Результаты поиска

Selective Oxidation of Alkylarenes to the Aromatic Ketones or Benzaldehydes with Water.

Here a palladium-catalyzed oxidation method for converting alkylarenes into the aromatic ketones or benzaldehydes with water as the only oxygen donor is reported. This C-H bond oxidation functionalization does not require other oxidants and hydrogen acceptors, and H2 is the only byproduct. The oxygen atom introduced into the products is confirmed to be from water by the MS analysis on the product of the 18O-labeled water reaction.

Development of a Potent QS-21-Derived Adjuvant Photoaffinity Probe: Identification of Cathepsin D as the Molecular Receptor.

The saponin natural product QS-21 is a potent immunological adjuvant used in human vaccines to enhance the immune response but suffers from scarcity, instability, and dose-limiting toxicity, precluding its advancement as a stand-alone adjuvant. Further, putative cellular receptor(s) and its molecular mechanisms of action are unknown, which has prevented the rational design of saponin adjuvants, emphasizing the need for discovering these receptors and elucidating mechanisms. Herein, we have developed novel saponin photoaffinity probes for molecular target identification, merging synthetic chemi

Prenatal Use of Sirolimus in Fetal Therapy: Current Evidence, Clinical Applications, and Future Directions.

Prenatal imaging, genomic diagnosis, and pathway-directed pharmacology increasingly permit treatment of selected fetal disorders before birt … ve not identified a consistent malformation pattern, but exposures are sparse and confounded, while product labeling warns of embryo-fetal toxicity based on animal studies. Prenatal sirolimus therefore remains an investigational intervention for carefully selected, life-threatening or organ-threatening fetal disease managed by specialized multidisciplinary teams. …

Quantifying the biological impacts of nightlights: implications for sleep and circadian health in children.

Given the widespread use of nightlights, we characterized an assortment of popular products to evaluate their potential to disrupt sleep and … hose would not support vision. Clear clinical guidance, public health recommendations, and improved product labeling standards are needed to reduce circadian disruption and promote healthier sleep in children.

Non-Equilibrium Growth Processes to Glyceraldehyde and Glycerol as Building Blocks of Interstellar Sugars and Phospholipids.

Complex organic molecules (COMs) such as aldoses and polyols are essential prebiotic compounds and serve as fundamental molecular building blocks for key biomolecules, including sugars and lipids. Despite their detection in star-forming regions and carbonaceous meteorites, the mechanisms of formation of these COMs in extraterrestrial environments remain largely controversial. Here, we demonstrate the bottom-up synthesis of a diverse set of COMs in the formaldehyde-water (H2CO-H2O) ice analogs subjected to simulated galactic cosmic rays (GCRs), including aldoses and polyols (glycolaldehyde, eth

Accidental Intravenous Administration of Oral Bacillus clausii Probiotic (Enterogermina) in a Toddler: A Case Report.

Acute diarrheal illness is a common cause of hospitalization in toddlers, and probiotics such as oral Bacillus clausii suspension (Enteroger … . It highlights the urgent need for strict medication safety protocols, staff training, and clearer product labeling to avoid such preventable errors in pediatric practice.

Изучение взаимодействия наркотиков между новыми антидепрессантами и лекарствами, используемыми для лечения неврологических расстройств.

ВВЕДЕНИЕ: В настоящем обзоре рассматриваются клинически значимые взаимосвязи между новыми антидепрессантами и лекарствами, используемыми для лечения неврологических расстройств, которые часто сочетаются с депрессией, включая болезнь Паркинсона, болезнь Альцгеймера, мигрень, множественный склероз и нейропатическую боль. ОБЛОЖКА: Статьи были получены из Pubmed, Web of Science, SCOPUS и Google Search, выполненные по каждому из новых антидепрессантов и неврологических препаратов. Были резюмированы фармакокинетические (PK) и фармакодинамические (PD) механизмы, лежащие в основе этих ДИ. Некоторые но

Совпадение в аннотации оригинала
INTRODUCTION: This review examines clinically relevant drug interactions (DIs) between newer antidepressants and medications used to manage … -oxidase-B inhibitors or triptans; these interactions are noted as warnings or contraindications in product labeling. EXPERT OPINION: Clinicians must remain alert to possible DIs between antidepressants and neurological medications. Understanding PK and PD principles, coupled with proactive measures, such as pharmacogenetic testing, therapeutic drug monitoring, u …

Accurate Visualization of C4d Complement Fragment in Immunohistochemistry by C-Terminal Linear Neoepitope-Specific Antibodies.

C4d is the end degradation product of activated complement component C4b that appears during the early steps of the classical and lectin complement pathways. Within the primary sequence of C4d, there is a reactive thioester group that binds covalently to nearby surfaces, thus labeling the locations of complement activation. This feature makes C4d a target for immunohistochemical staining aimed to aid the diagnosis of, among others, the antibody-mediated rejection of transplanted organs, membranous glomerulonephritis, bullous pemphigoid, or inflammatory myopathies. However, the credibility of C

Analytical chromatography approaches during the synthesis and conjugation of methoxypolyethylene glycol-succinimidyl butanoate (mPEG-SBA) to epoetin beta.

Conjugation of epoetin beta (EPO) with methoxypolyethylene glycol-succinimidyl butanoate (mPEG-SBA) was studied. The compound mPEG-SBA was synthesized from mPEG, and the obtained intermediates and final product were analyzed by a reversed-phase chromatographic system equipped with an evaporative light scattering detector. Labeling the hydroxyl group in PEGs with benzoyl chloride and succinimide with benzylamine was applied to resolve and characterize different PEGs. The synthesized mPEG-SBA was used for the PEGylation of EPO. A size-exclusion chromatographic method monitored the reaction, simu

Metabolic Usage and Glycan Destinations of GlcNAz in E. coli.

Bacteria use a diverse range of carbohydrates to generate a profusion of glycans, with amino sugars, such as N-acetylglucosamine (GlcNAc), being prevalent in the cell wall and in many exopolysaccharides. The primary substrate for GlcNAc-containing glycans, UDP-GlcNAc, is the product of the bacterial hexosamine pathway and a key target for bacterial metabolic glycan engineering. Using the strategy of expressing NahK, to circumvent the hexosamine pathway, it is possible to directly feed the analogue of GlcNAc, N-azidoacetylglucosamine (GlcNAz), for metabolic labeling in Escherichia coli. The cyt

Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue.

Primary obstructive megaureter (POM) morphogenesis is not fully known. The aim of the study was to evaluate the appearance of different factors that might take part in the pathogenesis of POM. Megaureter tissues of 14 children were stained with hematoxylin and eosin as well as with immunohistochemistry for protein gene product 9.5, nerve growth factor receptor, transforming growth factor beta 1 (TGFβ1), fibroblast growth factor receptor 1 (FGFR1), matrix metalloproteinase 2 (MMP-2), angiotensin 2 receptor type 2, and sonic hedgehog (SHH) protein. Apoptosis was detected by terminal dUTP nick-en

Physiologically based pharmacokinetic modeling of altered tizanidine systemic exposure by CYP1A2 modulation: Impact of drug-drug interactions and cigarette consumption.

Tizanidine is an alpha2-adrenergic agonist, used to treat spasticity associated with multiple sclerosis and spinal injury. Tizanidine is pri … interactions and illustrate the potential application in drug development, specifically to support product labeling.

Effects of high-dose alacepril on left atrial pressure and central aortic pressure in awake dogs with mitral valve regurgitation.

The purpose of this study was to clarify how alacepril in amounts greater than those recommended on the product labeling approved by drug regulatory agencies affects left atrial pressure (LAP) and central aortic pressure in dogs with experimentally induced mitral valve regurgitation (MR). Six healthy Beagle dogs were surgically induced for MR and received alacepril at either 1.5mg/kg/12-h (3.0mg/kg/day) or 3.0mg/kg/12-h (6.0mg/kg/day) per one administration for seven days. After a four-week washout period, another dosage was administrated as a crossover study. Dogs were randomised to receive 3…

Detection and Specific Elimination of EGFR+ Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach.

PURPOSE: Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge. The aim of this study is to detect and eliminate ovarian cancer cells o

Quantitative detection of nitroxyl upon trapping with glutathione and labeling with a specific fluorogenic reagent.

Donors of nitroxyl (HNO) have shown promise for treatment of stroke, heart failure, alcoholism and cancer. However, comparing the pharmacological capacities of various donors is difficult without first quantifying the amount of HNO released from each donor. Detection and quantitation of HNO has been complicated by the rapid self-consumption of HNO through irreversible dimerization, poor selectivity of trapping agents against other nitrogen oxides, and/or low sensitivity towards HNO. Here, an assay is described for the trapping of HNO by glutathione (GSH) followed by labeling of GSH with the fl

Depletion of Beclin-1 due to proteolytic cleavage by caspases in the Alzheimer's disease brain.

The Beclin-1 protein is essential for the initiation of autophagy, and recent studies suggest this function may be compromised in Alzheimer's disease (AD). In addition, in vitro studies have supported a loss of function of Beclin-1 due to proteolytic modification by caspases. In the present study, we examined whether caspase-cleavage of Beclin-1 occurs in the AD brain by designing a site-directed caspase-cleavage antibody based upon a known cleavage site within the protein at position D149. We confirmed that Beclin-1 is an excellent substrate for caspase-3 and demonstrates cleavage led to the

Shell shock and mild traumatic brain injury: a historical review.

Mild traumatic brain injury is now claimed to be the signature injury of the Iraq and Afghanistan conflicts. During World War I, shell shock came to occupy a similar position of prominence, and postconcussional syndrome assumed some importance in World War II. In this article, the nature of shell shock, its clinical presentation, the military context, hypotheses of causation, and issues of management are explored to discover whether there are contemporary relevancies to the current issue of mild traumatic brain injury. When shell shock was first postulated, it was assumed to be the product of

Occurrence of apoptosis, secondary necrosis, and cytolysis in eosinophilic nasal polyps.

The paradigm states that inflammatory cells disappear from airway tissues through apoptosis and phagocytosis. However, cells may also be cleared through primary cytolysis, necrosis secondary to apoptosis, or transepithelial migration. This study examines the occurrence of apoptosis, secondary necrosis, and cytolysis of eosinophils in human nasal polyps in vivo and blood eosinophils in vitro. Eosinophils abounded in subepithelium and in paracellular epithelial pathways. Macrophages commonly occurred but without engulfed eosinophils. Scattered cells, including epithelial cells, were stained by a

Expression and clinical significance of the G1-S modulators in carcinoma of the extrahepatic bile duct.

Expression of cell cycle modulators at the G1-S boundary, the retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D1 as well as Ki-67 was investigated with 39 extrahepatic bile duct carcinomas (BDC). The Ki-67 labeling index (LI) was higher in cases with poor differentiation, lymph node metastasis and stage III or IV. Cyclin D1 overexpression was seen in 14 cases (35.8%). This phenomenon could be observed more frequently in cases of hilar carcinoma and with poor differentiation, perineural invasion, lymphatic invasion and lymph node metastasis. Furthermore, Ki-67 LI was higher in cyc

Identification of endothelin receptor subtypes in rat ciliary body using subtype-selective ligands.

The endothelins are important vasoactive ocular peptides and there is some evidence that they may modulate intraocular pressure. We investigated the existence and localization of endothelin receptor subtypes using subtype selective ligands in rat ciliary body. Scatchard transformation of saturation binding experiments revealed that the KD and Bmax for [125I]ET-1 and [125I]ET-3 to membranes from ciliary body were 41.7+/-9 pM and 236+/-20 fmol mg-1 protein and 37. 8+/-0.4 pM and 160+/-2.0 fmol mg-1 protein, respectively. Competitive experiments in the presence of cyclic pentapeptide BQ123 (selec