Synthesis,Antimicrobial Activity,and Behavioral Response Effects of N-Substituted 4-Aryl-2-Hydroxy-4-Oxobut-2-Enoic Acid Hydrazides and Their Metal Complexes

Pharmaceutical Chemistry Journal - N-Substituted 4-aryl-2-hydroxy-4-oxobut-2-enoic acid hydrazides and their complexes with Ni(II), Mn(II), Co(II), Cu(II), and Zn(II) were prepared. Their...     

Insights from examination of hearts from adults dying suddenly to the understanding of congenital cardiac malformations

Congenital heart disease is a rare but important finding in adults who experience sudden death. Examination of the congenitally malformed heart has historically been considered esoteric and best left to those with expertise. The Cardiac Risk in the Young cardiovascular pathology laboratory based at St George's University of London has now received over 6,000 cases. Of these, 21 congenitally malformed hearts were retained for research and educational purposes. Hearts were assessed using sequential segmental analysis, and causes of death were adjudicated based on thorough macroscopic examination and histology. Congenital malformations that were encountered included atrial septal defects, ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries in both its regular and congenitally corrected variants. Findings also included hearts with mirror-imaged and isomeric atrial appendages. Direct causes of death included myocardial fibrosis, pulmonary hypertension, and hemorrhage. A small but notable proportion did not reveal a substrate for arrhythmia, raising the question of whether the terminal event was due to the congenital heart disease itself, or an underlying channelopathy. Here, we demonstrate the value of simple sequential segmental analysis in describing and categorizing the cases, with the concept of the “morphological method” serving to identify the distinguishing features of the cardiac components. Clin. Anat. 33:394–404, 2020. © 2019 Wiley Periodicals, Inc.     

Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis

ObjectivesCocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness.AimsWe conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs.Materials and MethodsQuality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline.ResultsOn a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively.ConclusionsWe find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.     

Inhibition of carbohydrate hydrolyzing enzymes associated with type 2 diabetes and antioxidative properties of some edible seeds in vitro

This study sought to evaluate the antioxidant properties and effects of some edible wild seeds [Afzelia africana Sm. (AFZ), Cyperus esculentus L. (CYP), Eleusine coracana Gaertn. (ELE), Irvingia gabonensis (Aubry-Lecomte ex O’Rorke) Baill. (IRV), Monodora myristica Dunal. (MON) and Parinari curatellifolia Planch. ex Benth. (PAR)] on α-amylase and α-glucosidase activities. The phenolic content and antioxidant activities of aqueous extracts of the seeds as typified by 1,1-diphenyl-2 picrylhydrazyl (DPPH) and hydroxyl (OH) radicals scavenging abilities and inhibition of Fe²⁺-induced malondialdehyde (MDA) production in rat’s pancreas in vitro were also assessed. ELE had significantly (p < 0.05) higher total phenol content than the other seeds; however, AFZ had the highest flavonoid content. The extracts scavenged DPPH· and OH· in a dose-dependent manner with aqueous extracts of PAR having the highest DPPH· scavenging ability, while extracts from IRV had the highest OH· scavenging ability and inhibition of Fe²⁺-induced MDA production in rat’s pancreas. Furthermore, all the extracts inhibited α-amylase and α-glucosidase activities in a dose-dependent manner. The α-amylase inhibitory effect of MON (IC₅₀ = 0.48 mg/mL) was comparable to that of acarbose (IC₅₀ = 0.40 mg/mL), while the α-glucosidase inhibitory effect of AFZ (IC₅₀ = 0.45 mg/mL) was comparable to that of acarbose (IC₅₀ = 0.39 mg/mL). The results suggest the potential use of the seeds in the dietary management of blood glucose levels associated with type 2 diabetes.