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Aquaporin 4: A key player in Parkinson's disease
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases which occur in aged people worldwide. Given that a sequence of cellular and molecular mechanisms, including oxidative stresses, apoptosis, inflammatory pathways, microglia, astrocyte activation, and aquaporin 4 (AQP4) are associated with initiation and the progression of PD. AQP4 may affect various pathways (i.e., α-synuclein, inflammatory pathways, and microglia and astrocyte activation). Few reports have evaluated the relationship between AQP4 and PD-related cellular and molecular pathways. Here, for the first time, we highlighted the relationship between AQP4 and molecular mechanisms involved in PD pathogenesis. © 2019 Wiley Periodicals, Inc
Relationship between dietary patterns and mild cognitive impairment (MCI) in elderly women
Context: Mild cognitive impairment (MCI) is a transitional stage in cognitive performance between changes seen in normal aging and those observed in dementia. Early diagnosis and intervention during the initial stages of mild cognitive impairment can delay or prevent the onset of dementia. Preventive behavioral interventions, for instance changes in dietary patterns, can play a major role in reducing the burden of this disease. Aim: The aim of this study was to determine the association between dietary patterns and MCI in the elderly. Methods and material: The present case-control study was performed on 82 cases and 163 controls constituted by 60 year-old or older women. We conducted interviews and completed a general questionnaire, IPAQ, FFQ, and MMSE. We used factor analysis and principal component analysis to derive dietary patterns and the chi-square test, independent t-test, and logistic regression to analyze the data. Results: There were significant differences between the two groups in terms of educational level (P = 0.033), employment (p = 0.001), and the number of minutes of study (P =0.020). We identified three dietary patterns including unhealthy, Western, and healthy dietary patterns. There was a statistically significant difference between the two groups only in terms of the healthy dietary pattern (P = 0.004). The odds ratio of developing MCI in people who were in the highest tertile of the healthy dietary pattern was 50 lower than those in the first tertile (OR=0.496, 95CI: 0.261, 0.943). Conclusion: Our present study demonstrated that only the healthy dietary pattern was significantly associated with MCI and reduced the risk of the disease. It is recommended that further prospective studies be conducted to find more robust relationships. © Mattioli 1885
Neuropathological and genomic characterization of glioblastoma-induced rat model: How similar is it to humans for targeted therapy?
Glioblastoma multiforme (GBM) is a unique aggressive tumor and mostly develops in the brain, while rarely spreading out of the central nervous system. It is associated with a high mortality rate; despite tremendous efforts having been made for effective therapy, tumor recurrence occurs with high prevalence. To elucidate the mechanisms that lead to new drug discovery, animal models of tumor progression is one of the oldest and most beneficial approaches to not only investigating the aggressive nature of the tumor, but also improving preclinical research. It is also a useful tool for predicting novel therapies' effectiveness as well as side effects. However, there are concerns that must be considered, such as the heterogeneity of tumor, biological properties, pharma dynamic, and anatomic shapes of the models, which have to be similar to humans as much as possible. Although several methods and various species have been used for this approach, the real recapitulation of the human tumor has been left under discussion. The GBM model, which has been verified in this study, has been established by using the Rat C6 cell line. By exploiting bioinformatic tools, the similarities between aberrant gene expression and pathways have been predicted. In this regard, 610 common genes and a number of pathways have been detected. Moreover, while magnetic resonance imaging analysis enables us to compare tumor features between these two specious, pathological findings provides most of the human GBM characteristics. Therefore, the present study provides genomics, pathologic, and imaging evidence for showing the similarities between human and rat GBM models. © 2019 Wiley Periodicals, Inc
A pilot study to evaluate the effects of oral N-acetyl cysteine on inflammatory and oxidative stress biomarkers in rheumatoid arthritis
Background: Rheumatoid Arthritis (RA) is a common inflammatory disease of the joints. Due to the importance of inflammation and oxidative stress in the pathogenesis of RA, drugs that have anti-oxidant and anti-inflammatory properties, such as N-acetyl Cysteine (NAC), can be used as adjunctive therapy in patients with RA. Aims: The aim of this study was to evaluate the effects of oral NAC on inflammatory cytokines and oxidative stress in patients with RA. Methods: Adjunct to standard treatment, the NAC group (23 patients) received 600 mg of NAC twice daily and the placebo group (19 patients) received identical placebo twice daily for 12 weeks. Serum levels of Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), nitric oxide (NO), Total Thiol Groups (TTG), Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR) were measured at baseline and at the end of the study. Results: Results showed that in the NAC group, the serum levels of MDA, NO, IL-6, TNF-α, ESR and CRP were significantly lower than the baseline. Also, the serum level of TAC and TTG, as antioxidant parameters, increased significantly. However, only NO, MDA and TTG showed a significant difference in the NAC group �as compared to the placebo group at the end of study. Conclusion: According to the results of this study, oral NAC can significantly reduce the several oxidative stress factors and inflammatory cytokines. These results need to be confirmed in larger studies while considering clinical outcomes of RA patients. © 2019 Bentham Science Publishers
Atomoxetine Efficacy in Methamphetamine Dependence during Methadone Maintenance Therapy
BACKGROUND: Co-occurring methamphetamine (METH) use during methadone maintenance therapy (MMT) is a highly prevalent and progressive problem in Iran. There are no registered pharmacological treatments for treating METH use disorder. The present study investigates the potential efficacy of atomoxetine in the treatment of these patients. METHODS: In a double-blind, controlled clinical trial, 86 METH-dependents on MMT randomly received either atomoxetine (40 mg/d) or placebo. We measured the craving scores with visual analog scale (VAS) on a weekly basis, and evaluated depression, anxiety and stress with the Depression Anxiety Stress Scales (DASS) on a monthly basis. Measurements were made in each weekly visit with urinary METH drug test. RESULTS: Atomoxetine significantly reduced METH craving (P < 0.001). Negative METH urine test increased significantly in the drug group compared to the placebo group (P = 0.007). While initially the METH urine test was positive for all patients, 56 (25/45) in the atomoxetine group and 26 (11/41) in the placebo group had negative METH urine tests after 8 weeks. DASS were decreased in both groups with a greater reduction in the atomoxetine group depression (P = 0.028), anxiety (P = 0.038), and stress (P = 0.031). Only mild side effects were observed. CONCLUSION: This study confirms the safety and clinical tolerance of atomoxetine, and its appropriate efficacy in suppressing METH craving and possible potential effects on its treatment. © 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Ecological and health risk assessment of exposure to atmospheric heavy metals
In the present study, we assessed the concentration of airborne HMs (Zn, Cu, Pb, and Cd) and their probable sources using the bark of Pinus eldarica as a bio-indicator. Hence, 47 tree bark samples were harvested according to the land uses and biomonitoring techniques in the city of Yazd, Iran. The potential health risks in 13 age groups, ecological risk, as well as the possible relationship between HM concentrations and traffic indicators, were evaluated. The order of average HM concentrations in the P. eldarica bark samples was as Zn > Pb > Cu > Cd. The mean values of non-carcinogenic risks of all HMs in entire age groups were within secure range (HQ < 1); however, the carcinogenic risk of Cd was higher than the allowed level (TCR > 1 � 10�6). About Pb, it was in the safe level. The main element causing potential ecological risks was Cd, indicating moderate to very high ecological risk in most of the study areas. There was an inverse significant association between distance from major roads and Pb concentration (β = �0.011 95 confidence interval (CI): 0.022, �0.0001). All HMs in bark samples render the negative Moran's index, representing a random spatial distribution pattern. Besides, according to principal component analysis (PCA), the first component accounted for 36.55 of the total variance, dominated by Cd, Pb, Cu, and Zn, respectively, and characterized by vehicle and industrial emissions. Our results infer that industrial activities and traffic are the main sources of HMs pollution in urban environments that should be considered by decision-makers. © 2019 Elsevier Inc
Association of A-197G polymorphism in interleukin-17 gene with chronic periodontitis: Evidence from six case-control studies with a computational biology approach
AIM: The aim of the present study was to evaluate the association of interleukin-17 (IL-17) A-197G gene polymorphism with chronic periodontitis (CP) in a case-control study, a meta-analysis, and an in silico approach. METHODS: In the case-control study, 122 cases with CP and 126 healthy controls were recruited; IL-17 A-197G genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. In the meta-analysis, comprehensive literature retrieval was performed on valid databases to identify relevant studies. Bioinformatics tools were employed to investigate the effects of A-197G transition on the promoter region of IL-17. RESULTS: Our case-control study revealed a significant association between IL-17 A-197G transition and CP. The overall meta-analysis revealed significant associations between the IL-17 A-197G polymorphism and CP risk in homozygote co-dominant and recessive models. The stratified analysis also showed a statistically significant association between the mentioned transition and CP risk in the Caucasian population. The in silico analysis revealed that the A-197G polymorphism could make changes in protein-binding sites of the IL-17 promoter region. CONCLUSIONS: Our study supports that IL-17 A-197G transition could be a genetic risk factor for CP. However, further studies with a larger sample size among different ethnicities are required to obtain a more accurate conclusion. © 2019 John Wiley & Sons Australia, Ltd
Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: A mechanistic study
Aim: Migraine is a neurological debilitating disorder. Previous studies have shown that cannabinoid receptor agonists have analgesic effects in various models of pain. In this study, therefore, we investigated anti-nociceptive effects of WIN 55,212-2, and the role of either CB1 or CB2 receptors in nitroglycerine (NTG)-induced animal model of migraine. Methods: The present study was conducted on both male and female rats receiving NTG (10 mg/kg, i.p.) to induce acute (single dose of NTG) and chronic (repetitive doses of NTG) models of migraine. Additionally, three groups received WIN 55,212-2 (0.33, 1, 3 mg/kg, i.p.) 45 min before behavioral tests. Additionally, AM251 and AM630 (CB1 and CB2 receptor antagonist, respectively, 1 mg/kg, i.p.) were used to evaluate the possible involvement of CB1 and CB2 receptors during the protective effects of WIN 55,212-2. Key findings: We found that NTG (10 mg/kg, i.p.) in both acute and chronic models increased sensitivity to pain. In acute model, we found that WIN 55,212-2 (almost high doses) decreases the level of pain mainly through CB1 receptor due to CB1 antagonist abrogates its protective effects, however, in formalin test CB2 receptors also had crucial roles in both phases at 3 mg/kg of WIN 55,212-2. In chronic model, WIN 55,212-2 (0.33, 1 and 3 mg/kg) significantly attenuated NTG-induced hyperalgesia through both CB1 and CB2 receptors. Significance: Our data supported the argument that activation of CB1 and CB2 receptors by WIN 55,212-2 may be considered a new medication for migraine, however in lack of each receptor leads to different responses from deletion to the reduction of analgesic effects. © 2019 Elsevier Inc
Types of poisoning in a tertiary care hospital in center of Iran (2014 to 2017)
The global problem of acute poisoning has steadily increased over the past decade. It is an importantcause of morbidity and mortality in developing countries. Better preventive and management strategiescan be developed if the incidence and pattern of acute poisoning is known. The study aims at analyzingthe pattern, cause and mortality rate of poisoning.The study was conducted in aurban and rural area in the center of Iran. This retrospective study was conducted fromJanuary 2014-March 2017. The data was analysed using descriptive and analytical statistics.:Out of the 1329 cases 754 were males and 575 females. Poisoning was common in the age group of 21-30 years. The poisons consumed were as follows:63.8 were suicides, 17.8 accidental and 18.4 had a variety of different reasons. Mortality rate was 6.5.The results of the study showed that the highest rate of poisoning in the young age group was due to suicidal ideation. Accurate training for youth and counseling is of particular importance.Establishment of strict policies against the sale and availability of pesticides and over the counter drugs is an effective way to control drug poisoning. © 2019, Advanced Scientific Research. All rights reserved
Long-term Vitamin D and high-dose n-3 fatty acids' supplementation improve markers of cardiometabolic risk in type 2 diabetic patients with CHD
This study was performed to evaluate the effects of vitamin D and n-3 fatty acids' co-supplementation on markers of cardiometabolic risk in diabetic patients with CHD. This randomised, double-blinded, placebo-controlled trial was conducted among sixty-one vitamin D-deficient diabetic patients with CHD. At baseline, the range of serum 25-hydroxyvitamin D levels in study participants was 6·3-19·9 ng/ml. Subjects were randomly assigned into two groups either taking 50A 000 IU vitamin D supplements every 2 weeks plus 2� 1000 mg/d n-3 fatty acids from flaxseed oil (n 30) or placebo (n 31) for 6 months. Vitamin D and n-3 fatty acids' co-supplementation significantly reduced mean (P = 0·01) and maximum levels of left carotid intima-media thickness (CIMT) (P = 0·004), and mean (P = 0·02) and maximum levels of right CIMT (P = 0·003) compared with the placebo. In addition, co-supplementation led to a significant reduction in fasting plasma glucose (β -0·40 mmol/l; 95A CI -0·77, -0·03; P = 0·03), insulin (β -1·66 μIU/ml; 95A CI -2·43, -0·89; P < 0·001), insulin resistance (β -0·49; 95A CI -0·72, -0·25; P < 0·001) and LDL-cholesterol (β -0·21 mmol/l; 95A CI -0·41, -0·01; P = 0·04), and a significant increase in insulin sensitivity (β +0·008; 95A CI 0·004, 0·01; P = 0·001) and HDL-cholesterol (β +0·09 mmol/l; 95A CI 0·01, 0·17; P = 0·02) compared with the placebo. Additionally, high-sensitivity C-reactive protein (β -1·56 mg/l; 95A CI -2·65, -0·48; P = 0·005) was reduced in the supplemented group compared with the placebo group. Overall, vitamin D and n-3 fatty acids' co-supplementation had beneficial effects on markers of cardiometabolic risk. © The Authors 2019