The role of gender differences in the outcome of juvenile social isolation: Emphasis on changes in behavioral, biochemical and expression of nitric oxide synthase genes alteration.

Social isolation can cause serious problem in performance of individuals in community. As gender differences may cause variation results in the severity of depressive behavior and response of patients to therapy, the impact of gender and the interaction of the level of endocrine secretion in depression were investigated in this study. Wistar rats of both sexes were subjected to post-weaning social isolation (PWSI) conditions and, together with the control group, experienced several behavioral tests including open-field Test (OFT), elevated plus maze (EPM), force swimming test (FST), splash test and novel object recognition test (NOR). Hippocampal tissue was isolated to measure biochemical factors such as nitric oxide level, FRAP amount, MDA level. In addition, real-time-PCR test was used to quantify the genes expression level of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). On the other hand, sexual hormone levels in blood were measured. Both cognitive and behavioral f unctions were declined as the result of PWSI induction in male and diestrus female rats. The consequent surge of estradiol during estrous phase seems to suppress the accumulation of reactive oxygen species (ROS), and modulate iNOS and nNOS expression. In conclusion, while the pattern of PWSI in surge cellular antioxidants, raising cellular ROS level is gender-specific, this alleviation was in relation with the drop of estradiol and unrelated with testosterone level.

Edaravone Improves Streptozotocin-Induced Memory Impairment via Alleviation of Behavioral Dysfunction, Oxidative Stress, Inflammation, and Histopathological Parameters.

Alzheimer's disease (AD), as the main cause of dementia, has a progressive and neurodegenerative pattern with number of cases increasing over the next decades. Therefore, discovering an effective treatment with the ability to invert memory impairment and pathophysiological events of AD seems to be required. The present study performed to investigate the probable effects of Edaravone (EDV) in AD-like disorder induced by intracerebroventricular streptozotocin (ICV-STZ) administration in mice. This study also compares the two different methods of ICV-STZ in the memory impairment induction. NMRI male mice were administrated with 3 mg/kg of STZ for two times during 48 hours span, and after 24 hours, animals were treated with EDV (5 and 10 mg/kg), Donepezil, and Memantine for 14 days. After behavioral tests regarding memory and cognitive function, animals were sacrificed, and the hippocampi were utilized for further analyses. Our results demonstrated that administration of STZ induced memory impairment in the Morris water maze (MWM) test and decreased the discriminative factor in novel object recognition (NOR). The biochemical output shows a significant decrease in ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels followed by increase in malondialdehyde (MDA) and protein carbonylation (PCO) levels. The output showed no difference between the patterns of AD-like disorder induction. Following our treatment groups, administration of EDV (5 and 10 mg/kg), Donepezil, and Memantine significantly improved memory performance and discriminatory behavior. Aforementioned treatments managed to improve FRAP and GSH content of hippocampus, while significantly attenuating MDA, PCO, and nitric oxide overproduction. In addition, no significant difference has been observed between the effect of 5 and 10 mg/kg EDV application. It was supposed that EDV managed to ameliorate memory dysfunction, discriminatory behavior, oxidative stress, and cellular antioxidant power in a dose-independent pattern in mice.

Enhancing the Neuroprotection Potential of Edaravone in Transient Global Ischemia Treatment with Glutathione- (GSH-) Conjugated Poly(methacrylic acid) Nanogel as a Promising Carrier for Targeted Brain Drug Delivery.

Ischemic stroke is the most common among various stroke types and the second leading cause of death, worldwide. Edaravone (EDV) is one of the cardinal antioxidants that is capable of scavenging reactive oxygen species, especially hydroxyl molecules, and has been already used for ischemic stroke treatment. However, poor water solubility, low stability, and bioavailability in aqueous media are major EDV drawbacks. Thus, to overcome the aforementioned drawbacks, nanogel was exploited as a drug carrier of EDV. Furthermore, decorating the nanogel surface with glutathione as targeting ligands would potentiate the therapeutic efficacy. Nanovehicle characterization was assessed with various analytical techniques. Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation were assessed. The outcome demonstrated a diameter of around 100 nm, sphere shape, and homogenous morphology. Encapsulation efficiency and drug loading were determined to be 99.9% and 37.5%, respectively. In vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously made the possibility of antioxidant effects on the brain in specific doses, which resulted in elevated spatial memory and learning along with cognitive function in Wistar rats. In addition, significantly lower MDA and PCO and higher levels of neural GSH and antioxidant levels were observed, while histopathological improvement was approved. The developed nanogel can be a suited vehicle for drug delivery of EDV to the brain and improve ischemia-induced oxidative stress cell damage.

Thymus daenensis extract prevents scopolamine­induced memory impairment through declining oxidative stress in rats.

Memory and cognitive impairment induced by oxidative stress are among the main hallmarks of Alzheimer's disease's (AD) pathology. The present study aimed to investigate the potential neuroprotective effects of Thymus daenensis (T. daenensis) extract against scopolamine­induced memory impairment and oxidative stress in rats. T. daenensis, widely distributed in Iran and Europe, is known to be a rich source of natural antioxidants and has been traditionally used for various medical purposes. The present study investigated the post­treatment effects of T. daenensis on learning and memory functions, antioxidant cellular defense, and oxidative stress using the scopolamine rat model of AD. The experiments were performed by intraperitoneal injection of scopolamine for 10 consecutive days in Wistar male rats (180-220 g). Additionally, the animals received T. daenensis extract (50­200 mg/kg) by gavage for 14 consecutive days after induction of memory impairment. The animals were divided into 8 groups, namely: control, 200 mg/kg of T. daenensis extract (D200), donepezil (DON), scopolamine (ALZ), ALZ animals treated with different doses of the extract (ALZ+D50 or 100 or 200 mg/kg) and ALZ animals treated with (ALZ+DON). The animals were then subjected to the Morris water maze (MWM) paradigm as a standard criterion for memory function assessment, and after extracting the brain tissues, the related biochemical oxidative stress parameters were determined in the brain. Our results indicated that T. daenensis extract significantly improved animals' performance in the MWM while significantly reducing oxidative stress and antioxidant imbalance. Furthermore, the extract did not show hepatotoxic effects on treated animals. In addition, the extract treatment significantly decreased both cellular malondialdehyde (MDA) and protein carbonyl (PCO) content while conversely increasing the total reduced glutathione (GSH) content and also the levels of total and endogenous antioxidants in the ferric reducing antioxidant power (FRAP) assay. It seems that the administration of T. daenensis significantly improved both cellular biochemical aspects and memory performance in animal models. Conclusively, it could be beneficial for scopolamine­induced neurotoxicity.

Protective effects of Vinca herbaceous extract against scopolamine-induced behavioral disturbances and brain oxidative stress in rats.

Ethnopharmacological relevance: Alzheimer's disease (AD) as the most common type of dementia, is affecting the life of many senior individuals around the world. Vinca herbacea Waldst. & Kit. (V. herbacea) as a middle east originated plant demonstrated antioxidant and antitumor effects. This plant traditionally used to treat diabetes and hypertension, but its mechanism remains unclear. Aim of the study: In the present study, post-treatment effects of V. herbacea on learning and memory functions, antioxidant cellular defense and oxidative stress were investigated using the scopolamine rat model of AD. Materials and methods: Wistar male rats (170-190 g) were administered Scopolamine, an anti-muscarinic drug, (2 mg/kg) for 10 days followed by V. herbacea extract (200, 300 and 400 mg/kg) and/or donepezil (DON; 1 mg/kg, which were administered before behavioral studies for 10 consecutive days. All the rats were then subjected to Morris water maze (MWM) task. Biochemical parameters of oxidative stress were quantified using the whole brain. Results: Our data showed significant decrease performance in target quadrant in water maze task following administration of scopolamine (SCOP). Also, V. herbacea and DON, did not induce any neurotoxicity and hepatotoxic effects at the highest utilized doses in healthy rats. Treatment with V. herbacea extract (200&400 mg/kg) and DON improved memory performance significantly in comparison with AD rats. In addition, V. herbacea extract in AD rats exhibited a decrease in malondialdehyde (MDA) and protein carbonyl (PCO) levels and an increase in total antioxidant capacity (FRAP) and glutathione (GSH) amounts in brain and liver. Conclusion: It seems that cholinergic deficits and oxidative stress are consistently associated with Alzheimer's disease (AD). The richness of V. herbacea in case of indole alkaloids and flavonoids confirms the potentials of this herb in management of oxidative stress, resorting synaptic acetylcholine level and improving cellular antioxidant resources.

Neuroprotective Effect of Apigenin on Depressive-Like Behavior: Mechanistic Approach.

Apigenin, as a natural flavonoid present in several plants is characterized with potential anticancer, antioxidant, and anti-inflammatory properties. Recent studies proposed that apigenin affects depression disorder through unknown mechanistic pathways. The effects of apigenin's anti-depressive properties on streptozocin-mediated depression have been investigated through the evaluation of behavioral tests, oxidative stress, cellular energy homeostasis and inflammatory responses. The results demonstrated anti-depressive properties of apigenin in behavioral test including forced swimming and splash tests and oxidative stress biomarkers such as reduced glutathione, lipid peroxidation, total antioxidant power and coenzyme Q10 levels. Apigenin, also, demonstrated its regulatory potency in cellular energy homeostasis and immune system gene expression through inhibiting Nlrp3 and Tlr4 overexpression. Furthermore, failure in energy production as the key factor in various psychiatric disorders was reversed by apigenin modulating effect on AMPK gene expression. Overall, 20 mg/kg of apigenin was recognized as the dose suitable for minimizing the undesirable adverse effects in the STZ-mediated depression model proposed in this study. Our data suggested that apigenin could be able to adjust behavioral dysfunction, biochemical biomarkers and recovered cellular antioxidant level in depressed animals. The surprising results were achieved by raise in COQ10 level, which could regulate the overexpression of the AMPK gene in stressful conditions. The regulatory effect of apigenin in inflammatory signaling pathways such as Nlrp3, and Tlr4 gene expression was studied at the surface part of the hippocampus.

Minocycline attenuates depressive-like behaviors in mice treated with the low dose of intracerebroventricular streptozotocin; the role of mitochondrial function and neuroinflammation.

Neuroinflammation and mitochondrial dysfunction are suggested as mechanisms which are implicated in the pathophysiology of depression. Streptozotocin (STZ) is known to produce immune-inflammatory responses and mitochondrial dysfunction in different types of animal models of disease (e.g. type-1 diabetes and Alzheimer's disease). Therefore, a single low dose of Streptozotocin (STZ; intracerebroventricular, i.c.v, 0.2 mg/mouse) was used to induce an animal model of depression. The present study aims to investigate the effects of short (24 h) and long (14 days) exposure to minocycline on STZ-induced depressive-like behaviors (n = 6-8), hippocampal oxidative state biomarkers (n = 4), and the expression of hippocampal genes related to innate immunity (n = 3) in the hippocampus of male adult mice. In addition, the protective effects of different modes of minocycline (acute pretreatment (20 mg/kg, 1 h before STZ), acute post-treatment (20 mg/kg, 24 h after STZ), chronic pretreatment (5 mg/kg/day for 14 days before STZ), and chronic post-treatment (5 mg/kg/day for 14 days after STZ) were compared with the STZ effects. As the data showed, both short and long effects of STZ were associated with the depressive-like behaviors, abnormal mitochondrial function, and upregulation of neuroinflammatory genes in the hippocampus. Different modes of minocycline treatment could attenuate the negative impact of STZ on animals. The data suggested that minocycline at a human therapeutic dose (5 mg/kg) had protective effects against acute cellular damage induced by oxidation and the consequent inflammatory responses.

Long-term immunogenicity of hepatitis B vaccine and impact of a booster dose on health care.

Background: Accidental exposure to sharp instruments is an important problem for health care students. Thus, the aim of this study was to determine the rate of immunity in health care students 2 decades after national neonatal hepatitis B (HB) vaccination. Methods: All junior students attending medicine, nursing and midwifery schools were screened for anti-HBs. One dose of hepatitis B vaccine was offered to all participants who did not have antibodies to HB surface antigen (anti-HBs) of > 10 IU/L; then, they were tested for anti-HBs after a month. The participants were classified into 3 groups: postboosting nonimmune, postboosting immune, and preboosting immune. Chi square test and ANOVA were used for data analysis. Results: In the first step, 65.20% of participants did not show immunity, but after receiving a booster dose, only 6.0% remained nonimmune. The mean age of nonimmune students was significantly higher than that of students who had postboosting immune and preboosting immune status (p=0.001 and 0.002, respectively). Also, the mean injection time from last shot was higher in postboosting immune group compared to preboosting immune group (p<0.001). Also, prebooster anti-HBs level was significantly different among participants with suboptimal response and those who developed anamnestic response, indicating preserved immune memory (p=0.001). Conclusion: High anamnestic response to HBV booster dose indicates sufficient immunity to HBV in the majority of health care students. However, identifying students who cannot respond to a booster dose of vaccine seems to be necessary at the beginning of health care courses.

Coenzyme Q10 Alleviated Behavioral Dysfunction and Bioenergetic Function in an Animal Model of Depression.

Coenzyme Q10 (CoQ10) is a natural compound, is involved in the mitochondrial electron transfer chain (ETC) and plays an important pattern in adenosine triphosphate (ATP) production. Amelioration of ATP is related to abnormalities in cognitive function and psychiatric diseases. Previous studies have shown that depression is accompanied by the induction of inflammatory and oxidative stress pathways and amelioration of antioxidant status. In a recent study, we investigated the beneficial effects of CoQ10 on behavioral dysfunction and CoQ10 level in the rat brain. Therefore, intracerebroventricular (ICV) infusion of a single dose of streptozotocin (STZ, 0.2 mg/mouse) was used in adult male mice to induce depression. The behavioral data revealed a significant difference between the depression and control groups regarding the forced swim test (FST) and splash test results at 24 h following STZ treatment. Also, the validated and accurate high-performance liquid chromatography (HPLC) technique showed decreased CoQ10 level in the brain samples of the STZ group, compared to the controls. Our findings revealed that behavioral abnormalities due to STZ target mitochondria and affect energy metabolism and hemostasis, resulting in the initiation of oxidative damage in the brain. Besides, 4-week administration of CoQ10 could reverse the depressive like behavior and bioenergetic effects of STZ in the treated groups.

Poverty as an independent risk factor for in-hospital mortality in community-acquired pneumonia: A study in a developing country population.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the most severe lower respiratory tract infections with a high in-hospital mortality. The aim of this study was to investigate the socioeconomic and medical risk factors affecting the prognosis of acute pneumonia. The results of this study can mention the value of socioeconomic backgrounds like poverty and illiteracy in clinical practice, even in a well-known biological phenomenon (eg acute pneumonia). METHODS: In this cross-sectional study, all admitted patients to a tertiary teaching hospital with a diagnosis of community acquired pneumonia in a 12-month period were enrolled. Socioeconomic and demographic characteristics, underlying conditions, clinical manifestations and para-clinical test results at admission registered prospectively. A logistic regression model was conducted using in-hospital mortality as the dependent variable. RESULTS: A total of 621 patients was included in this study. Among them, 47 patients (7.6%) died during the hospitalisation period. In multiple logistic regression analysis, pleural effusion, a higher CURB-65 score, hyponatremia, hyperglycaemia and poverty (being in the lower economic class) were identified as independent risk factors for in-hospital mortality in community-acquired pneumonia. CONCLUSION: Numerous factors can influence the prognosis of CAP. In addition to the CURB-65 score and some other medical risk factors, socioeconomic backgrounds can also affect the early outcome in CAP. In this study, being in the lower economic class (as an indicator of poverty) is interpreted as an independent risk factor for a poor prognosis in CAP.