Application of raman spectroscopy in pharmaceuticals

Experimental research on the use of Raman spectroscopy as an in- and on-line sensing tool and a complementary characterization technique for pharmaceutical applications is presented in this thesis. In the first chapter following a broad overview, the use of Raman spectroscopy, together with x-ray powder diffraction, scanning electron microscopy (SEM) and differential scanning calorimetry, for multilevel characterization of cryomilled powders, and the melt-grown amorphous phase of griseofulvin, a model active pharmaceutical ingredient (API), is presented and discussed in detail. A key feature was the observation of a broad inelastic background superimposed on the Raman spectra of cryomilled powders, which is attributed to lattice disorder and Mie scattering generated by mechanical processing and sub-micron particle interfaces. In the following chapter, polymorphs of another model API, acetaminophen (APAP), were studied by Raman spectroscopy with supporting information obtained from x-ray diffraction, SEM images and intrinsic dissolution profiles. An important result was the stabilization and characterization of the metastable type II orthorhombic phase of APAP which is highly desired for its unique tabletting properties which are important for pharmaceutical manufacturing. Stabilization of metastable type II APAP was achieved by micronizing or nanocoating stable monoclinic crystallites of type I APAP. In addition, as an Appendix to the thesis, micro-Raman spectroscopy of single crystal APAP as a function of crystal orientation and of temperature was measured to provide an understanding of the lattice properties of APAP for input into models to predict its behavior under mechanical milling conditions widely used in pharmaceutical processing. Molecular behavior obtained from the above studies guided simulated in-line and off-line characterization of griseofulvin as thin gel films made from micronized powders and nanosuspensions. By employing complementary near infrared and Raman imaging for newly developed films, it was possible to extract valuable information on the spatial distribution and crystallinity of the embedded particles in a polymeric matrix at different scales of scrutiny. Chemometrics processing of spectroscopic data for films and nanosuspensions allowed for qualitative and quantitative particle size determinations of the API’s in the films and nanosuspensions. In the final chapter a photonic crystal substrate for surface enhanced Raman spectroscopic (SERS) sensing was employed to detect and study griseofulvin and APAP down to 10-8 M levels with enhancement factors approaching 1099. Detection sensitivities of the aromatic griseofulvin and APAP molecules were also compared with those of less aromatic and non-aromatic energetic molecules in order to understand the Raman enhancement process

Acute Jaundice in a Six-year-old: An Unusual Presentation of Atypical Kawasaki Disease

Kawasaki disease (KD) is a rare vasculitis of childhood that is critical to recognize and treat due to associated morbidity and mortality. A six-year-old male presented to our emergency department (ED) afebrile but with reported recent fevers. Exam revealed jaundice and erythematous tongue with papules, and laboratory studies indicated a direct hyperbilirubinemia. Admitted for evaluation, he developed continuous fever, increasing maculopapular rash, and subsequent desquamation of hands and feet. He ultimately met criteria for incomplete KD, was treated with intravenous immunoglobulin, and avoided cardiac complications. This presentation of incomplete KD with hyperbilirubinemia is rare because the patient was afebrile at ED presentation

MRI Shows More Severe Hippocampal Atrophy and Shape Deformation in Hippocampal Sclerosis Than in Alzheimer's Disease

While hippocampal atrophy is a key feature of both hippocampal sclerosis (HS) and Alzheimer's disease (AD), the pathology underlying this finding differs in these two conditions. In AD, atrophy is due primarily to loss of neurons and neuronal volume as a result of neurofibrillary tangle formation. While the etiology of HS is unknown, neuron loss in the hippocampus is severe to complete. We compared hippocampal volume and deformations from premortem MRI in 43 neuropathologically diagnosed cases of HS, AD, and normal controls (NC) selected from a longitudinal study of subcortical ischemic vascular disease (IVD Program Project). HS cases (n = 11) showed loss of neurons throughout the rostral-caudal extent of the hippocampus in one or both hemispheres. AD cases (n = 24) met NIA-Reagan criteria for high likelihood of AD. Normal control cases (n = 8) were cognitively intact and showed no significant AD or hippocampal pathology. The mean hippocampal volumes were significantly lower in HS versus AD groups (P < .001). Mean shape deformations in the CA1 and subiculum differed significantly between HS versus AD, HS versus NC, and AD versus NC (P < .0001). Additional study is needed to determine whether these differences will be meaningful for clinical diagnosis of individual cases

Spacelab Life Sciences-1

This report provides an historical overview of the Spacelab Life Sciences-1 (SLS-1) mission along with the resultant biomaintenance data and investigators' findings. Only the nonhuman elements, developed by Ames Research Center (ARC) researchers, are addressed herein. The STS-40 flight of SLS-1, in June 1991, was the first spacelab flown after 'return to orbit', it was also the first spacelab mission specifically designated as a Life Sciences Spacelab. The experiments performed provided baseline data for both hardware and rodents used in succeeding missions

Sex-specific differences of adenosine triphosphate levels in red blood cells isolated from ApoE/LDLR double-deficient mice

In this study for the first time, we investigated the correlation between sex-specific differences in adenosine triphosphate (ATP) levels in red blood cells (RBCs) and their mechanical, biochemical, and morphological alterations during the progression of atherosclerosis in ApoE/LDLR double-deficient ($ApoE/LDLR^{-/-}$) mice. Our results indicate that both sex and age affect alterations in RBCs of both $ApoE/LDLR^{-/-}$ and C57BL/6J mice. When compared with male RBCs, female RBCs were characterized by lower basal ATP and mean corpuscular hemoglobin concentration (MCHC), higher hemoglobin concentration (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), deformability, and phosphatidylserine (PS) exposure levels, regardless of age in both, $ApoE/LDLR^{-/-}$ and C57BL/6J mice. $ApoE/LDLR^{-/-}$ mice compared with age-matched controls showed lower basal ATP levels regardless of age and sex. Intracellular ATP level of RBCs was decreased solely in senescent female C57BL/6J mice, while it was elevated in males. Basal extracellular ATP levels were 400 times lower than corresponding intracellular level. In conclusion, basal ATP levels, RBC morphology, deformability, PS exposure levels alterations are sex-dependent in mice. Changes in basal ATP levels were correlated with PS exposure and trends of changes in MCV. Trends of changes of the most RBC parameters were similar in both sexes of $ApoE/LDLR^{-/-}$ mice compared with age-matched controls, however, their kinetics and levels vary greatly between different stages of disease progression

Residual Adhesive Removal Methods for Rebonding of Debonded Orthodontic Metal Brackets: Systematic Review and Meta-Analysis

Debonding of orthodontic brackets is a common occurrence during orthodontic treatment. Therefore, the best option for treating debonded brackets should be indicated. This study aimed to evaluate the bond strength of rebonded brackets after different residual adhesive removal methods. This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Web of Science, The Cochrane Library, SciELO, Scopus, LILACS, IBECS, and BVS databases were screened up to December 2020. Bond strength comparisons were made considering the method used for removing the residual adhesive on the bracket base. A total of 12 studies were included for the meta-analysis. Four different adhesive removal methods were identified: sandblasting, laser, mechanical grinding, and direct flame. When compared with new orthodontic metallic brackets, bond strength of debonded brackets after air abrasion (p = 0.006), mechanical grinding (p = 0.007), and direct flame (p < 0.001) was significantly lower. The use of an erbium-doped yttrium aluminum garnet (Er:YAG) laser showed similar shear bond strength (SBS) values when compared with those of new orthodontic brackets (p = 0.71). The Er:YAG laser could be considered an optimal method for promoting the bond of debonded orthodontic brackets. Direct flame, mechanical grinding, or sandblasting are also suitable, obtaining clinically acceptable bond strength values

Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP)