Subfatin, asprosin, alamandine and maresin-1 in cerebral ischemia, intracranial and subarachnoid hemorrhages.

OBJECTIVE: Cerebrovascular diseases (CVDs) remain an important public health issue due to the increasing number of deaths worldwide. Changes in the synthesis and release of peptides in CVDs may play an important role in elucidating the physiopathology of the disease. Therefore, this study was to investigate the fate of maresin-1 (MaR-1), subfatin (SUB), asprosin (ASP), and alamandine (ALA) levels in patients with cerebral infarction (CI), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH) evaluated within the scope of CVDs, and voluntary healthy controls. PATIENTS AND METHODS: The study participants were divided into 4 groups: CI patients, ICH patients, SAH patients, and healthy volunteers. The diagnosis of CVDs was made based on the National Institutes of Health Stroke Scale (NIHSS), Intracerebral Hemorrhage Score (ICHS), Botterel-Hunt-Hess Scale (BHHS), and cranial computed tomography (CT). The levels of MaR-1 (ng/mL), SUB (ng/mL), ASP (ng/mL), and ALA (pg/mL) in the blood samples collected from the participants were studied using the ELISA method. Other parameters included in the study were obtained from the patient records of our hospital. RESULTS: The comparison of MaR-1 [(control 1.38 ± 0.14), SAH (0.98 ± 0.087), CI (0.67 ± 0.04), ICH (0.51 ± 0.03)], SUB [(control (13.2 ± 1.4), SAH (10.1 ± 1.2), CI (7.9 ± 0.8), ICH (5.8 ± 0.5)], and ALA [(control (67.2 ± 7.9), SAH (58.2 ± 4.3), CI (42.1 ± 3.7), and ICH (34.2 ±3.9)] values revealed a significant decrease compared to the control values. The comparison of the ASP values of SAH, CI, and ICH patients and control values (11.6 ± 1.2) showed significantly higher asprosin values in SAH (13.8 ± 1.1), CI (15.4 ± 1.2) and ICH (28.9 ± 2.8) patients. Similarly, systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose levels of CKD patients were also high. CONCLUSIONS: Decreased MaR-1, SUB, ALA and increased ASP compared to the control values may play a role in the physiopathology of these diseases. MaR-1, SUB, ALA, and ASP differences between SAH, CI and ICH patients may also guide clinicians along with SBP, DBP and glucose values.

LC determination of diphemanil methylsulfate: application to stability study of stored pharmaceutical formulations.

Diphemanil methylsulfate (DMS) is a synthetic antimuscarinic agent classically used in infants for vagal hypertonia-related symptoms. A normal-phase, isocratic liquid chromatographic method was developed for the quantitative determination of DMS in bulk drugs and in pharmaceutical forms. The method has been completely validated and robustness of this method has been studied. The limit of detection (LOD) for DMS impurities namely, impurity 1 and 2 were found to be 11 and 46 ng/ml. The limit of quantitation (LOQ) was found to be 49 and 139 ng/ml for impurity 1 and 2, respectively. The stability studies have been performed for 2 and 10 mg DMS tablets subjected at various temperatures: 25 degrees C (long term storage condition) and 40 degrees C (accelerated storage condition) for 18 and 6 months, respectively. At 25 degrees C, the samples were found to be stable for the study period. At 40 degrees C, 2 and 10 mg DMS tablets showed degradation up to 5 and 10% over a 6-month period.

XAS applied to pharmaceuticals: drug administration and bioavailability.

We present selected XAS applications, focused towards practical hospital questions of drug administration and bioavailability, where the technique is driven up to its limits of sensitivity. i) XAS was used to study the interactions between the components of parenteral nutrition solutions, in particular zinc and aminoacids, possibly modifying their bioavailability. ii) We studied by EXAFS a series of binary and ternary copper-aminoacid complexes, in view of the development of an efficient oral drug against copper deficiencies in Menkes disease. iii) EXAFS and XANES analysis allowed us to characterise the solution form of a new arsenic containing drug against leukaemia. In parallel to the XAS measurements, we analysed trace elements levels along patients' hairs, using X-ray fluorescence excited by synchrotron radiation. The measurements along the hair allow for a monitoring of essential trace elements during therapy.

Stability of stored methacholine solutions: study of hydrolysis kinetic by IP-LC.

Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to hydrolysis in aqueous solutions in acetic acid and beta-methylcholine. In the present work, kinetics of hydrolysis with different solvents (water and phosphate-buffered saline (PBS) pH 7.4) at different temperatures have been studied using a newly developed high-performance liquid chromatography. At 4 degrees C, kinetic determination of hydrolysis in methacholine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degrees C, concentration of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degrees C, concentration of unbuffered methacholine chloride has degradation up to 5% and buffered methacholine chloride solutions have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different concentrations. We have studied pH and osmolality for methacholine solutions prepared with different diluents potentially used in hospital pharmacies, i.e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that methacholine solutions prepared with deionized water at 50 mg/ml and diluted with PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness.