving CNP before radiation in comparison with the radiation group. CONCLUSION: The results suggested the possibility of using CNP as a future radioprotector due to its ability to protect normal cells against radiation-induced damage.

Intellectual disability, muscle weakness and characteristic face in three siblings: A newly described recessive syndrome mapping to 3p24.3-p25.3.

We report on a sister and two brothers born to healthy Iranian parents with mild intellectual disability, progressive muscle weakness, and characteristic facies. including highly arched eyebrows, down-slanting palpebral fissures, prominent nasal bridge, prominent nose, columella extending below alae nasi, narrow mouth, narrow palate, and dental caries, and in one of them an inability to abduct the left eye. Electrophysiological studies showed signs of myopathy, and muscle biopsies demonstrated only nonspecific signs. Brain MRIs in two of the sibs showed leukencephalopathy with delayed myelination, frontal and parietal hyperintensities, and hippocampal atrophy in one. We have been unable to find a description of this association of features in literature. Based on the occurrence in siblings, no significant difference in phenotype between the brothers and sister, absence of manifestations in parents, and a likely consanguinity between parents we performed a homozygosity mapping. A single identical-by-descent bloc encompassing 57 genes located at 3p24.3-p25.3 was found to segregate within the family with this phenotype. © 2015 Wiley Periodicals, Inc.

Clonidine Versus Chloral Hydrate for Recording Sleep EEG in Children.

OBJECTIVE: One of the difficulties to conduct electroencephalography (EEG) in pediatric patient population is that they are not always cooperative during the procedure. Different medications are used to induce sedation during EEG recording. In order to find a medication with the least adverse effects and high efficacy, the current study aimed at comparing clonidine and chloral hydrate as a premedication prior to EEG recording in pediatric population. MATERIALS & METHODS: A prospective, randomized, single-blinded, controlled trial was conducted on 198 children (9 to 156 months old) to investigate the sedative and adverse effects of clonidine and chloral hydrate. Patients, partially sleep-deprived the night before, were randomly divided into two groups of clonidine (n=100) and chloral hydrate (n=98) on an alternative day basis. RESULTS: The average sleep onset latency was significantly longer in the clonidine group than chloral hydrate group (the Mann-Whitney test, p <0.0001). Sleep duration ranged 15 to 150 minutes and it was not significantly different between the two groups (the Mann-Whitney test, p = 0.2). Drowsiness terminated faster with chloral hydrate than clonidine.Drowsiness after arousal was observed in 58% and 26.1% of patients in the clonidine and chloral hydrate groups, respectively; the difference between the groups was significant (the Mann-Whitney test, p = 0.058). EEG results were reported normal in 77 subjects in the chloral hydrate group (77%) and 69 subjects (69%) in the clonidine group (p = 0.161). Generalized epileptiform discharges were significant in the clonidine group (the Mann-Whitney test, p = 0.006). CONCLUSION: The results of the current study showed that both 5% chloral hydrate (1 mL/kg) and clonidine (4 µg/kg) could be administered as a premedication prior to EEG recording in children, although drowsiness after arousal was higher with clonidine than chloral hydrate. However, the yield of generalized epileptiform discharges in the clonidine group was greater than that of the chloral hydrate group.

Neuralgic Amyotrophy with Cervical Root and Cranial Nerves Involvement in a Child.

Idiopathic neuralgic amyotrophy (INA) is a disorder presented with acute severe pain in the upper extremity, followed by muscle weakness, paralysis and atrophy. INA is rare in children and few reports are found in the literature. Here, we report a case of INA in an 8-yr old boy from Iran following pharyngitis.

Stool-based DNA testing, a new noninvasive method for colorectal cancer screening, the first report from Iran.

AIM: To detect tumor-associated DNA changes in stool samples among Iranian patients with colorectal cancer (CRC) compared to healthy individuals using BAT-26, p16 hypermethylation and long DNA markers. METHODS: Stool DNA was isolated from 45 subjects including 25 CRC patients and 20 healthy individuals using a new, fast and easy extraction method. Long DNA associated with tumor was detected using polymerase chain reaction method. Microsatellite studies were performed utilizing denaturating polyacrylamide gel to determine the instability of BAT-26. Methylation status of p16 promoter was analyzed using methylation-specific PCR (MSP). RESULTS: The results showed a significant difference in existence of long DNA (16 in patients vs 1 in controls, P < 0.001) and p16 (5 in patients vs none in controls, P = 0.043) in the stool samples of two groups. Long DNA was detected in 64% of CRC patients; whereas just one of the healthy individuals was positive for Long DNA. p16 methylation was found in 20% of patients and in none of healthy individuals. Instability of BAT-26 was not detected in any of stool samples. CONCLUSION: We could detect colorectal cancer related genetic alterations by analyzing stool DNA with a sensitivity of 64% and 20% and a specificity of 95% and 100% for Long DNA and p16 respectively. A non-invasive molecular stool-based DNA testing can provide a screening strategy in high-risk individuals. However, additional testing on more samples is necessary from Iranian subjects to determine the exact specificity and sensitivity of these markers.

Rapid DNA extraction protocol from stool, suitable for molecular genetic diagnosis of colon cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common forms of cancers in the world and is curable if diagnosed at the early stage. Analysis of DNA extracted from stool specimens is a recent advantage to cancer diagnostics. Many protocols have been recommended for DNA extraction from stool, and almost all of them are difficult and time consuming, dealing with high amount of toxic materials like phenol. Their results vary due to sample collection method and further purification treatment. In this study, an easy and rapid method was optimized for isolating the human DNA with reduced PCR inhibitors present in stool. METHODS: Fecal samples were collected from 10 colonoscopy-negative adult volunteers and 10 patients with CRC. Stool (1 g) was extracted using phenol/chloroform based protocol. The amplification of P53 exon 9 was examined to evaluate the extraction efficiency for human genomic targets and also compared its efficiency with Machiels et al. and Ito et al. protocols. RESULTS: The amplification of exon 9 of P53 from isolated fecal DNA was possible in most cases in 35 rounds of PCR using no additional purification procedure for elimination of the remaining inhibitors.inhibitors. CONCLUSION: A useful, rapid and easy protocol for routine extraction of DNA from stool was introduced and compared with two previous protocols.

Pharmacogenetic Study on the Impact of Rivastigmine Concerning Genetic Variants of A2M and IL-6 Genes on Iranian Alzheimer's Patients.

Alzheimer's disease (AD) is a polygenic and multifactorial disease with a complex inheritance caused by the formation of amyloid plaques and neurofibrillary tangles in the brain. Increasing evidence indicates that many genes including interleukin-6 (IL-6) and alpha 2-macroglobulin (A2M) may contribute to the pathogenesis of AD. The A2M gene encodes α2-macroglobulin which specifically binds with the beta-amyloid peptides and prevents fibril formation. Protein of the IL-6 gene linked to beta-amyloid (ßA) aggregation was detected in ßA plaques in the brain of AD patients. The aim of the present study is to investigate the relationship of the IL-6 and A2M gene polymorphisms with AD and also the impact of rivastigmine on AD patients regarding their genotypes on IL-6 and A2M genes in 150 Iranian AD patients under rivastigmine therapy and 150 matched healthy controls. The results indicated that IL-6 G and C alleles had significant positive and negative association with AD, respectively, (P = 0.0001, relative risks (RR) = 1.39) and frequency of AD patients carrying IL-6 GG genotype was significantly in higher proportion in familial Alzheimer's disease (FAD) patients compared to controls (P = 0.02, RR = 2.25), and the IL-6 CC genotype was significantly protective against AD (P = 0.0003, RR = 0.65). Genotype analysis of A2M gene showed a significant positive correlation between A2M AA genotype and the AD patients (sporadic Alzheimer's disease (SAD) and FAD) (P = 0.001, RR = 1.56), proposing it as a possible risk factor for AD. Drug response from pharmacogenetic viewpoint after 3-year follow-up of AD patients and Clinical Dementia Rating (CDR) analysis demonstrated that AD patients carrying bigenic genotype IL-6 CC-A2M AG (ΔCDR = 4.5) and male patients with IL-6 CC genotype (ΔCDR = 3.83) provided the best response and the A2M GG genotype (ΔCDR = 7.97) and bigenic genotype IL-6 GG-A2M GG (ΔCDR = 8.5) conferred the worst response to the rivastigmine, suggesting likely involvement of genotype-specific response to rivastigmine therapy in AD patients. The results also propose that in view of the fact that C and G alleles created by nucleotide changes in the promoter region of IL-6 gene and this may affect the expression of the IL-6 gene and, hence, susceptible and protective role of GG and CC genotype in AD might be caused by higher and lower expression of IL-6 cytokine, respectively.

Brain on FIRES: Super Refractory Seizure in a 7 yr Old Boy.

We present a 7 yr old boy afflicted with super-refractory seizure that responded poorly to antiepileptic drugs and sustained a long course of hospitalization and complications of high doses of medications as well as longstanding stay in hospital. The differential diagnoses were, fever-induced refractory epileptic encephalopathy (FIRES), and infectious and autoimmune encephalitis. However, work-ups had not revealed any evidence of any specific diagnosis, so we assumed that he was afflicted by viral infectious encephalitis as he had, fever, vomiting, and prodromal symptoms of infectious (most probably viral) disease prior to onset of the seizure attacks.

Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its Relation with Disease-free Survival.

BACKGROUND: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. MATERIALS AND METHODS: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. RESULTS: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. CONCLUSIONS: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.

Metabolic improvement of morbid obese patients following Roux-en-Y gastric bypass surgery: A prospective study in Mashhad, Iran.

BACKGROUND AND AIM: Obesity is one of the greatest public health concerns worldwide. Weight loss surgeries have been increased in recent decades due to the world's epidemic of obesity. The aim of this prospective study is investigating metabolic factors of morbid obese patients following Roux-en-Y gastric bypass surgery. METHODS: This was a nonrandomized prospective cohort study conducted from 2010 to 2013 on 60 consecutive patients who had body mass index (BMI) of more than 40 kg/m(2) and met the surgical indication criteria of bariatric surgery. Upon discharge, patients were followed in outpatient clinic of Qaem Hospital, Mashhad, Iran, each 3 months for 12 months. Measurement of anthropometric and metabolic indices was done in each postoperative visit. RESULTS: Mean BMI reduction was 15.26 ± 3.45 kg/m(2) in the patients with an average value of 28.84 ± 3.94 (range from 22 to 40 kg/m(2)), which was significantly lower than the base value (p < 0.001). After a 12-month follow up, patients had lower low-density lipoprotein, triglycerides, and total cholesterol (p < 0.001 for all the variables), while achieving a greater high-density lipoprotein (p = 0.004). An improvement was seen in all of hypertensive patients after a 3-month follow up and blood pressure remained within normal limit in further follow ups. Complete remission was observed in all the patients with obstructive sleep apnea. CONCLUSION: It appears reasonable that multidisciplinary treatment including surgical alternatives should be concerned for all morbidly obese patients, considering high rate of failure of conservative medical therapy in this setting.

A Novel Mutation in Aspartoacylase Gene; Canavan Disease.

Objective Canavan disease (CD) is a type of vacuolating leukodystrophy with autosomal recessive inheritance. Aspartoacylase deficiency results in decrease of myelin biosynthesis, dysmyelination and brain edema. Although CD is a very common in Ashkenazi Jews patients, several cases have been reported from non-Jewish population. This report is based on a homozygous C.202G>A mutation in the ASPA gene identified from an Iranian patient. To our knowledge, this type of mutation has not been reported in non-Jewish population in the literature.

Diffuse dermal melanocytosis in two patients with Sandhoff disease and mucopolysaccharidosis VI.

Dermal melanocytosis (DM) is described as the presence of ectopic melanocytes in the dermis and could be a normal cutaneous finding. However, diffuse DM or extensive Mongolian spots must be considered as an early sign of neurometabolic diseases, in particular lysosomal storage disorders. The presence of extensive DM should alert the physician to the presence of such disorders, making early diagnosis possible. We describe for the first time the presence of DM in two patients with Sandhoff disease and mucopolysaccharidosis VI.

Efficacy of pregabalin in childhood refractory partial seizure.

OBJECTIVE: About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. METHODS: In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Findings : Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. CONCLUSION: This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures.

Alexander Disease: Report of Two Unrelated Infantile Form Cases, Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran.

BACKGROUND: Alexander disease (AD) is a sporadic leukodystrophy that predominantly affects infants and children and usually results in death within ten years after onset. The infantile form comprises the most of affected individuals. It presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly and frontal bossing, seizures, pyramidal signs and ataxia. The diagnosis is based on magnetic resonance imaging (MRI) findings and confirmed by GFAP gene molecular testing. GFAP gene encodes glial fibrillary acidic protein, is the only gene in which mutation is currently known to cause AD which is inherited in autosomal dominant manner. CASE PRESENTATION: In this article we report the first two Iranian cases of infantile AD and their clinical, brain MRI and molecular findings. We report two novel mutations too in the GFAP gene that are associated with infantile form of AD. CONCLUSION: GFAP gene mutations are a reliable marker for infantile AD diagnosed according to clinical and MRI defined criteria. A genotype-phenotype correlation had been discerned for the two most frequently reported GFAP gene mutations in infantile type of AD (R79 and R239), with the phenotype of the R79 mutations appearing much less severe than that of the R239 mutations. Our findings confirm this theory.

Effects of miglustat on stabilization of neurological disorder in niemann-pick disease type C: Iranian pediatric case series.

Niemann-Pick disease type C is a rare neurodegenerative disorder with autosomal recessive inheritance that can be broadly categorized into different forms dependent on age at disease onset: pre-/perinatal, early infantile, late infantile, juvenile, and adolescent/adult. This study was conducted to define the age at onset, clinical manifestations, neuroimaging findings and response to treatment in 21 patients diagnosed with Niemann-Pick disease type C and managed in the neurology departments of hospitals in Tehran, Iran. The effects of miglustat on patient ambulation, fine and gross motor function, swallowing, hearing, speech, seizures, psychomotor development, and ocular movements were evaluated for up to 26 months of treatment. Ambulation, fine and gross motor movements, swallowing, speech, and supranuclear gaze palsy were generally stabilized during therapy, and psychomotor delay appeared to be improved in early- and late-infantile onset patients. However, miglustat had no effect on organomegaly or other systemic manifestations of the disease. Miglustat was well tolerated.

Positivity of HIV, hepatitis B and hepatitis C in patients enrolled in a confidential self-exclusion system of blood donation: a cross-sectional analytical study.

CONTEXT AND OBJECTIVE: Selection of healthy blood donors is essential to ensure blood safety. A confidential self-exclusion (CSE) system was designed so that high-risk donors could confidentially exclude their blood from use in transfusions. This study aimed to compare the demographic characteristics and the results from human immunodeficiency virus (HIV), hepatitis B surface (HBS) and hepatitis C virus (HCV) screening tests on donors who opted to get into and out of CSE. DESIGN AND SETTING: Analytical cross-sectional study on all volunteer donors at Shiraz Blood Transfusion Organization from March 21, 2006, to March 21, 2008. METHODS: The results from the abovementioned tests were compared between donors who opted into and out of CSE. RESULTS: 100,148 donors in 2006 and 104,271 in 2007 gave blood. Among these donors, respectively, 829 (0.82%) and 592 (0.57%) opted for the CSE. The prevalence of HIV antibodies, HBS antigens and HCV antibodies in CSE donors was significantly higher than in donors who did not choose CSE (p < 0.05). The prevalence of at least one of these three infections among CSE donors was 3.12% in 2006 and 3.04% in 2007, and was significantly higher than the prevalence among non-CSE donors (0.58% and 0.57%, respectively). CONCLUSION: Because of the higher prevalence of HBS, HCV and HIV positivity in blood donors who chose the CSE option, offering CSE to blood donors could be a potentially useful method for improving blood safety, since it could increase the detection of infected blood during the window period.

Positivity of HIV, hepatitis B and hepatitis C in patients enrolled in a confidential self-exclusion system of blood donation: a cross-sectional analytical study / Positividad del VIH, la hepatitis B y hepatitis C en pacientes incluidos en un confidencial sistema de exclusión de la donación de sangre: un estudio transversal analítico

CONTEXT AND OBJECTIVE: Selection of healthy blood donors is essential to ensure blood safety. A confidential self-exclusion (CSE) system was designed so that high-risk donors could confidentially exclude their blood from use in transfusions. This study aimed to compare the demographic characteristics and the results from human immunodeficiency virus (HIV), hepatitis B surface (HBS) and hepatitis C virus (HCV) screening tests on donors who opted to get into and out of CSE. DESIGN AND SETTING: Analytical cross-sectional study on all volunteer donors at Shiraz Blood Transfusion Organization from March 21, 2006, to March 21, 2008. METHODS: The results from the abovementioned tests were compared between donors who opted into and out of CSE. RESULTS: 100,148 donors in 2006 and 104,271 in 2007 gave blood. Among these donors, respectively, 829 (0.82 percent) and 592 (0.57 percent) opted for the CSE. The prevalence of HIV antibodies, HBS antigens and HCV antibodies in CSE donors was significantly higher than in donors who did not choose CSE (p < 0.05). The prevalence of at least one of these three infections among CSE donors was 3.12 percent in 2006 and 3.04 percent in 2007, and was significantly higher than the prevalence among non-CSE donors (0.58 percent and 0.57 percent, respectively). CONCLUSION: Because of the higher prevalence of HBS, HCV and HIV positivity in blood donors who chose the CSE option, offering CSE to blood donors could be a potentially useful method for improving blood safety, since it could increase the detection of infected blood during the window period.

CONTEXTO Y OBJETIVO: La identificación y selección de donantes de sangre sanos es el primer paso para asegurar la seguridad de la sangre. Este estudio tiene como objetivo comparar las características demográficas y los resultados de los virus de la inmunodeficiencia humana (VIH), la superficie de la hepatitis B (HBS) y viru de la hepatitis C (VHC) las pruebas de cribado en los donantes que optaron por entrar y salir de la libre y confidencial de exclusión. DISEÑO Y EMPLAZAMIENTO: Estudio transversal de todos los donantes voluntarios que acudieron a la Shiraz Blood Transfusion Organization entre el 21 de Marzo del 2006 y el 21 de Marzo del 2008. MÉTODOS: Los resultados de las pruebas antes mencionadas fueron comparados entre los donantes que optaron por entrar y salir de CSE. RESULTADOS: 100.148 donantes en 2006 y 104.271 en 2007 donaron sangre. Entre estos donantes, respectivamente, 829 (0,82 por ciento) y 592 (0,57 por ciento) optaron por el CSE. La prevalencia de anticuerpos contra el VIH, los antígenos HBS y anticuerpos contra el VHC en donantes de CSE fue significativamente mayor que en los donantes que no eligió CSE (P < 0,05). La prevalencia de al menos una de estas tres infecciones entre los donantes CSE fue 3,12 por ciento en 2006 y 3,04 por ciento en 2007, y fue significativamente mayor que la prevalencia entre los donantes no CSE (0,58 por ciento y 0,57 por ciento, respectivamente). CONCLUSIONES: Debido a la mayor prevalencia de BA, el VHC y la infección con VIH en donantes de sangre que eligieron la opción del CSE, ofreciendo CSE para los donantes de sangre podría ser un método potencialmente útil para mejorar la seguridad de la sangre, ya que podría aumentar la detección de sangre infectada durante el período de ventana.