Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for K<inf>ATP</inf> channel

Aims Although approving new anticonvulsants was a major breakthrough in the field of epilepsy control, so far we have met limited success in almost one third of patients suffering from epilepsy and a definite and reliable method is yet to be found. Levosimendan demonstrated neuroprotective effects and reduced mortality in conditions in which seizure can be an etiology of death; however, the underlying neuroprotective mechanisms of levosimendan still eludes us. In the light of evidence suggesting levosimendan can be a KATP channel opener and nitrergic pathway activator, levosimendan may exert antiseizure effects through KATP channels and nitrergic pathway. Main methods In this study, the effects of levosimendan on seizure susceptibility was studied by PTZ-induced seizures model in mice. Key findings Administration of a single effective dose of levosimendan significantly increased seizures threshold and the nitrite level in the hippocampus and temporal cortex. Pretreatment with noneffective doses of glibenclamide (a KATP channel blocker) and L-NAME (a non-selective NOS inhibitor) neutralize the anticonvulsant and nitrite elevating effects of levosimendan. While 7-NI (a neural NOS inhibitor) blocked the anticonvulsant effect of levosimendan, Aminoguanidine (an inducible NOS inhibitor) failed to affect the anticonvulsant effects of levosimendan. Cromakalim (a KATP channel opener) or L-arginine (an NO precursor) augmented the anticonvulsant effects of a subeffective dose of levosimendan. Moreover, co-administration of noneffective doses of Glibenclamide and L-NAME demonstrated a synergistic effect in blocking the anticonvulsant effects of levosimendan. Significance Levosimendan has anticonvulsant effects possibly via KATP/nNOS/NO pathway activation in the hippocampus and temporal corte

Two-photon fluorescence imaging of intracellular hydrogen peroxide with chemoselective fluorescent probes

Abstract. We present the application of two-photon fluorescence (TPF) imaging to monitor intracellular hydrogen peroxide (H2O2) production in brain cells. For selective imaging of H2O2 over other reactive oxygen species, we employed small-molecule fluorescent probes that utilize a chemoselective boronate deprotection mechanism. Peroxyfluor-6 acetoxymethyl ester detects global cellular H2O2 and mitochondria peroxy yellow 1 detects mitochondrial H2O2. Two-photon absorption cross sections for these H2O2 probes are measured with a mode-locked Ti:sapphire laser in the wavelength range of 720 to 1040 nm. TPF imaging is demonstrated in the HT22 cell line to monitor both cytoplasmic H2O2 and localized H2O2 production in mitochondria. Endogenous cytoplasmic H2O2 production is detected with TPF imaging in rat astrocytes modified with d-amino acid oxidase. The TPF H2O2 imaging demonstrated that these chemoselective probes are powerful tools for the detection of intracellular H2O2

DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2

Global systematic review of primary immunodeficiency registries

Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.Peer reviewe

The Effectiveness of Cognitive Behavioral Group Therapy on Quality of Life of Cardiovascular Patients

Abstract Background: The aim of this study was to determine the effectiveness of cognitive-behavioral group therapy on quality of life of patients with cardiovascalar diseases. Materials and Methods: This semi-experimental study was done based on a pretest -posttest design with control group. Statistical population included all of the patients with cardiovascular diseases referred to Amir-Kabir educational and medical center of Arak, and sample included 30 persons who selected by screening and simple random sampling and assigned into two control and experimental groups. Research instrument included Mcnew quality of life scales which participants answered it during two pre-test and post-test steps; also, experimental group participated in 9 cognitive-behavioral therapy meetings. Results: There was a significant difference between mean quality of life and its components in both experimental and control groups. Conclusion: Results analysis showed that group-based cognition- behavior theray has an influence on life quality (emotional, physical and social domains)(p>0.05)

The skin prick test results to saffron, sumac and barberry in patients with atopy

Background: Food allergens appear to play a role in the etiology and deteriorating of atopy in some patients, little is known about hypersensitivity to some common food additives in these patients. The purpose of this study was to identify probable sensitization to saffron, sumac and barberry in patients with atopy.Materials and Methods: This cross- sectional study included 390 patients with atopy and 300 healthy individuals with no history of atopic diseases. Skin tests were performed in both patient and control group with saffron, sumac and barberry.</p

The satisfaction of infertile patients with the quality of medical services in Tehran university of medical sciences hospitals during the year 2020-2021

Background: Patient satisfaction is considered as one of the most important elements of the evaluation of healthcare centers. In this research, the level of satisfaction of infertile patients was evaluated. Methods: This study is a cross-sectional descriptive study. The research population is infertile patients who referred to the infertility clinic (at least 4 visits) and hospitalized in four hospitals affiliated with the Tehran University of Medical Sciences. The satisfaction questionnaire was valid researcher-made which included 56 questions in 9 areas, and were collected from May 2021 to September 2022. In order to comply with the ethical principles in research, hospitals were named 1-4.The results were analyzed using the chi-square test or Fisher's exact test for qualitative variables and analysis of variance for quantitative variables in SPSS software, version 24 (SPSS Inc., Chicago, IL, US). Results Three hundred–four infertile women in four hospitals were studied. The mean age of the participants was 33.8 years, with a standard deviation of 5.8 years. The average satisfaction with admission and discharge services, medical services, nutrition, accounting, and insurance services in the number-1 Hospital had the highest score, and the average satisfaction with nursing or midwifery services, diagnostic and therapeutic services (radiology/laboratory), hospital services, charter patient rights, management services, paid expenses in Hospital 4 received the most points. The mean score of satisfaction was the highest among those who visited the infertility clinic of Hospital 3 (161.54±21.41). Average satisfaction with admission and discharge services, medical services, nutrition, accounting, and insurance services in Hospital No. 1 had the highest score, and average satisfaction with nursing or midwifery services, medical diagnostic services (radiology/laboratory), hospital services, respecting the patient's rights, management services, paid expenses in hospital number 4 got the most points. The average of nursing or midwifery services, respecting the patient's rights, and hotelling in all hospitals received the highest score, respectively, and nutrition services and paid expenses received the lowest points (most dissatisfaction) (P<0.05). Conclusion: The level of satisfaction of women referring to the infertility clinic in 35.9% of cases was considered to be at an appropriate and exceptional level, in 49.3% of cases it was at a partially appropriate level, and in 14.8% at an inappropriate level

Clinical Features and Types of Von Willebrand Disease in Women with Menorrhagia Referred to Hematology Clinic of Kermanshah

Menorrhagia is the most common symptom that is experienced by women with bleeding disorders. Von Willebrand disease (VWD) is the most common congenital human bleeding disorder that is manifested as a quantitative deficiency in Von Willebrand factor (VWF) or dysfunction of this factor. The frequency of VWD is similar in both men and women. However, VWD is more readily detected in women due to the presence of severe bleeding associated with menstrual cycles and childbirth. The present study was carried out to find the frequency of VWD, its types, and clinical features of the disease among women with menorrhagia who referred to the Hematology Clinic of the Kermanshah University of Medical Sciences. The study comprised 482 women with menorrhagia. After excluding patients with confounding factors, 56 (11.6%) patients were evaluated for inherited bleeding disorders. We detected 31 (55.3%) patients with VWD. Type 3 of VWD was the most frequent subtype (45.1%) followed in frequency by type 2, (32.2%), and type 1 (22.5%). In conclusion, our study indicated that menorrhagia can be the first symptom of VWD. Therefore, rare coagulation disorders should be considered in women with idiopathic menorrhagia, particularly in regions with high rates of consanguinity