Revisiting Preclinical Observations of Several Histamine H3 Receptor Antagonists/Inverse Agonists in Cognitive Impairment, Anxiety, Depression, and Sleep-Wake Cycle Disorder.

A relationship appears to exist between dysfunction of brain histamine (HA) and various neuropsychiatric brain disorders. The possible involvement of brain HA in neuropathology has gained attention recently, and its role in many (patho)physiological brain functions including memory, cognition, and sleep-wake cycle paved the way for further research on the etiology of several brain disorders. Histamine H3 receptor (H3R) evidenced in the brains of rodents and humans remains of special interest, given its unique position as a pre- and postsynaptic receptor, controlling the synthesis and release of HA as well as different other neurotransmitters in different brain regions, respectively. Despite several disappointing outcomes for several H3R antagonists/inverse agonists in clinical studies addressing their effectiveness in Alzheimer's disease (AD), Parkinson's disease (PD), and schizophrenia (SCH), numerous H3R antagonists/inverse agonists showed great potentials in modulating memory and cognition, mood, and sleep-wake cycle, thus suggesting its potential role in neurocognitive and neurodegenerative diseases such as AD, PD, SCH, narcolepsy, and major depression in preclinical rodent models. In this review, we present preclinical applications of selected H3R antagonists/inverse agonists and their pharmacological effects on cognitive impairment, anxiety, depression, and sleep-wake cycle disorders. Collectively, the current review highlights the behavioral impact of developments of H3R antagonists/inverse agonists, aiming to further encourage researchers in the preclinical drug development field to profile the potential therapeutic role of novel antagonists/inverse agonists targeting histamine H3Rs.

Role of Brain Modulators in Neurodevelopment: Focus on Autism Spectrum Disorder and Associated Comorbidities.

Autism spectrum disorder (ASD) and associated neurodevelopmental disorders share similar pathogenesis and clinical features. Pathophysiological changes in these diseases are rooted in early neuronal stem cells in the uterus. Several genetic and environmental factors potentially perturb neurogenesis and synaptogenesis processes causing incomplete or altered maturation of the brain that precedes the symptomology later in life. In this review, the impact of several endogenous neuromodulators and pharmacological agents on the foetus during pregnancy, manifested on numerous aspects of neurodevelopment is discussed. Within this context, some possible insults that may alter these modulators and therefore alter their role in neurodevelopment are high-lighted. Sometimes, a particular insult could influence several neuromodulator systems as is supported by recent research in the field of ASD and associated disorders. Dopaminergic hy-pothesis prevailed on the table for discussion of the pathogenesis of schizophrenia (SCH), atten-tion-deficit hyperactivity disorder (ADHD) and ASD for a long time. However, recent cumulative evidence suggests otherwise. Indeed, the neuromodulators that are dysregulated in ASD and comorbid disorders are as diverse as the causes and symptoms of this disease. Additionally, these neuromodulators have roles in brain development, further complicating their involvement in comorbidity. This review will survey the current understanding of the neuromodulating systems to serve the pharmacological field during pregnancy and to minimize drug-related insults in pa-tients with ASD and associated comorbidity disorders, e.g., SCH or ADHD.

COVID-19 Treatment Guidelines: Do They Really Reflect Best Medical Practices to Manage the Pandemic?

SARS-CoV-2 (COVID-19) has been changing the world since December 2019. A comprehensive search into many COVID-19 treatment guidelines was conducted and reported in this article. This is a review paper to probe differences in COVID-19 managing strategies and explore the most common treatment plans among countries. Published guidelines from 23 countries and three references guidelines-until the end of 2020-were included in this article. The majority of COVID-19 treatment options were reported in this review and it includes antiviral drugs, antimalarial drugs, antibiotics, corticosteroids, immunotherapy, anticoagulants, and other pharmacological treatment. The presence of such information from different countries in a single comprehensive review article could help in understanding and speculation of variation in the recommended treatment in each country. This might be related to the cost of medications, the access to the medications, availability of medication that could potentially be useful in managing COVID-19 cases, and the availability/capacity of healthcare facilities. Finally, although there are various treatment groups listed in the published therapeutic guidelines worldwide, unfortunately, there is no evidence for effectiveness of most of these medications in reducing the COVID-19 mortality curve over more than one year of this global pandemic.

Ovarian reserve after salpingectomy: a systematic review and meta-analysis.

INTRODUCTION: Although there has been a growing concern over the possible damaging effect of salpingectomy on ovarian reserve, this issue remains uncertain. The purpose of this meta-analysis was to test the hypothesis that salpingectomy may compromise ovarian reserve. MATERIAL AND METHODS: A detailed search was conducted using MEDLINE, Embase, Dynamed Plus, ScienceDirect, TRIP database and the Cochrane Library from January 2000 to November 2016. All cohort, cross-sectional and randomized controlled studies investigating changes in circulating anti-Müllerian hormone (AMH) after salpingectomy were considered. Thirty-seven studies were identified, of which eight were eligible. Data were extracted and entered into RevMan software for calculation of the weighted mean difference (WMD) and 95% CI. Two groups of studies were analyzed separately: group 1 (six studies, n = 464) comparing data before and after salpingectomy and group 2 (two studies) comparing data in women who have undergone salpingectomy (n = 169) vs. healthy controls (n = 154). RESULTS: Pooled results of group 1 studies showed no statistically significant change in serum AMH concentration after salpingectomy (WMD, -0.10 ng/mL; 95% CI -0.19 to 0.00, I2 = 0%). Similarly, meta-analysis of group 2 showed no statistically significant difference in serum AMH concentration between salpingectomy group and controls (WMD, -0.11 ng/mL; 95% CI -0.37 to 0.14, I2 = 77%). Subgroup analyses based on laterality of surgery, type of AMH kit and participants' age (<40 years) still showed no statistically significant changes in circulating AMH. CONCLUSION: Salpingectomy does not seem to compromise ovarian reserve in the short-term. However, the long-term effect of salpingectomy on ovarian reserve remains uncertain.