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BACKGROUND: The use of dual antiplatelet therapy (DAPT) after coronary revascularization for left-main disease is still debated. The study aimed to characterize patients who received dual versus single antiplatelet therapy (SAPT) after coronary artery bypass grafting (CABG) for unprotected left-main disease and compare the outcomes of those patients. RESULTS: This multicenter retrospective cohort study included 551 patients who were grouped into 2 groups: patients who received SAPT (n = 150) and those who received DAPT (n = 401). There were no differences in age ( P = 0.451), gender ( P = 0.063), smoking ( P = 0.941), diabetes mellitus ( P = 0.773), history of myocardial infarction ( P = 0.709), chronic kidney disease ( P = 0.615), atrial fibrillation ( P = 0.306), or cerebrovascular accident ( P = 0.550) between patients who received SAPT versus DAPT. DAPTs were more commonly used in patients with acute coronary syndrome [87 (58%) vs. 273 (68.08%); P = 0.027], after off-pump CABG [12 (8%) vs. 73 (18.2%); P = 0.003] and in patients with radial artery grafts [1 (0.67%) vs. 32 (7.98%); P < 0.001]. While SAPTs were more commonly used in patients with low ejection fraction [55 (36.67%) vs. 61 (15.21%); P < 0.001] and in patients with postoperative acute kidney injury [27 (18%) vs. 37 (9.23%); P = 0.004]. The attributed treatment effect of DAPT for follow-up major adverse cerebrovascular and cardiac events was not significantly different from that of SAPT [ß, -2.08 (95% confidence interval (CI), -20.8-16.7); P = 0.828]. The attributed treatment effect of DAPT on follow-up all-cause mortality was not significantly different from that of SAPT [ß, 4.12 (CI, -11.1-19.32); P = 0.595]. There was no difference in bleeding between groups ( P = 0.666). CONCLUSIONS: DAPTs were more commonly used in patients with acute coronary syndrome, after off-pump CABG, and with radial artery grafts. SAPTs were more commonly used in patients with low ejection fraction and acute kidney injury. Patients on DAPT after CABG for left-main disease had comparable major adverse cerebrovascular and cardiac events and survival to patients on SAPT, with no difference in bleeding events.
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Síndrome Coronario Agudo , Lesión Renal Aguda , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/cirugía , Síndrome Coronario Agudo/inducido químicamente , Estudios Retrospectivos , Resultado del Tratamiento , Puente de Arteria Coronaria/efectos adversos , Hemorragia/inducido químicamente , Lesión Renal Aguda/inducido químicamenteRESUMEN
BACKGROUND: The optimal revascularization strategy in patients with left main coronary artery (LMCA) disease in the emergency setting is still controversial. Thus, we aimed to compare the outcomes of percutaneous coronary interventions (PCI) vs. coronary artery bypass grafting (CABG) in patients with and without emergent LMCA disease. METHODS: This retrospective cohort study included 2138 patients recruited from 14 centers between 2015 and 2019. We compared patients with emergent LMCA revascularization who underwent PCI (n = 264) to patients who underwent CABG (n = 196) and patients with non-emergent LMCA revascularization with PCI (n = 958) to those who underwent CABG (n = 720). The study outcomes were in-hospital and follow-up all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Emergency PCI patients were older and had a significantly higher prevalence of chronic kidney disease, lower ejection fraction, and higher EuroSCORE than CABG patients. CABG patients had significantly higher SYNTAX scores, multivessel disease, and ostial lesions. In patients presenting with arrest, PCI had significantly lower MACCE (P = 0.017) and in-hospital mortality (P = 0.016) than CABG. In non-emergent revascularization, PCI was associated with lower MACCE in patients with low (P = 0.015) and intermediate (P < 0.001) EuroSCORE. PCI was associated with lower MACCE in patients with low (P = 0.002) and intermediate (P = 0.008) SYNTAX scores. In non-emergent revascularization, PCI was associated with reduced hospital mortality in patients with intermediate (P = 0.001) and high (P = 0.002) EuroSCORE compared to CABG. PCI was associated with lower hospital mortality in patients with low (P = 0.031) and intermediate (P = 0.001) SYNTAX scores. At a median follow-up time of 20 months (IQR: 10-37), emergency PCI had lower MACCE compared to CABG [HR: 0.30 (95% CI 0.14-0.66), P < 0.003], with no significant difference in all-cause mortality between emergency PCI and CABG [HR: 1.18 (95% CI 0.23-6.08), P = 0.845]. CONCLUSIONS: PCI could be advantageous over CABG in revascularizing LMCA disease in emergencies. PCI could be preferred for revascularization of non-emergent LMCA in patients with intermediate EuroSCORE and low and intermediate SYNTAX scores.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Estudios Retrospectivos , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugíaRESUMEN
INTRODUCTION: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. METHODS: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19-15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79-3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71-1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90-1.39], p = 0.312). CONCLUSIONS: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía , Riñón/cirugíaRESUMEN
Type 2 diabetes mellitus (T2DM) and hypertension are leading risk factors for death and disability in the Middle East. Both conditions are highly prevalent, underdiagnosed and poorly controlled, highlighting an urgent need for a roadmap to overcome the barriers to optimal glycaemic and blood pressure management in this region. This review provides a summary of the Evidence in Diabetes and Hypertension Summit (EVIDENT) held in September 2022, which discussed current treatment guidelines, unmet clinical needs and strategies to improve treatment outcomes for patients with T2DM and hypertension in the Middle East. Current clinical guidelines recommend strict glycaemic and blood pressure targets, presenting several treatment options to achieve and maintain these targets and prevent complications. However, treatment targets are infrequently met in the Middle East, largely due to high clinical inertia among physicians and low medication adherence among patients. To address these challenges, clinical guidelines now provide individualised therapy recommendations based on drug profiles, patient preferences and management priorities. Efforts to improve the early detection of prediabetes, T2DM screening and intensive, early glucose control will minimise long-term complications. Physicians can use the T2DM Oral Agents Fact Checking programme to help navigate the wide range of treatment options and guide clinical decision-making. Sulfonylurea agents have been used successfully to manage T2DM; a newer agent, gliclazide MR (modified release formulation), has the advantages of a lower incidence of hypoglycaemia with no risk of cardiovascular events, weight neutrality and proven renal benefits. For patients with hypertension, single-pill combinations have been developed to improve efficacy and reduce treatment burden. In conjunction with pragmatic treatment algorithms and personalised therapies, greater investments in disease prevention, public awareness, training of healthcare providers, patient education, government policies and research are needed to improve the quality of care of patients with T2DM and/or hypertension in the Middle East.
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Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factores de Riesgo , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Compuestos de Sulfonilurea/uso terapéutico , Presión SanguíneaRESUMEN
BACKGROUND: Real-world data for managing patients with diabetes and left main coronary artery (LMCA) disease are scarce. We compared percutaneous coronary intervention (PCI) outcomes versus coronary artery bypass grafting (CABG) in diabetes and LMCA disease patients. METHODS: We retrospectively studied patients with LMCA presented to 14 centers from 2015 to 2019. The study included 2138 patients with unprotected LMCA disease; 1468 (68.7 %) had diabetes. Patients were grouped into; diabetes with PCI (n = 804) or CABG (n = 664) and non-diabetes with PCI (n = 418) or CABG (n = 252). RESULTS: In diabetes, cardiac (34 (5.1 %) vs. 22 (2.7 %); P = 0.016), non-cardiac (13 (2 %) vs. 6 (0.7 %); P = 0.027) and total hospital mortality (47 (7.1 %) vs. 28 (3.5 %); P = 0.0019), myocardial infarction (45 (6.8 %) vs. 11 (1.4 %); P = 0.001), cerebrovascular events (25 (3.8 %) vs. 12 (1.5 %); P = 0.005) and minor bleeding (65 (9.8 %) vs. 50 (6.2 %); P = 0.006) were significantly higher in CABG patients compared to PCI; respectively. The median follow-up time was 20 (10-37) months. In diabetes, total mortality was higher in CABG (P = 0.001) while congestive heart failure was higher in PCI (P = 0.001). There were no differences in major adverse cerebrovascular events and target lesion revascularization between PCI and CABG. Predictors of mortality in diabetes were high anatomical SYNTAX, peripheral arterial disease, chronic kidney disease, and cardiogenic shock. CONCLUSIONS: In this multicenter retrospective study, we found no significant difference in clinical outcomes during the short-term follow-up between PCI with second-generation DES and CABG except for lower total mortality and a higher rate of congestive heart failure in PCI group of patients. Randomized trials to characterize patients who could benefit from each treatment option are needed.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Revascularización Miocárdica , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19), an infectious disease caused by an enveloped RNA beta coronavirus, has become a pandemic, with a mortality rate ranging from 0.7% to 10.8%. Although older adults with comorbidity are more likely to suffer severe disease and eventual mortality, diabetes mellitus (DM) is one of the most frequently reported noncommunicable diseases shown to predict poor prognosis in COVID-19 patients. AIM: To determine the knowledge, attitudes, and practices (KAP) of COVID-19 safety measures and factors associated with poor knowledge and practice among type 1 diabetes mellitus (T1DM) patients at King Abdulaziz University Hospital (KAUH), Jeddah. METHODOLOGY: This cross-sectional study included 267 patients with T1DM aged 18-65, admitted to the hospital from January to June 2020. Data were collected via phone interviews during September 2020. The questionnaire consisted of 15 questions for knowledge, five for attitude, and eight concerning practices, and some questions were based on diabetes and COVID-19 specifically. RESULTS: Overall, 64 participants with a median age of 53 years were studied. The median COVID-19 knowledge score showed poor (11.50%), average (43.75%), and good knowledge (6.25%). Most of the participants practiced precautionary measures outside their homes. CONCLUSION: In conclusion, half of the population had poor COVID-19 knowledge, 60.9% of the participants felt anxious, and most of them performed precautionary measures, including wearing a facemask, maintaining a 1-m distance, and washing their hands regularly.
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Infectious diseases are the second major cause of death worldwide, and the ability to resist multiple classes of antibiotics is the key factor in enabling pathogenic organisms to survive and spread in the nosocomial environment. Unfortunately, the available ß-lactamase inhibitors are not efficient against ß-lactamase B, C, and D which necessitates discovering either broad spectrum ß-lactamase inhibitors or new ß-lactam antibiotics resistant to bacterial enzymes. In this regard, products of natural origin have prompted the disclosure of new compounds and medicinal leads. Chloroform fraction of Clutia myricoides (Soa'bor) showed a pronounced activity against extended-spectrum ß-lactamase (ESBL) strains. Bio-guided fractionation resulted in isolation of two new compounds; 2-methoxy chrysophanol (2) and Saudin-I (5) in addition to three known compounds that were identified as chrysophanol (1), stigmasterol (3) and ß-sitosterol (4). Antibacterial and anti ESBL activities of the isolated compounds were performed. No antibacterial activities were detected for any of the tested compounds. Meanwhile, compound 2 showed promising anti ESBL activity. Compound 2 has shown an obvious activity against K. pneumoniae ATCC 700603 with a marked enlargement of inhibition zones (>5mm) in combination with third generation cephalosporin antibiotics. To further understand the mechanism of action of compound 2, molecular docking was carried out against CTX-M-27 ESBL. The results showed binding site interactions strikingly different from its analogue, compound 1, allowing compound 2 to be active against ESBL. These results proposed the concomitant use of these active compounds with antibiotics that would increase their efficiency. Nevertheless, the interaction between this active compound and antibiotics should be taken into consideration. Therefore, in order to evaluate the safety of this active compound, further in vitro and in vivo toxicity assays must be carried out.
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Magnoliopsida/química , Inhibidores de beta-Lactamasas/química , beta-Lactamasas/química , Antibacterianos/farmacología , Sitios de Unión , Bioensayo , Cefalosporinas/química , Cloroformo/química , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Furanos/química , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/enzimología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Simulación del Acoplamiento Molecular , Unión Proteica , Inhibidores de beta-Lactamasas/farmacologíaRESUMEN
ABSTRACT A new xanthone: mangostanaxanthone VIIII [1,3,5,6,7-pentahydroxy-2-(3-methylbut-2-enyl)-8-(3-hydroxy-3-methylbut-1-enyl) xanthone] (5) and four known xanthones: mangostanaxanthones I (1) and II (2), γ-mangostin (3), and mangostanaxanthone VII (4) were separated and characterized from the acetone fraction of Garcinia mangostana L., Clusiaceae (mangosteen) pericarps. Their structures were established based on various spectroscopic analyses in addition to HRMS and comparison with the literature. The α-amylase inhibitory potential of the isolated metabolites was evaluated. Compounds 1, 2, and 5 had the highest activity with % inhibition 72.5, 86.5, and 81.8, respectively compared to acarbose (97.1%, reference α-amylase inhibitor). The molecular docking study of the tested metabolites was estimated to shade up the rational explanation of the α-amylase inhibitory activity results. Moreover, the pharmacokinetic parameters were assessed using Swiss ADME. It is noteworthy that 1, 2, and 5 had similar binding poses as the X-ray crystal structure of acarbose, whereas the other metabolites possessed different binding mode that decreased their inhibitory capacity. Thus, these data reinforced the health benefit of mangosteen as an alternative medicine to help lowering the postprandial glucose absorption. Therefore, it could have a good potential for the treatment of diabetes.
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OBJECTIVES: Type 2 diabetes mellitus (DM-II) is highly prevalent in Saudi Arabia and only few studies have assessed it as a risk factor for hypothyroidism. This study aimed to examine the association between DM-II and hypothyroidism. SUBJECTS AND METHODS: We conducted a hospital-based case-control study. As cases, we included all adults admitted to King Abdulaziz University Hospital (KAUH) with laboratory-confirmed hypothyroidism. As controls, we drew a random sample of patients admitted to the orthopedic clinic at KAUH with laboratory-confirmed absence of hypothyroidism. We extracted data from the medical records regarding age, sex, presence of DM-II, HbA1c, comorbidities, treatment, and complications. We used multivariate logistic regression to identify factors associated with hypothyroidism. RESULTS: We included 121 cases and 121 controls. In comparison to controls, cases were older (P=0.005), had higher prevalence of DM-II (P<0.001), had higher levels of HbA1c (P=0.03), used insulin (P<0.001) and oral hypoglycemic drugs (P<0.001) more often, and suffered more often from hypertension (P<0.001), coronary artery disease (CAD) (P<0.001), stroke (P=0.04), diabetic foot (P<0.001), and nephropathy (P<0.001). According to multivariate regression, the risk of hypothyroidism was significantly increased among patients with DM-II (OR=4.14; 95% CI=20.20-7.80; P<0.001) and CAD (OR=14.15; 95% CI=1.80-111.43; P=0.01). CONCLUSION: Patients with DM-II were at increased risk of developing hypothyroidism. Adequate management and control of DM-II might reduce the risk of developing hypothyroidism. Further research using a prospective cohort study design is needed to confirm these findings. KEY MESSAGES: Patients with DM-II had an increased risk of developing hypothyroidism.
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ABSTRACT Cyperus rotundus L. (Suada, Sueda, family: Cyperaceae) is vastly spread in several world's subtropical and tropical regions. It had variable traditional uses and bioactivities. A new flavonol derivative: cyperaflavoside (myricetin 3,3',5'-trimethyl ether 7-O-β-D-glucopyranoside) and five flavonoids: vitexin, orientin, cinaroside, quercetin 3-O-β-D-glucopyranoside, and myrcetin 3-O-β-D-glucopyranoside were separated from the methanolic extract of C. rotundus aerial parts. Their structures were verified based on UV, IR, NMR (1D and 2D), HRESIMS, and comparison with literature. All metabolites were assessed for their 5-lipoxygenase inhibitory potential. All compounds possessed 5-lipoxygenase inhibitory potentials with IC50s 5.1, 4.5, 5.9, 4.0, 3.7, and 2.3 µM, respectively, in comparison to indomethacin (IC50 0.98 µM). These results supported the traditional uses of C. rotundus in treating inflammation and its related symptoms.
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AIM: To assess the association of inter-ethnic vs intra-ethnic marriage with severity of coronary artery disease (CAD) in men undergoing angiography. METHODS: We conducted a prospective multicenter, multi-ethnic, cross sectional observational study at five hospitals in Saudi Arabia and the United Arab Emirates, in which we used logistic regression analysis with and without adjustment for baseline differences. RESULTS: Data were collected for 1068 enrolled patients undergoing coronary angiography for clinical indications during the period of April 1st, 2013 to March 30th, 2014. Ethnicities of spouses were available only for male patients. Of those enrolled, 687 were married men and constituted the cohort for the present analysis. Intra-ethnic marriages were reported in 70% and inter-ethnic marriages in 30%. After adjusting for baseline differences, inter-ethnic marriage was associated with lower odds of having significant CAD [adjusted odds ratio 0.52 (95%CI: 0.33, 0.81)] or multi-vessel disease (MVD) [adjusted odds ratio 0.57 (95%CI: 0.37, 0.86)]. The adjusted association with left main disease showed a similar trend, but was not statistically significant [adjusted odds ratio 0.74 (95%CI: 0.41, 1.32)]. The association between inter-ethnic marriage and the presence of significant CAD and MVD was not modified by number of concurrent wives (P interaction > 0.05 for both). CONCLUSION: Among married men undergoing coronary angiography, inter-ethnic, as compared to intra-ethnic, marriage is associated with lower odds of significant CAD and MVD.
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A comparative investigation of hydro-distilled essential oils from aerial parts of Mentha longifolia L. (ML), Mentha microphylla K.Koch (MM), Mentha australis R.Br. (MA), and Teucrium polium L. (TP) growing in Al Madinah Al Munawwarah, Saudi Arabia, was carried out. The total numbers of identified constituents were 22, 23, 14, and 20 in ML, MM, MA, and TP oils, representing 93.0, 99.3, 78.1, and 81.1% of the total oil composition, respectively. Pulegone (40.7%) and cineole (33.4%) were the major components in ML, whereas carvone (64.6%) was the major one in MM. Furthermore, ß-linalool (22.9%) and α-terpineol (12%) were the major components in MA, whereas, (E)-3-caren-2-ol accounted for 12.1% in TP. The essential oils of TP and MA exhibited promising activities against Leishmania donovani promastigotes with IC50 values of 2.3 and 3.7 µg/mL, respectively. In contrast, MA essential oils exhibited antifungal activities towards Candida krusei and C. glabrata with IC50 values of 1 and 1.2 µg/mL, respectively.
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Mentha/química , Aceites Volátiles/aislamiento & purificación , Aceites de Plantas/aislamiento & purificación , Teucrium/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Evaluación Preclínica de Medicamentos , Hongos/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Leishmania donovani/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Plasmodium falciparum/efectos de los fármacos , Arabia Saudita , Especificidad de la EspecieRESUMEN
Advanced glycation end-products (AGEs) are associated with a non-enzymatic reaction between the amino group of a protein and the carbonyl group of a sugar during hyperglycemia. The precipitation of AGEs in different tissues leads to many complications, such as endothelial dysfunction, cardiovascular complications, atherosclerosis, retinopathy, neuropathy, and Alzheimer's disease. Garcinia mangostana L. (Clusiaceae) (GM) was selected owing to the ability of its polar and non-polar fractions to inhibit AGE formation. For the first time, the bioguided fractionation of its pericarp MeOH extract (GMT) gave rise to two new xanthones, namely, mangostanaxanthones III (1) and IV (3), in addition to six known compounds, ß-mangostin (2), garcinone E (4), rubraxanthone (5), α-mangostin (6), garcinone C (7), and 9-hydroxycalabaxanthone (8), from the non-polar faction. Their structures were verified by various spectroscopic methods, including 1D and 2D NMR studies and high-resolution MS data. All of the isolated xanthones significantly inhibited both sugar (ribose) and dicarbonyl compound (methylglyoxal)-induced protein glycation in a dose-dependent manner. This is explained by the ability of the isolated xanthones to inhibit protein oxidation, as indicated by the decreases in dityrosine and N'-formylkynurenine formation.
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Frutas/química , Garcinia mangostana/química , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura MolecularRESUMEN
BACKGROUND: Exaggerated vasoconstriction plays a very important role in the hypertension, a major component of metabolic syndrome (MetS). In the current work, the potential protective effect of methanol extract of fruit hulls of Garcinia mangostana L. on the exaggerated vasoconstriction in MetS has been investigated. In addition, the bioactive fraction and compounds as well as the possible mechanism of action have been illustrated. METHODS: The effect of methanol extract of G. mangostana (GMT) fruit hulls on the vascular reactivity of aorta isolated from animals with MetS was investigated through bioassay-guided fractionation procedures. GMT was partitioned with chloroform (I) and the remaining mother liquor was fractionated on a Diaion HP-20 with H2O, 50 and 100 % methanol to give fractions II, III, and IV, respectively. The effect of total extract (GMT), bioactive fraction and the bioactive compounds on the vasoconstriction were examined in aortae isolated from animals with MetS by incubation for 30 min before exposing aortae to cumulative concentrations of phenylephrine (PE). The direct relaxant effect was also examined by adding cumulative concentrations of the bioactive fraction and its bioactive compounds to PE precontracted vessels. In addition, aortic nitric oxide (NO) and reactive oxygen species (ROS) production was investigated. RESULTS: Bioassay-guided fractionation of GMT revealed isolation of garcimangosone D (1), aromadendrin-8-C-ß-D-glucopyranoside (2), 2,4,3'-trihydroxy benzophenone-6-O-ß-D-glucopyranoside (3), maclurin-6-O-ß-D-glucopyranoside (rhodanthenone) (4), epicatechin (5), and 2,3',4,5',6-pentahydroxy benzophenone (6). Only compounds 2, 4, and 5 significantly alleviated the exaggerated vasoconstriction of MetS aortae and in the same time showed significant vasodilation of PE pre-contracted aortae. To further illustrate the mechanism of action, the observed vasodilation was completely blocked by the nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester hydrochloride and inhibited by guanylate cyclase inhibitor, methylene blue. However, vasodilation was not affected by the potassium channel blocker, tetraethylammonium or the cyclooxygenase inhibitor, indomethacin. In addition, compounds 2, 4, and 5 stimulated NO generation from isolated aortae to levels comparable with acetylcholine. Furthermore, 4 and 5 inhibited reactive oxygen species generation in MetS aortae. CONCLUSION: The phenolic compounds 2, 4, and 5 ameliorated the exaggerated vasoconstriction in MetS aortae through vasodilatation-NO generation mechanism.
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Garcinia mangostana/química , Síndrome Metabólico/metabolismo , Óxido Nítrico/metabolismo , Fenoles/farmacología , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Vasoconstricción/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Masculino , Fenoles/química , Extractos Vegetales/química , Sustancias Protectoras/química , Ratas , Ratas Wistar , Vasodilatación/efectos de los fármacosRESUMEN
Incretin-based therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists (RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors have gained prominence in recent years for the treatment of type 2 diabetes (T2D). Such therapies offer the potential to stimulate endogenous insulin activity in proportion to circulating glucose levels; thereby, lowering the risk of hypoglycemic episodes. The synthetic GLP-1 RA exenatide, the human GLP-1 RA liraglutide, and the DPP-4 inhibitor sitagliptin are the first agents in their respective classes to be approved for the treatment of T2D and their efficacy and safety has been studied extensively in clinical trials. This article reviewed the efficacy of liraglutide once daily in achieving clinical guidelines-recommended glycated hemoglobin A1c levels in patients with T2D compared with exenatide twice daily, or sitagliptin once daily, based on published literature, with an aim to elucidate the preferred choice of incretin-related therapy in treating uncontrolled T2D.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Péptidos/uso terapéutico , Fosfato de Sitagliptina/uso terapéutico , Ponzoñas/uso terapéutico , Esquema de Medicación , Exenatida , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Liraglutida/administración & dosificación , Péptidos/administración & dosificación , Fosfato de Sitagliptina/administración & dosificación , Ponzoñas/administración & dosificaciónRESUMEN
AIM: To evaluate the safety profile of insulin detemir (IDet) in people with Type 2 diabetes mellitus (T2DM) in the Gulf countries in the 32-week, noninterventional LevSafe study. METHODS: People with T2DM whose physicians had opted to start IDet therapy were included in the study. Safety parameters, including serious adverse drug reactions (SADRs) and hypoglycemia, and changes in body weight and glycemic control were evaluated at baseline, week 16 and week 32. RESULTS: A total of 686 patients were exposed to IDet therapy with a mean (±standard deviation) age, body mass index, and diabetes duration of 51.3 ± 11.0 years, 31.3 ± 5.5 kg/m(2), and 10.2 ± 6.1 years, respectively. The mean total daily dose of IDet was 32.0 ± 32.8 U at baseline and 44.7 ± 60.7 U at week 32. No SADRs were reported during the study. Total hypoglycemia decreased from 435 events at baseline to 204 events at week 32 (mean change analyzed by Wilcoxon signed rank test: -0.34; P = 0.0115), and no major hypoglycemia was reported at week 32. Over the 32-week treatment period, the mean body weight decreased from 85.7 ± 15.2 kg to 85.4 ± 14.5 kg (P = 0.0203), glycated hemoglobin A1c from 9.9 ± 1.67% to 7.7 ± 1.36% (P < 0.0001), and fasting plasma glucose from 11.9 ± 3.27 mmol/L to 7.4 ± 1.85 mmol/L (P < 0.0001). CONCLUSION: IDet therapy was well-tolerated and was associated with a decreased number of hypoglycemic events and improved glycemic control after 32 weeks in patients with T2DM in the Gulf countries.
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Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG) as a positive control. Including G. mangostana total methanol extract (GMT) in the reaction mixture of bovine serum albumin (BSA) and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (1), aromadendrin-8-C-glucopyranoside (2), epicatechin (3), and 2,3',4,5',6-pentahydroxybenzophenone (4). All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound 3 (epicatechin) was found to be the most potent. In search for the level of action, addition of GMT, and compounds 2-4 inhibited fructosamine (Amadori product) and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (3) to reaction mixture increased protein thiol in both glucose and ribose while compounds 1, 2 and 4 only increased thiol in case of ribose. In conclusion, phenolic compounds 1-4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol.
Asunto(s)
Garcinia mangostana/química , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Agregación Patológica de Proteínas/tratamiento farmacológico , Compuestos de Sulfhidrilo/química , Animales , Benzofenonas/química , Benzofenonas/aislamiento & purificación , Benzofenonas/uso terapéutico , Catequina/química , Catequina/aislamiento & purificación , Catequina/uso terapéutico , Bovinos , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Glucosa/química , Glucósidos/química , Glucósidos/aislamiento & purificación , Glucósidos/uso terapéutico , Productos Finales de Glicación Avanzada/química , Extractos Vegetales/química , Albúmina Sérica Bovina/químicaRESUMEN
In the course of our continuing efforts to identify bioactive secondary metabolites from Red Sea marine invertebrates, we have investigated the sponge Hemimycale arabica. The antimicrobial fraction of an organic extract of the sponge afforded two new hydantoin alkaloids, hemimycalins A and B (2 and 3), together with the previously reported compound (Z)-5-(4-hydroxybenzylidene)imidazolidine-2,4-dione (1). The structures of the compounds were determined by extensive 1D and 2D NMR (COSY, HSQC and HMBC) studies and high-resolution mass spectral determinations. Hemimycalins A (2) and B (3) represent the first examples of the natural N-alkylated hydantoins from the sponge Hemimycale arabica. Compounds 1-3 displayed variable antimicrobial activities against E. coli, S. aureus, and C. albicans. In addition, compound 1 displayed moderate antiproliferative activity against the human cervical carcinoma (HeLa) cell line. These findings provide further insight into the chemical diversity as well as the biological activity of this class of compounds.
Asunto(s)
Alcaloides/farmacología , Antiinfecciosos/farmacología , Hidantoínas/farmacología , Poríferos/metabolismo , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Femenino , Células HeLa , Humanos , Hidantoínas/química , Hidantoínas/aislamiento & purificación , Océano Índico , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Metabolismo Secundario , Staphylococcus aureus/efectos de los fármacos , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
Clostridium jeddahense strain JCD(T) (= CSUR P693 = DSM 27834) is the type strain of C. jeddahense sp. nov. This strain, whose genome is described here, was isolated from the fecal flora of an obese 24 year-old Saudian male (BMI=52 kg/m(2)). Clostridium jeddahense strain JCD(T) is an obligate Gram-positive bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 3,613,503 bp long genome (1 chromosome, no plasmid) exhibits a G+C content of 51.95% and contains 3,462 protein-coding and 53 RNA genes, including 4 rRNA genes.
RESUMEN
One new compound, (2S)-1-O-(Z)-tetracos-6-enoate glycerol (1) named urgineaglyceride A, along with six known compounds, 3,5,7,3',5'-pentahydroxydihydroflavonol (2), stigmasterol (3), (25S)-5ß-furostane-3ß-22α-26-triol (4), scillaridin A (5), (2S)-(+)-2-hydroxynaringenin-4'-O-ß-D-glucopyranoside (6) and quercetin-3'-O-ß-D-glucopyranoside (7), were isolated from the EtOAc fraction of Drimia maritima (L.) Stearn bulbs. Their structures were secured based on their IR, UV, 1D and 2D NMR data, in addition to HR-MS data and comparison with the literature data. The isolated compounds were evaluated for their in vitro growth inhibitory activity against A549 non-small cell lung cancer (NSCLC), U373 glioblastoma (GBM) and PC-3 prostate cancer cell lines. Compounds 2 and 3 displayed variable activities against the tested cancer cell lines. Compound 2 was a selective inhibitor of the NSCLC cell line with an IC50 of 2.3 µM, whereas 3 was selective against GBM with IC50 of 0.5 µM and against PC-3 with 2.0 µM.