Theoretical Study on HF Elimination and Aromatization Mechanisms: A Case of Pyridoxal 5′ Phosphate-Dependent Enzyme

Pyridoxal 5-phosphate (PLP), the phosphorylated and the oxidized form of vitamin B6 is an organic cofactor. PLP forms a Schiff base with the ϵ-amino group of a lysine residue of PLP-dependent enzymes. γ-Aminobutyric acid (GABA) aminotransferase is a PLP-dependent enzyme that degrades GABA to succinic semialdehyde, while reduction of GABA concentration in the brain causes convolution besides several neurological diseases. The fluorine-containing substrate analogues for the inactivation of the GABA-AT are synthesized extensively in cases where the inactivation mechanisms involve HF elimination. Although two proposed mechanisms are present for the HF elimination, the details of the base-induced HF elimination are not well identified. In this density functional theory (DFT) study, fluorine-containing substrate analogue, 5-amino-2-fluorocyclohex-3-enecarboxylic acid, is particularly chosen in order to explain the details of the HF elimination reactions. On the other hand, the experimental studies revealed that aromatization competes with Michael addition mechanism in the presence of 5-amino-2-fluorocyclohex-3-enecarboxylic acid. The results allowed us to draw a conclusion for the nature of HF elimination, besides the elucidation of the mechanism preference for the inactivation mechanism. Furthermore, the solvent phase calculations carried out in this study ensure that the proton transfer steps should be assisted either by a water molecule or a base for lower activation energy barriers

Extrapulmonary tuberculosis: 7 year-experience of a tertiary center in Istanbul

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Background: Although a decreasing trend of tuberculosis (TB) was reported in Turkey, higher proportion of extrapulmonary tuberculosis (EPT) was revealed. Material and methods: In this retrospective study, clinical and laboratory data of 141 EPT patients were evaluated for a seven-year period by using descriptive statistics, and parametric and non-parametric tests where appropriate. Results: The most frequent types of EPT were meningeal TB (23%) and TB lymphadenitis (21%), respectively. Other types of EPT were skeletal, miliary, peritoneal, abscess, genitourinarial, cutaneous and gastrointestinal involvement which ranged between 18% and 1%. Mean age was 42 and female/male ratio was almost equal. All patients were born in Turkey. Although all of them were permanent residents of Istanbul, 73% of the patients came from East and Southeast Region of Turkey. For the patients, being older than 40 years old (p < 0.01), having miliary TB (p < 0.05) and high CRP levels (p < 0.05) were found to be associated with mortality. Conclusions: EPT still remains as a significant morbidity and mortality reason in lower income populations and developing countries. In our study, although all patients were residents of Istanbul approximately two thirds of them have migrated from East and Southeast parts of the country. The relatively high prevelance of tuberculosis cases in Istanbul may be due to the permanent migration from other parts of the country. Early diagnosis and initiation of appropriate treatment are the keys for reducing morbidity and mortality in patients with EPT, particularly in the cases of older age

Extrapulmonary tuberculosis: 7 year-experience of a tertiary center in Istanbul

WOS: 000327765300035PubMed ID: 24028930Background: Although a decreasing trend of tuberculosis (TB) was reported in Turkey, higher proportion of extrapulmonary tuberculosis (EPT) was revealed. Material and methods: In this retrospective study, clinical and laboratory data of 141 EPT patients were evaluated for a seven-year period by using descriptive statistics, and parametric and non-parametric tests where appropriate. Results: The most frequent types of EPT were meningeal TB (23%) and TB lymphadenitis (21%), respectively. Other types of EPT were skeletal, miliary, peritoneal, abscess, genitourinarial, cutaneous and gastrointestinal involvement which ranged between 18% and 1%. Mean age was 42 and female/male ratio was almost equal. All patients were born in Turkey. Although all of them were permanent residents of Istanbul, 73% of the patients came from East and Southeast Region of Turkey. For the patients, being older than 40 years old (p < 0.01), having miliary TB (p < 0.05) and high CRP levels (p < 0.05) were found to be associated with mortality. Conclusions: EPT still remains as a significant morbidity and mortality reason in lower income populations and developing countries. In our study, although all patients were residents of Istanbul approximately two thirds of them have migrated from East and Southeast parts of the country. The relatively high prevelance of tuberculosis cases in Istanbul may be due to the permanent migration from other parts of the country. Early diagnosis and initiation of appropriate treatment are the keys for reducing morbidity and mortality in patients with EPT, particularly in the cases of older ages. (C) 2013 European Federation of Internal Medicine. Published by Elsevier B. V. All rights reserved

Ertapenem for the treatment of complicated urinary tract ınfections caused by extended-spectrum β-lactamase-producing bacteria: A case series report

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Urinary tract infections with extended-spectrum beta-lactamases (ESBL) are an increasing public health concern. We evaluated our experience with the use of ertapenem for complicated urinary tract infections (cUTI) caused by ESBL- producing bacteria. Sixty-four patients aged >18 years who had a cUTI caused by ESBL- producing microorganisms that were treated with ertapenem at Sisli Etfal Training and Research Hospital, from January 1st, 2010 to December 31st, 2011, were included in this study. Data on patients demographic, clinical and laboratory results were collected. The median age was 65.8 years (range, 30 to 95). All patients had at least one risk factor complicating factor except two of them. The most common underlying problem was prior antibiotic exposure. The pathogens isolated from urine samples were ESBL-producing E. coli in 49, ESBL-producing K. pneumoniae in 12 and ESBL-producing K. oxytoca in 2 patients. All were susceptible to ertapenem in vitro. The average duration of ertapenem therapy was 14+/-4 days for upper UTI and 11+/-2 days for lower UTI. All patients achieved clinical cure and bacteriological eradication in urine. One patient had relapse and six of them had reinfection. Only one case had diarrhea which did not require discontinuation of therapy. Our results demonstrate that ertapenem is suitable for the treatment of cUTI cause by ESBL-producing bacteria

A Theoretical Study On Rh(I) Catalyzed Enantioselective Conjugate Addition Reactions of Fluoroalkylated Olefins

In this study, quantum mechanical calculations have been performed to elucidate the mechanism and enantioselectivity in rhodium-catalyzed 1,4-conjugate addition reaction of a series of aryl groups to electron-deficient 4,4,4-trifluoro-1-phenyl-2-buten-1-one in the presence of (<i>S</i>)-BINAP. Conjugate addition of unsubstituted, <i>o</i>-CH₃, <i>p</i>- and <i>o</i>-Cl substituted phenyl groups were considered to explain steric and electronic effects on the reaction mechanism. The activation energy difference between benzene and <i>o</i>-toluene-substituted systems (8.1 kcal/mol for the <i>R</i> isomer) has shown the impact of steric effects of substituents at the ortho position. The electronic effect of a Cl substituent at the ortho position was demonstrated by an even higher energy barrier (11.9 kcal/mol of energy difference between benzene and <i>o</i>-Cl for R enantiomer). The experimental unreactivity of the <i>o</i>-Cl-substituted system was also confirmed with the calculated high activation energies for both <i>R</i> and <i>S</i> (29.9 and 31.7 kcal/mol for <i>R</i> and <i>S</i>, respectively) product formations. The system with para-positioned Cl revealed almost the same barriers for benzene, indicating that substituents at the para position do not have significant electronic or steric effects in this reaction. In all the modeled sets, experimental <i>R</i> product predominance could be reproduced. The quantitative trend was satisfied with the B3LYP/6-31G* functional, where the LANL2DZ effective core potential was used for Rh, P, S, and Cl atoms. Benchmark calculations have been performed to validate the level of theory in this study