Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Synthesis and characterization some flavonoids derivatives

The flavonoids represent an important group of pigment that occurs in the plant kingdom. The flavones, one of the flavonoids, possess interesting biological actions. The antioxidant activity of flavones is reported to be associated with those bearing hydroxyl functions. In the present study, several steps of reaction have been carried out to synthesize the derivatives of luteolin, which are polyhydroxyl flavones. The first step of the reaction was the methylation of 2,4,6-trihydroxyacetophenone with methyl iodide to afford 2-hydroxy-4,6-dimethoxyacetophenone. On aldol condensation of 2-hydroxy-4,6- dimethoxyacetophenone with 3,4-dimethoxybenzaldehyde yielded 3,4,4,6- tetramethoxychalcone. This was followed by the oxidative cyclisation of chalcone with SeO2 to give 3,4,5,7-tetramethoxyflavone. The protection of hydroxyl functions of 2,4,6-trihydroxyacetophenone and 3,4-dihydroxybenzaldehyde with methoxy methyl chloride to form 2-hydroxy-4,6-bis(methoxymethyloxy)-acetophenone and 3,4-bis (methoxymethyloxy)-benzaldehyde was carried out. Both compounds were reacted via the aldol condensation to form 3,4,4,6-tetrakis(methoxymethyloxy)-chalcone. Treatment of 3,4,4,6-tetrakis(methoxymethyloxy)-chalcone with excessive sodium acetate afforded us 3,4,5,7-tetrahydroxyflavanone or eriodictyol (39) as a single product in high yield.The free radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by synthesized flavonoids using the electron spin resonance (ESR) technique and UV spectrophotometry method showed that 3,4,5,7- tetrahydroxyflavanone is a strong antioxidant. Compounds were characterized by spectroscopic techniques, i.e. infrared (IR), ultraviolet (UV) spectrophotometry, mass spectrometry (MS) and nuclear magnetic resonance (1H NMR and 13C NMR)

Antimicrobial, antioxidant, anti-inflammatory and cytotoxic activities of Garcinia Eugenifolia and Calophyllum Enervosum

Chemical investigation of Garcinia eugenifolia and Calophyllum enervosum yielded six compounds. One of these was found to be a novel compound identified as enervosanone. Five known compounds cambogin, epicatechin, osajaxanthone, rubraxanthone and isocowanol, were also isolated. These compounds were tested for their bioactivity as antimicrobial, antioxidant and cytotoxicagents. Antimicrobial assay was performed using disc diffusion method. The antioxidative activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method by electron spin resonance. The cytotoxicity was measured by the MTT assay against MCF7 cell line. Enervosanone and rubraxanthone were active against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus with MIC value of 26.82, 26.82, 26.82, 26.82 and 60.97, 30.48, 60.97, 60.97 mM, respectively. Rubraxanthone and epicatechin exhibited antioxidant activities with IC50 of 0.89 mM and 2.6 mM, respectively. The cytotoxicity assay on MCF7 cell line showed that enervosanone was found to be active in inhibiting cell proliferation of MCF7 with IC50 of 1.07 mM

Erratum to "A polyisoprenylated ketone from Calophyllum enervosum" [Phytochemistry 66 (2005) 723-726]

A polyisoprenylated ketone named enervosanone has been isolated from the stem bark of Calophyllum enervosum together with three known compounds, cambogin, osajaxanthone and epicatechin. Their structures were determined by spectroscopic analysis. The antimicrobial evaluations of the isolated compounds were also reported

Kimia organik: kumpulan berfungsi

Buku Kimia Organik: Kumpulan Berfungsi ditulis khusus untuk semua yang memerlukan pengetahuan asas kimia organik sebagai tahap permulaan dalam bidang sains khususnya kimia, biokimia, dan biologi, kejuruteraan kimia, dan farmasi. Buku ini mengandungi sepuluh bab, memperkenalkan pengelasan sebatian organik mengikut kumpulan berfungsi, iaitu bahagian yang mencirikan sebatian organik yang terlibat dalam semua tindak balas. Setiap bab dilengkapi dengan pengenalan, sifat penamaan, penyediaan, tindak balas berserta mekanisme tindak balas, contoh soalan serta penyelesaian, ringkasan dan soalan latihan. Buku ini menekankan pemahaman kaitan antara satu kumpulan berfungsi dengan kumpulan berfungsi yang lain. Hidrokarbon merupakan rangka asas kepada semua sebatian organik. Pengikatan kumpulan berfungsi, hidroksil, karbonil, halogen dan amino kepada rangka hidrokarbon memberikan sebatian organik dengan kelas tertentu, iaitu alkohol, fenol, aldehid, keton, amina, asid karboksilik dan terbitan asid karboksilik. Di samping itu, pengubahsuaian satu kumpulan berfungsi kepada kumpulan berfungsi lain menggunakan reagen tertentu dibantu dengan mekanisme tindak balas untuk memahamkan konsep tindak balas kimia organik

In vitro inhibitory effect of Rubraxanthone isolated from Garcinia psrvifolia on platelet- Activating factor receptor binding

Rubraxanthone and isocowanol isolated from Garcinia parvifolia Miq. were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets using 3H-PAF as a ligand. Rubraxanthone showed a strong inhibition with IC 50 value of 18.2 microM. The IC 50 values of macluraxanthone, 6-deoxyjacareubin, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone, 2-(3-methylbut-2-enyl)-1,3,5,6-tetrahydroxyxanthone and 1,3,5-trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)-xanthone were also determined for comparison. In the course of our study on structure-activity relationship of xanthones, the results revealed that a geranyl group substituted at C-8 was beneficial to the binding while a hydroxylated prenyl group at C-4 resulted in a significant loss in binding to the PAF receptor

Synthesis and antimicrobial activity of 4′,5,7-trihydroxy-3′- prenylflavanone

4′,5,7-Trihydroxy-3′-prenylflavanone was synthesized and tested for antibacterial effects against Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The synthesized compounds were characterized using UV, IR, MS and 1H and 13C NMR data. The antibacterial screening of the synthesized compounds were performed in vitro by the filter paper disc diffusion method

Antiplatelet aggregation activity of compounds isolated from guttiferae species in human whole blood

Twenty compounds isolated from Calophyllum inophyllum L., C. inophylloides King, Garcinia opaca King, G. bancana Miq., and G. parvifolia Miq. (Guttiferae) were evaluated for their ability to inhibit platelet aggregation in human whole blood induced by arachidonic acid (AA), collagen, and adenosine diphosphate (ADP). The compounds inhibited platelet aggregation in a dose-dependent manner. Among the compounds tested, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone and 2-(3-methylbut-2-enyl)-1,3,5,6- tetrahydroxyxanthone showed strong inhibitory activity on platelet aggregation induced by AA with IC50 values of 115.9 and 113.0µM, respectively. Rubraxanthone showed inhibitory activity against aggregation caused by the three inducers, and was the most effective antiplatelet compound against collagen-induced platelet aggregation with an IC50 value of 47.0µM. Macluraxanthone, GB-1a, pyranoamentoflavone, and a neoflavonoid showed selective inhibitory activity on platelet aggregation induced by ADP

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially