Statistical optimization of photo-induced biofabrication of silver nanoparticles using the cell extract of Oscillatoria limnetica: insight on characterization and antioxidant potentiality

Silver nanoparticles were successfully fabricated through a very simple, rapid, one-step photo-induced green approach. The formation of silver nanoparticles was accomplished using the bioactive compounds in the aqueous extract of fresh Oscillatoria limnetica biomass, which acted as a reducing and capping agent at the same time. The biosynthesis of Oscillatoria-silver nanoparticles (O-AgNPs) was investigated under the influence of different light intensities 57.75, 75.90 and 1276.51 μmol m⁻² s⁻¹ (bright sunlight). UV-Vis (UV) and Fourier transform infrared (FT-IR) spectroscopy were applied to approve the synthesis of AgNPs. Further, the synthesis process under the exposure to sunlight was adjusted via utilizing one factor at a time, and 0.5 mM AgNO₃ concentration, 5 mL O. limnetica solution, pH 6.7 and 30 min sunlight (1276.51 μmol m⁻² s⁻¹) were applied. Furthermore, the central composite design (CCD) was applied to boost the biosynthesis process of O-AgNPs (manufactured at light intensity 75.90 μmol m⁻² s⁻¹). The maximum production of O-AgNPs was attained with 4 detected variables: initial pH level (6.7), AgNO₃ concentration (0.3 mM), O. limnetica extract concentration (3.50 mL) and incubation time (48 h). Moreover, TEM, in addition to SEM, images exposed that the biosynthesized AgNPs were quasi-spherical in shape with a small monodisperse nature, and the size range was between 6.98–23.48 nm in the case of light-induced synthesis (75.90 μmol m⁻² s⁻¹) and 11.58–22.31 nm with sunlight (1276.51 μmol m⁻² s⁻¹).

Silver nanoparticles were successfully fabricated through a very simple, rapid, one-step photo-induced green approach.     

Efficient radiosynthesis and preclinical evaluation of [18F]FOMPyD as a positron emission tomography tracer candidate for TrkB/C receptor imaging

Herein we report an efficient radiolabeling of a ¹⁸F-fluorinated derivative of dual inhibitor GW2580, with its subsequent evaluation as a positron emission tomography (PET) tracer candidate for imaging of two neuroreceptor targets implicated in the pathophysiology of neurodegeneration: tropomyosin receptor kinases (TrkB/C) and colony stimulating factor receptor (CSF-1R). [¹⁸F]FOMPyD was synthesized from a boronic acid pinacolate precursor via copper-mediated ¹⁸F-fluorination concerted with thermal deprotection of the four Boc groups on a diaminopyrimidine moiety in an 8.7±2.8% radiochemical yield, a radiochemical purity >99%, and an effective molar activity of 187±93 GBq/μmol. [¹⁸F]FOMPyD showed moderate brain permeability in wild-type rats (SUV_max = 0.75) and a slow washout rate. The brain uptake was partially reduced (ΔAUC_40–90 = 11.6%) by administration of the nonradioactive FOMPyD (up to 30 μg/kg). In autoradiography, [¹⁸F]FOMPyD exhibits ubiquitous distribution in rat and human brain tissues with relatively high nonspecific binding revealed by self-blocking experiment. The binding was blocked by TrkB/C inhibitors, but not with a CSF-1R inhibitor, suggesting selective binding to the former receptor. Although an unfavorable pharmacokinetic profile will likely preclude application of [¹⁸F]FOMPyD as a PET tracer for brain imaging, the concomitant one-pot copper-mediated ¹⁸F-fluorination/Boc-deprotection is a practical technique for the automated radiosynthesis of acid-sensitive PET tracers.     

Evaluation of the antiparasitic activities of imidazol-2-ylidene–gold(I) complexes

A series of cationic gold(I)–carbene complexes with various 4,5-diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. major amastigotes and T. gondii and distinct selectivity for T. gondii cells when compared with the activity against nonmalignant Vero cells. The ferrocene derivatives 1a–c are generally more active against the L. major amastigotes and the T. gondii tachyzoites than the other tested anisyl gold complexes and the approved drugs atovaquone and amphotericin B. Compounds 1a and 1e showed the highest selectivities for L. major amastigotes. Compounds 1d and 1f showed the highest selectivities for L. major promastigotes; 1f was the most active compound against L. major promastigotes of this series of compounds. The 3,4,5-trimethoxyphenyl analog 1b also exhibited a much greater selectivity for T. b. brucei cells when compared with its activity against human HeLa cells.     

Relationship of Right Ventricular Size and Function with Respiratory Status in Duchenne Muscular Dystrophy

The relationship between pulmonary function and right ventricle (RV) in Duchenne muscular dystrophy (DMD) has not been evaluated. Using cardiac magnetic resonance (CMR), we describe the relationship of RV size and function with spirometry in a DMD cohort. Fifty-seven boys undergoing CMR and pulmonary function testing within 1 month at a single center (2013–2015) were enrolled. Comparisons of RV ejection fraction (RVEF) and end-diastolic volume index (RVEDVI) were made across categories of percent forced vital capacity (FVC%), and relationships were assessed. Mean age was 15.5 ± 3.5 years. Spirometry and CMR were performed within 3.9 ± 4.1 days. Median FVC% was 92.0 % (67.5–116.5 %). Twenty-three (40 %) patients had abnormal FVC% (<80 %) of which 13 (57 %) had mild (FVC% 60–79 %), 6 (26 %) had moderate (FVC% 40–59 %), and 4 (17 %) had severe (FVC <40 %) reductions. Mean RVEF was 58.3 ± 3.7 %. Patients with abnormal FVC% were older and had lower RVEF and RVEDVI. Both RVEF and RVEDVI were significantly associated with FVC% (r = 0.31, p = 0.02 and r = 0.39, p = 0.003, respectively). In a large DMD cohort, RVEF and RVEDVI were related to FVC%. Worsening respiratory status may guide monitoring of cardiac function in these patients.     

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).     

Immunohistological analysis of immune cells in blistering skin lesions

BACKGROUND: Bullous skin lesions are characterised by the presence of intraepidermal or subepidermal bullae. Although inflammatory cell infiltrate is a constant feature in these lesions, their immunophenotypic characterisation is still incomplete. AIM: To determine whether the development of bullous skin diseases is associated with changes in the inflammatory cell infiltrate. Materials and methods: 34 cases representing lesions with both intraepidermal and subepidermal bullae were examined using immunoperoxidase staining methods and antibodies targeting antigens for histiocytes (CD68), B cells (CD20+), T cells (CD3+), T cells with cytotoxic potential (T cell intracellular associated antigen, TIA1+) and activity (granzyme B, GRB+). The adjacent normal skin (lesions) and an additional five cases of normal skin were also examined (controls). RESULTS: The transition from normal skin to lesional skin (lesions with intraepidermal and subepidermal bullae) was associated with a significant increase (p< or =0.05) in the density of total inflammatory cell infiltrate, CD68+ cells, CD3+ T lymphocytes, CD20+ B lymphocytes, TIA1+ -resting cytotoxic T cells and GRB+ T cells with cytotoxic activity. CONCLUSIONS: The increase in inflammatory cell infiltrate during the transition from normal to lesional skin may reflect the presence of an increased antigenicity of the lesional cells or a response to some basement membrane components. CD68+ and CD3+ cells, especially the resting cytotoxic ones, achieved numerical dominance in these lesions. Cell-mediated immunity seems to have critical role in the development of these lesions.     

Locally delivered antimicrobials in the management of periodontitis: a critical review of the evidence for their use in practice

Plaque bacteria are the primary initiators of periodontal disease in susceptible persons and therapy is largely based on mechanical bacterial biofilm disruption. Patients' response to periodontal treatment is unpredictable and periodontal stability is not always achieved. Locally delivered antimicrobials (LDAs) may be used as adjuncts to mechanical therapy in treatment of recalcitrant deep (> or = 5mm), active, non-responding sites, providing the patient's oral hygiene is adequate. Their use as a monotherapy cannot be justified. The literature reveals that LDAs are safe and that they achieve statistically significant, yet clinically modest, gains in clinical attachment and reductions in pocket depths. Clinical Relevance: It has been suggested that LDAs may improve the clinical outcome in the treatment of recurrent and refractory cases of periodontitis when used as an adjunct to scaling and root surface instrumentation. This paper examines and discusses the evidence.