Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.     

Hypothalamic-hypophyseal-testicular abnormalities and erectile dysfunction

Forty-five men presenting with erectile dysfunction were evaluated through history and nocturnal penile tumescence, Doppler, and EMG studies. Fifteen were classified as having organic and 30 as having psychogenic impotence. Three men had mild hypergonadotropism with low testosterone levels. One had hyperprolactinemia. No case of hypogonadotropic hypogonadism was detected. Six patients who had psychogenic impotence had low levels of testosterone.     

Estrogen synthesis by osteoblast cell lines.

Estrogens play a central role in modulating bone turnover and in the postmenopausal female are formed almost exclusively by peripheral conversion of sex steroid precursors derived from the adrenals. In this study we have demonstrated that three human osteoblastic cell lines [HOS, U20S (HTB96) and MG63] possess the enzymes necessary for estrogen synthesis and metabolism. Aromatase, estradiol 17 beta-hydroxysteroid dehydrogenase (reductive and oxidative) and estrone sulfatase activities were measured in whole cell monolayers over a 20 h period by isotopic assay techniques. Significant aromatase activity was detected in all three cell lines ranging from 1.8 +/- 0.2 fmol/20 h/10(6) cells (mean +/- S.D., n = 3) for MG63 cells to 51 +/- 1.5 fmol/20 h/10(6) cells for HOS cells. The specific aromatase inhibitor, 4-hydroxyandrostenedione (1 mumol/L) completely inhibited aromatase activity in these cells. Two of the cell lines, HOS and MG63, had significant estradiol 17 beta-hydroxysteroid dehydrogenase activity with oxidative (32.7 +/- 1.9 and 1068.4 +/- 40.2 fmol/20 h/10(6) cells respectively) predominant over reductive activity (1.6 +/- 0.4 and 38.7 +/- 1.8 fmol/20 h/10(6) cells). All three cell lines were able to hydrolyse estrone sulfate to estrone with activities ranging from 13.3 +/- 1.5 fmol/20 h/10(6) cells for U20S cells to 482.2 +/- 3.7 fmol/20 h/10(6) cells for MG63 cells. Since estrogen has been implicated as a critical factor in the modulation of bone resorption and formation, the regulation of skeletal estrogen production, particularly at the time of the menopause, is likely to be an important mechanism by which bone volume is determined in physiological and pathological states.     

Pneumatocele of the orbit

PURPOSE: To describe an uncommon sinus condition that can cause proptosis. METHODS: Intermittent unilateral proptosis and diplopia developed in a 29-year-old man. Computed tomography showed an enlarged frontal sinus with erosion of the floor of the sinus and air in the orbit. RESULTS: Endoscopic ethmoidectomy and frontal sinusotomy corrected an outlet check valve of the nasal frontal duct and eliminated the proptosis. CONCLUSION: Pneumatocele of the orbit is an uncommon cause of proptosis and diplopia and can be corrected with endoscopic sinus surgery.     

Serum Lactate Dehydrogenase Enzyme as a Tumor Marker in Potentially Malignant Disorders: A Systematic Review and Meta–Analysis

Background:Oral cancer is often preceded by Potentially Malignant Disorders (PMDs) and important role of biochemical markers for early diagnosis has been well documented; however, there is limited evidence of Serum lactate dehydrogenase (SLDH) as an effective biochemical marker in diagnosis of PMDs. The present meta-analysis was conducted to assess if serum LDH can be a used as standard biomarker for PMDs and consequently aid in diagnosis of oral cancer. Methods:A comprehensive search was conducted in Medline, Scopus, Web of Science, EBSCO host, Cochrane databases and Google Scholar for studies evaluating estimation of SLDH in PMDs. Search strategy included all types of studies evaluating level of SLDH in patients with PMDs. PRISMA guidelines were followed for the meta-analysis. Fixed-effects model was used to assess the mean differences in SLDH levels between healthy controls and PMDs. Results:A total number of nine studies were included in meta-analysis after screening for inclusion and exclusion criteria. Potentially malignant disorder was significantly associated with increased serum LDH level compared to healthy controls (pooled SMD: 1.83 (95% CI, 1.52, 2.15) (P < 0.00001; Subgroup analysis of OSMF (Oral Submucous Fibrosis) studies showed significant association with increased serum LDH level compared to healthy controls (pooled SMD: 2.57 (95% CI, 2.16, 2.98; P < 0.00001). Sensitivity analysis for the five studies reflected a significant reduction in I² values to 24 % (P=0.26). Funnel plots were derived for any evidence of publication bias among the studies. Conclusion:Meta-analysis suggests that SLDH is increased in potentially malignant disorders compared to healthy controls. The results of this metanalysis should encourage use of SLDH as a biomarker in diagnosis of PMDs.Key Words: Potentially malignant disorders (PMDs), oral cancer, lactate dehydrogenase enzyme, precancerous lesion     

Advances in rectal drug delivery systems

Abstract

Drug delivery via the rectum is a useful alternative route of administration to the oral route for patients who cannot swallow. Traditional rectal dosage forms have been historically used for localized treatments including delivery of laxatives, treatment of hemorrhoids and for delivery of antipyretics. However, the recent trend is showing an increase in the development of novel rectal delivery systems to deliver drug directly into the systemic circulation by taking advantage of porto-systemic shunting. The present review is based on research studies carried out between years 1969–2017. Data for this review have been derived from keyword searches using Scopus and Medline databases. Novel rectal drug delivery systems including hollow-type suppositories, thermo-responsive and muco-adhesive liquid suppositories, and nanoparticulate systems incorporated into an appropriate vehicle have offered more control over delivery of drug molecules for local or systemic actions. In addition, various methods for in vitro–in vivo evaluation of rectal drug delivery systems are covered which is as important as the formulation, and must be carried out using appropriate methodology. Continuous research and development in this field of drug delivery may unleash the hidden potential of the rectal drug delivery systems.     

An eleven-year review of the pharmacy literature: documentation of the value and acceptance of clinical pharmacy

The primary objectives of the article were accomplished by providing both a bibliography of articles dealing with clinical pharmacy services in acute-care facilities and summaries of those constituting original research reports on clinical pharmacy services. However, in the process, we made the following interesting observations. We found that articles reporting impacts on cost, quality, and attitude numbered 48, 58, and 24, respectively. Most articles relating to drug therapy monitoring, with minor exceptions, dealt with either the quality or cost-savings impact or a combination of both. Also, articles concerning drug therapy monitoring comprised almost half of all those summarized (40 articles). Articles detailing drug information and education (category 2) numbered 28 and dealt mainly with attitudes or quality impacts with minor reference to cost-savings. It was also interesting, albeit expected, to observe that the bulk of attitudinal studies fell in category 2. We found category 5, controlling medication administration, had 13 articles, primarily concerned with cost and or quality. Category 4, reporting and detection of adverse drug reactions, contained a total of eight articles mainly studying the impact on quality. The other categories contained very few, if any, articles. From these results, it is evident that the profession has made significant strides in building a strong scientific data base to support the value of its clinical services. However, there is ample room for additional original research reports. Although it can be argued that alone many of the studies could not justify clinical pharmacy as cost-effective, organized as one reference they provide an invaluable resource. Although it might be unreasonable to expect each pharmacy department to be able to cost-justify its existence, this work presents the background data needed to begin or develop such efforts.