Global initiative for chronic obstructive lung disease for chronic obstructive pulmonary disease: GOLD opportunity for lung disorders

Background. The purpose of this study was to assess the agreement of asthma and chronic obstructive pulmonary disease (COPD) treatment prescribed by physicians and pulmonologists in comparison to asthma and COPD guidelines and the need of the implementation of COPD guidelines in primary health care physicians. Methods. Eighty-three asthma patients and 100 COPD patients were chosen and classified in relation to the agreement of their treatment prescribed by a health care physician and that mentioned by global initiative for chronic obstructive lung disease (GOLD) The COPD patients were classified according to their stage of the disease too. Results. Both pulmonologists and primary health care physicians manage asthma patients following asthma guidelines, while great proportion of COPD patients are undertreated by primary health care physicians. The proportion of undertreated COPD patients is decreased as the stage of disease is progressing. Conclusions. COPD patients mainly are undertreated by primary health care physicians when they are in the primary stages of the disease. The overtreatment of some patients consists of high doses of inhaled steroids prescribed by both pulmonologists, and mainly, primary health care physicians. Therefore, it can be concluded that there is the need of the implementation of COPD guideline by primary health care physicians and the need of COPD patients to, be, diagnosed in early stages by performing spirometry. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved

Crystal structure of fac-aqua[(E)-4-(benzo[d]thiazol-2-yl)-N-(pyridin-2-ylmethylidene)aniline-κ2N,N′]tricarbonylrhenium(I) hexafluoridophosphate methanol monosolvate

In the title compound, fac-[Re(C19H13N3S)(CO)3(H2O)]PF6·CH3OH, the coordination environment of the ReI atom is octahedral with a C3N2O coordination set. In this molecule, the N,N′ bidentate ligand, (E)-4-(benzo[d]thiazol-2-yl)-N-(pyridin-2-ylmethylidene)aniline, and the monodentate aqua ligand occupy the three available coordination sites of the [Re(CO)3]+ core, generating a `2 + 1' mixed-ligand complex. In this complex, the Re—C bonds of the carbonyl ligands trans to the coordinating N,N′ atoms of the bidentate ligand are longer than the Re—C bond of the carbonyl group trans to the aqua ligand, in accordance with the intensity of their trans effects. The complex is positively charged with PF6− as the counter-ion. In the structure, the complexes form dimers through π–π intermolecular interactions. O—H...O and O—H...N hydrogen bonds lead to the formation of stacks parallel to the a axis, which further extend into layers parallel to (0\overline{1}1). Through O—H...F hydrogen bonds between the complexes and the PF6−counter-anions, a three-dimensional network is established

Design, Synthesis, and Biological Evaluations of Novel Thiazolo[4,5-d]pyrimidine Corticotropin Releasing Factor (CRF) Receptor Antagonists as Potential Treatments for Stress Related Disorders and Congenital Adrenal Hyperplasia (CAH)

Corticotropin-releasing factor (CRF) is a key neuropeptide hormone that is secreted from the hypothalamus. It is the master hormone of the HPA axis, which orchestrates the physiological and behavioral responses to stress. Many disorders, including anxiety, depression, addiction relapse, and others, are related to over-activation of this system. Thus, new molecules that may interfere with CRF receptor binding may be of value to treat neuropsychiatric stress-related disorders. Also, CRF1R antagonists have recently emerged as potential treatment options for congenital adrenal hyperplasia. Previously, several series of CRF1 receptor antagonists were developed by our group. In continuation of our efforts in this direction, herein we report the synthesis and biological evaluation of a new series of CRF1R antagonists. Representative compounds were evaluated for their binding affinities compared to antalarmin. Four compounds (2, 5, 20, and 21) showed log IC50 values of −8.22, −7.95, −8.04, and −7.88, respectively, compared to −7.78 for antalarmin. This result indicates that these four compounds are superior to antalarmin by 2.5, 1.4, 1.7, and 1.25 times, respectively. It is worth mentioning that compound 2, in terms of IC50, is among the best CRF1R antagonists ever developed in the last 40 years. The in silico physicochemical properties of the lead compounds showed good drug-like properties. Thus, further research in this direction may lead to better and safer CRF receptor antagonists that may have clinical applications, particularly for stress-related disorders and the treatment of congenital adrenal hyperplasia

Crystal structure of fac-tricarbonyl(quinoline-2-carboxylato-κ2N,O)(triphenylarsane-κAs)rhenium(I)

In the title compound, [Re(C10H6NO2)(CO)3{As(C6H5)3}], the coordination environment of ReI is that of a distorted octahedron. Three coordination sites are occupied by three carbonyl groups in a facial arrangement and the remaining three sites by triphenylarsane and deprotonated quinaldic acid in As-mono- and N,O-bidentate fashions, respectively. In the crystal, the complexes are linked through weak C—H...O hydrogen bonds, forming a three-dimensional network. It worth noting that, as far as we know, this complex is the first ReI triphenylarsane tricarbonyl compound to be reported

New <i>fac</i>-[Re(CO)₃(OO)(L)] and [Re(CO)₂(OO)(L)₂] Complexes Bearing Two Natural Food Additives, Maltol and Kojic Acid, as OO Ligands

The synthesis and structural characterization of new “2+1” mixed ligand fac-[Re(CO)3(OO)(L)] and Re(CO)2(OO)(L)2 complexes are reported herein. Maltol and kojic acid were chosen as bidentate OO ligands, while imidazole, isocyanocyclohexane or triphenylphosphine were selected as the monodentate ligands. The synthesis of the rhenium complexes was based on the reaction of [NEt4]2[Re(CO)3Br3] with maltol and kojic acid to generate the intermediate aqua complex fac-[Re(CO)3(OO)(H2O)], followed by the replacement of the labile aqua ligand by the monodentate ligand. Structural characterization of all Re complexes was established by NMR and IR spectroscopies, as well as two of them by single-crystal X-ray crystallography, revealing distorted octahedral geometry around the Re center. In the crystal lattice, the complexes form supramolecular networks due to the development of intermolecular interactions of the N-H⋯O, C-H⋯O and C-H⋯π type

Design, synthesis, structural optimization, SAR, in silico prediction of physicochemical properties and pharmacological evaluation of novel & potent thiazolo[4,5-d]pyrimidine corticotropin releasing factor (CRF) receptor antagonists

Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide secreted from the hypothalamus and is the main regulator of the hypothalamus-pituitary-adrenocortical (HPA) axis. CRF is the master hormone which modulates physiological and behavioral responses to stress. Many disorders including anxiety, depression, addictive disorders and others are related to over activation of the CRF system. This suggests that new molecules which can interfere with CRF binding to its receptors may be potential candidates for neuropsychiatric drugs to treat stress-related disorders. Previously, three series of pyrimidine and fused pyrimidine CRF receptor antagonists were synthesized by our group and specific binding assays, competitive binding studies and determination of the ability to antagonize the agonist-stimulated accumulation of cAMP (the second messenger for CRF receptors) were reported. In continuation of our efforts in this direction, in the current manuscript, we report the synthesis & biological evaluation of a new series of CRF receptor antagonists. Seven compounds showed promising binding affinity with the best two compounds (compounds 6 & 43) displaying a superior binding affinity to all of our previous compounds. Compounds 6 & 43 have only 4 times and 2 times less binding affinity than the standard CRF antagonist antalarmin, respectively. Thus, our two best lead compounds (compound 6 & 43) can be considered potent CRF receptor antagonists with binding affinity of 41.0 & 19.2 nM versus 9.7 nM for antalarmin

Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)5 and fac-[NEt4]2[ReBr3(CO)3] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)3] (5a) and fac-[Re(SNO)(CO)3] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[99mTc(CO)3]+ core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[99mTc][Tc(OH2)3(CO)3]+ precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC50 = 8.85 ± 2.62 μM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC50 value of 26.11 nM. Biodistribution studies of the 99mTc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system

Researching refugees: Methodological and ethical considerations

Research with refugees involves particular conceptual, ethical and methodological issues. In this chapter, we outline a number of approaches to refugee research. The merits and limitations of the dominant trauma approach are reviewed, noting the particular tendency of this approach to exclude indigenous forms of knowledge and understanding. We review the emergence of alternative or complementary approaches which strive to integrate qualitative and quantitative methodologies and emphasise a return to human experience and a deeper eco-social and cultural understanding of the refugee experience. One such methodology, interpretative phenomenological analysis is described in greater detail. We then extend our chapter to examine some of the ethical issues which emerge in refugee-related research. This section locates the research enterprise within the broader socio-political context of engaged research. Researching refugee - Ethical issue - Methodological issue - Cultural understanding - Interpretative Phenomenology - Socio-political context of research - Sudanese refugee - Mental healt