Synthesis, microstructural and optical characterizations of sol-gel grown gadolinium doped cerium oxide ceramics.

In this study, through the utilization of the sol-gel combustion tactic, gadolinium (Gd)-doped cerium oxide (CeO2), Ce1-xGdxO2 (x = 0.00, 0.10, 0.20 and 0.30 (GDC)) ceramics were attained. The synthesized GDC ceramics were investigated using X-ray diffraction (XRD) to scrutinize their crystal structures and phase clarities. The obtained GDC ceramics have a single-phase cubic structure and belong to the crystallographic space group fm3̄m (225). The measurement of the diffraction angle of each reflection and the subsequent smearing of the renowned Bragg's relation provided coarse d-interplanar spacings. The stacking fault (SF) values of pure and Gd-doped CeO2 ceramics were assessed. To muse the degree of preferred orientation (σ) of crystallites along a crystal plane (h k l), the texture coefficient (Ci) of each XRD peak of GDC ceramics is gauged. By determining the interplanar distance (dh k l), the Bravais theory sheds light on the material's development. By exploiting Miller indices for the prime (1 1 1) plane, the lattice constants of GDC ceramics and cell volumes were obtained. Multiple techniques were employed to ascertain the microstructural parameters of GDC ceramics. A pyrometer substantiated the density of GDC ceramics. The room temperature (RT) Fourier transform infrared (FTIR) spectra of both un-doped and Gd-doped CeO2 were obtained. The UV-vis-NIR spectrometer recorded the GDC ceramics' reflectance (R) spectra at RT. For both undoped and Gd-doped CeO2, the absorption coefficient (α) spectra showed two distinct peaks. The R-dependent refractive index (η) and the α-dependent extinction coefficient (k) were determined for all GDC samples. The optical band gap (Eg) was obtained by integrating the Tauc and Kubelka-Munk approaches for GDC ceramics. For each GDC sample, the imaginary (εi) and real (εr) dielectric constants, as well as the dissipation factor (tan δ), were determined local to the characteristic wavelength (λc). Calculations were made for the Urbach energy (EU) and Urbach absorption coefficient (α0) for GDC ceramics. The minimum and maximum values of optical (σo) and electrical (σe) conductivity for GDC ceramics were determined. The volume (VELF) and surface (SELF) energy loss functions, which depend on the constants εi and εr, were used to measure electrons' energy loss rates as they travel across the surface. Raman spectroscopy revealed various vibrational modes in GDC ceramics. Finally, the implications are discussed herein.

Contemporary management of keratosis obturans: a systematic review.

OBJECTIVE: This study aimed to examine the medical literature regarding the natural history and management of keratosis obturans. METHOD: PubMed was queried via the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol, and the methodological quality of each study was assessed using the Methodological Index for Non-Randomized Studies criteria. RESULTS: Fifty-one studies were abstracted, and dual investigator screening resulted in five retrospective studies for final analysis. All studies included patients afflicted with either unilateral (n = 75) or bilateral keratosis obturans (n = 8). The definition of keratosis obturans was present in three studies: a desquamated keratin plug within the external auditory canal. Mean and median Methodological Index for Non-Randomized Studies scores were 9.5 and 9.5, respectively. All patients underwent keratosis obturans exenteration with microscopy. Two studies reported an outcome instrument to evaluate endpoints: marked stillette and audiometry. No complications were observed with follow-up periods from 3 weeks to 3.5 years. CONCLUSION: This comprehensive review highlights a lack of published evidence relating to keratosis obturans. However, it appears keratosis obturans treatment is safe and efficacious with identifiable clinical practice patterns.

Otologic manifestations of Susac syndrome.

Susac syndrome, a rare autoimmune disorder first described as a classic triad (encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss) in 1979 by renowned physician John O. Susac, has been an advancing area of clinical interest and scientific research over the last several decades. This comprehensive review aims to succinctly highlight the breadth and detail of this enigmatic disease, with a primary focus on otologic manifestations. Topics discussed include epidemiology, pathophysiology, clinical manifestations, differential diagnoses, classification schema, laboratory investigations, characteristic audiometric findings, high-yield radiographic imaging, temporal bone histopathology, treatment strategies and overall prognosis.

Magnetic resonance imaging findings in Ménière's disease.

OBJECTIVES: To identify and evaluate cranial magnetic resonance imaging findings associated with Ménière's disease. METHODS: Seventy-eight patients with a documented diagnosis of Ménière's disease and 35 controls underwent 1.5 T or 3 T magnetic resonance imaging of the brain. Patients also underwent otological, vestibular and audiometric examinations. RESULTS: Lack of visualisation of the left and right vestibular aqueducts was identified as statistically significant amongst Ménière's disease patients (left, p = 0.0001, odds ratio = 0.02; right, p = 0.0004, odds ratio = 0.03). Both vestibular aqueducts were of abnormal size in the Ménière's disease group, albeit with left-sided significance (left, p = 0.008, odds ratio = 10.91; right, p = 0.49, odds ratio = 2.47). CONCLUSION: Lack of vestibular aqueduct visualisation on magnetic resonance imaging was statistically significant in Ménière's disease patients compared to the general population. The study findings suggest that magnetic resonance imaging can be useful to rule out retrocochlear pathology and provide radiological data to support the clinical diagnosis of Ménière's disease.

The aetiopathologies of Ménière's disease: a contemporary review.

Ménière's disease, a condition first described in the 1800's, has been an advancing area of clinical interest and scientific research in recent decades. Guidelines published by the American Academy of Otolaryngology - Head and Neck Surgery remained nearly static for almost 20 years, although we have certainly expanded our knowledge of the aetiology of the disease since that time. This review of the literature highlights the breadth and detail of the current theories in understanding the pathophysiology of this enigmatic disease. Histopathological specimens providing evidence of many of the aetiologies are presented as well. We aim to provide a centralised and updated resource regarding current and emerging theories for Ménière's disease.

Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride.

In situ gels are systems which are applied as solutions or suspensions and are capable of undergoing rapid sol-to-gel transformation triggered by external stimulus such as temperature, pH etc. on instillation. The aim of the present study was to formulate and evaluate pH responsive in-situ gel for ophthalmic delivery. Ciprofloxacin hydrochloride is popularly used as a broad spectrum antibiotic in the treatment of corneal ulcers of ocular infections. However, rapid dilution on instillation, wash out, poor retention of drug concentration delimit the therapeutic benefits of the drug when used in form of conventional eye drops. Sodium alginate, an ophthalmic gel forming mucoadhesive polymer was chosen as polymer which undergoes instantaneous gel formation due to formation of calcium alginate by virtue of its interaction with divalent cation (Ca(+2)) present in lachrymal fluid. Hydroxy Propyl Methyl Cellulose (HPMC K4M and E5 0LV) was further incorporated as a viscosity enhancer in order to achieve the desired consistency so as to facilitate sustained drug release. The developed formulations were evaluated for clarity, pH measurement, gelling capacity, drug content, rheological study, and in vitro drug release. Thus, in situ gel based systems containing gums can be a valuable approach for ophthalmic drug delivery when compared to conventional systems.

Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate.

Tamoxifen Citrate (TC) is an estrogen receptor antagonist and drug of choice for hormone sensitive breast cancer. Solid Lipid Nanoparticles loaded with TC were prepared by High Shear Homogenization followed by Ultrasonication. The aim of the present work is to study the effect of four different Solid Lipids and three Surfactants on Formulation and Stability of SLN. They were characterized for Particle size, Polydispersity Index and Zeta Potential by Zetasizer Nano. SLN prepared by Solid Lipid Compritol 888 (Glyceryldibehenate) and Tween 80 (1%) showed desired Particle Size of 206.9 nm, PDI of 0.046 and Zeta Potential of 9.32 mV.

Defect in insulin-like growth factor-1 survival mechanism in atherosclerotic plaque-derived vascular smooth muscle cells is mediated by reduced surface binding and signaling.

Apoptosis of vascular smooth muscle cells (VSMCs) is increased in atherosclerosis compared with normal vessels, where it may contribute to plaque rupture. We have previously found that human plaque-derived VSMCs (pVSMCs) are intrinsically sensitive to apoptosis and not responsive to the protective effects of insulin-like growth factor-1 (IGF-1). We therefore examined the mechanism underlying this defect. Human pVSMCs showed <25% (125)I-IGF-1 surface binding, <20% IGF-1 receptor (IGF-1R) expression than that of normal medial VSMCs, and <40% Akt kinase activity in response to IGF-1. pVSMCs expressed and secreted high levels of IGF-1 binding proteins (IGFBPs), and the IGF-1 analogues, long R3 and Des 1,3 IGF-1, which do not bind to IGFBPs, were able to increase pVSMC survival to normal medial VSMC levels. The long R3 survival effect was phosphatidylinositol 3-kinase-mediated, but it was not dependent on Akt activity alone. Intimal pVSMCs in vivo showed reduced IGF-1R expression compared with medial VSMCs, in particular at the shoulder regions of plaques. We conclude that human pVSMCs show an intrinsic sensitivity to apoptosis caused in part by defective expression of IGF-1R, impaired IGF-1-mediated survival signaling and increased IGFBP secretion. This impaired IGF-1 protection against apoptosis may promote VSMC loss and plaque instability in atherosclerosis.

Apoptosis during goitre involution - the role of Bcl-2.

Goitrogenesis is accompanied by hyperplasia and hypertrophy and involves tissue remodelling and angiogenesis. During the involution of the goitre there must be removal of this increased thyroid volume, in addition to further remodelling, which may involve apoptosis. We investigated apoptosis in the involuting rat thyroid using male Fisher rats that were on a goitrogenic regimen for 14 days and then returned to a normal diet. Thyroid weights increased fourfold with the goitrogenic regimen. During involution, the largest decrease in weight was between day 2 and day 4 after withdrawal of treatment. After 34 days of involution, the thyroid weight plateaued, but had not returned to control values. High levels of Bcl-2 immunoreactivity were observed in normal and goitrous rat thyroids. These high levels were significantly reduced at 2 days of involution, after which high levels of Bcl-2 immunoreactivity returned. In situ end-labelling of apoptotic cells showed that there was an increase in the number of cells undergoing DNA fragmentation during goitrogenesis (1.0+/-0.8 cells/100 cells, n=9) compared with controls, in which no positive staining was observed. After 2 days of goitrogen withdrawal, there was a further fourfold increase in the number of in situ end-labelled cells (day 16: 4.1+/-1.7, n=9). Numbers of positive cells returned to low levels after 4 days of involution (day 18: 0.3+/-0.8, n=9). Using antiserum to apoptosis-specific protein, we found increased immunoreactivity during goitrogenesis and after 2 days of involution that was localised predominantly with the stromal and vascular tissue at both time points. The data show that rapid downregulation of Bcl-2 accompanies thyroid involution, which involves increased levels of apoptosis within the stromal compartment.

Changes in the immunohistochemical localisation of fibroblast growth factor-2, transforming growth factor-beta 1 and thrombospondin-1 are associated with early angiogenic events in the hyperplastic rat thyroid.

Administration of a goitrogen (methimazole) and a low iodine diet to rats over a two-week period resulted in hypothyroidism and thyroid hyperplasia compared with controls (control: total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight; experimental: T4 undetectable, thyroid weight 27 +/- 4 mg/100 g body weight after 2 weeks of treatment; mean +/- S.D., n = 10). Immunohistochemistry carried out using a specific endothelial cell marker, CD31, and morphometric analysis (point counting of immunopositive cells) revealed that the progression of goitre in the rat thyroid is accompanied by an increase in capillary endothelial cell growth (neovascularisation). Fibroblast growth factor-2 (FGF-2) immunohistochemistry revealed widespread staining for the protein in the follicular cells of control glands. Less intense staining was found in the stroma and follicular cell nuclei. During hyperplasia and subsequent neovascularisation there was a progressive increase in the FGF-2 immunoreactivity at all locations during the two-week treatment period. Thrombospondin-1 (TSP1) immunoreactivity in the control rat thyroid was found in the stroma and in the endothelial cells, while weak follicular cell staining was also present. In the goitrous rat thyroid the TSP immunoreactivity was present after 1 week of treatment in the endothelial cells and most follicular cells, whilst stroma localisation was weak. After week 2 of treatment the endothelial cell and stromal localisation was no longer apparent, although a follicular localisation was still present. Transforming growth factor-beta 1 (TGF beta 1) immunoreactivity was present in the cytoplasm of a minority of the follicular cells in control rat thyroids, while their nuclei were unstained. In the goitrous rat thyroid an increase intensity of staining for TGF beta 1 was seen in all follicular cells, many of which now also demonstrated immuno-positive nuclei, within one week of goitrogen administration. These results show that in the hyperplastic thyroid increases in FGF-2 and TGF beta 1, and decreases in TSP1 accompany angiogenesis. These factors may interact in an autocrine/paracrine relationship to stimulate the neovascularisation that occurs during goitre formation.

Acute and chronic ethanol treatment on beta-endorphin and catecholamine levels.

The effect of acute (2.0 g/kg, intragastrically) and chronic (8.0-11.0 g/kg/day for 10 days, intragastrically) ethanol exposure on beta-endorphin levels in plasma, hypothalamus and pituitary were examined in rats. Hypothalamic and plasma catecholamines and plasma corticosterone were also measured in these animals. Plasma beta-endorphin, norepinephrine (NE) and corticosterone levels were significantly increased and dopamine (DA) was unchanged in acute and chronic ethanol-treated rats. Compared to controls, plasma epinephrine (E) levels were increased in acute ethanol-treated rats but no significant change was observed in chronic ethanol-treated rats. Plasma dopamine were significantly decreased following chronic ethanol treatment while no significant change was observed after acute treatment. In the hypothalamus, beta-endorphin and dopamine contents were increased and norepinephrine levels were reduced in response to ethanol exposure. Beta-endorphin levels were decreased significantly in the anterior pituitary and the neurointermediate lobe of the pituitary in ethanol-treated animals except in the neurointermediate lobe of the chronic ethanol-treated animals. These findings together suggest that there is an interaction between beta-endorphin, catecholamines, corticosterone and ethanol in response to acute and chronic ethanol exposure in rats.

Effects of ethanol on plasma corticosterone and rectal temperature modification by U50488H and WIN 44441-3.

Endogenous opiates are believed to subserve various behaviors and physiological functions. We have examined the effect of U50488H (0-12 mg/kg), a kappa agonist, and WIN 44441-3 (0-4.0 mg/kg), a kappa antagonist, on ethanol (ET)-induced changes in rectal temperature and in plasma corticosterone (CS) levels in rats. The 12 mg/kg dose of U50488H produced marked hypothermia, the other doses either produced hyperthermia comparable to that seen in control animals, or had no effect. The 0.5 mg/kg of WIN44441-3 had a small hypothermic effect while the 4.0 mg/kg produced hyperthermia. U50488H potentiated and the low dose of WIN 44441-3 reversed the hypothermic effect of ethanol. By contrast, neither WIN 44441-3 nor U50488H pretreatments affected the ethanol-induced elevation in plasma CS. These results indicate that kappa agonists increase plasma CS concentration and affect thermoregulatory mechanisms. Furthermore, our data indicate a possible role of endogenous kappa opioids in the hypothermic effect of ethanol, but not in the elevation of plasma CS.

Interaction of stress and ethanol: effect on beta-endorphin and catecholamines.

To examine the interaction of ethanol (ET) and stress on beta-endorphin and catecholamine (CA) levels, male rats pretreated with ET (3.0 g/kg, i.p.) or saline were immobilized for 30 min and killed 90 min after the initial injection. Stress resulted in (a) an increase in plasma levels of norepinephrine (NE, 243%), epinephrine (E, 175%), beta-endorphin (220%) and corticosterone (CS, 151%) and a decrease in dopamine (DA, 54%); (b) a decrease in hypothalamic NE (15%) and beta-endorphin (33%) levels and an increase E (23%) and DA (58%) levels; (c) a decrease in pituitary beta-endorphin levels in both the neurointermediate (23%) and anterior (131%) lobes. Treatment with ET resulted in: (a) an increase in plasma NE (81%), E (53%), CS (71%), and beta-endorphin (33%) levels and decrease in DA (54%); (b) a decrease in the hypothalamic NE (12%) levels and an increase DA (27%) and beta-endorphin (46%) levels, and (c) a decrease in beta-endorphin (15.5%) in the intermediate lobe of the pituitary. Treatment with ET of stressed animals had only a small effect: (a) in plasma NE, E, CS, and beta-endorphin levels decreased by 30, 31, 14, and 36%, respectively; (b) in the hypothalamus DA levels decreased by 40% and beta-endorphin increased by 71%; (c) in the pituitary beta-endorphin increased in both the intermediate lobe (25%) and anterior (50%) lobes. Thus when the data of the stressed ET-treated group is compared to that of the nonstressed saline injected group, none of the measures differ significantly. These results confirm our earlier work indicating a significant interaction of ET and stress.

Linkage analysis in von Willebrand disease.

We studied a 3-generation kindred to determine whether the gene responsible for one form of von Willebrand disease (vWD) is linked to 1) the HLA locus, or 2) a polymorphic locus for a serum enzyme or red cell antigen. HLA haplotypes were determined in 12 affected family members, in 10 cases by direct analysis and in 2 cases by deduction. Seven of 12 affected individuals were A2, B7, as compared to 0 of 9 unaffected. However, the maximum lod score was only 0.41 at a recombination frequency of 0.2. Of the 17 serum red cell and plasma protein markers studied, 5 (Kell, ADA, AK1, BF, GC) did not segregate, and 12 (ABO, Rh, JK, Fy, P, PGM1, ACP1, ESD, GLO1, MN, HP, GPT) gave lod scores less than + 1.0. We conclude that there is no strong evidence for linkage between the locus for vWD and any of the markers studied.

Hypermodal cells in amniotic fluid cultures: frequency, interpretation, and clinical significance.

Specimens of amniotic fluid were studied to assess the frequency of hypermodal cells and their significance. Multiple cultures were initiated on each specimen, and thorough cytogenetic analysis was performed routinely. Of 1,000 specimens, 59 (5.9%) contained a total of 64 hypermodal cells. However, true fetal mosaicism was not detected. An additional structurally abnormal chromosome accounted for 32 of the 64 hypermodal cells, and, in each case, cytogenetic analysis offered an explanation that obviated clinical concern. In 17 of the 32 cases, hypermodality was only apparent, the result of a single chromosome broken into two parts to produce a spuriously elevated count; in the other 15 cases, the extra chromosome was an unidentified fragment. In the 32 other hypermodal cells, an additional morphologically normal chromosome was present; however, in each case, failure to detect similar aberrations in other cultures initiated from the same specimen minimized the possibility that such cells reflected true fetal mosaicism. Indeed, clinical outcome was normal in all cases. Thus, for clinical purposes, routine banding techniques and analysis of multiple cultures seem to be adequate to exclude fetal mosaicism; laborious in situ methodology seems to be unnecessary. Future cytogenetic efforts should emphasize processing of more specimens of amniotic fluid, rather than more detailed analysis of individual specimens.

Localization of the nucleolar organizer by computer-aided analysis of a variant no. 21 in a human isolate.

A variant chromosome no. 21 consisting of two stalks and two satellites in tandem was detected during a survey of a human isolate. The variant segregated in three generations of a large kindred. One male had the variant no. 21, a metacentric Y, and a 47,XXY complement; however, no other evidence of chromosomal nondisjunction was found. Computer-aided analysis of sequentially stained variant no. 21 chromosomes indicated that silver-stained material corresponded to the proximal stalk region (as defined by Giemsa), but often covered both the distal stalk and satellite (also as defined by Giemsa). These data support the hypothesis that human nucleolar organizers are localized to the stalks of acrocentric chromosomes.