Ru(ii)–N-heterocyclic carbene complexes: synthesis,characterization, transfer hydrogenation reactions and biological determination

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions. All new compounds were characterized by spectroscopic and analytical methods. These ruthenium(ii)–NHC complexes were found to be efficient precatalysts for the transfer hydrogenation of ketones by using 2-propanol as the hydrogen source in the presence of KOH as a co-catalyst. The antibacterial activity of ruthenium N-heterocyclic carbene complexes 3a–f was measured by disc diffusion method against Gram positive and Gram-negative bacteria. Compounds 3d exhibited potential antibacterial activity against five bacterial species among the six used as indicator cells. The product 3e inhibits the growth of all the six tested microorganisms. Moreover, the antioxidant activity determination of these complexes 3a–f, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) as reagent, showed that compounds 3b and 3d possess DPPH and ABTS antiradical activities. From a concentration of 1 mg ml⁻¹, these two complexes presented a similar scavenging activity to that of the two used controls gallic acid (GA) and butylated hydroxytoluene (BHT). From a concentration of 10 mg ml⁻¹, the percentage inhibition of complexes 3b and 3d was respectively 70% and 90%. In addition, these two Ru–NHC complexes exhibited antifungal activity against Candida albicans. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a, 3b, 3d and 3e exhibited good activity at 100 μg ml⁻¹ and product 3d is the most active. In a cytotoxicity study the complexes 3 were evaluated against two human cancer cell lines MDA-MB-231 and MCF-7. Both 3d and 3e complexes were found to be active against the tested cell lines showing comparable activity with examples in the literature.

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions.     

Microcephaly with or without chorioretinopathy,lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.     

Efficacy of Vitamin D in patients with active rheumatoid arthritis receiving methotrexate therapy

To determine the efficacy of oral vitamin D [25(OH)D] in patients with active rheumatoid arthritis (RA) who are in methotrexate (MTX) therapy, patients receiving stable doses of MTX were randomized to one of two dose groups and received 12?weeks of double-blind vitamin D[25(OH)D] (50,000?IU per week) or matching placebo. The moderate and major efficacy measure was the proportion of patients with >0.6 and >1.2 improvement in RA based on the Disease Activity Score 28(DAS 28) at 12?weeks. Safety measures included adverse events and laboratory assessments. On a background of MTX, the percentage of patients with a moderate/major DAS 28 response at week 12 in the vitamin D groups (76/44%) was not significantly different from placebo (64.6/33.4%). Adverse events were typically mild and included small hepatic enzyme elevation; we did not have any undesirable events resulting in discontinuation of study drug. In patients with active RA receiving stable doses of MTX, vitamin D showed non-significant improvement in efficacy outcomes compared to placebo.     

Therapeutic Liposomal Dry Powder Inhalation Aerosols for Targeted Lung Delivery

Therapeutic liposomal powders (i.e., lipospheres and proliposomes) for dry powder inhalation aerosol delivery, formulated with phospholipids similar to endogenous lung surfactant, offer unique opportunities in pulmonary nanomedicine while offering controlled release and enhanced stability. Many pulmonary diseases such as lung cancer, tuberculosis (TB), cystic fibrosis (CF), bacterial and fungal lung infections, asthma, and chronic obstructive pulmonary disease (COPD) could greatly benefit from this type of pulmonary nanomedicine approach that can be delivered in a targeted manner by dry powder inhalers (DPIs). These delivery systems may require smaller doses for efficacy, exhibit reduced toxicity, fewer side effects, controlled drug release over a prolonged time period, and increased formulation stability as inhaled powders. This state-of-the-art review presents these novel aspects in depth.     

Aspergillosis in a gyrfalcon (Falco rusticolus) in Saudi Arabia

A mixed case of chronic tracheal (syringeal) and pulmonary (lungs and air sacs) aspergillosis was diagnosed in an adult female gyrfalcon (Falco rusticolus). The bird presented with a 4-week history of severe dyspnea, exercise intolerance, depression and reduced appetite. Physical examination revealed slight emaciation. Hematological analysis showed leucocytosis, heterophilia, monocytosis, and thrombocytosis. Radiographic examination showed thickening of the air sac walls and increased radiopacity within the lung field. Caseous granulomatous lesions were observed during tracheoscopy and laparoscopy procedures. Cytological examination of specimens obtained from these lesions demonstrated Aspergillus species, which was isolated in culture and identified as Aspergillus flavus.     

Effect of Mica Reinforcement on the Flexural Strength and Microhardness of Polymethyl Methacrylate Denture Resin

Purpose : Conventional denture base polymethyl methacrylate (PMMA) is low in strength, soft, and brittle on impact. Improvements in the mechanical properties of denture base materials have been sought by adding different reinforcing phases to the PMMA matrix. The purpose of this work was to study the effects of mica reinforcement on the mechanical properties, flexural strength, and microhardness of PMMA denture base resin. Materials and Methods : Wet ground muscovite mica and Lucitone 199 original shade denture base resin were used. Two micas were tested: W200 and P66 with average particle sizes (d50) of 131 μm and 30 μm, respectively. The mica was silane treated in a solution of 3‐methacryloxypropyl trimethoxysilane, ethanol, and water, and then dried. The specimens were fabricated using the denture base resin manufacturer's instructions with a powder : liquid ratio of 21 g/10 ml and a mixing time of 30 seconds. Five treatment groups were produced with differing amounts of mica added to the PMMA denture base resin: (A) control group with 0 vol% mica, (B) 10 vol% W200 mica, (C) 20 vol% W200 mica, (D) 10 vol% P66 mica, (E) 20 vol% P66 mica. The mica replaced equal volumes of the PMMA powder component to minimize changes in viscosity. The three‐point bending flexural strength specimens were 70 × 11 × 3 mm³. Seven specimens were prepared for each treatment group. The hardness specimens were prepared from the ends of the three‐point bend specimens after they were broken (N = 7). After deflasking, the specimens were polished with 600 grit silicon carbide paper to achieve smooth surfaces. A standard three‐point bending jig with a span length of 50 mm was attached to an Instron universal testing machine. The specimens were placed on the jig, and loading was carried out using a 1 mm/min crosshead speed until failure. Microhardness was measured using a Clark microhardness tester with a Knoop indenter. The load was set to 200 g and the dwell time to 15 seconds. ANOVA and Tukey tests were used for statistical analyses (Alpha = 0.05). Results : The flexural strength of the control group was between 77% and 94% higher than all the mica‐containing groups (p≤ 0.05). No significant differences were found within the four mica groups. Microhardnesses of the 20% mica groups (both fine and coarse) were 33% and 26% higher than the control (p≤ 0.05). The 10% mica groups had higher hardness than the control group, but the increase was not statistically significant (p > 0.05). Conclusion : Mica additions to denture PMMA reduced flexural strength; however, with the specimens containing highest mica concentrations (20%), microhardness significantly increased.