Fluphenazine dihydro­chloride dimethanol solvate

In the title compound {systematic name: 1-(2-hy­droxy­eth­yl)-4-[3-(2-trifluoro­methyl-10H-phenothia­zin-10-yl)prop­yl]piperazine-1,4-diium dichloride dimethanol disolvate}, C22H28F3N3OS2+·2Cl−·2CH3OH, the dihedral angle between the planes of the two outer benzene rings of the tricyclic phenothia­zine system is 46.91 (13)°. The piperazine ring adopts a chair conformation. The crystal structure is stabilized by O—H⋯Cl, N—H⋯Cl, C—H⋯O, C—H⋯Cl and C—H⋯F hydrogen bonds and contacts

Clinical significance of oxidation and acetylation genetic polymorphism in patients with hyperthyreosis

Introduction: The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease was aroused much interest. The aim of our study was to evaluate whether patients with hyperthyreosis differ from healthy persons in their ability to oxidize sparteine and acetylate sulphadimidine as model drugs. Oxidation and acetylation were estimated in 48 patients with hiperthyreosis. Material and methods: The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 60 healthy volunteers for comparison of acetylation phenotype. The phenotyping of oxidation revealed two distinct populations among 40 patients with hyperthyreosis: 38 persons (95%) were extensive metabolizers (EM) of sparteine and 2 persons (5%) was poor metabolizers (PM). In 160 healthy persons (91.2%) were EM and 14 persons (8.8%) were PM. The difference between frequency distribution of PM and EM in healthy persons and in patients with hyperthyreosis was not statistically significant. Results: The phenotyping of acetylation showed among 48 patients with hyperthyreosis 8 persons (13%) were rapid acetylators (RA) and 40 persons (87%) were slow acetylators (SA). In 60 healthy volunteers the phenotype of rapid acetylation was observed in 31 persons (51%) and slow acetylation in 29 persons (49%). Relative risk (odds ratio) of development of thyroid diseases was 5.34 times higher for SA in comparison to RA. The prevalence of SA among patients with hyperthyreosis in comparison to healthy volunteers was statistically significant (p < 0.0002). Conclusions: The results of our study may suggest that slow acetylation phenotype is associated with increased risk of the development of hyperthyreosis.Wstęp: Badania nad udziałem czynników genetycznych w powstawaniu niektórych chorób prowadzi się w coraz szerszym zakresie. Celem pracy było stwierdzenie, czy między grupą chorych na nadczynność tarczycy a grupą kontrolną zdrowych ochotników istnieje różnica w zdolności utleniania sparteiny i acetylacji sulfadimidyny jako leków modelowych. Materiał i metody: Badaniami objęto 268 osób. W tej grupie 48 osób było chorych na nadczynność tarczycy. Grupę kontrolną dla fenotypu oksydacji stanowiło 160 zdrowych ochotników, natomiast dla fenotypu acetylacji 60 osób zdrowych. Wyniki: Wśród 40 chorych z nadczynnością tarczycy stwierdzono 38 (95%) ekstensywnych metabolizerów (EM, extensive metabolizers) i 2 (5%) słabych metabolizerów (PM, poor metabolizers) sparteiny. W grupie kontrolnej 160 ochotników, 146 (91,2%) okazało się EM, a 14 (8,8%) - PM. Niewielka przewaga częstości występowania PM wśród pacjentów z nadczynnością tarczycy w porównaniu z grupą osób zdrowych nie była statystycznie istotna. Wśród 48 chorych na nadczynność tarczycy wyróżniono 13% szybkich acetylatorów (RA, rapid acetylators) (8 osób) i 87% wolnych acetylatorów (SA, slow acetylators) (40 osób). Natomiast u 60 zdrowych ochotników stwierdzono 51% RA (31 osób) i 49% SA (29 osób). Odsetek szybkich i wolnych acetylatorów w grupie chorych z nadczynnością tarczycy różnił się w sposób statystycznie istotny w porównaniu z odsetkiem w grupie osób zdrowych (p < 0,0002). Względne ryzyko zachorowania na nadczynność tarczycy, wyrażone za pomocą proporcji szans (OR, odds ratio), jest ponad 5 razy większe dla wolnych niż dla szybkich acetylatorów. Wnioski: Wyniki niniejszych badań mogą sugerować, że osoby z fenotypem wolnej acetylacji są predysponowane do zapadalności na nadczynność tarczycy

Essentials of Aquaphotomics and Its Chemometrics Approaches

Aquaphotomics is a novel scientific discipline involving the study of water and aqueous systems. Using light-water interaction, it aims to extract information about the structure of water, composed of many different water molecular conformations using their absorbance bands. In aquaphotomics analysis, specific water structures (presented as water absorbance patterns) are related to their resulting functions in the aqueous systems studied, thereby building an aquaphotome-a database of water absorbance bands and patterns correlating specific water structures to their specific functions. Light-water interaction spectroscopic methods produce complex multidimensional spectral data, which require data processing and analysis to extract hidden information about the structure of water presented by its absorbance bands. The process of extracting information from water spectra in aquaphotomics requires a field-specific approach. It starts with an appropriate experimental design and execution to ensure high-quality spectral signals, followed by a multitude of spectral analysis, preprocessing and chemometrics methods to remove unwanted influences and extract water absorbance spectral pattern related to the perturbation of interest through the identification of activated water absorbance bands found among the common, consistently repeating and highly influential variables in all analytical models. The objective of this paper is to introduce the field of aquaphotomics and describe aquaphotomics multivariate analysis methodology developed during the last decade. Through a worked-out example of analysis of potassium chloride solutions supported by similar approaches from the existing aquaphotomics literature, the provided instruction should give enough information about aquaphotomics analysis i.e. to design and perform the experiment and data analysis as well as to represent water absorbance spectral pattern using various forms of aquagrams-specifically designed aquaphotomics graphs. The explained methodology is derived from analysis of near infrared spectral data of aqueous systems and will offer a useful and new tool for extracting data from informationally rich water spectra in any region. It is the hope of the authors that with this new tool at the disposal of scientists and chemometricians, pharmaceutical and biomedical spectroscopy will substantially progress beyond its state-of-the-art applications

Application of two-dimensional correlation analysis to Raman optical activity

Raman optical activity (ROA) is an incisive probe of structural dynamics and its combination with two-dimensional correlation analysis is an attractive method for the investigation of conformational transitions in proteins. In this paper we show that pretreatment of data is essential for the generation of reliable 2D ROA and 2D Raman correlations. Specific experimental parameters and available information of ROA and Raman studies have facilitated the development of four pretreatment processes, baseline subtraction, smoothing, normalization and further baseline correction. The bisignate nature of ROA spectra has a significant effect on the interpretation of synchronous 2D correlation plots when bands at wavenumbers of both positive and negative intensity are compared, while interpretation of asynchronous plots remains unchanged. We introduce a notation format to make interpretation of 2D correlations from bisignate spectra clearer. With appropriate application of 2D correlation analysis to ROA spectra, 2D ROA and 2D Raman/ROA heterocorrelation are potentially valuable tools for the analysis of conformational transitions in polypeptides and proteins. (c) 2006 Elsevier B.V. All rights reserved