Are There Gender Differences in Coronary Artery Disease? The Malaysian National Cardiovascular Disease Database – Percutaneous Coronary Intervention (NCVD-PCI) Registry

Objectives

To assess whether gender differences exist in the clinical presentation, angiographic severity, management and outcomes in patients with coronary artery disease (CAD).

Methods

The study comprised of 1,961 women and 8,593 men who underwent percutaneous coronary intervention (PCI) and were included in the Malaysian NCVD-PCI Registry from 2007–2009. Significant stenosis was defined as ≥70% stenosis in at least one of the epicardial vessels.

Results

Women were significantly older and had significantly higher rates of diabetes mellitus, hypertension, chronic renal failure, new onset angina and prior history of heart failure whereas smokers and past history of myocardial infarction were higher in men. In the ST-elevation myocardial infarction (STEMI) cohort, more women were in Killip class III-IV, had longer door-to-balloon time (169.5 min. vs 127.3 min, p<0.052) and significantly longer transfer time (300.4 min vs 166.3 min, p<0.039). Overall, women had significantly more left main stem (LMS) disease (1.3% vs 0.6%, p<0.003) and smaller diameter vessels (<3.0 mm: 45.5% vs 34.8%, p<0.001). In-hospital mortality rates for all PCI, STEMI, Non-STEMI (NSTEMI) and unstable angina for women and men were 1.99% vs 0.98%, Odds ratio (OR): 2.06 (95% confidence interval (CI): 1.40 to 3.01), 6.19% vs 2.88%, OR: 2.23 (95% CI: 1.31 to 3.79), 2.90% vs 0.79%, OR: 3.75 (95% CI: 1.58 to 8.90) and 1.79% vs 0.29%, OR: 6.18 (95% CI: 0.56 to 68.83), respectively. Six-month adjusted OR for mortality for all PCI, STEMI and NSTEMI in women were 2.18 (95% CI: 0.97 to 4.90), 2.68 (95% CI: 0.37 to 19.61) and 2.66 (95% CI: 0.73 to 9.69), respectively.

Conclusions

Women who underwent PCI were older with more co-morbidities. In-hospital and six-month mortality for all PCI, STEMI and NSTEMI were higher due largely to significantly more LMS disease, smaller diameter vessels, longer door-to-balloon and transfer time in women.     

Synthesis and Antiviral Activity of Some C2-, C4-, and C6-Substituted Pyrazolo[3,4-D]Pyrimidine Acyclonucleosides with the Alkylating Chains of ACV,HBG, and ISO-DHPG

A useful route to obtain trisubstituted pyrazolo[3,4-d]pyrimidines 14–17 is described. Those later were coupled with the alkylating agents 18–20 as in ACV, HBG, and iso-DHPG to give, after deprotection, the desired acylonucleosides 33–44. Almost all of the new compounds were evaluated for their inhibitory effects against the replication of various DNA viruses in culture.     

Highly Sensitive Spectrofluorimetric Method for Determination of Certain Aminoglycosides in Pharmaceutical Formulations and Human Plasma

A simple, reliable, highly sensitive and selective spectrofluorimetric method has been developed for determination of certain aminoglycosides namely amikacin sulfate, tobramycin, neomycin sulfate, gentamicin sulfate, kanamycin sulfate and streptomycin sulfate. The method is based on the formation of a charge transfer complexes between these drugs and safranin in buffer solution of pH 8. The formed complexes were quantitatively extracted with chloroform under the optimized experimental conditions. These complexes showed an excitation maxima at 519–524 nm and emission maxima at 545–570 nm. The calibration plots were constructed over the range of 4–60 pg mL⁻¹ for amikacin, 4–50 pg mL⁻¹ for gentamicin, neomycin and kanamycin, 4–40 pg mL⁻¹ for streptomycin and 5–50 pg mL⁻¹ for tobramycin. The proposed method was successfully applied to the analysis of the cited drugs in dosage forms. The proposed method was validated according to ICH and USP guidelines with respect to specificity, linearity, accuracy, precision and robustness. The high sensitivity of the proposed method allowed determination of amikacin and gentamicin in spiked and real human plasma.Key words: aminoglycosides, dosage forms, human plasma, safranin, spectrofluorimetry     

The Role of Initiator tRNAi met in Fidelity of Initiation of Protein Synthesis

The proper arrangement of amino acids in a protein determines its proper function, which is vital for the cellular metabolism. This indicates that the process of peptide bond formation requires high fidelity. One of the most important processes for this fidelity is kinetic proofreading. As biochemical experiments suggest that kinetic proofreading plays a major role in ensuring the fidelity of protein synthesis, it is not certain whether or not a misacylated tRNA would be corrected by kinetic proofreading during the peptide bond formation. Using 2-layered ONIOM (QM/MM) computational calculations, we studied the behavior of misacylated tRNAs and compared the results with these for cognate aminoacyl-tRNAs during the process of peptide bond formation to investigate the effect of nonnative amino acids on tRNAs. The difference between the behavior of initiator tRNA_i ^met compared to the one for the elongator tRNAs indicates that only the initiator tRNA_i ^met specifies the amino acid side chain.     

Synthesis of Novel Peptidyl Adenosine Antibiotic Analogs

A small library of peptidyl adenosine antibiotic analogs was synthesized, under the Pilot Scale Library Program of the NIH Roadmap initiative, from 2′,3′-O-isoproylideneadenosine-5′-carboxylic acid 2 in excellent yield. The coupling of the amino terminus of L-2-aminophenylbutyric methyl ester to a free 5′-carboxylic acid moiety of 2 followed by sodium hydroxide treatment led to carboxylic acid analog 4. Hydrolysis of this latter gave unprotected nucleoside analog 5. Intermediate 4 served as the precursor for the preparation of novel peptidyl adenosine analogs 6–18 in good yields and high purity through peptide coupling reactions to diverse amine derivatives. No marked anticancer and antimalaria activity was noted on preliminary cellular testing; however these analogs should be useful candidates for other types of biological activity.     

Synthesis and General Biological Activity of a Small Adenosine-5′-(Carboxamide and Sulfanilamide) Library

A small library of fifty-five adenosine peptide analogs was synthesized, under the Pilot Scale Library (PSL) Program of the NIH Roadmap initiative, from 2′,3′-O-isopropylideneadenosine-5′-carboxylic acid 2. The coupling of amine or sulfanilamide reactants to the free 5′-carboxylic acid moiety of 2, in automated solution-phase fashion, led after acid-mediated hydrolysis to target compounds 3–57 in good yields and high purity. No marked anticancer or antimalarial activity was noted on preliminary cellular testing. Initial screening through the MLPCN program, however, indicates that these analogs may show diverse and interesting biological activities.     

A chimerical phagocytosis model reveals the recruitment by Sertoli cells of autophagy for the degradation of ingested illegitimate substrates

Phagocytosis and autophagy are typically dedicated to degradation of substrates of extrinsic and intrinsic origins respectively. Although overlaps between phagocytosis and autophagy were reported, the use of autophagy for ingested substrate degradation by nonprofessional phagocytes has not been described. Blood-separated tissues use their tissue-specific nonprofessional phagocytes for homeostatic phagocytosis. In the testis, Sertoli cells phagocytose spermatid residual bodies produced during germ cell differentiation. In the retina, pigmented epithelium phagocytoses shed photoreceptor tips produced during photoreceptor renewal. Spermatid residual bodies and shed photoreceptor tips are phosphatidylserine-exposing substrates. Activation of the tyrosine kinase receptor MERTK, which is implicated in phagocytosis of phosphatidylserine-exposing substrates, is a common feature of Sertoli and retinal pigmented epithelial cell phagocytosis. The major aim of our study was to investigate to what extent phagocytosis by Sertoli cells may be tissue specific. We analyzed in Sertoli cell cultures that were exposed to either spermatid residual bodies (legitimate substrates) or retina photoreceptor outer segments (illegitimate substrates) the course of the main phagocytosis stages. We show that whereas substrate binding and ingestion stages occur similarly for legitimate or illegitimate substrates, the degradation of illegitimate but not of legitimate substrates triggers autophagy as evidenced by the formation of double-membrane wrapping, MAP1LC3A-II/LC3-II clustering, SQSTM1/p62 degradation, and by marked changes in ATG5, ATG9 and BECN1/Beclin 1 protein expression profiles. The recruitment by nonprofessional phagocytes of autophagy for the degradation of ingested cell-derived substrates is a novel feature that may be of major importance for fundamentals of both apoptotic substrate clearance and tissue homeostasis.     

Correlating Stiffness,Ductility, and Morphology of Polymer:Fullerene Films for Solar Cell Applications

The development of flexible and physically robust organic solar cells requires detailed knowledge of the mechanical behavior of the heterogeneous material stack. However, in these devices there has been limited research on the mechanical properties of the active organic layer. Here, two critical mechanical properties, stiffness and ductility, of a widely studied organic solar cell active layer, a blend film composed of poly(3‐hexylthiophene) (P3HT) and [6,6]‐phenyl C61‐butyric acid methyl ester (PCBM) are reported. Processing conditions are varied to produce films with differing morphology and correlations are developed between the film morphology, mechanical properties and photovoltaic device performance. The morphology is characterized by fitting the absorption of the P3HT:PCBM films to a weakly interacting H‐aggregate model. The elastic modulus is determined using a buckling metrology approach and the crack onset strain is determined by observing the film under tensile strain using optical microscopy. Both the elastic modulus and crack onset strain are found to vary significantly with processing conditions. Processing methods that result in improved device performance are shown to decrease both the compliance and ductility of the film.     

Progress and challenges for abiotic stress proteomics of crop plants

Plants are continually challenged to recognize and respond to adverse changes in their environment to avoid detrimental effects on growth and development. Understanding the mechanisms that crop plants employ to resist and tolerate abiotic stress is of considerable interest for designing agriculture breeding strategies to ensure sustainable productivity. The application of proteomics technologies to advance our knowledge in crop plant abiotic stress tolerance has increased dramatically in the past few years as evidenced by the large amount of publications in this area. This is attributed to advances in various technology platforms associated with MS‐based techniques as well as the accessibility of proteomics units to a wider plant research community. This review summarizes the work which has been reported for major crop plants and evaluates the findings in context of the approaches that are widely employed with the aim to encourage broadening the strategies used to increase coverage of the proteome