Antidepressant mechanism of ketamine: perspective from preclinical studies

A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine’s rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine’s antidepressant mechanism of action. Recent preclinical studies indicate that ketamine’s antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3B) inactivation. Adjunct GSK-3B inhibitors, such as lithium, can enhance ketamine’s efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue

Coronavirus-positive Nasopharyngeal Aspirate as Predictor for Severe Acute Respiratory Syndrome Mortality

Severe acute respiratory syndrome (SARS) has caused a major epidemic worldwide. A novel coronavirus is deemed to be the causative agent. Early diagnosis can be made with reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate samples. We compared symptoms of 156 SARS-positive and 62 SARS-negative patients in Hong Kong; SARS was confirmed by RT-PCR. The RT-PCR–positive patients had significantly more shortness of breath, a lower lymphocyte count, and a lower lactate dehydrogenase level; they were also more likely to have bilateral and multifocal chest radiograph involvement, to be admitted to intensive care, to need mechanical ventilation, and to have higher mortality rates. By multivariate analysis, positive RT-PCR on nasopharyngeal aspirate samples was an independent predictor of death within 30 days

Synthesis, characterization and photophysical study of a series of neutral isocyano rhodium(I) complexes with pyridylindolide ligands

Pyridylindole ligand and its chloro substituted derivatives have been synthesized and incorporated into the square planar bis(phenylisocyano) rhodium(I) complexes to give a series of neutral rhodium(I) complexes with general formula of [Rh( X-pyind)(CNR) 2] (R = 2,6-(CH 3) 2-4-BrC 6H 2, 2,4-Cl 2-6-(CH 3O)C 6H 2, 2,4,6-Br 3C 6H 2, 2,4,6-Cl 3C 6H 2 ; L = 2-(2′-pyridyl)indole, 5-chloro-2-(2′-pyridyl)indole, 4,6-dichloro-2-(2′-pyridyl)indole). The structures of two complex precursors [Rh(cod)( Cl-pyind)] and [Rh(cod)( Cl 2pyind )], and the target complex [Rh( pyind)(CNC 6H 2-2,4-Cl 2-6-(OCH 3)) 2] were determined by X-ray crystallography. The UV–vis absorption properties of these complexes and their responses towards the change of temperature were also investigated. A new class of neutral square planar bis(phenylisocyano) rhodium(I) complexes with pyridylindolide ligands with general formula of [Rh( X-pyind)(CNR) 2] has been synthesized. The UV–vis absorption and thermochromic properties of these complexes were also investigated

Aggregation and DNA intercalation properties of Di(isocyano) rhodium(I) Diimine complexes

A series of di(isocyano) rhodium(I) diimine complexes has been synthesized and characterized. Owing to the aggregation affinity of these complexes, they were found to exhibit thermochromism. To provide further insights into the aggregation affinity of these complexes, the enthalpy (δH) and entropy (δS) changes of dimerizations of some of the complexes have been determined. In addition, the DNA intercalation properties of these complexes have also been investigated by the DNA unwinding assay

Normally-Off p-GaN Gated AlGaN/GaN MIS-HEMTs with ALD-Grown Al2O3/AlN Composite Gate Insulator

A metal–insulator–semiconductor p-type GaN gate high-electron-mobility transistor (MIS-HEMT) with an Al2O3/AlN gate insulator layer deposited through atomic layer deposition was investigated. A favorable interface was observed between the selected insulator, atomic layer deposition–grown AlN, and GaN. A conventional p-type enhancement-mode GaN device without an Al2O3/AlN layer, known as a Schottky gate (SG) p-GaN HEMT, was also fabricated for comparison. Because of the presence of the Al2O3/AlN layer, the gate leakage and threshold voltage of the MIS-HEMT improved more than those of the SG-HEMT did. Additionally, a high turn-on voltage was obtained. The MIS-HEMT was shown to be reliable with a long lifetime. Hence, growing a high-quality Al2O3/AlN layer in an HEMT can help realize a high-performance enhancement-mode transistor with high stability, a large gate swing region, and high reliability

Synthesis, Structures, and Photophysical Properties of Ruthenium(II) Quinolinolato Complexes

Reaction of [Ru^II(PR₃)₃Cl₂] with 2-methyl<b>-</b>8-quinolinolate (MeQ) in the presence of Et₃N in MeOH produced the neutral carbonyl hydrido complexes [Ru^II(MeQ)­(PR₃)₂(CO)­(H)] (R = Ph (<b>1</b>), MeC₆H₄ (<b>2</b>), MeOC₆H₄ (<b>3</b>)). An analogous reaction occurs between [Ru^II(PPh₃)₃Cl₂] and MeQH in ethanol to give [Ru^II(MeQ)­(PPh₃)₂(CO)­(CH₃)] (<b>4</b>). The carbonyl, hydride, and methyl ligands of these complexes are most likely derived from the decarbonylation of ROH. Reaction of [Ru^II(PPh₃)₃(CO)­(H)₂] with 5-substituted quinolinolato ligands (XQ, X = H, Cl, Ph) produced the neutral complexes [Ru^II(XQ)­(PPh₃)₂(CO)­(H)] (XQ = Q (<b>5</b>), ClQ (<b>6</b>), PhQ (<b>7</b>)). Treatment of <b>1</b> and <b>5</b>–<b>7</b> with excess KCN in MeOH following by metathesis with PPh₄Cl afforded PPh₄⁺ salts of the anionic carbonyl dicyano complexes [Ru^II(XQ)­(CO)­(CN)₂(PPh₃)]⁻ (XQ = MeQ (<b>8</b>), Q (<b>9</b>) ClQ (<b>10</b>), PhQ (<b>11</b>)). Under similar conditions, reaction of <b>1</b> with excess CyNC in the presence of NH₄PF₆ afforded [Ru^II(MeQ)­(CyNC)₂(CO)­(PPh₃)]⁺ (<b>12</b>). All complexes have been characterized by IR, ESI/MS, ¹H NMR and elemental analysis. The crystal structures of complexes <b>3</b>, <b>4</b>, <b>8</b>, and <b>12</b> have been determined by X-ray crystallography. The UV and emission spectra of these complexes have also been investigated. All complexes exhibit short-lived quinolinolate-based LC fluorescence in solution at room temperature and dual emissions derived from LC fluorescence and phosphorescence at 77 K glassy medium. These emissions are relatively insensitive to the nature of the ancillary ligands but are readily tunable by varying the substituents on the quinolinolato ligand

Synthesis, Structures, and Photophysical Properties of Ruthenium(II) Quinolinolato Complexes

Reaction of [Ru^II(PR₃)₃Cl₂] with 2-methyl<b>-</b>8-quinolinolate (MeQ) in the presence of Et₃N in MeOH produced the neutral carbonyl hydrido complexes [Ru^II(MeQ)­(PR₃)₂(CO)­(H)] (R = Ph (<b>1</b>), MeC₆H₄ (<b>2</b>), MeOC₆H₄ (<b>3</b>)). An analogous reaction occurs between [Ru^II(PPh₃)₃Cl₂] and MeQH in ethanol to give [Ru^II(MeQ)­(PPh₃)₂(CO)­(CH₃)] (<b>4</b>). The carbonyl, hydride, and methyl ligands of these complexes are most likely derived from the decarbonylation of ROH. Reaction of [Ru^II(PPh₃)₃(CO)­(H)₂] with 5-substituted quinolinolato ligands (XQ, X = H, Cl, Ph) produced the neutral complexes [Ru^II(XQ)­(PPh₃)₂(CO)­(H)] (XQ = Q (<b>5</b>), ClQ (<b>6</b>), PhQ (<b>7</b>)). Treatment of <b>1</b> and <b>5</b>–<b>7</b> with excess KCN in MeOH following by metathesis with PPh₄Cl afforded PPh₄⁺ salts of the anionic carbonyl dicyano complexes [Ru^II(XQ)­(CO)­(CN)₂(PPh₃)]⁻ (XQ = MeQ (<b>8</b>), Q (<b>9</b>) ClQ (<b>10</b>), PhQ (<b>11</b>)). Under similar conditions, reaction of <b>1</b> with excess CyNC in the presence of NH₄PF₆ afforded [Ru^II(MeQ)­(CyNC)₂(CO)­(PPh₃)]⁺ (<b>12</b>). All complexes have been characterized by IR, ESI/MS, ¹H NMR and elemental analysis. The crystal structures of complexes <b>3</b>, <b>4</b>, <b>8</b>, and <b>12</b> have been determined by X-ray crystallography. The UV and emission spectra of these complexes have also been investigated. All complexes exhibit short-lived quinolinolate-based LC fluorescence in solution at room temperature and dual emissions derived from LC fluorescence and phosphorescence at 77 K glassy medium. These emissions are relatively insensitive to the nature of the ancillary ligands but are readily tunable by varying the substituents on the quinolinolato ligand

An Avoidable Complication of Percutaneous Coronary Intervention—Entrapment of Stent and Disconnected Balloon Catheter

During percutaneous coronary intervention, entrapment of catheter materials is a rare but life-threatening complication that sometimes requires emergency surgical treatment. Coronary artery stents have been developed to prevent acute coronary closure and reduce restenosis after coronary angioplasty. The most frequently reported complications of coronary stents are related to stent thrombosis and anticoagulation problems. This case study describes a 60-year-old female who had stable angina pectoris and underwent stent insertion into the left circumflex artery. Unfortunately, the coronary stent with balloon catheter was entrapped while crossing the angulated segment between the left circumflex and left main coronary artery. The stent catheter was surgically removed, and the patient underwent coronary artery bypass grafting successfully. Physicians should keep in mind that extremely angulated segments may reduce the successful rate of coronary stenting and contribute to the stent entrapment complication