Budjetti v. 1941, 14 A Pl Yk

Puhe

Budjetti, 18 Pl

Puhe

Use of NIR spectroscopy and multivariate process spectra calibration methodology for pharmaceutical solid samples analysis

Accomplish high quality of final products in pharmaceutical industry is a challenge that requires the control and supervision of all the manufacturing steps. This request created the necessity of developing fast and accurate analytical methods. Near infrared spectroscopy together with chemometrics, fulfill this growing demand. The high speed providing relevant information and the versatility of its application to different types of samples lead these combined techniques as one of the most appropriated. This study is focused on the development of a calibration model able to determine amounts of API from industrial granulates using NIR, chemometrics and process spectra methodology.

Profiling of counterfeit medicines by vibrational spectroscopy

Counterfeit pharmaceutical products have become a widespread problem in the last decade. Various analytical techniques have been applied to discriminate between genuine and counterfeit products. Among these, Near-infrared (NIR) and Raman spectroscopy provided promising results.The present study offers a methodology allowing to provide more valuable information fororganisations engaged in the fight against counterfeiting of medicines.A database was established by analyzing counterfeits of a particular pharmaceutical product using Near-infrared (NIR) and Raman spectroscopy. Unsupervised chemometric techniques (i.e. principal component analysis - PCA and hierarchical cluster analysis - HCA) were implemented to identify the classes within the datasets. Gas Chromatography coupled to Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used to determine the number of different chemical profiles within the counterfeits. A comparison with the classes established by NIR and Raman spectroscopy allowed to evaluate the discriminating power provided by these techniques. Supervised classifiers (i.e. k-Nearest Neighbors, Partial Least Squares Discriminant Analysis, Probabilistic Neural Networks and Counterpropagation Artificial Neural Networks) were applied on the acquired NIR and Raman spectra and the results were compared to the ones provided by the unsupervised classifiers.The retained strategy for routine applications, founded on the classes identified by NIR and Raman spectroscopy, uses a classification algorithm based on distance measures and Receiver Operating Characteristics (ROC) curves. The model is able to compare the spectrum of a new counterfeit with that of previously analyzed products and to determine if a new specimen belongs to one of the existing classes, consequently allowing to establish a link with other counterfeits of the database.

A double-quadrature radiofrequency coil design for proton-decoupled carbon-13 magnetic resonance spectroscopy in humans at 7T

Purpose Carbon-13 magnetic resonance spectroscopy (13C-MRS) is challenging because of the inherent low sensitivity of 13C detection and the need for radiofrequency transmission at the 1H frequency while receiving the 13C signal, the latter requiring electrical decoupling of the 13C and 1H radiofrequency channels. In this study, we added traps to the 13C coil to construct a quadrature-13C/quadrature-1H surface coil, with sufficient isolation between channels to allow simultaneous operation at both frequencies without compromise in coil performance. Methods Isolation between channels was evaluated on the bench by measuring all coupling parameters. The quadrature mode of the quadrature-13C coil was assessed using in vitro 23Na gradient echo images. The signal-to-noise ratio (SNR) was measured on the glycogen and glucose resonances by 13C-MRS in vitro, compared with that obtained with a linear-13C/quadrature-1H coil, and validated by 13C-MRS in vivo in the human calf at 7T. Results Isolation between channels was better than â^'30 dB. The 23Na gradient echo images indicate a region where the field is strongly circularly polarized. The quadrature coil provided an SNR enhancement over a linear coil of 1.4, in vitro and in vivo. Conclusion It is feasible to construct a double-quadrature 13C-1H surface coil for proton decoupled sensitivity enhanced 13C-NMR spectroscopy in humans at 7T. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Deep thiopental anesthesia alters steady-state glucose homeostasis but not the neurochemical profile of rat cortex.

Barbiturates are regularly used as an anesthetic for animal experimentation and clinical procedures and are frequently provided with solubilizing compounds, such as ethanol and propylene glycol, which have been reported to affect brain function and, in the case of (1)H NMR experiments, originate undesired resonances in spectra affecting the quantification. As an alternative, thiopental can be administrated without any solubilizing agents. The aim of the study was to investigate the effect of deep thiopental anesthesia on the neurochemical profile consisting of 19 metabolites and on glucose transport kinetics in vivo in rat cortex compared with alpha-chloralose using localized (1)H NMR spectroscopy. Thiopental was devoid of effects on the neurochemical profile, except for the elevated glucose at a given plasma glucose level resulting from thiopental-induced depression of glucose consumption at isoelectrical condition. Over the entire range of plasma glucose levels, steady-state glucose concentrations were increased on average by 48% +/- 8%, implying that an effect of deep thiopental anesthesia on the transport rate relative to cerebral glucose consumption ratio was increased by 47% +/- 8% compared with light alpha-chloralose-anesthetized rats. We conclude that the thiopental-induced isoelectrical condition in rat cortex significantly affected glucose contents by depressing brain metabolism, which remained substantial at isoelectricity.

Chemical characterization and infrared spectroscopy of soil organic matter from two southern brazilian soils

Soil organic matter from the surface horizon of two Brazilian soils (a Latosol and a Chernosol), in bulk samples (in situ SOM) and in HF-treated samples (SOM), was characterized by elemental analyses, diffuse reflectance (DRIFT) and transmission Fourier transform infrared spectroscopy (T-FTIR). Humic acids (HA), fulvic acids (FA) and humin (HU) isolated from the SOM were characterized additionally by ultraviolet-visible spectroscopy (UV-VIS). After sample oxidation and alkaline treatment, the DRIFT technique proved to be more informative for the detection of "in situ SOM" and of residual organic matter than T-FTIR. The higher hydrophobicity index (HI) and H/C ratio obtained in the Chernosol samples indicate a stronger aliphatic character of the organic matter in this soil than the Latosol. In the latter, a pronounced HI decrease was observed after the removal of humic substances (HS). The weaker aliphatic character, the higher O/C ratio, and the T-FTIR spectrum obtained for the HU fraction in the Latosol suggest the occurrence of surface coordination of carboxylate ions. The Chernosol HU fraction was also oxygenated to a relatively high extent, but presented a stronger hydrophobic character in comparison with the Latosol HU. These differences in the chemical and functional group composition suggest a higher organic matter protection in the Latosol. After the HF treatment, decreases in the FA proportion and the A350/A550 ratio were observed. A possible loss of FA and condensation of organic molecules due to the highly acid medium should not be neglected.

Multi-modal assessment of long-term erythropoietin treatment after neonatal hypoxic-ischemic injury in rat brain.

Erythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury. Timing, dose and length of treatment in preterm brain damage remain to be defined. We have evaluated the effects of high dose and long-term EPO treatment in hypoxic-ischemic (HI) injury in 3 days old (P3) rat pups using histopathology, magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as functional assessment with somatosensory-evoked potentials (SEP). After HI, rat pups were assessed by MRI for initial damage and were randomized to receive EPO or vehicle. At the end of treatment period (P25) the size of resulting cortical damage and white matter (WM) microstructure integrity were assessed by MRI and cortical metabolism by MRS. Whisker elicited SEP were recorded to evaluate somatosensory function. Brains were collected for neuropathological assessment. The EPO treated animals did not show significant decrease of the HI induced cortical loss at P25. WM microstructure measured by diffusion tensor imaging was improved and SEP response in the injured cortex was recovered in the EPO treated animals compared to vehicle treated animals. In addition, the metabolic profile was less altered in the EPO group. Long-term treatment with high dose EPO after HI injury in the very immature rat brain induced recovery of WM microstructure and connectivity as well as somatosensory cortical function despite no effects on volume of cortical damage. This indicates that long-term high-dose EPO induces recovery of structural and functional connectivity despite persisting gross anatomical cortical alteration resulting from HI.

Diffusion-weighted spectroscopy: a novel approach to determine macromolecule resonances in short-echo time 1H-MRS.

Quantification of short-echo time proton magnetic resonance spectroscopy results in >18 metabolite concentrations (neurochemical profile). Their quantification accuracy depends on the assessment of the contribution of macromolecule (MM) resonances, previously experimentally achieved by exploiting the several fold difference in T(1). To minimize effects of heterogeneities in metabolites T(1), the aim of the study was to assess MM signal contributions by combining inversion recovery (IR) and diffusion-weighted proton spectroscopy at high-magnetic field (14.1 T) and short echo time (= 8 msec) in the rat brain. IR combined with diffusion weighting experiments (with δ/Δ = 1.5/200 msec and b-value = 11.8 msec/μm(2)) showed that the metabolite nulled spectrum (inversion time = 740 msec) was affected by residuals attributed to creatine, inositol, taurine, choline, N-acetylaspartate as well as glutamine and glutamate. While the metabolite residuals were significantly attenuated by 50%, the MM signals were almost not affected (< 8%). The combination of metabolite-nulled IR spectra with diffusion weighting allows a specific characterization of MM resonances with minimal metabolite signal contributions and is expected to lead to a more precise quantification of the neurochemical profile.

PPARγ Agonist-Induced Fluid Retention Depends on αENaC Expression in Connecting Tubules.

BACKGROUND/AIMS: Thiazolidinediones (TZDs, like rosiglitazone (RGZ)) are peroxisome proliferator-activated receptor γ (PPARγ) agonists used to treat type 2 diabetes. Clinical limitations include TZD-induced fluid retention and body weight (BW) increase, which are inhibited by amiloride, an epithelial-sodium channel (ENaC) blocker. RGZ-induced fluid retention is maintained in mice with αENaC knockdown in the collecting duct (CD). Since ENaC in the connecting tubule (CNT) rather than in CD appears to be critical for normal NaCl retention, we aimed to further explore the role of ENaC in CNT in RGZ-induced fluid retention. METHODS: Mice with conditional inactivation of αENaC in both CNT and CD were used (αENaC lox/lox AQP2-Cre; 'αENaC-CNT/CD-KO') and compared with littermate controls (αENaC lox/lox mice; 'WT'). BW was monitored and total body water (TBW) and extracellular fluid volume (ECF) were determined by bioelectrical impedance spectroscopy (BIS) before and after RGZ (320 mg/kg diet for 10 days). RESULTS: On regular NaCl diet, αENaC-CNT/CD-KO had normal BW, TBW, ECF, hematocrit, and plasma Na(+), K(+), and creatinine, associated with an increase in plasma aldosterone compared with WT. Challenging αENaC-CNT/CD-KO with a low NaCl diet unmasked impaired NaCl and K homeostasis, consistent with effective knockdown of αENaC. In WT, RGZ increased BW (+6.1%), TBW (+8.4%) and ECF (+10%), consistent with fluid retention. These changes were significantly attenuated in αENaC-CNT/CD-KO (+3.4, 1.3, and 4.3%). CONCLUSION: Together with the previous studies, the current results are consistent with a role of αENaC in CNT in RGZ-induced fluid retention, which dovetails with the physiological relevance of ENaC in this segment. © 2014 S. Karger AG, Basel.

1H-[13C] NMR spectroscopy of the rat brain during infusion of [2-13C] acetate at 14.1 T.

Full signal intensity (1)H-[(13)C] NMR spectroscopy, combining a preceding (13)C-editing block based on an inversion BISEP (B(1)-insensitive spectral editing pulse) with a spin-echo coherence-based localization, was developed and implemented at 14.1 T. (13)C editing of the proposed scheme was achieved by turning on and off the (13)C adiabatic full passage in the (13)C-editing block to prepare inverted and noninverted (13)C-coupled (1)H coherences along the longitudinal axis prior to localization. The novel (1)H-[(13)C] NMR approach was applied in vivo under infusion of the glia-specific substrate [2-(13)C] acetate. Besides a approximately 50% improvement in sensitivity, spectral dispersion was enhanced at 14.1 T, especially for J-coupled metabolites such as glutamate and glutamine. A more distinct spectral structure at 1.9-2.2 ppm(parts per million) was observed, e.g., glutamate C3 showed a doublet pattern in both simulated (1)H spectrum and in vivo (13)C-edited (1)H NMR spectra. Besides (13)C time courses of glutamate C4 and glutamine C4, the time courses of glutamate C3 and glutamine C3 obtained by (1)H-[(13)C] NMR spectroscopy were reported for the first time. Such capability should greatly improve the ability to study neuron-glial metabolism using (1)H-observed (13)C-edited NMR spectroscopy.