Regio- and diastereoselective synthesis of spiropyrroloquinoxaline grafted indole heterocyclic hybrids and evaluation of their anti-Mycobacterium tuberculosis activity

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel hybrid heterocycles comprising spiropyrrolidine, indenoquinoxaline and indole structural units in excellent yields, has been achieved through a one-pot multicomponent process involving 1,3-dipolar cycloaddition as a key step. The 1,3-dipolar component is the azomethine ylide generated in situ from indenoquinoxaline and l-tryptophan and reacts with various substituted β-nitrostyrenes affording the spiroheterocyclic hybrids. The ring system thus created possesses two C–C and three C–N bonds and four adjacent stereogenic carbons, one of which is quaternary and the reaction proceeded with full diastereomeric control. All the synthesized compounds were assayed for their in vitro activity against Mycobacterium tuberculosis H37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 μg mL⁻¹) to ethambutol against Mycobacterium tuberculosis H37Rv.

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel spiropyrrolidine tethered indole hybrids in excellent yields employing a one-pot multicomponent 1,3-dipolar cycloaddition strategy.     

Nutrition therapy for critically ill and injured patients

Background

Nutrition support has undergone significant advances in recent decades, revolutionizing the care of critically ill and injured patients. However, providing adequate and optimal nutrition therapy for such patients is very challenging: it requires careful attention and an understanding of the biology of the individual patient’s disease or injury process, including insight into the consequent changes in nutrients needed.

Objective

The objective of this article is to review the current principles and practices of providing nutrition therapy for critically ill and injured patients.

Methods

Review of the literature and evidence-based guidelines.

Results

The evidence demonstrates the need to understand the biology of nutrition therapy for critically ill and injured patients, tailored to their individual disease or injury, age, and comorbidities.

Conclusion

Nutrition therapy for critically ill and injured patients has become an important part of their overall care. No longer should we consider nutrition for critically ill and injured patients just as “support” but, rather, as “therapy”, because it is, indeed, a key therapeutic modality.     

Prevalence and risk factors of clopidogrel non-response among Saudi patients undergoing coronary angiography

Objectives:

To estimate the prevalence of clopidogrel non-response and identify its risk factors among Saudi patients.

Methods:

This cross-sectional study was conducted at Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia between January and June 2013, to assess the degree of platelet inhibition using the VerifyNow assay (Accumetrics, San Diego, CA, USA) after receiving clopidogrel standard loading dose. Clopidogrel resistance was defined as ≤15% platelet inhibition or >213 P2Y12 reaction units (PRU).

Results:

Three hundred and four patients were included in the study. The mean age was 60.3 ± 11.4 years, and 73% were males. Clopidogrel doses were 300 mg (57%), 600 mg (27%), and 75 mg (16%). All patients used aspirin (81 mg in 94%). Approximately 66% (200/304) showed in vitro clopidogrel non-response, 54% had low platelet inhibitions, and 61% had high post-loading PRU. Using multivariate regression analysis that included all significant characteristics; only diabetes (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.30-4.27, p=0.005) and higher preloading PRU (OR: 2.39, 95% CI: 1.40-4.11, p=0.002) remained significantly associated with higher clopidogrel non-response while myocardial infarction (OR: 0.34, 95% CI: 0.15-0.81, p=0.014) remained significantly associated with lower clopidogrel non-response. The associations of morbid obesity and diuretics use with higher clopidogrel non-response were slightly attenuated.

Conclusion:

Our findings indicate a high rate of clopidogrel in-vitro non-response among Saudi patients undergoing coronary angiography.Platelets play a critical role in the pathogenesis of atherothrombotic diseases such as coronary artery disease (CAD). The rupture of atherosclerotic plaques initiates a complex process of platelet adhesion, activation, and aggregation.1 Recently, clopidogrel and aspirin were the cornerstones of oral antiplatelet therapy for preventing ischemic events of atherothrombotic disease such as myocardial infarction and stroke.2,3 Clopidogrel was shown to be even more effective than aspirin in preventing such events of atherothrombotic disease.4 Clopidogrel is a prodrug and the active metabolite is generated by the cytochrome P450 system.5 The active metabolite acts by inhibiting platelet aggregation in response to adenosine diphosphate (ADP) through binding and blocking the platelet P2Y12 receptors.5 Variability in individual responsiveness to the antiplatelet effects of clopidogrel may lead to the occurrence of thromboembolic events despite regular antiplatelet therapy.6,7 This may be clinically translated into poor procedural and long-term morbidity and mortality outcomes.8,9 The prevalence of clopidogrel non-response (resistance) is highly variable in different studies and populations. A review10 estimated the non-response rate to range from 4-30%. This variability is partly caused by the lack of standard definition and the different assessment methods of clopidogrel non-response.11,12 A number of studies examined the patients characteristics associated with clopidogrel non-response but failed to identify any, probably due to small sample sizes and the presence of multiple confounding factors.13-15 Although, approximately 84% of Saudi patients admitted with acute coronary syndrome are treated with clopidogrel,16 there is lack of estimates of clopidogrel non-response and the associated risk factors in this population. The objective of the current study was to estimate the prevalence of clopidogrel non-response and to identify its risk factors among Saudi patients undergoing coronary angiography at a specialized cardiac center in Kingdom of Saudi Arabia (KSA).     

Radioiodination and biodistribution of newly synthesized 3-benzyl-2-([3-methoxybenzyl]thio)benzo[g]quinazolin-4-(3H)-one in tumor bearing mice

3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, ¹H and ¹³C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2?±?1.22% and the in vitro studies showed that the target compound was stable for up to 24?h. The thyroid was among the other organs in which the uptake of ¹²⁵I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells.     

Recent advances in syntheses,properties and applications of TiO2 nanostructures

TiO₂ is a compound of great importance due to its remarkable catalytic and distinctive semiconducting properties. It is also a chemically stable, non-toxic and biocompatible material. Nano TiO₂ is strong oxidizing agent with a large surface area and, hence, high photo-catalytic activities. With low production cost and a high dielectric constant, it is an inexpensive material. It can be prepared by diverse procedures such as solution and gas phase procedures. Nowadays, TiO₂ is being used frequently for photo degradation of organic molecules and water splitting for hydrogen generation. Most important applications include purification, disinfection of waste water, self-cleaning coatings for buildings in urban areas and the production of the green currency of energy (hydrogen) by splitting water. The review describes the advances in the syntheses, properties and applications of TiO₂ nano structures. Besides, efforts are also made to discuss the working mechanism and future challenges and perspectives.

TiO₂ is a compound of great importance due to its remarkable catalytic and distinctive semiconducting properties.     

Impact of infliximab therapeutic drug level monitoring on outcomes of patients with inflammatory bowel disease: A real-world experience from a Middle Eastern cohort

Background and study aimTherapeutic drug monitoring (TDM) through measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) is performed to guide IFX intensification strategies and improve its efficacy. We conducted this study to explore the relationship between clinical and endoscopic/radiological remission and IFX and ATI levels in patients with inflammatory bowel disease (IBD) treated with IFX and to evaluate the appropriateness of treatment decision post TDM.Patients and methodsThis was a cross-sectional study of a cohort of adult patients with IBD. Serum IFX trough concentrations and ATI were measured.ResultsA total of 129 patients [104] with ulcerative colitis (UC) and 25 with Crohn’s disease (CD)] were included in this study, of whom 61.2% were men. The mean disease duration was 6.7 years, and 72% of patients with UC had extensive colitis. The mean serum IFX trough level was 4.1 µg/mL; the IFX trough levels were subtherapeutic in 75 patients (58%), therapeutic in 37 patients (29%), and supratherapeutic in 17 patients (13%). Positivity to ATI was found in 16 patients (12.4%). Only 43 patients (33.3%) underwent an appropriate change in therapy after TDM, patients with penetrating CD disease had low IFX levels and higher C-reactive protein levels at 12 months before TDM.ConclusionsPatients with IBD with therapeutic IFX levels tend to have increased endoscopic/radiological remission rates. However, an appropriate change in management based on TDM was absent in the majority of patients, potentially reflecting the need to have a dashboard to support and guide clinicians in decision-making.     

Antibiofilm and Protein-Repellent Polymethylmethacrylate Denture Base Acrylic Resin for Treatment of Denture Stomatitis

Candida albicans (C. albicans) biofilm is a common etiological factor in denture stomatitis. The purpose of this study was to investigate the effects of incorporating 2-methacryloyloxyethyl phosphorylcholine (MPC) as a protein repellent into a new high-impact denture acrylic (HIPA) resin on the surface roughness, solution pH, and C. albicans biofilm adhesion to the denture base. The new acrylic denture resin base was formulated by mixing MPC into HIPA resin at mass fractions of 1.5%, 3%, and 4.5%. Surface roughness was measured using a Mitutoyo surface roughness tester. C. albicans biofilm growth and viability were assessed via colony forming unit counts. The pH of the biofilm growth medium was measured using a digital pH meter. Adding MPC to the HIPA resin at percentages of 1.5% and 3% increased the roughness values significantly (p < 0.05), while adding 4.5% MPC resulted in no difference in roughness values to that of the control group (p > 0.05). All experimental groups demonstrated neutral pH values (pH ≅ 7) and were not significantly different from each other (p > 0.05). Incorporating 2-methacryloyloxyethyl phosphorylcholine at 4.5% resulted in a significant (≅1 log) colony-forming unit reduction compared with the control group with 0% MPC (p < 0.05). A fungal-retarding denture acrylic resin was developed through the incorporation of MPC for its protein-repelling properties. This newly developed denture acrylic material has the potential to prevent oral microbial infections, such as denture stomatitis.     

Compliance to hepatitis B vaccination and subsequent development of seroprotection among health care workers of a tertiary care center of Saudi Arabia

BACKGROUND: There is lack of reliable data on compliance to hepatitis B virus (HBV) vaccine and development of seroprotective levels of antibodies among health care workers (HCWs) from the countries with high HBV endemicity such as Saudi Arabia. This study aimed to assess the compliance with HBV vaccine and subsequent levels of seroprotection among HCWs of a large tertiary care center of the Eastern Province of Saudi Arabia. METHODS: All the HCWs (n = 1302) involved in direct patient care, including 374 (28.7%) physicians, 619 (47.6%) nurses, and 309 (23.7%) technicians, were enrolled for the study. Those having antibody to hepatitis B surface antigens (anti-HBs) levels less than 10 mIU/mL were advised to take 3 doses of yeast-derived recombinant HBV vaccine at 0, 1, and 6 months of 1 mL (20 microg/mL) in the deltoid muscle. Blood samples were checked for anti-HBs antibody levels by enzyme immunoassay during the initial screening of HCWs and 3 months after the third dose of HBV vaccine. The group of physicians included 34.5% (129/374) of consultants, 16.8% (63/374) of specialists, and 48.6% (182/374) of residents. RESULTS: An overall HBV vaccine compliance rate of 71.6% (932/1302) was observed among HCWs including that of 79.5% (492/619) among nurses, 78.3% (242/309) among technicians, and 52.9% (198/374) among physicians. Thus, physicians recorded the lowest compliance (OR, 3.211; 95% CI, 2.259-4.567; P < .0001) to HBV vaccine. Among physicians, the lowest compliance of 42.3% (77/182) was observed in residents (OR, 3.690; 95% CI, 1.067-3.703; P < .0001). The overall seroprotection after vaccination was achieved in 92.2% of the compliant HCWs, and 7.8% of them failed to mount adequate response to HBV vaccine. Nonresponders included mainly the physicians (OR, 2.229; P = .05)-consultants in particular (OR, 3.476; P < .0001). The mean age of nonresponders was higher than those who mounted an adequate anti-HBs response (46.7 +/- 6.3 vs. 32.2 +/- 3.3 years OR, 1.845; 95% CI, 0.999-3.414; P < .05). CONCLUSIONS: Poor compliance to HBV vaccine among physicians--residents in particular-is an issue of immense concern, which demands close examination and identification of the specific action that needs to be taken to enhance the uptake of the vaccine by this target population.