Simultaneous determination of lidocaine hydrochloride, hydrocortisone and nystatin in a pharmaceutical preparation by RP-LC

A liquid chromatographic (LC) method was developed to analyze a formulation (mouthwash) containing lidocaine hydrochloride, hydrocortisone and nystatin. A single LC method with UV detection was developed. A Waters Symmetry C18 HPLC column (150 mm ×  4.6 mm, 5 μm) was used as stationary phase and the assay was performed with gradient elution using mobile phases containing methanol - 0.1 M NaH₂PO₄ with a pH that was previously adjusted to 4.5 with dilute phosphoric acid. The sample pretreatment was performed by treating the formulation with methanol followed by filtration. After method development, the influence of the different chromatographic parameters on the separation, the interference of other active compounds and excipients, linearity, accuracy, repeatability and intermediate precision were investigated. The method was shown to be selective, linear, accurate, precise and repeatable. Finally, the content of the compounds in the formulation was determined.     

Intracellular hypoxia of tumor tissue estimated by noninvasive electron paramagnetic resonance oximetry technique using paramagnetic probes

Electron paramagnetic resonance (EPR) oximetry at 700 MHz operating frequency employing a surface coil resonator is used to assess tissue partial pressure of oxygen (pO(2)) using paramagnetic media whose linewidth and decay constant are related to oxygen concentration. Differences in extracellular and intracellular pO(2) in squamous cell carcinoma (SCC) tumor tissue were tested using several types of water-soluble paramagnetic media, which localize extracellularly or permeate through the cell membrane. The nitroxide carboxy-PROXYL (CxP) can only be distributed in blood plasma and extracellular fluids whereas the nitroxides carbamoyl-PROXYL (CmP) and TEMPOL (TPL) can permeate cell membranes and localize intracellularly. EPR signal decay constant and the linewidth of the intravenously administered nitroxides in SCC tumor tissues implanted in mouse thigh and the contralateral normal muscle of healthy mice breathing gases with different pO(2) were compared. The pO(2) in the blood can depend on the oxygen content in the breathing gas while tissue pO(2) was not directly influenced by pO(2) in the breathing gas. The decay constants of CmP and TPL in tumor tissue were significantly larger than in the normal muscles, and lower linewidths of CmP and TPL in tumor tissue was observed. The SCC tumor showed intracellular hypoxia even though the extracellular pO(2) is similar to normal tissue in the peripheral region.     

Demethylation-linked activation of urokinase plasminogen activator is involved in progression of prostate cancer

Increased expression of urokinase plasminogen activator (uPA) has been reported in various malignancies including prostate cancer. However, the mechanism by which uPA is abnormally expressed in prostate cancer remains elusive. Here, we show that uPA is aberrantly expressed in a high percentage of human prostate cancer tissues but rarely expressed either in tumor-matched nonneoplastic adjacent tissues or benign prostatic hyperplasia samples. This aberrant expression is associated with cancer-linked demethylation of the uPA promoter. Furthermore, treatment with demethylation inhibitor S-adenosylmethionine or stable expression of uPA short hairpin RNA significantly inhibits uPA expression and tumor cell invasion in vitro and tumor growth and incidence of lung metastasis in vivo. Collectively, these findings strongly suggest that DNA demethylation is a common mechanism underlying the abnormal expression of uPA and is a critical contributing factor to the malignant progression of human prostate tumors.     

Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis

PURPOSE: To investigate the relationship between immune cell secretion of brain-derived neurotrophic factor (BDNF) with clinical and MRI variables in multiple sclerosis (MS) patients. BACKGROUND: BDNF exerts beneficial effects on neuronal growth and repair and is secreted by both neurons and immune cells. Consequently, it may mediate the crosstalk between the immune system and CNS in autoimmune diseases such as MS. METHODS: Fifty-two relapsing MS patients (41 females, age: 48.8+/-6.6 years, disease duration: 12.7+/-8.4 years) were enrolled. Clinical and MRI measurements (including, T1-, T2- and contrast-enhancing (CE) lesion volumes (LVs); normalized measures of whole brain, white matter (WM) and gray matter (GM) volumes; diffusion weighted imaging measure of mean whole brain (WB) parenchyma diffusivity and magnetization transfer ratio (MTR) measures were obtained. RESULTS: Immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation was positively associated with increased CE-LV (p=0.026). The MTR of CE-LV and normal-appearing (NA) WM (NAWM) were negatively associated with immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation. Immune cell BDNF secretion after anti-CD3 plus anti-CD28 was positively associated with higher WM volume (p=0.027). Immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation was decreased with increasing disease duration (p=0.031). The BDNF secretion was independent of the BDNF Val66Met (dBSNP ID: rs6265) SNP genotype. CONCLUSIONS: Immune cell BDNF secretion is associated with the sites of higher inflammatory activity as evidenced by CE lesions and may represent an important factor associated with the WM volume of patients with MS.     

Dynamic analysis of exercise oxygen consumption predicts outcomes in advanced heart failure

It is unclear whether cardiopulmonary stress testing provides prognostic information in patients with very advanced heart failure receiving contemporary medical therapy. Analysis of cardiopulmonary treadmill stress data in a group of patients with advanced heart failure and severe functional impairment was performed (N=102, peak exercise oxygen consumption [VO2] < or =14 mL/kg/min, 47% receiving beta-blockers). Dynamic variables (peak - baseline values) better predicted outcomes than did single value peak measurements, especially DeltaVO2. Multivariate analysis showed that usage of beta-blockers and DeltaVO2 (both P<.05) independently and significantly predicted outcomes. Subgroup analysis showed that DeltaVO2 was particularly useful in predicting outcomes in patients with ischemic cardiomyopathy or who were not receiving beta-blockers. Thus, in patients with very advanced heart failure, cardiopulmonary stress testing-derived DeltaVO2 provides important prognostic information useful to help predict clinical deterioration or death, particularly for patients with ischemic cardiomyopathy or who are not receiving beta-blockers.     

Analysis of fractal and fast fourier transform spectra of human electroencephalograms induced by odors

Fast Fourier transform (FFT) and fractal dimension (FD) are computed to discover the evoked potentials (EPs) in the base human electroencephalograms (EEGs) corresponding to six types of odor inhalation, one at a time. During the first 20 s of the EEG recording, the patient breathes normally and the rest of the recording time 21-64 s, inhales an odor, when both the eye open and closed modes. FFT spectral analysis cannot discriminate the potential due to olfactory stimuli from the base EEG. However, fractal spectra analysis predicts the evoked potential due to inhalation of English rose, jasmine, lemon, orange, rose garden, and sandalwood concentrates. Similar results are obtained for three of the patients examined and on computing for five EEG recordings of two patients during inhalation of six types of odor.     

Core-controlled polymorphism in virus-like particles

This study concerns the self-assembly of virus-like particles (VLPs) composed of an icosahedral virus protein coat encapsulating a functionalized spherical nanoparticle core. The recent development of efficient methods for VLP self-assembly has opened the way to structural studies. Using electron microscopy with image reconstruction, the structures of several VLPs obtained from brome mosaic virus capsid proteins and gold nanoparticles were elucidated. Varying the gold core diameter provides control over the capsid structure. The number of subunits required for a complete capsid increases with the core diameter. The packaging efficiency is a function of the number of capsid protein subunits per gold nanoparticle. VLPs of varying diameters were found to resemble to three classes of viral particles found in cells (T=1, 2, and 3). As a consequence of their regularity, VLPs form three-dimensional crystals under the same conditions as the wild-type virus. The crystals represent a form of metallodielectric material that exhibits optical properties influenced by multipolar plasmonic coupling.     

Sentinel Lymph Node Biopsy in Histologically Ambiguous Melanocytic Tumors With Spitzoid Features (So-Called Atypical Spitzoid Tumors)

Background The distinction of Spitz nevi from melanomas with spitzoid morphology can be difficult. For lesions with overlapping histopathologic features, it may be impossible to predict their malignant potential with certainty. The current study evaluated the role of sentinel lymph node (SLN) biopsy in patients with such atypical spitzoid tumors. Methods The clinical and histopathologic features of 21 patients with atypical spitzoid tumors who underwent SLN biopsy were reviewed and correlated with the presence or absence of metastatic tumor in their corresponding SLNs. Results The atypical histopathologic features that were most frequently present included incomplete maturation (11 patients, 52%), two or more dermal mitoses per square millimeter (13 patients, 62%), and deep dermal mitoses (11 patients, 52%). Six patients (29%) showed SLN metastasis. There were histopathologic differences between tumors with positive SLN when compared with tumors with negative SLN: mean tumor thickness (3.38 mm vs. 2.04 mm), incomplete maturation (83% vs. 40%), median dermal mitotic rate (3.5/mm² vs. 2/mm²), deep dermal mitoses (83% vs. 47%), and expansile dermal nodules (50% vs. 13%). However, of these, only the difference in mean tumor thickness reached statistical significance (P < .05). Conclusions SLN biopsy offers a means of assessing the metastatic potential of atypical spitzoid tumors and aids in the management of these patients by selecting patients who may benefit from a regional node field dissection and those in whom the use of adjuvant therapies could be considered.