Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

A STUDY AND DETERMINATION OF BAMIPINE WITH OTHER ASSOCIATED DRUGS USING H.P.L.C.

THE EXPERIMENTAL PART OF THE THESIS IS DIVIDED INTO TWO PARTS. IN THE FIRST PART THE CHROMATOGRAPHIC BEHAVIOR OF BAMIPINE WAS STUDIED BY USING REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (H.P.L.C.). SPECIFICALLY THE CHANGES OF SOLVENT STRENGTH WERE STUDIED DEPENDING ON THEIR POLARITY AND PH. THE FACTORS WHICH AFFECT THE ABSORPTION OF THE CHROMATOGRAPHIC PEAKS, THAT IS, THE FLOW RATE, WAVELENGTH AND SOLVENT STRENGTH OF THE MOBILE PHASE WERE ALSO INVESTIGATED. IN THE SECOND PART OF THE THESIS, SIMULTANEOUS QUANTITATIVE DETERMINATION OF BAMIPINE AND OTHER DRUGS COMBINED WITH IT WERE CARRIED OUT. FOUR DIFFERENT CHROMATOGRAPHIC SYSTEMS WERE CHOSEN AND USED FOR THE FOLLOWING PHARMACOLOGICAL COMBINATIONS OF DRUGS. (SHORTENED)ΤΟ ΠΕΙΡΑΜΑΤΙΚΟ ΜΕΡΟΣ ΤΗΣ ΠΑΡΟΥΣΑΣ ΔΙΔΑΚΤΟΡΙΚΗΣ ΔΙΑΤΡΙΒΗΣ ΑΠΟΤΕΛΕΙΤΑΙ ΑΠΟ ΔΥΟ ΕΝΟΤΗΤΕΣ. ΣΤΗΝ ΠΡΩΤΗ ΕΝΟΤΗΤΑ ΓΙΝΕΤΑΙ ΜΕΛΕΤΗ ΤΗΣ ΧΡΩΜΑΤΟΓΡΑΦΙΚΗΣ ΣΥΜΠΕΡΙΦΟΡΑΣ ΤΟΥ ΑΝΤΙΣΤΑΜΙΝΙΚΟΥ ΒΑΜΙΠΙΝΗ ΜΕ ΧΡΗΣΙΜΟΠΟΙΗΣΗ ΥΓΡΗΣ ΧΡΩΜΑΤΟΓΡΑΦΙΑΣ ΥΨΗΛΗΣ ΑΠΟΔΟΣΗΣ. ΕΙΔΙΚΟΤΕΡΑ ΜΕΛΕΤΗΘΗΚΕ Η ΕΠΙΔΡΑΣΗ ΤΗΣ ΕΚΛΟΥΣΤΙΚΗΣ ΙΚΑΝΟΤΗΤΑΣ, ΤΟΥ ΡΗ ΚΑΙ ΤΗΣ ΤΑΧΥΤΗΤΑΣ ΡΟΗΣ ΤΗΣ ΚΙΝΗΤΗΣ ΦΑΣΗΣ ΚΑΘΩΣ ΕΠΙΣΗΣ ΚΑΙ Η ΤΙΜΗ ΤΟΥ ΜΗΚΟΥΣ ΚΥΜΑΤΟΣ ΑΝΙΧΝΕΥΣΗΣ ΥΠΕΡΙΩΔΟΥΣ, ΣΤΗΝ ΧΡΩΜΑΤΟΓΡΑΦΙΚΗ ΣΥΜΠΕΡΙΦΟΡΑ ΤΗΣ ΒΑΜΙΠΙΝΗΣ ΚΑΙ ΣΤΗΝ ΕΥΑΙΣΘΗΣΙΑ ΤΗΣ ΒΑΜΙΠΙΝΗΣ ΜΕ ΑΛΛΑ ΦΑΡΜΑΚΑ ΜΕ ΤΑ ΟΠΟΙΑ ΜΠΟΡΕΙ ΝΑ ΣΥΝΥΠΑΡΧΕΙ ΣΕ ΦΑΡΜΑΚΕΥΤΙΚΑ ΣΚΕΥΑΣΜΑΤΑ. ΤΕΤΟΙΟΙ ΗΤΑΝ: Α) ΒΑΜΙΠΙΝΗ ΜΕ ΤΕΡΒΟΥΤΑΛΙΝΗ 'Η ΣΑΛΒΟΥΤΑΜΟΛΗ ΚΑΙ ΒΑΜΙΠΙΝΗ ΜΕ ΣΥΜΠΑΘΟΜΙΜΗΤΙΚΕΣ ΑΜΙΝΕΣ ΚΑΙ ΔΕΞΤΡΟΜΕΘΟΡΦΑΝΗ. (ΠΕΡΙΚΟΠΗ

Recent Trends in Pharmaceutical Analytical Chemistry

Modern analytical chemistry plays a vital role in pharmaceutical sciences [...

Development and Validation of an HPLC-DAD Method for the Determination of Seven Antioxidants in a Nano-Emulsion: Formulation and Stability Study

Oxidative stress degrades skin collagen and elastin and causes inflammatory reactions that affect mitochondrial DNA leading to aging. In the present study, a potential cosmetic nano-emulsion (o/w) of seven substances (chlorogenic acid, caffeine, rutin, hesperidin, quercetin, α-tocopherol and retinol) with antioxidant and anti-aging properties was prepared and analyzed. The lipophilic components were entrapped in the dispersed nanoparticles (jojoba) of the emulsion while the hydrophilic ones dissolved in the aqueous phase (glycerol/water). Suitable excipients were selected using an experimental design methodology with two mixtures and two responses (particle size and zeta potential). The quantitative extraction of chlorogenic acid and caffeine from Crithmum maritimum L. plant and coffee beans (Coffea arabica L.) and their stability were also studied. The analysis of the substances was carried out on an HPLC-DAD, with a phenyl column and gradient elution system (solvent A: water with 0.2% formic acid and B: acetonitrile with 0.2% formic acid). Validation of the method was performed in terms of linearity (r2 > 0.998), precision and repeatability (%RSD < 2) while the limits of detection (LLODs) and quantification (LLOQs) were also determined. The antioxidants were quantified after being extracted from the substrate (%recovery 96.7–102.5, %RSD < 2)

Development and Validation of an HPLC-FLD Method for the Determination of NDMA and NDEA Nitrosamines in Lisinopril Using Pre-Column Denitrosation and Derivatization Procedure

In order to meet the analytical requirements of the European Medicines Agency (EMA), a new HPLC-FLD method was successfully developed using dansyl chloride for the derivatization and determination of the genotoxic impurities N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in Lisinopril API and its final product. Samples’ pretreatment includes liquid–liquid microextraction, denitrosation, and derivatization steps. To optimize the process, the parameters contributing to high sensitivity and yielding reliable results were thoroughly studied and optimized using one-factor-at-a-time and experimental design approaches. The analytes were pre-column derivatized with Dansyl-Cl and analyzed by HPLC-fluorescence (λem/λem = 340/530) using a C18 column and a mixture of phosphate buffer (pH = 2.8; 20 mM)/acetonitrile 55:45 v/v as the mobile phase. The six-level concentration calibration was shown to be linear, with R equal to 0.9995 for both analytes. The limit of detection (LOD) was satisfactory and equal to 4.7 and 0.04 ng/mL for NDMA and NDEA, respectively. Precision was less than 13.4% in all cases, and the average recoveries were equal to 109.2 and 98.1% for NDMA and NDEA, respectively. The proposed procedure is relatively easy, rapid, and suitable for the determination of the two nitrosamines in routine analysis tests

Development and Validation of an HPLC-FLD Method for the Determination of NDMA and NDEA Nitrosamines in Lisinopril Using Pre-Column Denitrosation and Derivatization Procedure

In order to meet the analytical requirements of the European Medicines Agency (EMA), a new HPLC-FLD method was successfully developed using dansyl chloride for the derivatization and determination of the genotoxic impurities N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in Lisinopril API and its final product. Samples&rsquo; pretreatment includes liquid&ndash;liquid microextraction, denitrosation, and derivatization steps. To optimize the process, the parameters contributing to high sensitivity and yielding reliable results were thoroughly studied and optimized using one-factor-at-a-time and experimental design approaches. The analytes were pre-column derivatized with Dansyl-Cl and analyzed by HPLC-fluorescence (&lambda;em/&lambda;em = 340/530) using a C18 column and a mixture of phosphate buffer (pH = 2.8; 20 mM)/acetonitrile 55:45 v/v as the mobile phase. The six-level concentration calibration was shown to be linear, with R equal to 0.9995 for both analytes. The limit of detection (LOD) was satisfactory and equal to 4.7 and 0.04 ng/mL for NDMA and NDEA, respectively. Precision was less than 13.4% in all cases, and the average recoveries were equal to 109.2 and 98.1% for NDMA and NDEA, respectively. The proposed procedure is relatively easy, rapid, and suitable for the determination of the two nitrosamines in routine analysis tests

Enabling Component Reuse From Existing Buildings Using Machine Learning - Using Google Street View to Enhance Building Databases

Intense urbanization has led us to rethink construction and demolition practices on a global scale. There is an opportunity to respond to the climate crisis by moving towards a circular built environment. Such a paradigm shift can be achieved by critically examining the possibility of reusing components from existing buildings. This study investigates approaches and tools needed to analyse the existing building stock and methods to enable component reuse. Ocular observations were conducted in Google Street View to analyse two building-specific characteristics: (1) façade material and (2) reusable components (window, doors, and shutters) found on building facades in two cities: Barcelona and Zurich. Not all products are equally suitable for reuse and require an evaluation metric to understand which components can be reused effectively. Consequently, tailored reuse strategies that are defined by a priority order of waste prevention are put forth. Machine learning shows promising potential to visually collect building-specific characteristics that are relevant for component reuse. The data collected is used to create classification maps that can help define protocols and for urban planning. This research can upscale limited information in countries where available data about the existing building stock is insufficient

Solid Dosage Forms of Dexamethasone Sodium Phosphate Intended for Pediatric Use: Formulation and Stability Studies

Undesirable taste has always been a key issue for oral dosage forms. The aim of the present study was to co-formulate dexamethasone sodium phosphate (DSP), in common pediatric oral forms, using sweet preserves and/or different types of chocolate as excipients. An array of different kinds of chocolate were co-formulated with DSP and were further characterized by means of dynamic light scattering (DLS), x-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transform infrared (FT-IR) spectroscopy. For the assay of active pharmaceutical ingredient (API), the chocolate samples were pre-treated by means of liquid extraction and analyzed using an high-performance liquid chromatographic (HPLC) method with a strong anion exchange column and a phosphate buffer (17 mM, pH = 3)/acetonitrile, 50:50 v/v as mobile phase. The developed chromatographic method was validated based on the International Conference on Harmonization (ICH) guidelines (%Mean Recovery = 99.4% and %Relative Standard Deviation, RSD = 0.43%). Furthermore, dissolution and in vitro digestion tests of chocolate formulations were evaluated. The DSP was found to be stable for at least 1 year in prepared preparations