Association between metabolic syndrome and stroke: a population based cohort study.

Both metabolic syndrome (MetS) and stroke are associated with increased risk of mortality. Here, we aimed to assess the prevalence of MetS among adults using three definitions (Adult Treatment Panel III (ATP-III), International Diabetes Federation (IDF) and IDF ethnic specific cut-off for Iranian criteria) and its association with stroke. We performed a cross-sectional study of a total of 9991 adult participants of Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN cohort study). The MetS prevalence was evaluated in participants according to the different criteria. Multivariate logistic regression analyses were conducted to assess the association between three definitions of MetS with stroke. We found that MetS was significantly associated with higher odds of stroke according to NCEP-ATP III (odds ratio (OR): 1.89, 95% confidence interval (CI) 1.30-2.74), international IDF (OR:1.66, 95% CI: 1.15-2.40) and Iranian IDF (OR:1.48, 95% CI: 1.04-2.09) after adjusted for variables confounders. Furthermore, after adjustment, in receiver operating characteristic (ROC) curve, the AUROC was 0.79 (95% CI = 0.75-0.82), 0.78(95% CI = 0.74-0.82) and 0.78(95% CI = 0.74-0.81) for presence of MetS according to NCEP-ATP III, international IDF and Iranian IDF, respectively. ROC analyses revealed that all of these three criteria for MetS are "moderately accurate" for the identification of increased stroke risk.In conclusion, our results showed that MetS was associated with increased odds of stroke. Our findings implicate the importance of early identification, treatment, and ultimately prevention of the metabolic syndrome.

Sleep duration, hypnotic drug use, and risk factors: cross- sectional study.

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle parameters and common non-communicable diseases. Additionally, we performed stratified analysis to investigate the association of sleep duration with the abovementioned factors and diseases, in groups with and without hypnotic drug use. We found higher odds of SSD significantly associated with age (P < 0.001), BMI (P < 0.001), physical activity (P < 0.001), and depression (P = 0.023). LSD displayed a positive association with the female sex (P < 0.001), opium consumption (P < 0.001), and history of MI (P = 0.045), and a reverse connection with education (P = 0.007), physical activity (P < 0.001) and alcohol consumption (P = 0.027). Stratifying for the hypnotic drug use, our sensitivity analyses indicated that in hypnotic drug users, education (P = 0.034) and physical activity (P < 0.001) were associated with LSD, in this group, significantly increased odds ratio of LSD were associated with opium consumption (P = 0.046) and thyroid dysfunction (P = 0.037). Our findings demonstrated the demographic and lifestyle factors and diseases associated with long and short sleep duration in the population of the RCS. Additionally, after stratifying for hypnotic drug use, our results indicated that some diseases are only associated with abnormal sleep duration upon using hypnotic drugs.

Outcome predictors in anterior and posterior ischemic strokes: a study based on the Iranian SITS registry.

Ischemic stroke is the major form of stroke with two separate vascular territories. Many risk factors are related to stroke outcomes in both territories. The present descriptive research was carried out on the basis of data obtained from the Safe Implementation of Treatments in Stroke (SITS) registry on Iranian intravenous thrombolysis ischemic stroke cases. Vascular territory involved in each case and three-month excellent outcome, functional independence, mortality rate, and brain hemorrhage occurrence were determined. Univariable and multivariable logistics regression analyses were utilized in order to investigate association of ischemic stroke outcomes with the vascular territory involved and other related factors. Among 1566 patients 95.4% was anterior circulation stroke patients and 4.6% was posterior circulation stroke cases. There is no significant association between vascular territory with mortality (OR of PCS vs ACS: 0.74, 95% CI 0.37-1.46), excellent functional outcome (OR 0.72, 95% CI 0.44-1.19), functional outcome (OR 0.86, 95% CI 0.52-1.42) and local hemorrhage (OR 0.98, 95% CI 0.30-3.21). Among major risk factors, age, diabetes, NIHSS score and admission duration, increased significantly odds of three-month mortality, excellent outcome, and functional independence in the multivariate analysis. The highest of odds was in NIHSS score with a dose-response association. The vascular territory was not an outcome predictor in ischemic strokes. The most important predictor was baseline NIHSS.

Effect of Short-time Exposure of Local Extremely Low-Frequency Magnetic Fields on Sleepiness in Male Rats.

Introduction: Lack of high-quality sleep causes severe side effects like anxiety and changes in plasma concentration of oxalate. The current study investigated the impact of local extremely low-frequency magnetic fields (ELF-MFs) on inducing sleep (sleepiness) and anxiety in male rats. Methods: In this experimental study, 40 male rats were divided into four groups (n=10 for each group). The ELF-MF exposure (0, 10, and 18 Hz) was applied with an intensity of 200µT for three days (10 min/d). The sham-treated animal did not receive ELF-MF. Serum levels of oxalic acid (OA) and sleepiness were measured before and after the last exposure to ELF-MF or sham. Anxiety, sleepiness, and OA were measured using the elevated plus maze, open-field test (OFT), and ELISA test. Results: A comparison of oxalate levels before and after exposure to ELF-MF revealed that ELF-MF (10 Hz) decreased the serum level of oxalate (P<0.05). Comparing open/closed arm entry (in an elevated plus maze) between before and after exposure to ELFMF revealed significant differences. Also, frequency, velocity, and distance moved were decreased in the open-field test. Conclusion: Results of the present study demonstrated that ELF-MF with short-time exposure may modulate the metabolism of OA and may modulate anxiety-like behavior or kind of induction of sleepiness in male rats. Highlights: Oxalate acid concentration may reduce after short time ELF-MF exposure.Locomotor activity in male rats may decrease after the ELF-MF exposure.Short time ELF-MF exposure may induce sleepiness in male rats that may be used to treat sleep disorders. Plain Language Summary: It is necessary for a person to have good sleep to feel happy during the day. The usual way to treat the patient's sleep disorders is drug therapy, but there are some non-pharmacological treatments such as cognitive behavioral therapy and proper diet. In this study we decided to evaluate the effect of ELF-MFs on sleep induction (sleepiness) in male rats by assessing behavioral tests and measuring oxalate acid density. The results showed that the activity of rats and oxalate acid concentration reduced after ELF-MF exposure. This was consistent with results of the plus maze test and the reduction of velocity, frequency and in the open-field test can be attributed to sleepiness. The results of this research showed that ELF-MF with short time exposure may modulate the anxiety-like behavior or kind of induction of sleepiness in male rats. This effect may be used to treat sleep disorders and requires further human studies.

Early and mid-term outcomes of carotid angioplasty and stent placement in 579 patients.

BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) could be considered for preventing stroke in patients with carotid artery stenosis. This study aimed to determine the incidence and the risk factors of the early and mid-term complications associated with CAS. METHODS: This is a retrospective cohort study conducted at Shiraz University of Medical Sciences from March 2011 to March 2019. Patients at high risk and standard risk for carotid endarterectomy were included. The primary composite outcome was defined as stroke, myocardial infarction (MI), and death in the first 30 days after CAS. All-cause mortality, vascular mortality, and stroke were investigated during mid-term follow-up. RESULTS: A total of 579 patients (618 CAS) were recruited (mean age: 71.52 years). Overall, 394 (68.40%), 211 (36.63%), 179 (31.07%), and 96 (16.72%) patients had hypertension, dyslipidemia, diabetes mellitus, or were cigarette smokers, respectively. Primary composite outcomes were observed in 2.59% of patients (1.55% stroke, 0.69% MI, and 1.72% death). Atrial fibrillation was a predictor of primary composite outcome in multivariate logistic regression (p = .048). The presence of total occlusion in the contralateral carotid artery was significantly associated with the risk of stroke in univariate logistic regression (p = .041). The patients were followed for a period ranging from 1 to 83 months. The overall survival rate for all-cause mortality was 93.48% at 1 year, 77.24% at 5 years, and 52.92% at 8 years. All-cause mortality was significantly higher among patients with symptomatic carotid stenosis (p = .014). CONCLUSION: CAS provides acceptable short-term and mid-term outcomes in a unique population of high- and standard-surgical-risk, symptomatic and asymptomatic, octogenarian, and nonoctogenarian patients.

Risk factors of kidney stone disease: a cross-sectional study in the southeast of Iran.

BACKGROUND: The prevalence of kidney stones in the world is increasing and environmental factors seem to play a major role in this issue. The aim of the present study was to investigate the prevalence of risk factors of kidney stones in the adult population of Rafsanjan city based on the data of the Rafsanjan Cohort Study (RCS). METHODS: In the baseline phase of this study, 10,000 people aged 35 to 70 years are enrolled in the RCS, as one of the prospective epidemiological research studies in Iran. From this population, 9932 participants completed related demographic questionnaires as well as reported a history of diabetes mellitus, kidney stone, and hypertension diseases. The obtained data were analyzed using univariable and multivariable logistics regression. RESULTS: According to the obtained results, 46.54% of the studied population were male and 53.46% were female. The mean age of the participants was 49.94 ± 9.56 years. 2392 people accounting for 24.08% of the population had kidney stones. After adjustment of the variables, six variables of gender, WSI, no consumption of purified water, BMI, and history of hypertension and diabetes were found to be significant related factors of kidney stone disease. CONCLUSIONS: Gender, hypertension, obesity, diabetes, and personal habits like alcohol consumption, opium use and, cigarette smoking are effective in the development of kidney stones. So, by identifying the susceptible patients and teaching them, the burden of the disease on society and the individual can be reduced. The results of this study are helpful to health care providers for preventive planning for kidney stone disease.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Brain magnetic resonance imaging without contrast significantly increased serum levels of IL-6, but not IL-10, IL-17A and TGF-ß.

Introduction: Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality. However, the effects of MRI on the immune system in the in vivo conditions are yet to be clarified. In this study we explored the effects of routine brain MRI on the protein and mRNA peripheral blood levels of interleukin-6 (IL-6), IL-10, IL-17A and transforming growth factor-beta (TGF-ß).Material and methods: 40 subjects, who referred for brain MRI, were entered for evaluating effects of routine brain MRI on the protein and mRNA peripheral blood levels of IL-6, IL-10, IL-17A and TGF-ß. Accordingly, peripheral blood were collected before and 3 hours after MRI from the participants. Protein levels of the cytokines were evaluated using ELISA. Also, mRNA levels were analyzed using Real-Time PCR techniques.Results: Brain MRI without contrast led to an increase in protein levels of IL-6 in the peripheral serum, but did not change protein and mRNA levels of IL-10, IL-17A and TGF-ß. IL-6 mRNA levels after MRI were higher in the participants with mild anxiety compared to those without anxiety.Conclusion: brain MRI without contrast can induce secretion of IL-6 and may be associated with its functions, such as development of plasma cells or induction of inflammation.

The effect of head cooling and remote ischemic conditioning on patients with traumatic brain injury.

Cerebral impairment caused by an external force to the head is known as traumatic brain injury (TBI). The aim of this study was to determine the role of local hypothermia and remote ischemic conditioning (RIC) on oxidative stress, inflammatory response after TBI, and other involved variables. The present study is a clinical trial on 84 patients with TBI who were divided into 4 groups. The head cooling for 1.5 to 6 hr was performed in the first three days after TBI. RIC intervention was performed within the golden time after TBI in the form of four 5-min cycles with full cuff and 5 min of emptying of cuff. The group receiving the head cooling technique recovered better than the group receiving the RIC technique. Generally, combination of the two interventions of head cooling and RIC techniques is more effective on the improvement of clinical status of patients than each separate technique.

Eotaxins and C-C chemokine receptor type 3 in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neuroinflammatory disorders and inflammatory processes seem to play an important role in the pathogenesis of PD. Chemokines as inflammatory mediators, which are involved in the recruitment of leukocytes, can play a role in the pathogenesis of PD. The aim of this study was to examine the serum level of eotaxins (CCL11, CCL24, and CCL26) and the expression of C-C chemokine receptor type 3 (CCR3) in patients with PD compared with healthy subjects. In this study, we measured the serum levels of CCL11, CCL24, and CCL26 with ELISA. In addition, gene and protein expression of CCR3 were measured by RT-PCR and flow cytometry techniques in PD patients (n = 30) and age- and sex-matched healthy subjects (n = 30). All patients suffering from PD were assessed clinically through Unified Parkinson's Disease Rating Scale, Motor Examination (UPDRS ME). The results of this study showed that there was no significant alteration in the serum level of these chemokines and also their receptor among patients with PD and healthy subjects. No significant correlation was observed between the eotaxins serum levels and the clinical measures of PD severity. Based on the results, it can be concluded that eotaxins cannot be considered as appropriate targets for the diagnosis or treatment of PD.

Impact of opium dependency on clinical and neuropsychological indices of multiple sclerosis patients.

The aim of this study was to determine the effect of opium on clinical and neuropsychological parameters in multiple sclerosis (MS) patients with substance dependency. A cross-sectional study was conducted on MS patients in Rafsanjan, Iran. Forty opium-addict MS patients (10 males and 30 females) aged between 18 and 50 years were compared with 40 MS patients with no addiction. Word-Pair Learning, Mini-Mental State Examination (MMSE), Wisconsin Card-Sorting Test (WCST), Depression, Anxiety, Expanded Disability Status Scale (EDSS), Fatigue, and the Multiple Sclerosis Functional Composite (MSFC) were measured and compared in the two groups. The comparison of two groups showed a significant increase trait anxiety (P < 0.001), fatigue (P = 0.009) and significant decrease in the executive function (P = 0.003), MMSE (P = 0.003), and working memory (P < 0.001) in addicted MS. It indicates the better efficiency of processing in the non-addicted MS patients. The MSFC z-score also was significantly higher in the non-addicted group (P < 0.001). The opium addiction has a negative impact on the clinical and neuropsychological outcome in MS patients.

Achillea millefolium is beneficial as an add-on therapy in patients with multiple sclerosis: A randomized placebo-controlled clinical trial.

BACKGROUND: Multiple sclerosis (MS) is a neurological disease for which to date there is no cure and the existing disease-modifying drugs just slow down the disease progression. PURPOSE: In this clinical trial we evaluated the efficacy of Achillea millefolium (A. millefolium) aqueous extract in MS patients. METHODS: A triple-blind randomized placebo-controlled parallel group trial was conducted on 75 MS patients. The patients were randomized into three groups including placebo and two groups receiving A. millefolium with two different doses, i.e. 250  mg/day and 500  mg/day, for 1 year. The primary outcome was the annualized relapse rate. Also, number and volume of lesions were obtained from magnetic resonance imaging (MRI) scans. Furthermore, we performed a comprehensive neurological and cognitive tests as follows: changes in the expanded disability status scale (EDSS), the multiple sclerosis functional composite (MSFC), fatigue severity scale (FSS), Ashworth spasticity assessment, Beck depression test, State-trait anxiety inventory (STAI), mini-mental status examination (MMSE), Wisconsin card sorting test (WCST), tower of London test (TOL), word-pair learning, paced auditory serial addition task (PASAT) and standard laboratory tests. RESULTS: This study showed one year administration of A. millefolium (both doses) decreased the annual relapse rate in MS patients. The mean volume change of lesions significantly decreased in the 500 mg A. millefolium group. The add-on therapy also increased time to first relapse and the MSFC z-score; it decreased the EDSS score and improved performance in word-pair learning, PASAT, and WCST. CONCLUSION: We found beneficial effects of A. millefolium aqueous extract as an add-on therapy in MS patients.

CXCL12 and CXCR4 in the Peripheral Blood of Patients with Parkinson's Disease.

OBJECTIVE: The role of CXCL12 and its receptor CXCR4 has not been fully examined in Parkinson's disease (PD). The purpose of this study was to investigate the role of CXCL12/CXCR4 in the peripheral blood of patients with PD and healthy controls. METHODS: CXCL12 serum levels and CXCR4 mRNA levels were measured in 30 PD patients and 40 controls using ELISA and real-time PCR, respectively. RESULTS: CXCL12 serum levels were significantly higher in PD patients compared to controls (p < 0.0001). Moreover, CXCR4 expression in peripheral blood mononuclear cells (PBMC) of PD patients was significantly increased compared to controls (p < 0.0001). CONCLUSIONS: Our findings provide new information on the expression of CXCL12/CXCR4 in PD. CXCR4 expression in PBMC or CXCL12 serum levels may be potential biomarkers of inflammation in PD patients.

CX691, as an AMPA receptor positive modulator, improves the learning and memory in a rat model of Alzheimer's disease.

OBJECTIVES: Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer's disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. MATERIALS AND METHODS: For induction of AD, amyloid-beta 1-42 (Aß1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. RESULTS: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals. CONCLUSION: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Vitiligo and social acceptance.

BACKGROUND AND AIM: Vitiligo is a chronic skin disease characterized by a total or partial loss of melanocytes from the epidermis and other tissues of the skin. It is placed in the class of secondary psychiatric disorders and can also lead to psychological problems. The main aim of this study was to assess social acceptance in vitiligo patients. METHODS: This cross-sectional study was conducted on all of the patients (n=150) with vitiligo who were referred to dermatology clinics in Rafsanjan, Iran. The patients completed a social acceptability questionnaire (Marlowe-Crowne Social Desirability Scale), and information regarding their demographic characteristics was also collected. Data were gathered and analyzed with descriptive and inferential statistics using SPSS-19 software. RESULTS: The mean age of the patients was 27.56±10.53 years and 65.9% were female. Mean score of social acceptance among the patients was 13.51±7.08. The results showed that the mean scores of social acceptance were significantly lower in women, in those with single marital status, in those with face and neck lesions, and in those with disease duration less than 5 years. CONCLUSION: The results showed that certain groups of patients with vitiligo are at greater risk of experiencing lower social acceptance.

JZL184, as a monoacylglycerol lipase inhibitor, down-regulates inflammation in a cannabinoid pathway dependent manner.

INTRODUCTION: Stroke is a prevalent disorder which is associated with several complications including inflammation. JZL-184 (JZL) inhibits arachidonic acid (AA) production and consequently results in two-arachidonoylglycerol (2-AG) accumulation. Both reduced production of AA metabolic products and increased 2-AG, the agonist of type 1 cannabinoid receptor (CB1), can result in reduced inflammation. In this study, we investigated the mechanisms of JZL in the improvement of stroke complications in mouse permanent cerebral ischemia (PPMCAO) model using AM251, the antagonist of CB1. MATERIAL AND METHODS: PMCAO mice were divided into six groups including intact, controls, vehicle, JZL, AM251 and JZL plus AM251 administrated groups. Brain infarction and edema, brain levels of matrix metalloperoteinase-9 (MMP9), interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) and behavioral functions have been examined in all groups. RESULTS: The results showed that JZL lowered brain infarction, neurological disorders, TNF-α and MMP9 more effectively than JZL plus AM251. JZL and JZL plus AM251 reduced brain edema and increased brain IL-10. JZL, AM251 and JZL plus AM251 improve behavioral functions. DISCUSSION: JZL reduces brain infarction and brain pro-inflammatory molecules in CB1 pathway dependent manner. JZL also reduces brain edema and increased IL-10 in CB1 pathways or decreased AA metabolites. Further, AM251 improves behavioral functions via unknown mechanisms.

Monoacylglycerol lipase inhibitor, JZL-184, confers neuroprotection in the mice middle cerebral artery occlusion model of stroke.

INTRODUCTION: Investigators are searching to find new therapeutic strategies to reduce stroke secondary injury. JZL-184 (JZL) is an inhibitory factor for production of arachidonic acid (AA). Thus, it suppresses production of AA metabolites which are the cause of inflammation and tissue edema. Therefore, JZL may be considered for suppression of stroke secondary injury in mice middle cerebral artery occlusion (MCAO) model. Additionally, Aspirin is a known anti-inflammatory factor which is used to reduce pro-inflammatory secondary injury. The aim of this study was to determine the effects of JZL on the reduction of stroke secondary injury and to compare them with Aspirin effects. MATERIAL AND METHODS: MCAO model has been induced and accordingly 83 male MCAO induced mice have been introduced to the study. The animals were divided to seven groups including intact, controls, vehicle, Aspirin, JZL 4, 8 and 16 mg/kg administrated groups. Brain edema and infarction, behavioral functions and brain levels of IL-10, TNF-α and matrix metaloperoteinase-9 (MMP9) have been examined in the evaluated groups. RESULTS: The results revealed that JZL reduced brain edema, infarction, brain levels of TNF-α and MMP9 and also increased brain levels of IL-10 as well as improved behavioral functions in all three concentrations. The therapeutic effects of JZL were observed as well as Aspirin. DISCUSSION: Based on the results, it seems that JZL can be considered as a good candidate for inhibition of stroke secondary injury in the case of delayed treatment.

TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats.

OBJECTIVES: Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats. MATERIALS AND METHODS: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. RESULTS: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. CONCLUSION: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

Bio-effectiveness of the main flavonoids of Achillea millefolium in the pathophysiology of neurodegenerative disorders- a review.

The Achillea millefolium L. (Yarrow) is a common herb which is widely being used, worldwide. Achillea is being used for treatment of many disorders since centuries. It is considered safe for supplemental use and flavonoids such as kaempferol, luteolin and apigenin are of main constituents present in Achillea. Most of both antioxidant and anti-inflammatory properties of this herb have been attributed to its flavonoid content. Oxidative and inflammatory processes play important roles in pathogenesis of neurodegenerative diseases. Present review was aimed to review the latest literature evidences regarding application of Achillea and/or its three main flavonoid constituents on epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and stroke.

Vitamin B12 in Association with Antipsychotic Drugs Can Modulate the Expression of Pro-/Anti-Inflammatory Cytokines in Alzheimer Disease Patients.

INTRODUCTION: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, and endothelin (ET)-1). MATERIAL AND METHODS: Serum levels of IL-6, IL-8, TGF-ß, TNF-α, and ET-1 were evaluated in the following groups: healthy controls, nonpsychotic AD patients, psychotic AD patients, psychotic AD patients under treatment with risperidone, psychotic AD patients under treatment with risperidone plus vitamin B12, psychotic AD patients under treatment with quetiapine, and psychotic AD patients under treatment with quetiapine plus vitamin B12. RESULTS: Treatment with antipsychotic drugs plus vitamin B12 led to a decreased expression of IL-8 and TNF-α and an increased expression of TGF-ß. Vitamin B12 in association with quetiapine reduced the pain in psychotic AD patients. DISCUSSION: Proinflammatory cytokines play important roles in the pathogenesis of psychosis in AD patients. Antipsychotic drugs plus vitamin B12 can reduce and induce the expression of proinflammatory and anti-inflammatory cytokines to improve psychotic symptoms in AD patients.