Publications by authors named "Leila Alizadeh"

28 Publications

  • Page 1 of 1

Protection of Beta Boswellic Acid against Streptozotocin-induced Alzheimer's Model by Reduction of Tau Phosphorylation Level and Enhancement of Reelin Expression.

Planta Med 2021 Jun 11. Epub 2021 Jun 11.

Laboratory of Neuro-organic Chemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Alzheimer's disease is a growing general health concern with huge implications for individuals and society. Beta boswellic acid, a major compound of the plant, has long been used for the treatment of various inflammatory diseases. The exact mechanism of beta boswellic acid action in Alzheimer's disease pathogenesis remains unclear. In the current study, the protective effect of beta boswellic acid on streptozotocin-induced sporadic Alzheimer's disease was surveyed. Alzheimer's disease model was induced using streptozotocin followed by an assessment of the treatment effects of beta boswellic acid in the presence of streptozotocin. The prevention effect of beta boswellic acid on Alzheimer's disease induction by streptozotocin was evaluated. Behavioral activities in the treated rats were evaluated. Histological analysis was performed. Phosphorylation of tau protein at residues Ser396 and Ser404 and the expression of reelin protein were determined. Glial fibrillary acidic protein immunofluorescence staining was applied in the hippocampus regions. Our findings indicated that beta boswellic acid decreased traveled distance and escape latency in the prevention (beta boswellic acid + streptozotocin) and treatment (streptozotocin + beta boswellic acid) groups compared to control during the acquisition test. It increased "time spent" (%) in the target quadrant. Reelin level was enhanced in rats treated with beta boswellic acid. Tau hyperphosphorylation (p-tau404) and glial fibrillary acidic protein were decreased in the prevention group while the expression of reelin protein in both groups was increased. We could suggest that the anti-inflammatory property of beta boswellic acid is one of the main factors involving in the improvement of learning and memory in rats. Therefore the antineurodegenerative effect of beta boswellic acid may be due to its ability to reactivate reelin protein.
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http://dx.doi.org/10.1055/a-1502-7083DOI Listing
June 2021

Circulating glucagon-like peptide-1 level in patients with liver cirrhosis.

Arch Physiol Biochem 2020 Oct 12:1-6. Epub 2020 Oct 12.

Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, USA.

Background: Glucagon-like peptide-1 (GLP-1), a gut-derived incretin hormone, plays a pivotal role in glucose-induced insulin secretion. Currently, the role of incretin hormones in the pathogenesis of cirrhosis is not clearly defined. This study aimed to investigate circulating levels of GLP-1 in liver cirrhosis and its association with the severity of liver disease.

Methods: A total of 80 participants including 39 patients with a definite diagnosis of liver cirrhosis and 41 healthy controls recruited in this cross-sectional study. Circulating levels of GLP-1 were determined using the ELISA method. The severity of liver cirrhosis was assessed according to the Child-Pugh, MELD (i), MELD-Na, MELD New, and UK end-stage liver disease score (UKELD) criteria.

Results: The mean age of patients and healthy subjects was 42.51 ± 12.80 and 42.07 ± 10.92 years, respectively ( value = .869). The mean MELD (i), MELD-Na, MELD New, UKELD, and Child-Pugh scores were 14.36 ± 4.26, 15.26 ± 4.81, 14.74 ± 4.66, 52.33 ± 3.82, and 7.28 ± 1.50, respectively. In this study, circulating levels of GLP-1 were statistically lower in cirrhotic patients compared with healthy controls (95.26 ± 17.15 vs 111.84 ± 38.14 pg/mL; value = .017).

Conclusion: Larger prospective studies are needed to explore the incretin effect in cirrhosis patients compared with healthy individuals.
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http://dx.doi.org/10.1080/13813455.2020.1828479DOI Listing
October 2020

The role of HSP90 molecular chaperones in hepatocellular carcinoma.

J Cell Physiol 2020 12 26;235(12):9110-9120. Epub 2020 May 26.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Misfolded proteins have enhanced formation of toxic oligomers and nonfunctional protein copies lead to recruiting wild-type protein types. Heat shock protein 90 (HSP90) is a molecular chaperone generated by cells that are involved in many cellular functions through regulation of folding and/or localization of large multi-protein complexes as well as client proteins. HSP90 can regulate a number of different cellular processes including cell proliferation, motility, angiogenesis, signal transduction, and adaptation to stress. HSP90 makes the mutated oncoproteins able to avoid misfolding and degradation and permits the malignant transformation. As a result, HSP90 is an important factor in several signaling pathways associated with tumorigenicity, therapy resistance, and inhibiting apoptosis. Clinically, the upregulation of HSP90 expression in hepatocellular carcinoma (HCC) is linked with advanced stages and inappropriate survival in cases suffering from this kind of cancer. The present review comprehensively assesses HSP90 functions and its possible usefulness as a potential diagnostic biomarker and therapeutic option for HCC.
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http://dx.doi.org/10.1002/jcp.29776DOI Listing
December 2020

Fecal transmission in COVID-19: A potential shedding route.

J Med Virol 2020 10 6;92(10):1731-1732. Epub 2020 Apr 6.

Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

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http://dx.doi.org/10.1002/jmv.25816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228240PMC
October 2020

Curcumin ameliorates health-related quality of life in patients with liver cirrhosis: A randomized, double-blind placebo-controlled trial.

Complement Ther Med 2020 Mar 19;49:102351. Epub 2020 Feb 19.

Departrment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA; Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, USA.

Objectives: Current study aimed to find the effects of curcumin on quality of life (QoL) in liver cirrhotic patients.

Design: In this randomized double-masked placebo-controlled trial, 70 cases with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1000 mg/day curcumin (n = 35) or placebo (n = 35) for 12 weeks. The health-related QoL (HRQoL) was assessed by CLDQ, LDSI 2.0, and SF-36.

Results: Fifty-eight patients (28 in curcumin and 30 in placebo groups) finished the research. Compared with baseline, overall scores as well as most of CLDQ domains (e.g. Fatigue, Emotional Function, Worry, Abdominal Symptoms, and Systemic Symptoms) and the Physical and Mental health (Total) scores and most of SF-36 domains (e.g. Physical Functioning, Bodily Pain, Vitality, Social Functioning, and Mental Health) increased considerably (P < 0.05) after curcumin administration. Furthermore, curcumin reduced most of LDSI 2.0 domains (e.g. Itch, Joint pain, Pain in the right upper abdomen, Sleeping during the day, Decreased appetite, Depression, Fear of complication, Jaundice, Hindrance in Financial Affairs, Change in use of time, Decreased sexual interest, and Decreased sexual activity) significantly (P < 0.05). Significant differences were noticed between two groups in CLDQ domains and overall scores, LDSI 2.0 domains and overall scores, SF-36 Physical and Mental health (total) scores and all its domains scores (P < 0.05), adjusting for baseline values and disease duration.

Conclusions: Curcumin improved QoL in liver cirrhotic patients according to CLDQ, LDSI 2.0, and SF-36 domains. Additional studies are warranted to consider curcumin as a safe, accessible, and low-cost complementary therapeutic option in cirrhosis.
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http://dx.doi.org/10.1016/j.ctim.2020.102351DOI Listing
March 2020

Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial.

Phytother Res 2020 Jun 3;34(6):1446-1454. Epub 2020 Feb 3.

Department of Pathology and Laboratory Medicine, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Recent reports indicated that curcumin had beneficial effects in animal models of liver injury and cirrhosis. Current study aimed to investigate the effects of curcumin supplementation in patients with liver cirrhosis. In this randomized double-blind placebo-controlled trial, 70 patients with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1,000 mg/day curcumin (n = 35) or placebo (n = 35) for 3 months. Model for end-stage liver disease (MELD) (i), MELD, MELD-Na, and Child-Pugh scores were used to assess the severity of cirrhosis. Sixty patients (29 in the curcumin group and 31 in the placebo group) completed the study. MELD(i) (15.55 ± 3.78 to 12.41 ± 3.07), MELD (15.31 ± 3.07 to 12.03 ± 2.79), MELD-Na (15.97 ± 4.02 to 13.55 ± 3.51), and Child-Pugh (7.17 ± 1.54 to 6.72 ± 1.31) scores decreased significantly in the curcumin group after 3-month intervention (p < .001, p < .001, p = .001, and p = .051, respectively), whereas they increased significantly in the placebo group (p < .001, p < .001, p < .001, p = .001, respectively). Significant differences were only observed between the two groups in MELD(i), MELD, MELD-Na, and Child-Pugh scores after 3-month intervention (p < .001 for all of them). In this pilot study, beneficial effects of curcumin supplementation were observed in decreasing disease activity scores and severity of cirrhosis in patients with cirrhosis.
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http://dx.doi.org/10.1002/ptr.6620DOI Listing
June 2020

The effect of Lipopolysaccharide (LPS) pretreatment on hippocampal apoptosis in traumatic rats.

Neurol Res 2020 Feb 8;42(2):91-98. Epub 2020 Jan 8.

Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.

: Traumatic brain injury (TBI) is a serious medical problem that affects the quality of life. Apoptosis is a form of programmed cell death that happens after trauma. Effector caspases are responsible for initiating apoptosis.: In the present study, we examined the effect of LPS preconditioning (0.1 and 0.5 mg/kg, ip; 5 days prior controlled cortical injury) on apoptosis, 4 and 12 hours after trauma. We investigated possible mechanisms on the expression of caspase3 and caspase7 in hippocampal CA1 and CA3 areas by using immunohistochemistry and Western blotting techniques and also TUNEL-positive cells.: Higher expression of caspase3 and caspase7 were accompanied by a higher number of dead neurons in traumatic rats 4 and 12 hours after trauma(P < 0.05). LPS preconditioning decreased caspase3 and caspase7over-expression and the number of dead neurons in the hippocampus(P < 0.05).: Our data indicate that LPS preconditioning inhibits neural damage and apoptosis induced by trauma in the hippocampus.
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http://dx.doi.org/10.1080/01616412.2019.1709139DOI Listing
February 2020

Wernicke encephalopathy following gastrojejunostomy: A case report and review of the literature.

Turk J Emerg Med 2019 Oct 22;19(4):154-156. Epub 2019 Aug 22.

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.

Introduction: Non-alcoholic Wernicke encephalopathy (WE) is a life-threatening condition, which is caused due to thiamine deficiency. We reported a case of non-alcoholic WE following gastrojejunostomy.

Case Presentation: A 31-year-old woman was admitted to our tertiary care center complaining about intractable nausea and vomiting following her gastrojejunostomy. She had undergone gastrojejunostomy because of gastric outlet obstruction after a suicide attempt with scale-remover. Two weeks after gastrojejunostomy, the altered mental status and confusion were reported and she also had a reduced range of motion, dysarthria, generalized muscle weakness, and vertical nystagmus. She gradually became uninterested in surroundings. WE was considered a differential diagnosis, which was confirmed by magnetic resonance imaging (MRI). High-dose intravenous thiamine administration was done for the patient and her symptoms were improved. We also reviewed the PubMed to evaluate studies on WE following gastrointestinal surgeries conducted through the last 10 years.

Conclusion: WE is a rare presentation of gastrojejunostomy and it should be considered as differential diagnosis when patient had impaired mental status and other related WE symptoms following gastrojejunostomy. Early diagnosis and management of WE in the Emergency Department can reduce the mortality and morbidity of WE.
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http://dx.doi.org/10.1016/j.tjem.2019.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819708PMC
October 2019

Conservative Management of Asymptomatic Pneumoperitoneum; Report of Two Cases.

Arch Acad Emerg Med 2019 3;7(1):e12. Epub 2019 Jan 3.

Department of Radiology, Tabriz University of Medical Sciences, Tabriz, Iran.

Peptic ulcer disease is a common gastrointestinal disorder, the prevalence of which has reduced in recent years due to effective new treatments. Peptic ulcer perforation is an emergent life-threatening condition that causes pneumoperitoneum and septic shock. It often requires surgical procedures. We describe two cases of peptic ulcer perforation with only mild discomfort on the epigastric region since several months before. The patients were treated with a high dose proton pump inhibitor and conservative treatment without surgical procedures. Weekly follow up of the cases showed that the clinical condition of patients remained stable without any new signs and symptoms. This report shows that noninvasive treatment alone can be effective in some cases with mild symptoms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377218PMC
January 2019

Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains.

Osong Public Health Res Perspect 2019 Feb;10(1):6-11

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

Objectives: Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans.

Methods: Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus.

Results: Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue.

Conclusion: These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease.
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http://dx.doi.org/10.24171/j.phrp.2019.10.1.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396821PMC
February 2019

Chitosan-based nanotherapeutics for ovarian cancer treatment.

J Drug Target 2019 09 11;27(8):839-852. Epub 2019 Feb 11.

a Department of Medical Biotechnology, Faculty of Advanced Medical Sciences , Tabriz University of Medical Sciences , Tabriz , Iran.

Chitosan is one of the low toxic and natural polysaccharides which is obtained from deacetylation of chitin. Chitosan-based nanoparticles have good biodegradation and bio-distribution in the biological milieu, which have made it as one of the most attractive nanocarriers for delivering different therapeutic agents to the tumour cells especially ovarian cancer cell lines. Chitosan can covalently and non-covalently be modified and attached to different polymers and targeting moieties through its free amine groups and reach to the tumour site through passive and active targeting strategies. Ovarian cancer is one of the most common and resistant cancers with poor prognosis among women, which scientists are trying to prepare new methods for improving their treatments outcomes in past decades. In this article, we tried to take an overview on the recent developments in different modifications of chitosan-based nanoformulations, which are utilised for ovarian cancer therapy.
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http://dx.doi.org/10.1080/1061186X.2018.1564923DOI Listing
September 2019

Late Cardiac Complications of Sulfur Mustard Poisoning in 38 Iranian Veterans.

Cardiovasc Toxicol 2019 06;19(3):220-228

School of Medicine, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

It was aimed to investigate possible late cardiac effects of Sulfur mustard (SM) exposure in Iranian veterans. Thirty-eight veterans with late complications of SM exposure were investigated. Clinical history, physical examinations, 12 leads electrocardiography and transthoracic echocardiography were performed. Computed tomography coronary angiography (CTCA) was performed as clinically indicated for angiographic assessment and patients were stratified according to the CTCA findings. Incomplete right bundle branch block and right axis deviation were detected in 3 (7.9%) and 4 (10.5%) cases, respectively. Mean value of left ventricular ejection fraction was 55.7 ± 2.9%. Different degrees of right ventricular dilation was observed in seven (18.4%) patients. All the patients showed mild to moderate degrees of tricuspid regurgitation. Increased pulmonary artery pressure (PAP) was detected in 16 (42.1%) patients. Out of 18 patients who underwent CTCA, non-obstructive and obstructive coronary artery disease (CAD) were observed in three (16.66%) and eight (44.44%) patients, respectively. CAD was stratified to single vessel (5.5%), two vessels (27.8%) and three vessels disease (11.1%). Mean coronary artery calcium score was 50.91 ± 115.58. SM has cardiovascular toxicity, as a delayed complication of this chemical warfare poisoning.
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http://dx.doi.org/10.1007/s12012-018-9481-zDOI Listing
June 2019

Switching from high-fat diet to foods containing resveratrol as a calorie restriction mimetic changes the architecture of arcuate nucleus to produce more newborn anorexigenic neurons.

Eur J Nutr 2019 Jun 21;58(4):1687-1701. Epub 2018 May 21.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: These days, obesity threatens the health for which one of the main interventions is calorie restriction (CR). Due to the difficulty of compliance with this treatment, CR mimetics such as resveratrol (RSV) have been considered. The present study compared the effects of RSV and CR on hypothalamic remodeling in a diet-switching experiment.

Methods: C57BL/6 male mice received high-fat diet (HFD) for 4 weeks, subsequently their diet switched to chow diet, HFD + RSV, chow diet + RSV or CR diet for a further 6 weeks. Body weight, fat accumulation, hypothalamic apoptosis and expression of trophic factors as well as generation and fate specification of newborn cells in arcuate nucleus (ARC) were evaluated.

Results: Switching diet to RSV-containing foods leading to weight and fat loss after 6 weeks. In addition, not only a significant reduction in apoptosis but also a considerable increase in production of newborn cells in ARC occurred following consumption of RSV-enriched diets. These were in line with augmentation of hypothalamic ciliary neurotrophic factor and leukemia inhibitory factor expression. Interestingly, RSV-containing diets changed the fate of newborn neurons toward generation of more proopiomelanocortin than neuropeptide Y neurons. The CR had effects similar to those of RSV-containing diets in the all-evaluated aspects besides neurogenesis in ARC.

Conclusions: Although both RSV-containing and CR diets changed the fate of newborn neurons to create an anorexigenic architecture for ARC, newborn neurons were more available after switching to RSV-enriched diets. It can be consider as a promising mechanism for future investigations.
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http://dx.doi.org/10.1007/s00394-018-1715-0DOI Listing
June 2019

Apoptosis Following Cortical Spreading Depression in Juvenile Rats.

Mol Neurobiol 2018 May 13;55(5):4225-4239. Epub 2017 Jun 13.

Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.

Repetitive cortical spreading depression (CSD) can lead to cell death in immature brain tissue. Caspases are involved in neuronal cell death in several CSD-related neurological disorders, such as stroke and epilepsy. Yet, whether repetitive CSD itself can induce caspase activation in adult or juvenile tissue remains unknown. Inducing repetitive CSD in somatosensory cortices of juvenile and adult rats in vivo, we thus aimed to investigate the effect of repetitive CSD on the expression caspase-3, caspase-8, caspase-9, and caspase-12 in different brain regions using immunohistochemistry and western blotting techniques. Higher numbers of dark neurons and TUNEL-positive cells were observed in the hippocampal CA1 and CA3 regions as well as in the entorhinal and somatosensory cortices after CSD in juvenile rats. This was accompanied by higher expressions of caspase-3, caspase-8, and caspase-9. Caspase-12 levels remained unchanged after CSD, suggesting that endoplasmic reticulum stress is not involved in CSD-triggered apoptosis. Changes in caspase expression were paralleled by a decrease of procaspase-3, procaspase-8, and procaspase-9 in juvenile rat brain tissue subjected to CSD. In contrast, repetitive CSD in adult rats did not result in the upregulation of caspase signaling. Our data points to a maturation-dependent vulnerability of brain tissue to repetitive CSD with a higher degree of apoptotic damage and caspase upregulation observed in juvenile tissue. Findings suggest a key role of caspase signaling in CSD-induced cell death in the immature brain. This implies that anti-apoptotic treatment may prevent CSD-related functional deficits in the immature brain.
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http://dx.doi.org/10.1007/s12035-017-0642-zDOI Listing
May 2018

Astrocyte-mediated inflammation in cortical spreading depression.

Cephalalgia 2018 04 3;38(4):626-638. Epub 2017 Apr 3.

1 Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran.

Background Cortical spreading depression (CSD) related diseases such as migraine, cerebrovascular diseases, and epilepsy have been associated with reactive astrocytosis, yet the mechanisms of these tissue changes remain unclear. CSD-induced inflammatory response has been proposed to play a role in some neurological disorders and thus may also contribute to reactive astrocytosis. Methods Using ex vivo brain slices and in vitro astrocytic cultures, we aimed to characterize CSD related changes in astrocytes and markers of inflammation by immunocyto- and immunohistochemistry. CSD was induced by application of KCl (3 mol/l) on neocortical tissues. The application of KCl was repeated weekly over the course of four weeks. Results CSD induced an increase in the mean number and volume of astrocytes in rat brain tissue when compared to controls, whereas no changes in neuronal numbers and volumes were seen. These cell-type specific changes, suggestive of reactive astrocytosis, were paralleled by an increased expression of protein markers indicative of astrocytes and neuroinflammation in ex vivo brain slices of animals undergoing CSD when compared to sham-treated controls. Cultured astrocytes showed an increased expression of the immune modulatory enzyme indoleamine 2,3-dioxygenase and an elevated expression of the pro-inflammatory markers, IL-6, IL-1β, and TNFα in addition to increased levels of toll like receptors (TLR3 and TLR4) and astrocytic markers after induction of CSD. Conclusion These findings indicate that CSD related reactive astrocytosis is linked to an upregulation of inflammatory markers. Targeting inflammation with already approved and available immunomodulatory treatments may thus represent a strategy to combat or ameliorate CSD-related disease.
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http://dx.doi.org/10.1177/0333102417702132DOI Listing
April 2018

In vitro differentiation of neural stem cells derived from human olfactory bulb into dopaminergic-like neurons.

Eur J Neurosci 2017 03 1;45(6):773-784. Epub 2017 Mar 1.

Brain and Spinal Cord Injury Research Center, Imam Khomeinin Hospital, Blv Keshavarz, Tehran University of Medical Sciences, Tehran, 1419733141, Iran.

This study describes a new accessible source of neuronal stem cells that can be used in Parkinson's disease cell transplant. The human olfactory bulb contains neural stem cells (NSCs) that are responsible for neurogenesis in the brain and the replacement of damaged cellular components throughout life. NSCs are capable of differentiating into neuronal and glial cells. We isolated NSCs from the olfactory bulb of brain-death donors and differentiated them into dopaminergic neurons. The olfactory bulb tissues obtained were cultured in Dulbecco's modified Eagle's medium/nutrient mixture F12, B27 supplemented with basic fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor. The NSCs and proliferation markers were assessed. The multipotentiality of olfactory bulb NSCs was demonstrated by their capacity to differentiate into neurons, oligodendrocytes and astrocytes. To generate dopaminergic neurons, olfactory bulb NSCs were differentiated in neurobasal medium, supplemented with B27, and treated with sonic hedgehog, fibroblast growth factor 8 and glial cell-derived neurotrophic factor from the 7th to the 21st day, followed by detection of dopaminergic neuronal markers including tyrosine hydroxylase and aromatic l-amino acid decarboxylase. The cells were expanded, established in continuous cell lines and differentiated into the two classical neuronal phenotypes. The percentage of co-positive cells (microtubule-associated protein 2 and tyrosine hydroxylase; aromatic l-amino acid decarboxylase and tyrosine hydroxylase) in the treated cells was significantly higher than in the untreated cells. These results illustrate the existence of multipotent NSCs in the adult human olfactory bulb that are capable of differentiating toward putative dopaminergic neurons in the presence of trophic factors. Taken together, our data encourage further investigations of the possible use of olfactory bulb NSCs as a promising cell-based therapeutic strategy for Parkinson's disease.
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http://dx.doi.org/10.1111/ejn.13504DOI Listing
March 2017

Comparison of histopathological effects of perineural administration of bupivacaine and bupivacaine-dexmedetomidine in rat sciatic nerve.

Exp Toxicol Pathol 2016 Nov 17;68(10):559-564. Epub 2016 Sep 17.

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran; Shefa Neuroscience Research Center, Khatam-Al-Anbia Hospital, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0.2ml of 0.5% bupivacaine (n=8) or 0.5% bupivacaine plus 0.005% DEX (n=8) or normal saline (0.9%, as control group) (n=4) in the left hind extremity. Sciatic nerves were harvested at 14days post-injection and analyzed for nerve damage using ultrastructure and histopathologic analysis. Histopathology of sciatic nerve at day 14 post-injection showed a variable degree of neuronal injury associated with perineural inflammation in each treatment group and was classified as none or mild, intermediate or severe. Administration of both LAs resulted in a significant decrease in the total number of myelinated fibers per nerve (95% CI for group difference: Bupivacaine, P=0.001, DEX-Bupivacaine, P=0.036) compared to the saline control group. Animals that received these perineural local anesthetics (LAs) injections showed increased severity of injury compared to the control group. Animals in the DEX-Bupivacaine group had higher perineural inflammation and nerve damage than those of the saline control group and less than those of the Bupivacaine group at day 14 post-injection. Quantitatively, average total nerve fiber per nerve and average myelinated nerve fiber density in the injured region of the Bupivacaine-treated group was less than that of the DEX-Bupivacaine-treated group. LAs injection into the nerve causes peripheral nerve damage and remains an important clinical danger. Bupivacaine is associated with considerable histopathological changes, including edema of the perineurium and myelin degeneration with Wallerian degeneration, when injected perineurally. Perineural DEX added to a clinical concentration of bupivacaine attenuates the Bupivacaine-induced injuries.
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http://dx.doi.org/10.1016/j.etp.2016.09.001DOI Listing
November 2016

Psychometric Properties of The Persian Version of The Prenatal Attachment Inventory in Pregnant Iranian Women.

Int J Fertil Steril 2016 Jul-Sep;10(2):184-9. Epub 2016 Jun 1.

Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Background: In 1993, Muller developed the Prenatal Attachment Inventory (PAI) which has been used widely in many studies and translated into several languages. The current study aimed to translate the PAI into Persian, assess the underlying structure of the PAI, and the appropriateness of the one-factor solution proposed by Muller.

Materials And Methods: In this cross-sectional study, we recruited a total of 322 primi- gravidae in their 27(th) to 34(th) gestational weeks that referred to private and governmental prenatal clinics in Tehran, Iran. All participants completed the Persian versions of the PAI and a demographic questionnaire. Participants were re-tested 2 weeks after the initial test- ing. The following psychometric properties of the PAI were investigated: construct validity by confirmatory factor analysis (CFA), internal consistency reliability with Cronbach's alpha, and test-retest reliability according to the intraclass correlation coefficient (ICC).

Results: The CFA results indicated that a single-factor model provided good fit to the data, which confirmed the original model by its developer. The Cronbach's alpha coef- ficient for PAI was 0.856 and the test-retest reliability with ICC was 0.784. Consider- ing the duration between marriage and pregnancy, women with low duration scored significantly higher than women with high duration on PAI (P=0.043).

Conclusion: The Persian version of the PAI showed that one factor structure was ad- equate and could be used for measuring psychological affectionate attachment between Iranian mothers and their fetuses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948070PMC
http://dx.doi.org/10.22074/ijfs.2016.4908DOI Listing
July 2016

Rapamycin Augments Immunomodulatory Properties of Bone Marrow-Derived Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis.

Mol Neurobiol 2017 05 12;54(4):2445-2457. Epub 2016 Mar 12.

Infectious Diseases Research Center, Department of Microbiology, Golestan University of Medical Sciences, P.O. Box 49175-1141, Gorgan, Iran.

The immunomodulatory and anti-inflammatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have been considered as an appropriate candidate for treatment of autoimmune diseases. Previous studies have revealed that treatment with BM-MSCs may modulate immune responses and alleviate the symptoms in experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Therefore, the present study was designed to examine immunomodulatory effects of BM-MSCs in the treatment of myelin oligodendrocyte glycoprotein (MOG) 35-55-induced EAE in C57BL/6 mice. MSCs were obtained from the bone marrow of C57BL mice, cultured with DMEM/F12, and characterized with flow cytometry for the presence of cell surface markers for BM-MSCs. Following three passages, BM-MSCs were injected intraperitoneally into EAE mice alone or in combination with rapamycin. Immunological and histopathological effects of BM-MSCs and addition of rapamycin to BM-MSCs were evaluated. The results demonstrated that adding rapamycin to BM-MSCs transplantation in EAE mice significantly reduced inflammation infiltration and demyelination, enhanced the immunomodulatory functions, and inhibited progress of neurological impairments compared to BM-MSC transplantation and control groups. The immunological effects of rapamycin and BM-MSC treatments were associated with the inhibition of the Ag-specific lymphocyte proliferation, CD8+ cytolytic activity, and the Th1-type cytokine (gamma-interferon (IFN-γ)) and the increase of Th-2 cytokine (interleukin-4 (IL-4) and IL-10) production. Addition of rapamycin to BM-MSCs was able to ameliorate neurological deficits and provide neuroprotective effects in EAE. This suggests the potential of rapamycin and BM-MSC combined therapy to play neuroprotective roles in the treatment of neuroinflammatory disorders.
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http://dx.doi.org/10.1007/s12035-016-9840-3DOI Listing
May 2017

Is Routine Iron Supplementation Necessary in Pregnant Women With High Hemoglobin?

Iran Red Crescent Med J 2016 Jan 27;18(1):e22761. Epub 2016 Jan 27.

Department of Health Education and Promotion, School of Public Health, Alborz University of Medical Sciences, Karaj, IR Iran.

Background: Iron supplementation is a chief component in prenatal care, with the aim of preventing anemia; however, extreme maternal iron status may adversely affect the birth outcome. Given the negative consequences of high maternal iron concentrations on pregnancy outcomes, it seems that iron supplementation in women with high hemoglobin (Hb) should be limited.

Objectives: The aim of this study was to examine the effect of iron supplementation on iron status markers in pregnant women with high Hb.

Patients And Methods: In a randomized, double-blind, placebo-controlled trial, 86 pregnant women with Hb > 13.2 g/dL and ferritin > 15 μg/l in the 16th - 20th week of pregnancy were randomized into experimental and control groups. From the 20th week until the end of pregnancy, the experimental group received one ferrous sulfate tablet containing 50 mg of elemental iron daily, while the control group received a placebo. Hb and ferritin levels at 37 - 39 weeks of pregnancy were evaluated and compared. In addition, after delivery the birth weight was measured in two groups and compared.

Results: There were statistically significant differences between the two groups in Hb (p = 0/03) and ferritin (p = 0/04) levels at the end of pregnancy, but the incidence of anemia exhibited no difference in either group (p < 0/001). In addition, the mean of birth weight in experimental group and control group were 3391/56 ± 422, 3314/06 ± 341, respectively and it was not significant difference (p = 0.2).

Conclusions: Not using iron supplementation did not cause of anemia in women with Hb concentrations greater than 13.2 g/dL during pregnancy; thus, the systematic care and control of iron status markers without iron supplementation is recommended for these women.
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http://dx.doi.org/10.5812/ircmj.22761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753023PMC
January 2016

Determination of the Best Concentration of Streptozotocin to Create a Diabetic Brain Using Histological Techniques.

J Mol Neurosci 2016 May 20;59(1):24-35. Epub 2016 Jan 20.

Laboratory of Neuro-Organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.

Alzheimer's disease (AD) is one of the most important disorders among neurodegenerative diseases which is characterized by neurofibrillary tangles and senile plagues. Intercerebroventricular (ICV) streptozotocin administration is a form of sAD which was applied to examine different factors following AD. Previous reports used different doses of streptozotocin (STZ) to create Alzheimer's model, but no standard dose has been introduced. Therefore, we decided to investigate the best concentration of STZ to induce a diabetic brain with lowest mortality rate and high severity of destruction. We treated rats with three different doses of STZ (STZ 1.5, 2.25, and 3 mg/kg, ICV). Spatial memory for treated rats was evaluated by Morris water maze (MWM). Locomotor activities of rats were assessed by open field test. Histological observation such as immunohistochemistry, immunofluorescence, and Nissl staining were performed on the brain especially in CA1, CA3, and DG regions of hippocampal neurons at residues P-ser396 and P-ser404. Our data suggest that although the percentage hyperphosphorylation of tau protein by injection of STZ 3 mg/kg was about 10 % more than STZ 2.25 mg/kg compared to the control group, we considered the latter doses due to no effect on motor activities and enhance the number of glial cells.
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http://dx.doi.org/10.1007/s12031-015-0702-7DOI Listing
May 2016

Lipopolysaccharide preconditioning prevents acceleration of kindling epileptogenesis induced by traumatic brain injury.

J Neuroimmunol 2015 Dec 4;289:143-51. Epub 2015 Nov 4.

Brain and Spinal cord injury Research Center, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

10-20% of symptomatic epilepsies are post-traumatic. We examined effect of LPS preconditioning on epileptogenesis after controlled cortical impact (CCI). LPS (0.01, 0.1 and 0.5 mg/kg) was injected i.p. to rats 5 days before induction of CCI to parieto-temporal cortex. Kindling started 24h after CCI by i.p. injection of 30 mg/kg of pentylenetetrazole every other day until manifestation of 3 consecutive generalized seizures. CCI injury accelerated the rate of kindled seizures acquisition. LPS (0.1 and 0.5 mg/kg) prevented the acceleration of kindling. LPS preconditioning significantly decreased IL-1β and TNF-α over-expression and the number of damaged neurons in the hippocampus of traumatic rats.
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http://dx.doi.org/10.1016/j.jneuroim.2015.11.003DOI Listing
December 2015

Recurrence and Five -Year Survival in Colorectal Cancer Patients After Surgery.

Iran J Cancer Prev 2015 Aug 24;8(4):e3439. Epub 2015 Aug 24.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

Background: Colorectal cancer (CRC) is a common malignancyworldwide and its outcome is most closely related to the extent of disease at presentation. Early diagnosis of an asymptomatic recurrence increases the likelihood of a complete surgical resection.

Objectives: The aim of this study was to evaluate the incidence of colorectal cancer recurrence and survival rate within 5 years, after surgery.

Patients And Methods: During the 9-year period since 21st Mar, 2004 to 20th Mar, 2013, patients whose primary colorectal cancer were resected in Taleghani hospital, Tehran, Iran were selected in a historical cohort. The necessary data such as demographic, age, gender, family history of CRC, site and size of tumor, stage of tumor, operation details, histological results, treatment method, histopathologic, etc. were collected. Then the recurrence and survival of colorectal cancer within 5 years after operation and their risk factors were evaluated. P value less than 0.05 were considered significant. All analysis was done using SPSS software.

Results: A total of 107 patients underwent resection for colorectal cancer during the study period, with mean age of 53.50 ± 12.68 years (range 24 - 76 years), survival rate of 73.8% (rectum 70.0% and colon 75.9%), and mean survival time of 142.17 ± 21.60 month. The recurrence rate of CRC patients, during five years after surgery was 5.7%. Regional lymph nodes, Distance metastasis and Adjuvant therapy were significant prognosis factors of survival after surgery.

Conclusions: The rate of recurrence in Iranian patients was low, which could be due to improvement of exactness and expertise of surgeons or better adjuvant therapy. The significant association between survival and adjuvant therapy clarifies this finding. Early diagnosis and primary detection could increase the rate of survival.
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http://dx.doi.org/10.17795/ijcp.3439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606369PMC
August 2015

Older People's Perspectives on Health, Physical Activity and Nutritional Behaviors.

Health Promot Perspect 2015 30;5(4):288-95. Epub 2016 Jan 30.

Department of Health Education and Promotion, School of Public Health, Alborz University of Medical Sciences, Karaj, Iran.

Background: Approaches for investigating health-promoting lifestyle generally focus on physical activity and regular diet. To explore the perspectives of Iranian elders regarding health, healthy eating and physical activity (PA) this study was conducted in 2012.

Methods: Participants in this qualitative study were selected through purposeful sampling. Ten focus groups were conducted with 60 older adults in 3 elderly centers in Tehran. A moderator's guideline that consisted of general and specific questions was used. Focus groups were audio recorded, transcribed verbatim and analysis was performed using conventional content analysis.

Results: Participants explained their perspectives regarding health, healthy eating and PA in the following 5 categories: meaning of health was represented based on issues such as absence of pain and disorder, complete body wellbeing, staying away from hazards, complete individual satisfaction, experiencing positive events, effective communication, faithfulness and trust in God. The healthy eating category was featured by adequate eating, age balanced diet, refraining from under or over nutrition and sensible consumption of fruits and vegetables. The PA was described - according to the level of performing outdoor activities or household tasks. Expressions about the perceived benefits and barriers of healthy eating and PA were aligned the two remaining categories.

Conclusions: Participants have referred to the association between both PA and dietary practices and health. Understanding how older people define physical activity and nutritional behavior and recognition of the most important perceived benefits and barriers that might contribute to have a healthy eating or adequate PA profile could procure insight into the type of interventions that are required to promote healthy lifestyle among Iranian older adults.
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http://dx.doi.org/10.15171/hpp.2015.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772799PMC
March 2016

Impact of maternal hemoglobin concentration on fetal outcomes in adolescent pregnant women.

Iran Red Crescent Med J 2014 Aug 1;16(8):e19670. Epub 2014 Aug 1.

Hematology Reaserch Center, Departement of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, IR Iran.

Background: Studies on the association between maternal hemoglobin (Hb) concentration and adverse pregnancy outcome have been inconsistent. Many studies have shown the impact of Hb concentration on pregnancy outcomes in adult women; however, it is not revealed in adolescent pregnant women.

Objectives: The aim of this study was to examine the effect of Hb concentration on birth outcomes in pregnant adolescents as a high-risk group.

Patients And Methods: In this cross-sectional study, 312 healthy and nonsmoker adolescent pregnant women with gestational age (GA) of 37-40 weeks were chosen by random sampling, and were followed until delivery. A complete history was obtained from women. In addition, clinical examination and Hb test were performed. After birth, the associations between Hb concentration during pregnancy and birth outcomes were investigated. Statistical analyses were performed using SPSS software by t-test, chi-square and ANOVA.

Results: In total, about 23.2 % were anemic, 58% had normal level of Hb (11-13.2 g/dL) and 18.8% had Hb > 13.2 g/dL. The mean birth weight was 3197.8 ± 398.25 grams and it was more in mothers with Hb = 10.5-12.5 g/dL than others (Hb < 10.5 or Hb > 12.5 g/dL) (P < 0.001). The lowest mean birth weight was found in mothers with Hb < 10.5 (3033.33 ± 422). Moreover, the mean birth weight of male newborns was more than females (P = 0.001). Eight percent of neonates had Apgar score less than eight. Low Apgar score in anemic group and mothers with high Hb concentration (Hb > 12.5 g/dL) was more than others.

Conclusions: Abnormal Hb concentrations increase the risk of adverse birth outcomes such as low birth weight (LBW) and low Apgar scores in pregnant adolescents, so intensive care is recommended for this group of pregnant women.
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http://dx.doi.org/10.5812/ircmj.19670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222017PMC
August 2014

Using fertile couples as embryo donors: An ethical dilemma.

Iran J Reprod Med 2014 Mar;12(3):169-74

Department of Epidemiology and Reproductive Health at Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. ; Medical Ethics and History of Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The use of donated embryos has offered hope for infertile couples who have no other means to have children. In Iran, fertility centers use fertile couples as embryo donors. In this paper, the advantages and disadvantages of this procedure will be discussed. We conclude that embryo-donation should be performed with frozen embryos thus preventing healthy donors from being harmed by fertility drugs. There must be guidelines for choosing the appropriate donor families. In countries where commercial egg donation is acceptable, fertile couples can be procured as embryo donors thus fulfilling the possible shortage of good quality embryos. Using frozen embryos seems to have less ethical, religious and legal problems when compared to the use of fertile embryo donors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009569PMC
March 2014

Round cell liposarcoma metastatic to the heart.

J Card Surg 2013 Nov 30;28(6):672-4. Epub 2013 Jun 30.

Department of Cardiac Surgery, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

Myxoid liposarcoma is a soft tissue tumor in adults with rare cardiac involvement. We report a 50-year-old female with high grade round cell liposarcoma of the left knee with metastases to the right heart chambers. The tumor was located in the right atrium with extension to right ventricle. The Patient underwent radiotherapy after surgical resection and 12-month follow-up revealed no recurrent cardiac disease.
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http://dx.doi.org/10.1111/jocs.12148DOI Listing
November 2013

Debate in embryo donation: embryo donation or both-gamete donation?

Reprod Biomed Online 2009 ;19 Suppl 1:29-33

Ethical department of Royan Institute, Tehran, Iran.

So far, more than 2 million babies have been born worldwide through assisted reproduction technologies. For many couples, there is no treatment except by involving a third party. Recently, embryo donation law has been approved by Iran's parliament and now it is legal in Iran. But there is a misunderstanding regarding the source of embryos: they can be obtained from surplus frozen embryos of infertile couples or embryos can be made from donated spermatozoa and eggs from fertile married couples. Here in this paper we discuss ethical, religious and legal aspects of these two procedures and present the advantages and disadvantages of them. Meanwhile, the new term 'both-gamete donation' was defined for the procedure that is practised here instead of 'embryo donation'. In conclusion we can say: (i) Iranian law means only embryo donation and covers only surplus embryos from other infertile couples and not both-gamete donation; (ii) as gamete donation is practised in Iran upon decrees of clergy leaders, we have no law or legislation against both-gamete donation; (iii) there are many ethical, legal and religious questions about both-gamete donation to be answered; (iv) ethical and religious questions are fewer concerning embryo donation compared with both-gamete donation; and (v) embryo sharing is a good way for donation of fresh embryos.
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http://dx.doi.org/10.1016/s1472-6483(10)60061-2DOI Listing
September 2009