Tennantite-tetrahedrite series from the Madan Pb-Zn deposits, Central Rhodopes, Bulgaria

Minerals from the tennantite-tetrahedrite series (fahlores) are found as single euhedral crystals and crustiform aggregates in hydrothermal veins of the Gradishte and Petrovitsa Pb-Zn deposits of the Madan ore field, southern Bulgaria. Unusually large compositional variations and fine oscillatory crystal zoning were investigated with electron microprobe analysis. The Gradishte samples correspond dominantly to tennantite, while Petrovitsa crystals have exclusively tetrahedrite composition. Fahlore compositions at Madan correspond to zincian varieties (1.6–1.95 apfu), with low Fe-content (<0.45 apfu). Minor silver is characteristic only for the Petrovitsa samples, reaching a maximum of 0.30 apfu. The (Cu+Ag) content of the Petrovitsa tennantites and the Cu content of the Gradishte tetrahedrites systematically exceed 10 apfu resulting in compensation of the excess Cu in the structure by Fe3+. Textural characteristics, mineral relationships and available fluid inclusion and stable isotope data suggest that fahlores precipitated in the late stages of mineralization at Madan, at temperature interval of 300–200 °C from oxidizing fluids with mixed (magmatic-meteoric) signatures

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients Aumento de homocisteína em acidente vascular cerebral isquêmico: análise post-hoc com casos controles em pacientes jovens

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased ‘normal’ homocysteinaemia, i.e., ‘hidden’ (‘pathologically dormant’) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001). An increase of THCY with 1.0 µmol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 µmol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68%) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.<br>OBJETIVO: Hiperhomocisteinemia tem sido postulada como um dos fatores de risco na patogênese do acidente vascular cerebral isquêmico (AVCI). Todavia, em adultos jovens existe a possibilidade de aumento significativo de risco de AVCI devido a aumento "normal" da homocisteinemia, "oculta" (patologicamente adormecida) dentro de uma variação definida como normal. Neste trabalho foi investigado um modelo post-hoc de dosagem de homocisteina no plasma (HC) em pacientes jovens com AVCI agudo pareados por gênero e idade. Foi avaliado também relações entre HC e prevalência de outros fatores de risco para AVCI em 41 pacientes e 41 controles normais. MÉTODO: Foi utilizado exame clínico, procedimentos instrumentais e de neuroimagem, exame de fatores de risco, dosagem da homocisteína no plasma, outros exames laboratoriais e análise estatística. RESULTADOS: Não foram encontradas diferenças quanto a presença de fumantes, dosagem de vitaminas, creatinina sérica e perfil lipídico entre os pacientes com AVCI e os controles normais. Todavia os pacientes com AVCI apresentaram diminuição de níveis de vitamina B6 e aumento de homocisteína, fibrinogênio e trigliceridios. A análise multivariada de regressão logística mostrou diferenças significativas apenas para HC e trigliceridios independentemente associadas para fatores de risco para AVCI (72% acuracia, p= 0,001). Um aumento de homocisteína de 1,0 µmol/L estava associado com aumento de 22% de risco de AVCI [OR=1,22 (95%IC 1,03-1,44)]. Foi evidenciado portanto um novo valor de cut-off para HC de 11,58 µmol/L em pacientes jovens com AVCI (ROC auc=0,67, 95% IC 0,55-0,78, p= 0,009). CONCLUSÃO: Este novo valor de cut-offpara a homocisteína discrimina claramente a ausência ou presença de AVCI (sensibilidade >63%, especificidade >68%) independente do gênero ou idade e deve ser aplicado para uma melhor avaliação precoce de pacientes jovens com risco de AVCI

Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved