The effect of morphine administration on GluN3B NMDA receptor subunit mRNA expression in rat brain.

Opioid addiction is critically dependent on the activation of N­methyl­D­aspartate (NMDA) receptors, which are widely found in the mesocorticolimbic system. Meanwhile, opioid addiction may affect the expression level of NMDA receptor subunits. The existence of GluN3 subunits in the NMDA receptor's tetramer structure reduces the excitatory current of the receptor channel. We evaluated the changes in the mRNA expression pattern of the GluN3B subunit of the NMDA receptor in rat brains following acute and chronic exposure to morphine. Chronic, escalating intraperitoneal doses of morphine or saline were administered twice daily to male Wistar rats for six days. Two other groups were injected with a single acute dose of morphine or saline. The mRNA level of the GluN3B subunit of the NMDA receptor in the striatum, hippocampus, and nucleus accumbens (NAc) was measured by real­time PCR. mRNA expression of the GluN3B subunit was considerably augmented (3.15 fold) in the NAc of animals chronically treated with morphine compared to the control group. The difference between rats that were chronically administered morphine and control rats was not statistically significant for other evaluated brain areas. In rats acutely treated with morphine, no significant differences were found for GluN3B subunit expression in the examined brain regions compared to the control group. It was concluded that chronic exposure to morphine notably increased the GluN3B subunit of the NMDA receptor in NAc. The extent of the impact of this finding on opioid addiction and its features requires further evaluation in future studies.

The effect of induced hypertension in aneurysmal subarachnoid hemorrhage: A narrative review.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 2-5% of all strokes, and 10%-15% of aSAH patients will not survive until hospital admission. Induced hypertension (IH) is an emerging therapeutic option being used for the treatment of vasospasm in aSAH. For patients with cerebral vasospasm (CVS) consequent to SAH, IH is implemented to increase systolic blood pressure (SBP) in order to optimize cerebral blood flow (CBF) and prevent delayed cerebral ischemia (DCI). Prophylactic use of IH has been associated with the development of vasospasm and cerebral ischemia in SAH patients. Various trials have defined several different parameters to help clinicians decide when to initiate IH in a SAH patient. However, there is insufficient evidence to recommend therapeutic IH in aSAH due to the possible serious complications like myocardial ischemia, development of posterior reversible encephalopathy syndrome (PRES), pulmonary edema, and even rupture of another unsecured aneurysm. This narrative review showed the favorable impact of IH therapy on aSAH patients; however, it is crucial to conduct further clinical and molecular experiments to shed more light on the effects of IH in aSAH.

Mesenchymal stem cells (MSCs) and MSC-derived exosomes in animal models of central nervous system diseases: Targeting the NLRP3 inflammasome.

The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is a multimeric protein complex that is engaged in the innate immune system and plays a vital role in inflammatory reactions. Activation of the NLRP3 inflammasome and subsequent release of proinflammatory cytokines can be triggered by microbial infection or cellular injury. The NLRP3 inflammasome has been implicated in the pathogenesis of many disorders affecting the central nervous system (CNS), ranging from stroke, traumatic brain injury, and spinal cord injury to Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, and depression. Furthermore, emerging evidence has suggested that mesenchymal stem cells (MSCs) and their exosomes may modulate NLRP3 inflammasome activation in a way that might be promising for the therapeutic management of CNS diseases. In the present review, particular focus is placed on highlighting and discussing recent scientific evidence regarding the regulatory effects of MSC-based therapies on the NLRP3 inflammasome activation and their potential to counteract proinflammatory responses and pyroptotic cell death in the CNS, thereby achieving neuroprotective impacts and improvement in behavioral impairments.

Comparison between clevidipine and nicardipine in cerebrovascular diseases: A systematic review and meta-analysis.

PURPOSE: The term "cerebrovascular diseases (CVDs)" refers to a broad category of diseases that affect the brain's blood vessels and cerebral circulation. Controlling acute hypertension (HTN) by antihypertensive drugs such as clevidipine and nicardipine can be a highly efficient method of lowering the incidence of CVDs. METHODS: This is a systematic review and meta-analysis study. The PubMed, Scopus, and Web of Science online databases and a gray literature search were performed to identify potentially eligible studies. The included studies were observational studies that compared adult patients receiving clevidipine or nicardipine for controlling HTN in the setting of CVD. RESULTS: We reviewed 5 final included articles, including 546 patients. The pooled standardized mean difference (SMD) for time to goal SBP was - 0.04 (95 % CI: [-0.66; 0.58], p-value: 0.86, I2: 79.0 %, pooled MD: -12.90 min), meaning that the clevidipine group had a shorter time to goal systolic blood pressure (SBP) than the nicardipine group. The pooled SMD for total volume infusion was - 0.52 (95 % CI: [-0.93; -0.12], p-value: 0.03, I2: 0.0 %, pooled MD: -1118.81 mL), showing a notably lower total volume infused into patients in the clevidipine group. CONCLUSIONS: We found that clevidipine reaches the SBP goal faster than nicardipine; however, there was no statistically significant difference between the two drugs. The total volume infused to achieve the goal SBP was significantly lower in the clevidipine group. Further prospective studies are needed to compare clevidipine and nicardipine in CVD patients on a large scale.

Potential biomarkers of addiction identified by real-time PCR in human peripheral blood lymphocytes: a narrative review.

Addiction-related neurobiological factors could be considered as potential biomarkers. The concentration of peripheral biomarkers in tissues like blood lymphocytes may mirror their brain levels. This review is focused on the mRNA expression of potential addiction biomarkers in human peripheral blood lymphocytes (PBLs). PubMed, EMBASE, Web of Science, Scopus and Google Scholar were searched using the keywords 'addiction', 'biomarker', 'peripheral blood lymphocyte', 'gene expression' and 'real-time PCR'. The results showed the alterations in the regulation of genes such as dopamine receptors, opioid receptors, NMDA receptors, cannabinoid receptors, α-synuclein, DYN, MAO-A, FosB and orexin-A as PBLs biomarkers in addiction stages. Such variations could also be found during abstinence and relapse. PBLs biomarkers may help in drug development and have clinical implications.

There are some peptides and proteins that are considered as non-invasive biomarkers in addiction. The level of such biomarkers in peripheral tissues like blood may be parallel to their concentrations in the brain. Here, we have reviewed the articles that have studied these biomarkers' expression levels in human peripheral blood lymphocytes (PBLs) using the real-time PCR technique. Previous studies have shown that in the process of addiction, some changes might occur in PBLs expression level of factors like dopamine, glutamate and opioid receptors, which are crucial in reward circuits and neurobiology of addiction. Studying the alterations in PBLs concentrations of these parameters (in stages of drug abuse, abstinence and relapse) could help investigators find a promising biomarker, which can help design new treatment strategies.

Paroxysmal sympathetic hyperactivity during traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of disability, morbidity, and mortality worldwide. Some of the more common etiologies of TBI include closed head injury, penetrating head injury, or an explosive blast head injury. Neuronal damage in TBI is related to both primary injury (caused by mechanical forces), and secondary injury (caused by the subsequent tissue and cellular damages). Recently, it has been well established that Paroxysmal Sympathetic Hyperactivity (PSH), also known as "Sympathetic Storm", is one of the main causes of secondary neuronal injury in TBI patients. The clinical manifestations of PSH include recurrent episodes of sympathetic hyperactivity characterized by tachycardia, systolic hypertension, hyperthermia, tachypnea with hyperpnea, and frank diaphoresis. Given the diverse manifestations of PSH and its notable impact on the outcome of TBI patients, we have comprehensively reviewed the current evidence and discussed the pathophysiology, clinical manifestations, time of onset and duration of PSH during TBI. This article reviews the different types of head injuries that most commonly lead to PSH, possible approaches to manage and minimize PSH complications in TBI and the current prognosis and outcomes of PSH in TBI patients.

Central nervous system manifestations in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic. METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, EMBASE, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between 1 January 2020 and 20 April 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456). RESULTS: Of 2,353 retrieved studies, we selected 64 studies with 11,687 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 was headache (8.69%, 95%CI: 6.76%-10.82%), dizziness (5.94%, 95%CI: 3.66%-8.22%), and impaired consciousness (1.90%, 95%CI: 1.0%-2.79%). CONCLUSIONS: The growing number of studies has reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes.

Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring.

Addiction to drugs, including opioids is the result of an interplay between environmental and genetic factors. It has been shown that the progeny of addict people is at higher risk for drug addiction. However, the mechanisms of such trans-generational effects of drugs are not so clear. Here we have evaluated the effects of parental morphine consumption on anxiety, morphine preference, and mRNA expression of dopamine receptors in F1 and F2 male offspring. Morphine was chronically administered to adult male and female Wistar rats followed by 14-day abstinence before mating. Morphine preference and anxiety-like behavior in the offspring were measured by two-bottle-choice paradigm and elevated-plus maze, respectively. Real-time PCR was used to measure the mRNA expression level of dopamine receptors in the striatum, nucleus accumbens, prefrontal cortex, and hippocampus of F1 animals. The results indicated that F1 but not the F2 male progeny of morphine-exposed parents had a greater preference for morphine, and more anxiety-like behavior compared to the offspring of saline-treated parents. In F1 male progeny of morphine-treated parents, D1 and D5 dopamine receptors were significantly increased in the prefrontal cortex and nucleus accumbens. D5 and D2 receptors were decreased in the hippocampus. D4 dopamine receptor was augmented in striatum and hippocampus and decreased in the prefrontal cortex. Adulthood exposure to chronic morphine in male and female rats before conception leads to higher morphine preference and increased anxiety in F1 but not F2 male progeny. Alterations of dopamine receptor expression in the reward system may be one mechanism responsible for observed changes in F1 offspring.

Expression of NMDA receptor subunits in human blood lymphocytes: A peripheral biomarker in online computer game addiction.

Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real-time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26). Results Expression levels of GluN2A, GluN2D, and GluN3B subunits were not statistically different between game addicts and the control group. However, the mRNA expression of the GluN3A subunit was downregulated in PBLs of game addicts. Discussion and conclusions Transcriptional levels of GluN2A and GluN2D subunits in online computer game addicts are similar to our previously reported data of opioid addiction and are not different from the control group. However, unlike our earlier finding of drug addiction, the mRNA expression levels of GluN3A and GluN3B subunits in PBLs of game addicts are reduced and unchanged, respectively, compared with control subjects. It seems that the downregulated state of the GluN3A subunit of NMDA receptor in online computer game addicts is a finding that deserves more studies in the future to see whether it can serve as a peripheral biomarker in addiction studies, where the researcher wants to rule out the confusing effects of abused drugs.

Chaperone potential of Pulicaria undulata extract in preventing aggregation of stressed proteins.

This study examined the effect of an aqueous extract of Pulicaria undulata on the 1,4-dithiothreitol (DTT)-induced aggregation of proteins. The effects of the chaperone properties of P. undulata extract on protein aggregation were determined by measuring light scattering absorption, fluorescence, and circular dichroism (CD) spectroscopy. The aqueous extract of P. undulata possesses good chaperone properties but the protection effect was varied in different protein. The extract showed a higher level of protection in high molecular weight proteins than in those of low molecular weight. Using a fluorescence study, the present study provides information on the hydrophobic area of proteins interacting with the P. undulata extract. In fact, by increasing the concentration of the P. undulata extract, the hydrophic area of the protein decreased. CD spectroscopy also revealed that DTT caused changes in both the tertiary and the secondary structure of the proteins, while in the presence of P. undulata extract, there was little change. Our finding suggests the possibility of using P. undulata extract for the inhibition of aggregation and the deposition of protein in disease.

In vitro detection of simulated apical root perforation with two electronic apex locators.

INTRODUCTION: The aim of this study was to evaluate the accuracy of two electronic apex locators (Smarpex and NovApex) in detecting apical perforation. MATERIALS AND METHODS: After access cavity preparations, the working length was determined by the first examiner before and after perforation with a stereomicroscope by introducing a K-file size 10 into the canal and size 25 K-file up to the perforation site, respectively. The specimens were embedded in a 17-well plastic box containing alginate. The root canals were irrigated with chlorhexidine 0.2% (CHX) through a 27-gauge needle. Two examiners measured the root canal length twice and the mean value was calculated. The data were analyzed using Kolmogorov-Smirnov and ANOVA tests. RESULTS: The results obtained with each Electronic Apex Locator were compared with the corresponding control length. The statistical analysis showed reliable accuracies in detecting the perforation site for the two experimental electronic apex locators (60% and 80% for NovApex and Smarpex, respectively). CONCLUSION: Although no significant difference was shown between Smarpex and NovApex, these results suggest that electronic apex locators can effectively and reproducibly detect root canal perforations.

Root Canal Configuration of One-rooted Mandibular Canine in an Iranian Population: An In Vitro Study.

BACKGROUND AND AIMS: A perfect endodontic treatment necessitates proper understanding of the morphology of canal and pulpal variations. This in vitro study was conducted to demonstrate the in-ternal anatomy of mandibular canine teeth in an Iranian population. MATERIALS AND METHODS: The samples consisted of 100 extracted mandibular permanent canines. The roots of the teeth were molded in acrylic boxes. The crowns of the teeth were cut and 2 mm cross sections were made from CEJ to the apex. Sections were examined using stereomicroscope to reveal the number and location of root canals. RESULTS: From 100 evaluated teeth, 12 (12%) had 2 canals from which 5 had type II canal configu-ration and 7 (7%) had type III. 88% of the specimens had one canal and none were seen to be of type IV. CONCLUSION: The findings of this study emphasize the importance of dentist's knowledge of varia-tions in root canal morphology, since leaving a canal untreated is one of the main reasons of endodontic failures. When treating mandibular canines, the existence of a second canal should be taken into consideration.

Serum Interleukin-6 as a Serologic Marker of Chronic Periapical Lesions: A Case-control Study.

BACKGROUND AND AIMS: Chronic periapical disease with pulpal origin is an inflammatory condition caused by bacterial infection. Chronic infection could affect general health by increasing the production of cytokines such as interleukin-6 (IL-6) that probably play a role in pathogenesis of pulpal and periapical diseases. The aim of the present study was a comparative evaluation of the level of serum IL 6 in patients with periapical lesions and healthy controls. MATERIALS AND METHODS: This analytical case-control study included 40 patients with chronic peri-apical lesions and 40 individuals without any oral diseases. All of the participants were in good general health. After obtaining an informed consent, clinical and radiographic examinations were carried out and blood samples were collected. Serum IL-6 was measured using ELISA. Data were analyzed using t-test by SPSS 14.0 computer software. RESULTS: Serum IL-6 concentration was significantly higher in test group compared to the controls (P < 0.05). CONCLUSION: The results of the present study indicate that IL-6 produced in periapical lesions may serve as a marker of pathologic inflammatory activities in chronic periapical lesions.

Comparison of cytotoxicity of three dentin bonding systems with two thicknesses of dentin barrier on l929 cell line.

INTRODUCTION: Along with introduction of dentin bonding agents (DBA), their clinical use as lining materials is increasing rapidly. Since remaining dentinal thickness (RDT) has always been a concern for cytopathic effect of restorative materials, its effect on reduction of cytotoxicity of these materials especially DBAs is critical. The purpose of this study was to evaluate and compare the cytotoxicity of three dentin bonding systems, belonged to the 4(th), 5(th) and 6(th) generation of DBAs on L929 cell line. MATERIALS AND METHODS: Thirty human premolar teeth were included. Class I cavity preparations were prepared on occlusal surfaces. After crown separation, a flat dentinal surface was provided and RDT (remaining dentinal thickness) was adjusted at 0.5 and 1.5 mm. Then, cavities were treated in three groups with experimental DBAs: Group 1: Scotchbond multipurpose, Group 2: Excite, Group 3: AdheSE. Blue inlay wax sealed the cavities. Crowns were immersed in culture medium for 24 hours and the cytotoxicity of the resultant toxic medium was measured quantitatively with MTT assay in 4 serial dilutions. Data were analyzed with ANOVA and Tukey's test at 95% significance level. RESULTS: MTT assay determined that only in neat dilution of 0.5 mm RDT, cell changes were significantly different from control. Besides, no significant differences were found between the three experimental DBAs regarding cytotoxic effect on L929 cell line. CONCLUSION: Considering the limitations of an in vitro study, if the RDT is less than 0.5 mm in vivo, regardless of the type of DBA, destructive cellular changes in pulp tissue can be expected.

Endodontic treatment of a taurodontism tooth: report of a case.

Taurodontism is a rare dental anomaly in which the involved tooth has an enlarged and elongated body and pulp chamber with apical displacement of the pulpal floor. Endodontic treatment of these teeth is challenging, because it is hard to identify the number of root canals. In this article a case of bilateral involvement of maxillary first molars is presented. Endodontic treatment of right maxillary first molar with taurodontism was indicated due to irreversible pulpitis. This article describes the procedures of root canal therapy.

A Comparative Study on the Amount of Extruded Material from the Apical Foramen with NiTi Rotary and Stainless Steel Hand Instruments.

INTRODUCTION: The purpose of the present study was to quantify and compare the amount of extruded debris from apical foramen after instrumentation of the root canal system with hand and rotary instruments. MATERIALS AND METHODS: Root canals of forty five fresh extracted single rooted human teeth with mature apexes and less than 15 degree of root curvature were instrumented in group A with stainless steel K-Type files, in group B with rotary NiTi Flex Master files, and in group C with rotary NiTi ProTaper files and followed weighting the extruded debris by a digital scale to within 0.0001 gram accuracy. RESULTS: In all groups, the mean weight of extruded debris was not more than 5 mg (P=0.0l) and was ranked as: Group A>Group B>Group C. There were statistically significant differences among three groups (p=0.0l). The mean value of extruded debris in the ProTaper and Flex Master groups were 0.652 and 0.788 mg, respectively. CONCLUSION: The study revealed that the amount of extruded debris from the apical foramen was minimal when ProTaper files were used.