Phytochemical profile and some biological activities of three Centaurea species from Turkey

Purpose: To characterise the phytochemical profile of whole plants of Centaurea balsamita, C. depressa and C. lycopifolia with LC-ESI-MS/MS, and as well as their antioxidant, anticholinesterase and antimicrobial activities.Methods: Organic and aqueous extracts of the three Centaurea species were evaluated for DPPH free radical, ABTS cation radical scavenging and cupric reducing antioxidant capacity (CUPRAC). Acetyland butyryl-cholinesterase enzyme inhibition abilities of the extracts using petroleum ether, acetone, methanol and water were studied to determine anticholinesterase activity, while antimicrobial activity was determined by disc diffusion method using appropriate antimicrobial standards and organisms. The phytochemical components of the methanol extracts were assessed by LC-MS/MS.Results: The methanol extract of C. balsamita exhibited much higher DPPH free and ABTS cation radicals scavenging activities (with IC50 of 62.65 ± 0.97 and 24.21 ± 0.70 mg/ml, respectively) than the other extracts. The petroleum ether extracts of the plant species exhibited moderate inhibitory activity against butyrylcholinesterase enzymes while the acetone extract of C. balsamita showed good antifungal activity against Candida albicans. Quinic acid (17513 ± 813 μg/g, 63874 ± 3066 μg/g and 108234 ± 5195 μg/g) was the major compound found in the methanol extracts of C. balsamita, C. depressa and C. Lycopifolia, respectively.Conclusion: These results indicate quinic acid is the major compound in the three plant species and that Centaurea balsamita has significant antioxidant, anticholinesterase and antimicrobial properties. Further studies to identify the compounds in the extracts responsible for the activities are required.Keywords: Centaurea, LC-ESI-MS/MS, Anticholinesterase, Antioxidant, Antimicrobia

When Is Antipsychotic Polypharmacy Supported by Research Evidence? Implications for QI

Background: Concurrent use of multiple standing antipsychotics (antipsychotic polypharmacy) is increasingly common among both inpatients and outpatients. Although this has often been cited as a potential quality-of-care problem, reviews of research evidence on antipsychotic polypharmacy have not distinguished between appropriate versus inappropriate use. Methods A MEDLINE search from 1966 to December 2007 was completed to identify studies comparing changes in symptoms, functioning, and/or side effects between patients treated with multiple antipsychotics and patients treated with a single antipsychotic. The studies were reviewed in two groups on the basis of whether prescribing was concordant with guideline recommendations for multiple-antipsychotic use. Results A review of the literature, including three randomized controlled trials, found no support for the use of antipsychotic polypharmacy in patients without an established history of treatment resistance to multiple trials of monotherapy. In patients with a history of treatment resistance to multiple monotherapy trials, limited data support antipsychotic polypharmacy, but positive outcomes were primarily found in studies of clozapine augmented with a second-generation antipsychotic. Discussion Research evidence is consistent with the goal of avoiding antipsychotic polypharmacy in patients who lack guideline-recommended indications for its use. The Joint Commission is implementing a core measure set for Hospital-Based Inpatient Psychiatric Services. Two of the measures address antipsychotic polypharmacy. The first measure assesses the overall rate. The second measure determines whether clinically appropriate justification has been documented supporting the use of more than one antipsychotic medication

Mission-based hull-form and propeller optimization of a transom stern destroyer for best performance in the sea environment

An overview is presented of the activities conducted within the NATO STO Task Group AVT-204 to “Assess the Ability to Optimize Hull Forms of Sea Vehicles for the Best Per- formance in a Sea Environment.” The objective is the development of a greater understanding of the potential and limitations of the hydrodynamic optimization tools. These include low- and high-fidelity solvers, automatic shape modification methods, and multi-objective optimiza- tion algorithms, and are limited here to a deterministic application. The approach includes simulation-based design optimization methods from different research teams. Analysis tools include potential flow and Reynolds-averaged Navier-Stokes equation solvers. Design modifica- tion tools include global modification functions, control point based methods, and parametric modelling by hull sections and basic curves. Optimization algorithms include particle swarm optimization, sequential quadratic programming, genetic and evolutionary algorithms. The ap- plication is the hull-form and propeller optimization of the DTMB 5415 model for significant conditions, based on actual missions at sea

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy

Alendronat’ın neden olduğu mide hasarının mekanizmasının ve buna karşı koruyucu ilaçların araştırılmasına yönelik bir araştırma

ÖZET:Bazı hastalarda Alendronat [AL] kullanımının üst gastrointestinal [GI] sistem mukozasında lokal irritasyon, kimyasal özofajit veya peptik ülsere sebep olabileceği belirlenmiştir. Bu çalışmada AL’ın sebep olduğu gastrik hasarın mekanizması aydınlatılmaya çalışılmış ve hasarda serbest radikallerin rolü incelenmiştir. Ayrıca bu hasarın tedavisinde melatonin [Mel] veya omeprazol [OMP]’un olası yararı incelenmiştir. Deneklere 4 gün boyunca; tedavi edici Mel veya OMP ile beraber veya tek başına olarak günde 20 mg/kg AL gavaj yolu ile uygulanmıştır. Son gün, ilaç uygulamasından sonra pilor ligasyonu uygulanmış ve 2 saat sonra hayvanlar öldürülerek mideleri çıkarılmış, gastrik asit ve doku ülser indeksi ölçülmüştür. Ayrıca doku örneklerinde serbest radikallerin etkisini incelemek için malondialdehid [MDA], miyeloperoksidaz [MPO] ve glutatyon [GSH] ölçümleri yapılarak, hasarda serbest radikallerin etkisi incelenmiştir. Oral uygulanan AL gastrik hasara ve asidite artışına neden olmuştur. Ayrıca lipid peroksidasyonu ve MPO aktivitesi artarken doku GSH seviyesinde azalma olduğu gözlenmiştir. OMP veya Mel ile tedavi edilen gruplarda ise gastrik hasar önlenmiş ve glutatyon seviyesindeki azalmanın önlendiği gözlenmiştir. Her iki ilaç da MDA düzeyi ve MPO aktivitesindeki artışı önlemiştir. Mel’in, mukoza korumasında, OMP’dan daha etkin olduğu görülmüştür. Intraperitoneal [ip] uygulanan AL gastrik hasar yapmadığı gibi gastrik asidite üzerine de etkisi gözlenmemiştir.Bu çalışmada AL’ın lokal irritant etki ile gastrik hasara neden olduğu görülmektedir. OMP asit salgısını azaltarak ve antioksidan özellikleri ile, Mel’in ise antioksidan özellikleri ile AL’ın neden olduğu gastrik hasarı önlediği gözlenmiştir. SUMMARYAlendronat [AL] can cause local irritation of the upper gastro-intestinal [GI] mucosa, chemical oesophagitis or peptic ulcer disease in some patient.In this study the probable mechanism of gastric irritation as well as the role of free radicals was investigated in the damage induced by AL. Rats were administrated 20mg/kg/AL by gavage for 4 days either alone or following treatment with melatonin [Mel] or omeprazole [OMP]. On the last day, following drug administration, pilor ligation was performed and 2h later, rats were killed, stomachs were removed, gastric acidity and tissue ulcer index values were determined. Tissue samples were taken to determine MDA levels as an index of lipid peroxidation, myeloperoxidase [MPO] activity and the glutathione [GSH] levels in the stomach tissue. Chronic oral administration of AL induced significant gastric damage and increased the acidity. It also increased MDA levels, demonstrating increased lipid peroxidation while tissue glutathione levels decreased. Increase in MPO activity, demonstrating neutrophil infiltration was observed. Treatment with OMP or Mel prevented this damage as well as preventing the decrease in GSH levels. Both drugs also prevented the increase in MDA levels or MPO activity. Mel appeared to be more efficient than OMP in protecting the mucosa. Intraperitoneal [ip] administration of AL did not cause much gastric irritation and did not increase the gastric acidity. Findings of the present study suggest that AL induces oxidative gastric damage by a local irritant effect. OMP protects against AL induced damage by decreasing acid secretion as well as by its antioxidant properties

Alendronat’ın neden olduğu mide hasarının mekanizmasının ve buna karşı koruyucu ilaçların araştırılmasına yönelik bir araştırma

: Bazı hastalarda Alendronat [AL] kullanımının üst gastrointestinal [GI] sistem mukozasında lokal irritasyon, kimyasal özofajit veya peptik ülsere sebep olabileceği belirlenmiştir. Bu çalışmada AL’ın sebep olduğu gastrik hasarın mekanizması aydınlatılmaya çalışılmış ve hasarda serbest radikallerin rolü incelenmiştir. Ayrıca bu hasarın tedavisinde melatonin [Mel] veya omeprazol [OMP]’un olası yararı incelenmiştir. Deneklere 4 gün boyunca; tedavi edici Mel veya OMP ile beraber veya tek başına olarak günde 20 mg/kg AL gavaj yolu ile uygulanmıştır. Son gün, ilaç uygulamasından sonra pilor ligasyonu uygulanmış ve 2 saat sonra hayvanlar öldürülerek mideleri çıkarılmış, gastrik asit ve doku ülser indeksi ölçülmüştür. Ayrıca doku örneklerinde serbest radikallerin etkisini incelemek için malondialdehid [MDA], miyeloperoksidaz [MPO] ve glutatyon [GSH] ölçümleri yapılarak, hasarda serbest radikallerin etkisi incelenmiştir. Oral uygulanan AL gastrik hasara ve asidite artışına neden olmuştur. Ayrıca lipid peroksidasyonu ve MPO aktivitesi artarken doku GSH seviyesinde azalma olduğu gözlenmiştir. OMP veya Mel ile tedavi edilen gruplarda ise gastrik hasar önlenmiş ve glutatyon seviyesindeki azalmanın önlendiği gözlenmiştir. Her iki ilaç da MDA düzeyi ve MPO aktivitesindeki artışı önlemiştir. Mel’in, mukoza korumasında, OMP’dan daha etkin olduğu görülmüştür. Intraperitoneal [ip] uygulanan AL gastrik hasar yapmadığı gibi gastrik asidite üzerine de etkisi gözlenmemiştir. Bu çalışmada AL’ın lokal irritant etki ile gastrik hasara neden olduğu görülmektedir. OMP asit salgısını azaltarak ve antioksidan özellikleri ile, Mel’in ise antioksidan özellikleri ile AL’ın neden olduğu gastrik hasarı önlediği gözlenmiştir. SUMMARY Alendronat [AL] can cause local irritation of the upper gastro-intestinal [GI] mucosa, chemical oesophagitis or peptic ulcer disease in some patient. In this study the probable mechanism of gastric irritation as well as the role of free radicals was investigated in the damage induced by AL. Rats were administrated 20mg/kg/AL by gavage for 4 days either alone or following treatment with melatonin [Mel] or omeprazole [OMP]. On the last day, following drug administration, pilor ligation was performed and 2h later, rats were killed, stomachs were removed, gastric acidity and tissue ulcer index values were determined. Tissue samples were taken to determine MDA levels as an index of lipid peroxidation, myeloperoxidase [MPO] activity and the glutathione [GSH] levels in the stomach tissue. Chronic oral administration of AL induced significant gastric damage and increased the acidity. It also increased MDA levels, demonstrating increased lipid peroxidation while tissue glutathione levels decreased. Increase in MPO activity, demonstrating neutrophil infiltration was observed. Treatment with OMP or Mel prevented this damage as well as preventing the decrease in GSH levels. Both drugs also prevented the increase in MDA levels or MPO activity. Mel appeared to be more efficient than OMP in protecting the mucosa. Intraperitoneal [ip] administration of AL did not cause much gastric irritation and did not increase the gastric acidity. Findings of the present study suggest that AL induces oxidative gastric damage by a local irritant effect. OMP protects against AL induced damage by decreasing acid secretion as well as by its antioxidant properties