Detection of Extended-Spectrum ß-Lactamases among Acinetobacter Baumannii Isolated from Hospitals of Qazvin, Iran.

BACKGROUND: Acinetobacter baumannii is a major contributor to nosocomial infections. Extended-spectrum ß-lactamase (ESBL)-producing A. baumannii is spreading worldwide. We aimed to determine the frequency of ESBL-encoding genes in clinical isolates of A. baumannii and to access their clonal relationship by repetitive extragenic palindromic-PCR (rep-PCR). METHODS: In this descriptive cross-sectional study, 203 isolates of A. baumannii were collected from Qazvin hospitals. The Identification of isolates was performed by standard laboratory methods. To verify ESBL production, all isolates were screened by disk agar diffusion and confirmed by the combined disk method. Subsequently, ESBL-encoding genes were detected by PCR and sequencing. Possible clonal association of ESBL-producing isolates was evaluated using rep-PCR. RESULTS: Two hundred (98.5%) isolates showed reduced susceptibility to one of the antibiotics used in the ESBL screening test, of which 127 isolates (62.6%) produced ESBL. PCR results showed blaOXA-1 (20.5%) was the most prevalent gene followed by blaTEM-1 (20%), blaGES-1 (15.7%), blaCTX-M-15 (7.9%), and blaPER-1 (1.6%). Rep-PCR results revealed that ESBL-producing isolates belonged to clones A (85%), B (13.4%), and C (1.6%). CONCLUSION: Our study showed the significant presence of blaOXA-1, blaTEM-1, blaGES-1, blaCTX-M-15, and blaPER-1 genes in ESBL-producing A. baumannii isolates in the studied hospitals. This is the first report on the emergence of blaOXA-1 gene in these isolates in Iran. The use of comprehensive antimicrobial treatment guidelines based on laboratory data and appropriate infection control interventions are essential.

Hydrogen sulfide attenuates induction and prevents progress of the 6-hydroxydopamine-induced Parkinsonism in rat through activation of ATP-sensitive potassium channels and suppression of ER stress.

PURPOSE: Studies argue in favor of hydrogen sulfide (H2S) as the next potent therapeutic agent for neurodegenerative diseases. In present study, we investigated the effect of long term treatment with NaHS (as donor of H2S) on induction and progress of the 6-hydroxydopamine (6-OHDA) -induced Parkinsonism in rat. METHODS: The 6-OHDA was injected into medial forebrain bundle of right hemisphere by stereotaxic surgery. Behavioral tests and treatments were carried out to eight weeks after the toxin. Immunohistochemistry and western blotting were carried out to evaluate the survival of tyrosine hydroxylase (TH) -positive neurons in substantia nigra (SN) and also expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), the markers of endoplasmic reticulum (ER) stress, in striatum and SN. RESULTS: Eight weeks assessment of the behavioral symptoms showed that NaHS especially at dose of 100 µmol/kg attenuates remarkably induction of the Parkinsonism and prevents its progress. NaHS also increased the survival of TH- positive neurons and suppressed 6-OHDA- induced overexpression of GRP78 and CHOP. Blockade of ATP-sensitive potassium (K-ATP) channels with glibenclamide (Glib) prevented markedly the effect of NaHS on both the induction phase and survival of TH- positive neurons. But Glib did not affect the preventing effect of NaHS on the progress phase and its suppressing effect on the overexpression of ER stress markers. CONCLUSION: H2S attenuates induction of the 6-OHDA- induced Parkinsonism and also increases the survival of dopaminergic neurons through activation of K-ATP channels. H2S also prevents progress of the Parkinsonism probably through suppression of ER stress.

Molecular mechanisms of drug resistance in ovarian cancer.

Ovarian cancer is the most lethal malignancy among the gynecological cancers, with a 5-year survival rate, mainly due to being diagnosed at advanced stages, recurrence and resistance to the current chemotherapeutic agents. Drug resistance is a complex phenomenon and the number of known involved genes and cross-talks between signaling pathways in this process is growing rapidly. Thus, discovering and understanding the underlying molecular mechanisms involved in chemo-resistance are crucial for management of treatment and identifying novel and effective drug targets as well as drug discovery to improve therapeutic outcomes. In this review, the major and recently identified molecular mechanisms of drug resistance in ovarian cancer from relevant literature have been investigated. In the final section of the paper, new approaches for studying detailed mechanisms of chemo-resistance have been briefly discussed.

Involvement of adenosine triphosphate-sensitive potassium channels in the neuroprotective activity of hydrogen sulfide in the 6-hydroxydopamine-induced animal model of Parkinson's disease.

Studies have shown that hydrogen sulfide (H2S) exerts a neuroprotective effect and may have a therapeutic value for treating neurodegenerative diseases including Parkinson's disease. However, little is known about the mechanisms underlying the neuroprotective activity of H2S in vivo. Here, we evaluated the effect of glibenclamide, an ATP-sensitive potassium channel blocker, on the neuroprotective activity of H2S in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson's disease. 6-OHDA was administered by stereotaxic surgery into the medial forebrain bundle. Sodium hydrosulfate (NaHS, 3 and 5.6 mg/kg), as a donor of H2S, alone or in combination with glibenclamide (5 mg/kg), was daily injected for 7 days starting 1-2 h before the stereotaxic surgery. After an apomorphine-induced rotational test, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was determined by immunofluorescence. The striatal dopamine level and oxidative stress markers were also measured in brain homogenates. Pretreatment with NaHS significantly attenuated 6-OHDA-induced motor asymmetry in the rotational test. Histological and biochemical evaluations demonstrated that NaHS, especially at high dose, increased the survival of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and reduced the decreasing effect of 6-OHDA on striatal dopamine levels. However, co-administration of glibenclamide reversed the antiparkinsonian and neuroprotective effects of NaHS. However, glibenclamide did not change the reducing effect of NaHS on 6-OHDA-induced overproduction of malondialdehyde. Our data show that ATP-sensitive potassium channels are involved in the antiparkinsonian and neuroprotective effects of H2S in the 6-OHDA animal model of Parkinson's disease.

Feasible Relation between Glutathione Peroxidase and Febrile Seizure.

OBJECTIVE: We aimed to determine the relationship between serum glutathione peroxidase and febrile seizure. MATERIALS & METHODS: In this case-control study, 43 children with simple febrile seizure (case group) were compared with 43 febrile children without seizure (control group) in terms of serum glutathione peroxidase level, measured by ELISA method. This study was conducted in Qazvin Children Hospital, Qazvin University of Medical Sciences in Qazvin, Iran in 2012-2013. The results were analyzed and compared in two groups. RESULTS: From 43 children 24 (53%) were male and 19 (47%) were female in children with simple febrile seizure, and 26 (60%) were male and 17 (40%) were female in febrile children without seizure (control group) (P=0.827). Serum glutathione peroxidase level was 166 U/ml (SD=107) in the case group and 141 U/ml (SD=90.5) in the control group of no significant difference. CONCLUSION: There was no significant relationship between serum glutathione peroxidase and simple febrile seizure. Thus, it seems that glutathione peroxidase, an essential component of antioxidant system, does not play any role in the pathogenesis of simple febrile seizure.

Development of Insulin Resistance through Induction of miRNA-135 in C2C12 Cells.

OBJECTIVE: Micro-RNAs (miRNAs) are a class of posttranscriptional regulators that play crucial roles in various biological processes. Emerging evidence suggests a direct link between miRNAs and development of several diseases including type 2 diabetes (T2D). In this study, we aimed to investigate the effect of predicted miRNA and target genes on insulin resistance. MATERIALS AND METHODS: This experimental study was conducted on the C2C12 cell line. Using bioinformatics tools miRNA-135 and two respective target genes-insulin receptor (Insr) and vesicle associated membrane protein 2 (Vamp2)were selected as potential factors involved in insulin resistance process. Levels of glucose uptake miRNA expression and respective gene targets were determined after cell transfaction by miR-135. RESULTS: It was determined that Insr gene expression was significantly down-regulated in miR-135 transfected C2C12 cell line (P≤0.05). Interestingly; these transfected cells have shown a significant difference in glucose uptake incomparision the positive control cells, while it was similar to the insulin resistant cell line (P≤0.05). In contrast, no significant alteration of Vamp2 gene expression was observed. CONCLUSION: Our data indicated no change on the Vamp2 expression level after miRNA transfection, while expression level of Insr was reduced and miR-135 expression was contrarily increased leading to poor stimulation of glucose uptake through insulin, and development of insulin resistance phenotype in C2C12 cell line.

Expression Change of miR-214 and miR-135 during Muscle Differentiation.

OBJECTIVE: MicroRNAs (miRNAs) are a class of small non-coding RNAs that play pivotal roles in many biological processes such as regulating skeletal muscle development where alterations in miRNA expression are reported during myogenesis. In this study, we aimed to investigate the impact of predicted miRNAs and their target genes on the myoblast to myocyte differentiation process. MATERIALS AND METHODS: This experimental study was conducted on the C2C12 cell line. Using a bioinformatics approach, miR-214 and miR-135 were selected according to their targets as potential factors in myoblast to myocyte differentiation induced by 3% horse serum. Immunocytochemistry (ICC) was undertaken to confirm the differentiation process and quantitative real-time polymerase chain reaction (PCR) to determine the expression level of miRNAs and their targets. RESULTS: During myoblast to myocyte differentiation, miR-214 was significantly down- regulated while miRNA-135, Irs2, Akt2 and Insr were overexpressed during the process. CONCLUSION: miR-214 and miR-135 are potential regulators of myogenesis and are involved in skeletal muscle development through regulating the IRS/PI3K pathway.

Short view of leukemia diagnosis and treatment in iran.

BACKGROUND: Early diagnosis and treatment of leukemia patients remains a fundamental aim in clinical oncology, especially in developing country. Present study highlights the basic requirements of these patients in Iran. Better understanding of these issues may lead to improve the healthcare standards toward leukemia diagnosis and treatment. METHODS: This descriptive study included 101 specialists in hematology-oncology and pathology serving in oncology centers. The participants were then asked to fill out a standard questionnaire on the issues around diagnosis and treatment of blood malignancies. RESULTS: According to specialists, unfair distribution of facilities across the country, delayed diagnosis of disease, absence of psychological support for patients, and insufficient financial support were the main reasons of inappropriate diagnosis and treatment in leukemia patients. CONCLUSIONS: Our results show that making an amendment to health policies by preparing well-equipped medical centers in all provinces, improving the morale of patients through consultation during the process of treatment, and above all, subsiding leukemia patients' financial problems will promote the health standard regarding the leukemia diagnosis and treatment in Iran.

Insulin resistance associated genes and miRNAs.

Type 2 diabetes mellitus is the result of resistance to insulin function along with inadequate insulin secretion, leading to a number of dysfunctions characterized by hyperglycemia, and it is associated with microvascular, macrovascular, and neuropathic complications. There is compelling evidence that the decline in both insulin sensitivity and insulin secretion has a genetic component. In addition, increasing evidence suggests that microRNAs (miRNAs) as key regulators of gene expression play significant roles in insulin production, secretion, and function that regulate the function of insulin-target tissues. The current review demonstrates the candidate genes and the related miRNAs involved in molecular pathogenesis of insulin resistance in type 2 diabetes mellitus. In doing so, it provides an opportunity for more focused investigations that may identify the genes and miRNAs with a role in the pathogenesis of type 2 diabetes mellitus and its treatment.

Effect of food deprivation on formalin-induced nociceptive behaviors and ß-endorphin and sex hormone concentration in rats.

BACKGROUND: The present study examined the possible role of endogenous opioidergic system in effect of food deprivation on formalin-induced nociceptive behaviors in male and female rats. Also, we investigated the effect of food deprivation on the plasma level of beta-endorphin and sex hormones. METHODS: Food was withdrawn 48 h prior to performing the formalin test, but water continued to be available ad libitum. The formalin was injected into hind plantar paw. RESULTS: There is significant difference between male and female control rats during phase 2B. Following 48-h food deprivation, both male and female rats exhibited enhanced nociceptive behavior in response to formalin. Food deprivation for 12 and 24 h increased and for 48 h decreased beta-endorphin level in male and female rats. Food deprivation for 24 h decreased testosterone level in male, while it had no significant effect on female rats and food deprivation for 48 h decreased testosterone level in both sexes. Food deprivation for 24 h increased estradiol level in female and that for 48 h had no significant effect on male and female rats. CONCLUSIONS: The present study demonstrates the existence of food deprivation for 48 h causes enhancement of nociception in the formalin test in male and female rats that has correlation with decrease in plasma beta-endorphin and testosterone levels.

Comparison of 16S rDNA-PCR Amplification and Culture of Cerebrospinal Fluid for Diagnosis of Bacterial Meningitis.

OBJECTIVE: Early and accurate diagnosis of bacterial meningitis is of critical concern. Optimum and rapid laboratory facilities are not routinely available for detecting the etiologic agents of meningitis. The objective of this study was to compare polymerase chain reaction (PCR) assay with culture for detection of bacteria in central nervous system (CNS) samples from patients suspected to have meningitis. METHODS: One-hundred cerebrospinal fluid (CSF) samples were obtained and divided into two parts. One part of samples was used for standard bacterial culture and gram staining. The remaining was used for DNA extraction. PCR assay was performed with universal primers for 16S rDNA gene of bacteria. Performance characteristics of the test were determined. FINDINGS: The PCR method was able to detect bacteria in all 36 culture-positive and in 38 of 64 culture-negative cases showing sensitivity and specificity of 100% and 40.6% respectively. Positive predictive value was 48.6% and negative predictive value 100%, however, Kappa coefficient showed the correlation of the 2 methods to be at 0.33. CONCLUSION: There are advantages and disadvantages in performance characteristics of the conventional CSF culture and universal CSF 16S rDNA PCR. Therefore, it is recommended to use both methods in clinical practice, particularly in suspicious contaminated samples, with presumable presence of fastidious or slow growing bacteria because of antibiotic consumption.

Antiandrogenic activities of Glycyrrhiza glabra in male rats.

Abnormal levels of androgens cause many diseases like benign prostatic hyperplasia and hormone dependent cancers. Although the reduction in serum testosterone (T) by Glycyrrhiza glabra has been reported, its effects on seminal vesicle (SV) and prostate tissues have never been reported. This study was carried out to investigate different aspects of antiandrogenic properties of this plant. Immature male rats were divided into five groups (n = 7): castrated rats without any treatment received only vehicle; castrated rats plus T replacement; three castrated groups with T replacement plus various doses of G. glabra extract (75, 150 and 300 mg/kg). All of the injections were carried out once daily in subcutaneous manner for 7 days. On the eighth day, blood samples were collected for total T measurement. Ventral prostate (VP), SV and levator ani muscle were dissected and weighed. Slides prepared from prostate were assessed histologically. The variation in the relative and absolute volume of the prostate tissue compartments was determined. Those receiving the doses of 150 and 300 mg/kg showed a significant reduction (p < 0.05) in prostate weight, total T and VP epithelium/stroma ratio (V/V). These results in SV and levator ani were shown in response to 300 mg/kg of extract. Increasing in T metabolism, down-regulation of androgen receptors or activation of oestrogen receptors could be involved mechanisms. This study showed that alcoholic extract of G. glabra has antiandrogenic properties.