Improving cognitive task in kindled rats by using low frequency stimulation during epileptogenesis

Numerous studies indicate that one of the bad effects of epilepsy is cognitive impairment. In this study we focused on the effect of LFS as a potential anticonvulsant agent, during epileptogenesis on cognitive impairments induced by amygdala kindling in rat. Twenty-one adult rats were divided into 3 groups including control (n?=?7), kindled (n?=?7), and Kindled+LFS (KLFS) (n?=?7). Animals in the kindled group received kindling stimulation in a rapid kindling manner (a 3 s train of 50 Hz monophasic pulses of 1 ms duration, 12 times a day) in amygdala whereas control animals had no stimulation. Four packages of LFS (each package consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz) were applied daily after termination of kindling stimulation in KLFS group. Spatial memory of all animals was tested using radial arm maze after termination of stimulation on acquisition trial days and 14 days after the final acquisition trial test. Epileptogenesis process significantly increased working and reference memory error compared to control groups whereas application of LFS immediately after kindling stimulation prevented this impairment in 8 arm radial maze and there was no significant difference between KLS and control groups. Our results indicated that application of LFS during kindling acquisition suppresses memory impairment in epileptogenesis by kindling stimulation.     

Effect of L-carnitine supplementation on maturation and early embryo development of immature mouse oocytes selected by brilliant cresyle blue staining

Purpose

The present study was designed to investigate the effect of L-carnitine treatment during IVM on nuclear and cytoplasmic maturation of immature oocytes selected by Brilliant Cresyle Blue (BCB) staining, and their subsequent developmental competence.

Materials & methods

Compact cumulus-oocyte complexes (COCs) were collected from NMRI mice ovaries and stained with BCB staining. BCB+ (colored cytoplasm) oocytes were then cultured in tissue culture medium (TCM) 199 with 0.0, 0.3 and 0.6 mg/ml L-carnitine.

Results

The both L-carnitine concentrations significantly increased the intracellular glutathione (P < 0.001), nuclear maturation (P < 0.01) and expression levels of cyclin-dependent kinase1 (CDK1) (P < 0.05). Moreover, treated oocytes with 0.6 mg/ml L-carnitine showed increased (P < 0.05) expression of mitogen-activated protein kinase1 (MAPK1) mRNA. Also, adding L-carnitine (0.6 mg/ml) to IVM medium significantly increased the cleavage rate (P < 0.05). The blastocyst development rate (BDR) in the both L-carnitine treated groups was significantly higher (P < 0.001) than the control group. L-carnitine had no significant effect on total blastocyst cell numbers.

Conclusions

These data indicated that L-carnitine supplementation during IVM of immature BCB+ oocytes improved preimplantation developmental competence of oocytes after IVF, probably by accelerating cytoplasmic and nuclear maturation of oocytes. It may provide a novel approach to improving ART outcomes in infertile couples.     

Association of Plasma Retinol Binding Protein-4 (RBP4) and Sonographic Grading of Fatty Liver in Obese Iranian Children

Background

The prevalence of obesity and its related comorbidities, such as fatty liver, in children is increasing worldwide mostly due to changes in diet and life-style. Many serological markers have been suggested for screening of fatty liver but investigations for finding more reliable factors are still in progress.

Objectives

This study aimed to investigate the correlation between the level of retinol binding protein-4 (RBP4) in the serum and sonographic grading of fatty-liver severity in obese Iranian children.

Patients and Methods

This case-control, double-blind study involved 51 obese children aged between five and 17 years as the case group. In addition, 35 healthy lean children with no liver problems were selected as the control group. Plasma RBP4 (using an ELISA), serum triglycerides (TG), low-density-lipoproteins (LDL), high-density-lipoproteins (HDL), total-cholesterol (Chol), and body mass index (BMI) were measured. Grading the severity of the fatty liver condition was done by an expert radiologist in the case group.

Results

RBP4 levels in obese children (19 482.9 ± 3 302.2 pg/ml) were higher than those found in the lean control group (14 295.68 ± 2 381.3 pg/ml) (P < 0.05). In the obese patients, RBP4 levels showed a significant correlation with the grade of fatty liver and BMI (P < 0.05).

Conclusions

It was found that the level of RBP4 had a strong correlation with the severity of fatty liver. Therefore, RBP4 may be considered as a useful, noninvasive predictive biomarker of intrahepatic lipid content in obese children prior to using radiological investigations. In particular, abdominal sonography, for the evaluation of intrahepatic lipid content in obese patients, as the sensitivity of a sonography is decreased due to the increased thickness of the abdominal wall as a result of fat deposits.     

Detection of West Nile virus genome and specific antibodies in Iranian encephalitis patients

West Nile virus (WNV) is a mosquito-borne flavivirus which circulates in birds, horses and humans. An estimated 80% of WNV infections are asymptomatic. Fewer than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. This study was conducted from January 2008 to June 2009 in Isfahan, Iran. Patients attending the emergency department with fever and loss of consciousness were consecutively included. Cerebrospinal fluids (CSF) were initially analysed through bacteriology and biochemistry examinations, resulting in those with evidence of meningitis being excluded. Patients' CSF and serum were diagnosed by serological and molecular assays. A total of 632 patients with fever and loss of consciousness were tested by CSF analyses. Samples of the remaining patients (39·4%) were referred for WNV investigation. Three (1·2%) of the patients were positive for both serum and CSF by RT-PCR, and six (2·4%) were positive only for IgG antibodies. History of insect bite, and blood transfusion and transplantation were risk factors for being positive by RT-PCR (P=0·048) and being IgG positive (P=0·024), respectively. The results of this study showed that the prevalence of West Nile fever is low in patients with encephalitis.     

Prevalence of thrombotic risk factors among β-thalassemia patients from Western Iran

Background There is evidence for increased risk of thrombosis in patients with β-thalassemia intermedia and β-thalassemia major. The present study investigated the prevalence of thromboembolic risk factors of prothrombin G20210A, factor V Leiden G1691A and methylentetrahydrofolate reductase (MTHFR) C677T, as well as the hematological and clinical profiles in β-thalassemia major and intermedia patients from Western Iran. Methods Patients consisted of 158 β-thalassemia patients, 151 β-thalassemia major and 7 β-thalassemia intermedia patients, including 82 males and 76 females aged 13.6 ± 6.3 years. The control group were 180 healthy blood donors and school students, consisting of 103 males and 77 females aged 16.8 ± 2.1. Genotyping was done by PCR-RFLP using Mnl I, Hind III and Hinf I for factor V Leiden and prothrombin G20210A and MTHFR, respectively. Results The prevalence of prothrombin G20210A variant in patients and healthy individuals were 1.3 and 3.3%, respectively. Factor V Leiden G1691A was insignificantly higher in β-thalassemia patients (prevalence 5.7% and allele frequency 3.2%) compared to healthy individuals (2.8%). This mutation was found in eight β-thalassemia major (5.3%) and one β-thalassemia intermedia (14.3%) patients. The prevalence of MTHFR C677T polymorphism was slightly higher in patients (50%) compared to healthy individuals (48.3%). Around 71% of β-thalassemia intermedia and 38.4% of β-thalassemia major patients had undergone splenectomy. In β-thalassemia major patients, 5.3% had insulin dependent diabetes mellitus (IDDM) and 6.6% had HCV antibodies. All patients with IDDM were splenectomized and in one of them the prothrombin G20210A variant was found. Two patients, a 7-year-old boy with β-thalassemia intermedia receiving regularly blood transfusion and a β-thalassemia major patient (a 22-year-old splenectomized female), were found to be homozygous for MTHFR 677TT and heterozygous for factor V Leiden G1691A. Double heterozygosity for factor V Leiden G1691A and MTHFR C677T and also homozygous factor V Leiden 1691AA were found in two β-thalassemia major patients. No thromboembolic event has been recorded in the files of patients. Conclusions The results of present study establish the prevalence of biological risk factors of thrombosis in β-thalassemia patients from Western Iran. It seems that thrombophilic mutations may not be associated with thrombotic events in thalassemic patients, which needs to be confirmed by the study of larger sample sizes.     

Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with <Superscript>111</Superscript>In using N-terminal DOTA,NOTA and NODAGA chelators in mice bearing prostate cancer xenografts

Purpose  

In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer.     

Burr-hole drainage for the treatment of acute epidural hematoma in coagulopathic patients: a report of eight cases

Craniotomy has been accepted as the treatment of choice for the management of acute epidural hematomas (AEDH). However, in practice, it seems possible to evacuate AEDH via a single burr hole instead of the traditional craniotomy in certain circumstances. Among 160 patients with AEDH meeting criteria for evacuation admitted to the emergency and accident division of our center between 2006 and 2009, we found 8 cases of hematoma appearing isodense to brain parenchyma on computed tomography (CT), who had concomitant coagulopathy. These patients were managed by burr-hole drainage for treatment of the liquefied AEDH. A closed drainage system was then kept in the epidural space for 3 days. In all 8 patients, AEDH was evacuated successfully via burr-hole placement over the site of hematoma. The level of consciousness and other symptoms improved within the first day, and no patient required an additional routine craniotomy. For patients with slowly-developing AEDH in the context of impaired coagulation, burr-hole evacuation and drainage might be a less invasive method of treatment compared to conventional craniotomy.     

Recombinant Nonstructural 3 Protein,rNS3, of Hepatitis C Virus Along With Recombinant GP96 Induce IL-12, TNFα and α5integrin Expression in Antigen Presenting Cells

Background

Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and to date there has been no vaccine development to prevent this infection. Among non-structural HCV proteins, NS3 protein is an excellent goal for a therapeutic vaccine, due to its large size and less variation in conserved regions. The immunogenic properties of heat shock proteins (HSPs) for instance GP96 have prompted investigations into their function as strong adjuvant to improve innate and adaptive immunity.

Objectives

The aim of this study was to examine additive effects of recombinant GP96 (rGP96) fragments accompanied by rNS3 on expression levels of α5integrin and pro-inflammatory cytokines, IL-12 and TNFα, in Antigen Presenting Cells (APCs).

Materials and Methods

Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal fragments of GP96 were produced and purified from E. coli in order to treat the cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages.

Results

Our results showed that rNT-GP96 alone significantly increases the expression level of IL-12, TNFα and α5integrin in THP-1 macrophages and DCs, while IL-12 and TNFα expression levels were unaffected by either rNS3 or rRGD-NS3. Interestingly, the co-addition of these recombinant proteins with rNT-GP96 increased IL-12, TNFα and α5integrin expression. Pearson Correlation showed a direct association between α5integrin with IL-12 and TNF-α expression.

Conclusions

we have highlighted the role of rNS3 plus rNT-GP96 mediated by α5integrin in producing IL-12 and TNFα. It can be suggested that rNT-GP96 could enhance immunity characteristic of rNS3 protein via production of pro-inflammatory cytokines.     

The β-GLobin Gene Haplotypes Associated With Hb D-Los Angeles [β121(GH4)Glu→Gln] in Western Iran

Hb D-Los Angeles is characterized by the substitution of glutamine for glutamic acid at position 121 of the β-globin chain. The present investigation is the first study on the β-globin gene haplotypes associated with β-D-Los Angeles in Western Iran. Thirty two individuals from 11 unrelated families from Western Iran were studied. The Hb D-Los Angeles status of all cases was confirmed using polymerase chain reaction (PCR) followed by digestion with EcoRI. The haplotype of the β‐globin gene cluster was determined by a PCR-RFLP (restriction fragment length polymorphism) procedure. The haplotype background of the β^A chromosomes was also determined in 35 normal subjects from the same geographic region. The β-globin gene haplotype analysis demonstrated that all β-D-Los Angeles genes (23 genes) were in linkage disequilibrium with haplotype I [+????++]. Among the 70 β^A chromosomes, 30 chromosomes (42.9%) were associated with haplotype I. The present study indicates the unicentric origin of the β-D-Los Angeles gene in Western Iran. It seems that this mutation may have occurred at the same chromosomal background common in the local population.