Idiopathic hypertrophic cranial pachymeningitis.

Idiopathic hypertrophic cranial pachymeningitis is a rare chronic inflammatory process of unknown origin that can cause neurological deficits owing to thickening of the dura. Patients with this condition commonly present with cranial neuropathy accompanied by localized headache. The clinical features, neuroimaging findings, histopathological features and treatment outcomes for three patients with this condition are reported here. The first patient presented with subacute dull headache in the left temporal area followed by left abducens nerve palsy. The second patient suffered from a cranial nerve IX-XII lesion accompanied by an occipital headache and the third patient presented with left optic neuropathy and mild headache in the frontal area. In all patients, MRI of the brain revealed prominent dural thickening, and histopathological study of the dura revealed chronic inflammatory cell infiltration. Combined therapy with corticosteroid and immunosuppressive drugs was effective, resulting in almost complete resolution of the symptoms and signs, except for visual impairment in one patient.     

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective,single arm,open label,dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy‐three pediatric patients with severe β thalassemias, age range 3.2–19 years, were recruited to a 1‐year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty‐four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.1±4.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml^?1. Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml^?1 had the most significant fall of SF at 1 year. A subgroup analysis by MRI‐T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug‐related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles. Am. J. Hematol. 88:251–260, 2013. © 2013 Wiley Periodicals, Inc.     

A novel enhanced green fluorescent protein (EGFP)-K562 flow cytometric method for measuring natural killer (NK) cell cytotoxic activity

Enhanced green fluorescent protein (EGFP) was stably expressed in human erythroleukaemia K562 cells (EGFP-K562) and used as target cells for measurement of natural killer (NK) cell cytotoxicity by flow cytometry. The compromised EGFP-K562 target cells were stained with propidium iodide (PI) and showed dual (green-red) fluorescent. Although the kinetic study demonstrated that the optimal incubation time for the assay was 4 h, a 2-h incubation period also gave comparable results. This new technique correlated strongly with the standard chromium (51Cr) release assay at the correlation coefficients of 0.87 and 0.89 at p-value <0.001 for 2- and 4-h incubation times, respectively. The EGFP-K562 stable cell line provides a novel method to measure NK cytotoxicity by flow cytometry without pre-staining or pre-labeling target cells.     

Docking study on anticancer activity of chromone derivatives

Several phenyl substituted chromones (also called flavonoids) have been reported to possess substantial anticancer properties; however, their modes of action have not been clearly defined. To preliminarily investigate the potential anticancer activity and mode of action of some synthetic chromone derivatives, the docking was performed using different enzymes and receptor proteins involved with cancer cell cycle, cell growth, and DNA replication, i.e., cyclin-dependent protein kinase-2 (CDK-2), CDK-6, DNA topoisomerases I and II, B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor receptor-2 (VEGFR-2), and the telomere: G-quadruplexes. The docking results revealed that chromone 32 exhibited better binding interactions to CDK-2 and Bcl-2 than the known CDK-2 and Bcl-2 inhibitors. Chromone 39 was found to bind to CDK-6 with tighter interaction than several reported CDK-6 inhibitors. Chromone 47 was best bound to both DNA topoisomerases I and II. Chromones 24 and 15 showed good binding interaction with VEGFR-2 and telomere: G-quadruplex, respectively. The inhibition constants (K _i) of each chromone compound against each target molecule were calculated. These K _i values could be used as a preliminary tool for screening specific inhibitors before performing experimental activity assay.     

Analysis of pharmaceutical heparins and potential contaminants using 1H-NMR and PAGE

In 2008, heparin (active pharmaceutical ingredient, API) lots were associated with anaphylactoid-type reactions. Oversulfated chondroitin sulfate (OSCS), a semi-synthetic glycosaminoglycan (GAG), was identified as a contaminant and dermatan sulfate (DS) as an impurity. While DS has no known toxicity, OSCS was toxic leading to patient deaths. Heparins, prepared before these adverse reactions, needed to be screened for impurities and contaminants. Heparins were analyzed using high-field ¹H-NMR spectroscopy. Heparinoids were mixed with a pure heparin and analyzed by ¹H-NMR to assess the utility of ¹H-NMR for screening heparin adulterants. Sensitivity of heparinoids to deaminative cleavage, a method widely used to depolymerize heparin, was evaluated with polyacrylamide gel electrophoresis to detect impurities and contaminants, giving limits of detection (LOD) ranging from 0.1% to 5%. Most pharmaceutical heparins prepared between 1941 and 2008 showed no impurities or contaminants. Some contained DS, CS, and sodium acetate impurities. Heparin prepared in 2008 contained OSCS contaminant. Heparin adulterated with heparinoids showed additional peaks in their high-field ¹H-NMR spectra, clearly supporting NMR for monitoring of heparin API with an LOD of 0.5–10%. Most of these heparinoids were stable to nitrous acid treatment suggesting its utility for evaluating impurities and contaminants in heparin API. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4017–4026, 2009     

MR imaging in human rabies

BACKGROUND AND PURPOSE: Whether human rabies of different forms, encephalitic (furious) and paralytic (dumb), share similar MR imaging patterns is unknown. We assessed the diagnostic value of MR imaging in both forms of the disease and compared the clinical and neuroimaging findings. METHODS: Three patients with paralytic and two with encephalitic rabies were examined during preserved or deteriorated levels of consciousness. Six MR examinations of the brain, three of the spinal cord, and one of the brachial plexus were performed with a 1.5-T superconducting magnet. RESULTS: No difference was noted between the MR findings in both clinical forms of human rabies. Nonenhancing, ill-defined, mild hyperintensity changes in the brain stem, hippocampi, hypothalami, deep and subcortical white matter, and deep and cortical gray matter were demonstrated on T2-weighted images in the noncomatose patients with rabies. Enhancement along the brachial plexus of the bitten arm was noted in one patient with encephalitic rabies who at that time had only local neuropathic pain symptoms. Enhancement with gadolinium-based contrast material was seen at the hypothalami, brain stem nuclei, spinal cord gray matter, and intradural cervical nerve roots only when the patients became comatose. CONCLUSION: Both forms of human rabies share a similar MR imaging pattern. Such pattern and the lack of enhancement in a noncomatose patient with suspected encephalitis may differentiate rabies from other viral encephalitides.     

High sex chromosome aneuploidy and diploidy rate of epididymal spermatozoa in obstructive azoospermic men

Purpose: To evaluate the frequencies of sex chromosome aneuploidy and diploidy rate of epididymal spermatozoa from obstructive azoospermic men and its impact on intracytoplasmic sperm injection (ICSI) outcomes. Methods: Epididymal spermatozoa retrieved from 24 obstructive azoospermic men and ejaculated spermatozoa from 24 fertile donors were analyzed using triple color fluorescence in situ hybridization (FISH) techniques, in order to investigate the rates of diploidy and aneuploidy for chromosomes 18, X and Y. Results: Epididymal spermatozoa from obstructive azoospermic men had total sex aneuploidy, disomy 18, and diploidy rates significantly higher than ejaculated spermatozoa from normozoospermic fertile controls (1.44% vs. 0.14%, 0.11% vs. 0.02%, and 0.18% vs. 0.02%, respectively; p < 0.005). There were no statistically significant differences in ICSI outcomes between the patients who had high and low epididymal sperm aneuploidy rate. Conclusions: Epididymal spermatozoa from obstructive azoospermic patients had an elevated sex chromosome aneuploidy and diploidy rate. The increased frequency of chromosomal abnormalities did not have a direct effect on the ICSI outcome.     

Intuitive eating and the nutrition transition in Asia

Current models of the nutrition transition focus on demographic changes and economic development. A further influence may be the adoption of western-based perceptions of beauty that lead to potentially harmful eating behaviours which contribute to overweight, obesity, and eating disorders. This paper proposes a comprehensive model of the nutrition transition that includes western influences on perceived attractiveness and subsequent eating styles. An exploratory test of this model for Asian countries explores differences in intuitive eating as a function of economic development and the adoption of western standards of beauty. The intuitive eating scale (IES), a measure of food consumption that is primarily characterized by the satisfaction of physical hunger, was used to evaluate agreement with intuitive eating principles in the US and four Asian countries (Japan, Thailand, the Philippines, and China). Although intuitive eating scores in the US and Thailand failed to follow predicted patterns on two of the four IES subscales, scores for the other two IES subscales and the total IES score followed predicted patterns for Asian countries. Intuitive eating appears to be a valid, measurable concept that is correlated with economic development and levels of western influence in Asian countries. The tentative findings of this exploratory study support further evaluation of cultural influences as an important component of the nutrition transition.