Copeptin for the differentiation of type 1 versus type 2 myocardial infarction or myocardial injury.

BACKGROUND: The rapid and reliable differentiation of myocardial infarction (MI) due to atherothrombosis (T1MI) from MI due to supply-demand mismatch (T2MI) or acute myocardial injury is of major clinical relevance due to very different treatments, but still a major unmet clinical need. This study aimed to investigate whether copeptin, a stress hormone produced in the hypothalamus, helps to differentiate between T1MI versus T2MI or injury. METHODS: In a retrospective analysis, 1271 unselected consecutive patients presenting with symptoms suggestive of MI to the emergency department were evaluated. Patients diagnosed with ST-elevation MI were excluded. All patients with elevated cardiac troponin I (cTnI) concentration possibly indicating MI were classified into T1MI, T2MI, or acute myocardial injury using detailed clinical assessment and coronary imaging. Copeptin plasma concentration was measured in a blinded fashion. A multicenter diagnostic study with central adjudication of the final diagnosis served as external validation cohort (n = 1390). RESULTS: Among 1161 patients, 154 patients had increased cTnI concentration. Of these, 78 patients (51%) were classified as T1MI and 76 (49%) as T2MI or myocardial injury. Patients with T2MI or myocardial injury had significantly higher copeptin plasma concentration between patients versus T1MI (21,4 pmol/l versus 8,1 pmol/l, p = 0,001). A multivariable regression analysis revealed that higher concentrations of copeptin and C-reactive protein, higher heart rate at presentation and lower frequency of smoking remained significantly associated with T2MI and myocardial injury. Findings were largely confirmed in the external validation cohort. CONCLUSION: In patients without ST-segment elevation, copeptin concentration was higher in T2MI and myocardial Injury versus T1MI and may help in their differential diagnosis.

Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients.

BACKGROUND AND STUDY AIMS: The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity. PATIENTS AND METHODS: This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed. RESULTS: Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002). CONCLUSIONS: MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.

Comparative LC-MS/MS-based molecular networking, DNA fingerprinting, and in vitro anti-Helicobacter pylori activity of three Egyptian Ficus cultivars.

Ficus species (Moraceae) have been used for nutrition and traditional medicine, and plants from this family are phytochemically abundant and serve as a potential source of natural products. As a result of the inherent complexity of the plant metabolomes and the fact that these Ficus species chemical space has not yet been fully decoded, it is still difficult to characterize their phytochemistry. Therefore, this study, we suggest the use of the molecular networking to elucidate the chemical classes existing in leaves of three Ficus species (F. deltoidei Jack, F. drupacea Thunb and F. sycomorus L.) and highlight the importance of molecular networking in examining their chemotaxonomy . By using computational tools, 90 metabolites were annotated , including phenolic acids, flavonoids, furanocoumarins, fatty acids and terpenoids. Phenolic acids were detected as the main class present in the three studied species. Flavonoids-C-glycosides, flavonoids-O-glycosides and isoflavonoids were mainly present in F. drupacea and F. sycomorus, while furanocoumarins were proposed in F. sycomorus. Vomifoliol-based sesquiterpenes were proposed in F. deltoidei. The chemotaxonomic differentiation agreed with the DNA fingerprinting using SCOT and ISSR markers. F. deltoidei, in particular, had a divergent chemical fingerprint as well as a different genotype. Chemotype differentiation using chemical fingerprints, in conjunction with the proposed genetic markers, creates an effective identification tool for the quality control of the raw materials and products derived from those three Ficus species. As well, F. drupacea exploited the most potent inhibition of H. pylori with MIC of 7.81 µg/ mL compared with clarithromycin. Overall, molecular networking provides a promising approach for the exploration of the chemical space of plant metabolomes and the elucidation of chemotaxonomy.

Phenolic acids-rich fraction from Ficus drupacea leaves for the prevention and treatment of ethanol-induced gastric mucosal injury in rats.

Bioactivity-guided fractionation of F. drupacea Thunb. extract revealed that the water fraction (FDWF) increased pH of the artificial gastric juice from 1.2 to 5.67 ± 0.015. The gastroprotective effect of FDWF against ulcer induced by ethanol was evaluated in rats. In ulcerogenic rats, increase in the gastric juice volume and ulcer lesions, and decrease in the gastric pH were evident. However, pretreatment with FDWF (100 mg/kg b.wt., p.o.) significantly inhibited lesion index, reduced gastric juice volume by 56.09% and increased gastric pH value. When given after ethanol, the same dose of FDWF led to significant healing of the gastric ulcer, with 75.60% reduction of gastric juice volume, and increase in pH value. In both prophylactic and therapeutic-treated groups, the level of superoxide dismutase and reduced glutathione in gastric homogenate were increased, while that of malondialdehyde was decreased. Also, the levels of succinate dehydrogenase and lactate dehydrogenase were increased, while that of acid phosphatase was decreased. In addition, the inflammatory markers; IL-10 and PGE2 were significantly increased. The histopathological results confirmed the above findings and indicated that the antiulcer effect of FDWF is mediated, at least in part, through antioxidant and anti-inflammatory mechanisms. Twenty-three compounds were tentatively identified in FDWF using UPLC-PDA-ESI-MS/MS and most of them were found to be phenolic acid derivatives. FDWF was standardized to contain 23.66 ± 2.62 mg/g and 8.86 ± 0.29 mg/g of quinic acid and chlorogenic acid, respectively. Accordingly, FDWF is a potential natural product that could increase the healing of gastric mucosal injury and prevents the development of ethanol-induced gastric mucosal injury in rats.

Cod Liver Oil's Encapsulation into Sodium Alginate/Lupin Protein Beads and Its Application in Functional Meatballs' Preparation.

Cod liver oil (CLO) is an essential source of healthy ω-3 fatty acids to be employed in functional meals. However, its autoxidation sensitivity, solubility, and odour present it as challenging to handle. Its encapsulation might mitigate these problems. This research studied using alginate/lupine protein as a wall material for CLO encapsulation as well as to characterise CLO microcapsules for their size, sphericity factor, encapsulation efficiency, morphology (scanning electron microscopy), in vitro release, and thermal stability. In this study, the oxidative stability, quality parameters, and sensory attributes of meatballs enriched with free CLOs and encapsulated CLOs throughout storage at 4 ± 1 °C for 16 days were assessed. The CLO microspheres had a homogeneous round shape, a diameter of 0.82 ± 0.06 mm, a sphericity factor of 0.092 ± 0.01, an encapsulation efficiency of 95.62% ± 1.13%, and an accumulative release rate of 87.10% after 270 min in the stimulated gastrointestinal conditions. Additionally, it was discovered that encapsulated oil was more stable than free CLOs to heat treatments (70-100 °C, 24 h). pH, thiobarbituric acid-reactive substances, peroxide value, conjugated dienes value, and carbonyl content of meatballs enriched with microencapsulated CLOs were significantly lower when compared to free CLOs and/or control samples. CLO microcapsules improved the sensory characteristics of meatballs throughout storage; however, meatballs directly containing CLOs were rejected. Thus, the viability of alginate/LPI complex microcapsules containing CLOs to enrich meat products subjected to storage with refrigeration could be indicated without any change in the characteristics.

Technological and Sensory Aspects of Macaroni with Free or Encapsulated Azolla Fern Powder.

Azolla might be considered an alternative and promising dietary ingredient for antioxidants. There have not been any reports on the incorporation of free Azolla fern powder (FAP) or its microcapsules in foods, especially fresh pasta, yet. Microencapsulation was used to mask the undesirable taste and odour of Azolla, as well as to preserve its antioxidant potential. The current study concentrated on two major goals. The first goal was to use alginate as a wall material for FAP encapsulation, as well as to characterise the FAP microcapsule for its encapsulation efficiency, solubility, and thermal stability. The second goal was to assess the impact of integrating FAP or its microcapsules into fresh macaroni on its colour parameters, cooking quality, texture properties, and sensory characteristics. The microspheres had a high encapsulation efficiency (88.19%) and a low water solubility (85.23 g/kg), making them suitable for use in foods that require cooking in water. When compared to free Azolla powder, encapsulation reduced the antioxidant activity loss rate by 67.73%. All the cooking and textural properties of fresh macaroni were not significantly affected, except for water absorption and weight gain, but the overall acceptability index (85.13%) was not affected by microcapsule incorporation.

Improvement of outcome prediction of hospitalized patients with COVID-19 by a dual marker strategy using high-sensitive cardiac troponin I and copeptin.

BACKGROUND: COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and high-sensitive cardiac troponin I (hs-cTnI) levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2-77.8] vs 17.2 pmol/L [IQR, 7.4-41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5-97.5] vs 10.2 ng/L [5.5-23.1], P < 0.001 respectively). ROC analysis demonstrated an optimal cut-off of 19.3 pmol/L for copeptin and 16.8 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995-9.154], P < 0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. CONCLUSION: The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of ICU admission or 28-day mortality in hospitalized patients with COVID-19.

Mid-regional pro-atrial natriuretic peptide independently predicts short-term mortality in COVID-19.

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID-19 yet. METHODS: This prospective, observational study of patients with COVID-19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR-proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 - 532] vs 75 pmol/L [IQR, 43 - 153], P < .001) compared to survivors and increased with disease severity and level of hypoxaemia. The area under the ROC curve for MR-proANP predicting 28-day mortality was 0.832 (95% CI 0.753 - 0.912, P < .001). An optimal cut-off point of 160 pmol/L yielded a sensitivity of 82.1% and a specificity of 76.2%. MR-proANP was a significant predictor of 28-day mortality independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (HR 2.77, 95% CI 1.21 - 6.37; P = .016), while NT-proBNP failed to independently predict 28-day mortality and had a numerically lower AUC compared to MR-proANP. CONCLUSION: Higher levels of MR-proANP at admission are associated with disease severity of COVID-19 and act as a powerful and independent prognostic marker of 28-day mortality.

Corneal Hysteresis, Central Corneal Thickness, and Intraocular Pressure in Rheumatoid Arthritis, and Their Relation to Disease Activity.

PURPOSE: To evaluate biomechanical properties, corneal thickness, and intraocular pressure (IOP) in patients with rheumatoid arthritis (RA) and correlate them with rheumatoid activity. PATIENTS AND METHODS: Forty RA eyes were enrolled in a cross-sectional study. Clinical Disease Activity Index (CDAI) was used to assess the rheumatoid activity by a rheumatologist. Corneal hysteresis (CH), corneal resistance factor (CRF), and IOP corneal compensated, IOP Goldmann corrected were assessed using ocular response analyzer (ORA), Corneal thickness was measured using optical coherence tomography, and IOP using Goldman applanation tonometer (IOP GAT). RESULTS: There was a positive correlation between CH and CRF (P < 0.001 and r = 0.818) and (P < 0.001 and r = 0.714) in the active and inactive groups respectively, also between CRF and central corneal thickness (CCT) (P value 0.05 and r = 0.0435) in Inactive Group only. No correlation was found between CDAI score and ORA parameters. There was a negative correlation between CDAI and CCT in Active Group only (P < 0.001 and r = -0.823). CONCLUSION: Corneal biomechanical properties could be affected in rheumatoid patients in both active and remission phases, which may indicate that any corneal changes may be irreversible. These changes are of important significance regarding IOP measurement in rheumatoid patients. CCT may be a new parameter in the follow up of disease activity.

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction.

BACKGROUND: Little is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission. METHODS: Biomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender. RESULTS: Overall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P < .001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8-100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV = 98.7%, CI: 97.5-99.8; and women, NPV = 98.7%, CI: 97.5-100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR = 2.37; CI: 1.61-3.49; P < .001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR = 0.98, 95% CI: 0.96-0.99), while positive predictors were current MI (OR = 2.16, 95% CI: 1.19-3.91), chronic renal insufficiency (OR = 3.58, 95% CI: 1.33-9.62), and atrial fibrillation (OR = 2.56, 95% CI: 1.23-5.32), respectively (all P < .05). In women, current MI (OR = 2.98, CI: 1.23-7.24), atrial fibrillation (OR = 2.90, CI: 1.26-6.70) and syncope-like events (OR = 7.56, CI: 2.26-25.30) were significant predictors of copeptin elevation. CONCLUSIONS: Men with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.

Effect of marathon and ultra-marathon on inflammation and iron homeostasis.

The physiological response to high-level endurance exercise, such as running a marathon, poses several beneficial but also potentially harmful metabolic changes. The objective of this study was to determine the impact of marathon (M) and ultra-marathon (UM) on inflammation and iron homeostasis in paired samples. Fifteen well-trained, non-professional endurance athletes (14 males, 1 female) performed both a 130 km ultra-marathon and a traditional 42.195 km marathon. We determined markers of inflammation and iron homeostasis before, immediately after, and within 5 days after finishing each run, respectively. Biomarkers of inflammation (leucocytes, neutrophil granulocytes, monocytes, and c-reactive protein [CRP]) increased significantly after both marathon and ultra-marathon with higher levels of CRP after ultra-marathon compared with marathon both immediately after the race (18.15 ± 12.41 vs 5.58 ± 9.65 mg/L, P < .001) and at follow-up (15.67 ± 16.97 vs 7.19 ± 7.75 mg/L, P = .045) Concentrations of ferritin also increased significantly after both races and remained high at follow-up. Higher levels of ferritin immediately after the race (111.5 ± 103.2 vs 84.8 ± 86.3, P = .001) and at follow-up (102.7 ± 79.5 vs 74.6 ± 65.6, P = .001) were found in ultra-marathon finishers. The observed increase of serum iron and transferrin saturation (TSAT) after marathon and the decrease of serum iron and TSAT after ultra-marathon resulted in a significant absolute difference between the two races. The present data suggest a higher degree of inflammation after ultra-marathon compared with marathon. Markers of iron homeostasis also showed different response patterns with regard to running distance.

Toll-like receptor 2 and 9 expression on circulating neutrophils is associated with increased mortality in critically ill patients.

BACKGROUND: Toll-like receptors (TLRs) play an important role in inflammatory processes in critically ill patients by binding to pathogen-associated molecular patterns and danger-associated molecular patterns (DAMPs). Whether neutrophil or monocyte TLR expression patterns are associated with outcome in critical illness is unknown. OBJECTIVES: To answer this question, we conducted a prospective, observational study including 215 consecutive patients admitted to a medical ICU at a tertiary care center. METHODS: Blood was drawn at admission and expression of TLR-2, TLR-4, and TLR-9 on neutrophils and monocytes were analyzed by flow cytometry. RESULTS: Median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 19, and 30-day mortality was 26%. TLR-2 expression on neutrophils was associated with APACHE II, Simplified Acute Physiology Score II, and Sepsis-related Organ Failure Assessment score. TLR-2 (P < 0.001) and TLR-9 (P < 0.05) expression on neutrophils was significantly higher in nonsurvivors. In contrast, neutrophil TLR-4 expression and monocyte TLR expression were not associated with survival. Neutrophil TLR-2 (odds ratio 3.8; 95% confidence interval 1.4-10.2; P < 0.05) and TLR-9 (odds ratio 4.0; 95% confidence interval 2.0-8.1; P < 0.001) expression in the third tertile predicted mortality independent from APACHE II, serum lactate, serum creatinine, and procalcitonin, respectively. CONCLUSION: We provide evidence for prognostic properties of neutrophil TLR-2 and TLR-9 expression regarding 30-day mortality in unselected critically ill patients, independent from baseline clinical characteristics, and laboratory values. These findings suggest that specific TLR-dependent activation of the innate immune system via neutrophils possibly caused by cell damage and release of otherwise intracellular components may play a significant role in the pathophysiology of critical illness.

Morphological, phytochemical and anti-hyperglycemic evaluation of Brachychiton populneus

Abstract Brachychiton populneus (Schott & Endl.) R.Br., Malvaceae, is one of five Brachychiton species cultivated in Egypt. Little information was found concerning the morphological, phytochemical and biological investigations of B. populneus. Morphological investigations of B. populneus were performed on fresh and dried leaves. Air-dried, ground leafy branches were extracted with 70% methanol/water yielding B. populneus extract. Seventeen flavonoids were isolated and identified using different chromatographic and spectroscopic techniques; eleven of them were reported for the first time from this plant. Potential activity of B. populneus extract against alloxan inducing oxidative stress and diabetes in male rats was preliminary investigated (four groups of ten rats /group). B. populneus extract (500 mg/kg bw i.p.) exhibited significant acute anti-hyperglycemic activity with blood glucose levels of 227.3 and 157.6 mg/dl after 4 and 24 h, respectively, compared to alloxan and standard Diamicron (5 mg/kg bw p.o.) groups, as well as to a normoglycemic control group at p < 0.05. The extract reverted the body weight values of the alloxan-induced diabetic rats to that of control animals after 24 h. In addition, B. populneus extract counteracted the effect of the oxidative stress induced by alloxan causing significantly increase in the glutathione content level (2.35 mmol/l) and relative decrease in the malondialdehyde level (21.31 nmol/l) and nitric oxide content (1.98 µmol/l) in serum after 24 h of treatment compared to alloxan-induced diabetic rats (1.01 mmol/l, 118.9 nmol/l, 4.69 µmol/l, respectively) and to normoglycemic control at p < 0.05. These effects appear to be related to the flavonoid principles. The intergeneric relationship of the genus Brachychiton and other related genera assessed well-supported differentiation between them. Furthermore, a significant dissimilarity was observed at interspecific level.

Diabetes and depression in Lebanon and association with glycemic control: a cross-sectional study.

BACKGROUND: Diabetes mellitus is a chronic noncommunicable disease characterized by hyperglycemia and is associated with chronic complications affecting the overall quality of life. As of 2017, the prevalence of diabetes in Lebanon is estimated to be 14.6%. Depression is noted to be common among Lebanese citizens, present in around 17.3%. This study aims to investigate the prevalence of depression among the diabetic Lebanese citizens and to study its relationship with poor glycemic control and diabetes complications. METHODS: In total, 436 diabetic patients participated in this cross-sectional study. Patients with diabetes mellitus attending several private clinics and health care centers were asked to fill out a well-structured questionnaire developed by an expert. Depression was assessed using Beck Depression Inventory (BDI). The study collected demographic information about the participants including their lifestyles, their last reported glycosylated hemoglobin values, and their reported microvascular and macrovascular complications. Data were collected, entered, and analyzed on SPSS software version 23.1. A descriptive analysis is carried out by calculating the mean and standard deviation for continuous variables and number and percentage for categorical ones. Association between categorical variables is evaluated using a chi-squared test. A P-value of <0.05 is considered to be significant. RESULTS: Depression was prevalent among 28.8% of the patients with diabetes mellitus. The average age of participants was 64.08 years. In total, 280 (64.2%) of the participants were females and the average diabetes duration was 8.89 years. There was no significant relationship found between depression and glycemic control. By contrast, a significant association between retinopathy, nephropathy, and stroke and depression was found. CONCLUSION: Depression was found to be present among 28.8% of the patients with diabetes mellitus in Lebanon; however, no association was established between depression and glycemic control.

Chemosystematic significance of flavonoids isolated from Diplotaxis acris (Brassicaceae) and related taxa.

The chemosystematic relationship of four Diplotaxis species; Diplotaxis acris, Diplotaxis erucoides, Diplotaxis harra and Diplotaxis muralis were surveyed from the flavonoids point of view. These species were found to produce 33 flavonoids (7 flavones and 26 flavonols), including 11 compounds were isolated in the present study from D. acris. Among them, seven flavonoids were identified for the first time; luteolin (4), kaempferol (8), kaempferol 3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside (13), quercetin 3-O-ß-glucopyranoside (16), quercetin 7-O-ß-glucopyranoside (20), isorhamnetin (22) and isorhamnetin 3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside (32). Their structures were recognized on the basis of chemical and spectroscopic techniques (1D & 2D NMR, UV, EI & ESI/MS). The isolated flavonoids may provide useful taxonomic characters at the infraspecific levels of classification where the flavonoid profile of D. acris and D. harra is similar and different from the other species.

Flavonoid constituents of Dobera glabra leaves: amelioration impact against CCl4-induced changes in the genetic materials in male rats.

CONTEXT: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations. OBJECTIVE: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials. MATERIALS AND METHODS: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200 mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl4 (0.5 mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats. RESULTS: Isorhamnetin-3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside, isorhamnetin-3-O-α-rhamnopyranoside-7-O-ß-glucopyranoside, kaempferol-3,7-di-O-α-rhamnopyranoside, isorhamnetin-3-O-ß-glucopyranoside, kaempferol-3-O-ß-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200 mg/kg bw) + CCl4 exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl4, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8 U/mg protein/min compared to CCl4 (1.8 U/mg protein/min). DISCUSSION AND CONCLUSION: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity.

Copeptin for the early rule-out of non-ST-elevation myocardial infarction.

Copeptin, a neuropeptide of unknown pathophysiological function that is stoichiometrically secreted with the antidiuretic hormone, is a non-specific marker of endogenous stress which has recently gained interest for its use within a dual-marker strategy in combination with cardiac troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI) in emergency department patients with suspected MI. Based on methodologically strong and consistent evidence from large diagnostic studies and even one randomized intervention study, current European Society of Cardiology Guidelines recommend copeptin and the dual-marker strategy for the early rule-out of MI when high-sensitivity cardiac troponin (hs-cTn) assays are not available. When used with conventional cTn assays, the incremental value of copeptin is large. When used with hs-cTn, the incremental value is very small and does not justify routine clinical use. This review aims to describe the structure, function, and release mechanism of copeptin; as well as to provide an explanation on why this biomarker should be used in the rule-out, and not in the rule-in, of NSTEMI.

In Vitro Synthesized RNA Generated from cDNA Clones of Both Genomic Components of Cucurbit yellow stunting disorder virus Replicates in Cucumber Protoplasts.

Cucurbit yellow stunting disorder virus (CYSDV), a bipartite whitefly-transmitted virus, constitutes a major threat to commercial cucurbit production worldwide. Here, construction of full-length CYSDV RNA1 and RNA2 cDNA clones allowed the in vitro synthesis of RNA transcripts able to replicate in cucumber protoplasts. CYSDV RNA1 proved competent for replication; transcription of both polarities of the genomic RNA was detectable 24 h post inoculation. Hybridization of total RNA extracted from transfected protoplasts or from naturally CYSDV-infected cucurbits revealed high-level transcription of the p22 subgenomic RNA species. Replication of CYSDV RNA2 following co-transfection with RNA1 was also observed, with similar transcription kinetics. A CYSDV RNA2 cDNA clone (T3CM8Δ) comprising the 5'- and 3'-UTRs plus the 3'-terminal gene, generated a 2.8 kb RNA able to replicate to high levels in protoplasts in the presence of CYSDV RNA1. The clone T3CM8Δ will facilitate reverse genetics studies of CYSDV gene function and RNA replication determinants.

Myricitrin and bioactive extract of Albizia amara leaves: DNA protection and modulation of fertility and antioxidant-related genes expression.

CONTEXT: Albizia species are reported to exhibit many biological activities including antiovulatory properties in female rats and antispermatogenic and antiandrogenic activities in male rats. OBJECTIVE: The present study investigates the flavonoids of Albizia amara (Roxb.) B. Boivin (Fabaceae) leaves and evaluates their activity on gene expression of fertility and antioxidant glutathione-S-transferase-related genes of treated female mice in addition to their effect on DNA damage. MATERIALS AND METHODS: Plant materials were extracted by using 70% methanol for 48 h, the extract was chromatographed on a polyamide 6S column, each isolated compound was purified by using Sephadex LH-20 column; its structure was elucidated by chemical and spectral methods. Both the leaves extract and myricitrin (200, 30 mg/kg bw/d, respectively) were assayed for their effect on DNA damage in female mice after four weeks treatment using Comet assay. Their modulatory activity on gene expression of fertility (aromatase CYP19 and luteinizing hormone LH) and antioxidant glutathione-S-transferase (GST)-related genes of treated female mice were investigated by real-time PCR (qPCR). RESULTS: Quercetin-3-O-gentiobioside, myricitrin, quercetin-3-O-α-rhamnopyranoside, myricetin, quercetin and kaempferol were isolated and identified from the studied taxa. Myricitrin and the extract induced low rate of DNA damage (4.8% and 5%, respectively), compared with the untreated control (4.2%) and significantly down-regulated the expression of CYP19 and LH genes and up-regulated GST gene. DISCUSSION AND CONCLUSION: Our results highlight the potential effect of the leaves extract of Albizia amara and myricitrin as fertility-regulating phytoconstituents with ability to protect DNA from damage and cells from oxidative stress.

Phytochemical constituents and chemosystematic significance of Chrozophora tinctoria (L.) Raf.

Twelve compounds were isolated from Chrozophora tinctoria (L.) Raf. They were identified as kaempferol, kaempferol 3-O-ß-glucopyranoside, kaempferol 3-O-(6″-α-rhamnopyranosyl)-ß-glucopyranoside, quercetin, quercetin 3-O-ß-glucopyranoside, quercetin 3-O-(6″-α-rhamnopyranosyl)-ß-glucopyranoside, apigenin, apigenin 7-O-ß-glucopyranoside, acacetin, gallic acid, methyl gallate and ß-sitosterol-3-O-ß-glucopyranoside. Their structures were elucidated by chemical and spectral methods. Furthermore, chemosystematics of the isolated compounds is briefly discussed. It was indicated that C. tinctoria is the only species of Chrozophora that has the capability to synthesis kaempferol aglycone and their glycosides, and the finding is supported by its distinct morphological and anatomical aspects.