R S Duman

Dysregulation of the glutamatergic system and its receptors in medial prefrontal cortex (mPFC) has been implicated in major depressive disorder. Recent preclinical studies have shown that enhancing NMDA receptor (NMDAR) activity can exert rapid antidepressant-like effects. AGN-241751, an NMDAR positive allosteric modulator (PAM), is currently being tested as an antidepressant in clinical trials, but the mechanism and NMDAR subunit(s) mediating its antidepressant-like effects are unknown. We therefore used molecular, biochemical, and electrophysiological approaches to examine the cell-type-specific role of GluN2B-containing NMDAR in mediating antidepressant-like behavioral effects of AGN-241751...

Context: Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective: We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design: Cross-sectional study. Subjects and Methods: Male patients over age 50 were included in the study...

BACKGROUND: Depression affects approximately 7.1% of the United States population every year and has an annual economic burden of over $210 billion dollars. Several recent studies have sought to investigate the pathophysiology of depression utilizing focused cerebrospinal fluid (CSF) and serum analysis. Inflammation and metabolic dysfunction have emerged as potential etiological factors from these studies. A dysregulation in the levels of inflammatory proteins such as IL-12, TNF, IL-6 and IFN-γ have been found to be significantly correlated with depression...

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The discovery of the strikingly rapid and robust antidepressant effects of r/s-ketamine for the treatment of antidepressant-resistant symptoms of depression has led to new insights into the biology of antidepressants and the FDA approval of its s-isomer, Esketamine (Spravato), the first mechanistically new treatment for depression in over 60 years. To view this Bench to Bedside, open or download the PDF.

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Ketamine, an NMDA receptor antagonist and fast acting antidepressant, produces a rapid burst of glutamate in the ventral medial prefrontal cortex (mPFC). Preclinical studies have demonstrated that pyramidal cell activity in the vmPFC is necessary for the rapid antidepressant response to ketamine in rodents. We sought to characterize the effects of ketamine and its stereoisomers (R and S), as well as a metabolite, (2R,6R)-hydroxynorketamine (HNK), on vmPFC activity using a genetically encoded calcium indicator (GCaMP6f)...

The pathophysiology and treatment of depression has been the focus of intense research and while there is much that remains unknown, modern neurobiological approaches are making progress. This work demonstrates that stress and depression are associated with atrophy of neurons and reduced synaptic connectivity in brain regions such as the hippocampus and prefrontal cortex that contribute to depressive behaviors, and conversely that antidepressant treatment can reverse these deficits. The role of neurotrophic factors, particularly brain derived neurotrophic factor (BDNF) have been of particular interest as these factors play a key role in activity dependent regulation of synaptic plasticity...

A single sub-anesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates these and its behavioral actions has not been identified. To address this question, we used a combination of viral shRNA and conditional mutation to produce cell specific knockdown or deletion of a key NMDAR subunit, GluN2B, implicated in the actions of ketamine...

Although the robust antidepressant effects of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine in patients with treatment-resistant depression are beyond doubt, the precise molecular and cellular mechanisms underlying its antidepressant effects remain unknown. NMDAR inhibition and the subsequent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation are suggested to play a role in the antidepressant effects of ketamine. Although (R)-ketamine is a less potent NMDAR antagonist than (S)-ketamine, (R)-ketamine has shown more marked and longer-lasting antidepressant-like effects than (S)-ketamine in several animal models of depression...

OBJECTIVE: The aim of our study is to determine whether there is a change in the plasma levels of copeptin and there is a relationship among the plasma levels of carboxyhemoglobin (COHb), lactate, and copeptin levels in patients presenting to the emergency department with carbon monoxide (CO) poisoning. METHODS: Fifty-seven patients admitted to the emergency department with CO poisoning were included in the study. The blood samples of the patients were collected on arrival 0th, 6th, and 12th hours for copeptin, lactate, and COHb levels...

Fecal contaminants are a major public concern that directly affect human health in the fish production industry. In this study, we aimed to determine the fecal coliform, spoilage bacteria, and antimicrobial-resistant bacterial contamination in rainbow trout ( Oncorhynchus mykiss) farms. Fish were sampled from rainbow trout farms that have a high production capacity and are established on spring water, stream water, and dammed lakes in six different regions of Turkey. A total of seven Enterobacter subspecies, two strains of Pseudomonas spp...

OBJECTIVE: The N -methyl-d-aspartate receptor antagonist ketamine produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. Vascular endothelial growth factor (VEGF) has been implicated in the effects of conventional monoamine-based antidepressants, but the role of VEGF in the rapid antidepressant actions of ketamine remains unclear. The authors examined whether neuronal VEGF signaling in the medial prefrontal cortex (mPFC) mediates the rapid antidepressant actions of ketamine...

Living donor liver transplantation is a widely accepted option to treat liver diseases in several indications. Risk of liver donation is being discussed and quality of life of donors is also studied. Changes and the change pattern of quality of life were analyzed in this prospective longitudinal study. PATIENTS AND METHODS: Fifty-five donors were included. The Medical Outcomes Study Short Form 36 (SF-36) was fulfilled either in-person or during a telephone interview each donor preoperatively and at the end of the third, sixth, and 12th months...

Ketamine, a noncompetitive N -methyl-d-aspartate (NMDA) receptor antagonist, produces rapid and long-lasting antidepressant effects in major depressive disorder (MDD) patients. (2 R ,6 R )-Hydroxynorketamine [(2 R ,6 R )-HNK], a metabolite of ketamine, is reported to produce rapid antidepressant effects in rodent models without the side effects of ketamine. Importantly, (2 R ,6 R )-HNK does not block NMDA receptors like ketamine, and the molecular signaling mechanisms for (2 R ,6 R )-HNK remain unknown. Here, we examined the involvement of BDNF/TrkB/mechanistic target of rapamycin complex 1 (mTORC1) signaling in the antidepressant actions of (2 R ,6 R )-HNK...

Calbindin-D28K is a widely expressed calcium-buffering cytoplasmic protein that is involved in many physiological processes. It has been shown to interact with other proteins, suggesting a role as a calcium sensor. Many of the targets of calbindin-D28K are of therapeutic interest: for example, inositol monophosphatase, the putative target of lithium therapy in bipolar disorder. Presented here is the first crystal structure of human calbindin-D28K. There are significant deviations in the tertiary structure when compared with the NMR structure of rat calbindin-D28K (PDB entry 2g9b), despite 98% sequence identity...

Aim: This study aimed to evaluate the clinical and pathological features of ocular adnexal lymphoma (OAL) and the treatment results in an eye care service center in Turkey. Materials and Methods: The data sets of the patients diagnosed with OAL acquired between January 2008 and January 2016 were collected and analyzed. Results: Fifteen patients were included in our study. The mean age was 55.80 ± 17.85 years. The age range was 7-85 years...

Aims and Objectives: The aim of the study was to analyze and quantify the pattern of corneal astigmatism in Caucasian cataract surgery patients using a new optical biometer (axial length [AL] Scan, NIDEK Co., Gamagori, Japan). Patients and Methods: The datasets of cataract surgery patients acquired between March 1, 2014, and April 15, 2016, were collected and analyzed. The corneal power (flat keratometry, steep keratometry, and mean keratometry), negative cylinder power, and axis of astigmatism were recorded...

PURPOSE: We aimed to determine the anatomical variations more comprehensively particularly at the level of superior sagittal sinus (SSS), confluence of sinuses (CS), transverse sinuses (TS), straight sinuses (SS) and occipital sinuses (OS) with the help of the images obtained via MRI venography, and to contribute to the classification efforts. METHODS: In our retrospective study, we evaluated 211 patients who admitted to our hospital with various complaints and cerebral MRI venography has been performed...

Conventional antidepressant medications, which act on monoaminergic systems, display significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that acts as an N-methyl-D-aspartate (NMDA) modulator with glycine-like partial agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces rapid antidepressant actions in depressed patients and in preclinical rodent models. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been characterized...