Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.

Context: The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists.

Objective: To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more.

Design, Setting, And Patients: Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status.

Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice.

The transcription-intermediary-factor-2 (TIF-2) is a coactivator of the glucocorticoid receptor (GR), and its disruption would be expected to influence glucocorticoid-mediated control of the hypothalamo-pituitary-adrenal (HPA) axis. Here, we show that its targeted deletion in mice is associated with altered expression of several glucocorticoid-dependent components of HPA regulation (e.g.

The toxicity of cadmium and resulting hazards for human health.

Cadmium (Cd) has been in industrial use for a long period of time. Its serious toxicity moved into scientific focus during the middle of the last century. In this review, we discuss historic and recent developments of toxicological and epidemiological questions, including exposition sources, resorption pathways and organ damage processes.

Early diagnosis of colorectal cancer: a preventive task in occupational health.

Morbidity of colorectal cancer is still accreting; therefore in 2003 a total of 57000 patients fell ill and about 28000 died due to colorectal carcinoma. According to the etiology, many different factors are currently in discussion. However, as in about 25-30% of the cases familial clustering can be observed one of the most probable might be the genetic predisposition.

Chronic cough due to occupational factors.

Within the large variety of subtypes of chronic cough, either defined by their clinical or pathogenetic causes, occupational chronic cough may be regarded as one of the most preventable forms of the disease. Next to obstructive airway diseases such as asthma or chronic obstructive pulmonary disease, which are sometimes concomitant with chronic cough, this chronic airway disease gains importance in the field of occupational medicine since classic fiber-related occupational airway diseases will decrease in the future. Apart from acute accidents and incidental exposures which may lead to an acute form of cough, there are numerous sources for the development of chronic cough within the workplace.

Air conditioning systems as non-infectious health hazards inducing acute respiratory symptoms.

Chronic and acute exposure to toxic aerosols belongs to frequent causes of airway diseases. However, asthma attacks due to long-distance inhalative exposure to organic solvents, transmitted via an air condition system, have not been reported so far. The present case illustrates the possibility of air conditioning systems as non-infectious health hazards in occupational medicine.

Serological assays for the detection of human andes hantavirus infections based on its yeast-expressed nucleocapsid protein.

Background: The objective of the study was to develop and evaluate IgM and IgG ELISAs and an IgG Western blot test for the serological detection of human infections with Andes virus (ANDV), the major cause of hantavirus cardiopulmonary syndrome (HCPS) in South America.

Methods: The entire nucleocapsid (N) protein-encoding sequence of ANDV (strain AH-1) was cloned and expressed in the yeast Saccharomyces cerevisiae. The polyhistidine-tagged recombinant N (rN) protein of ANDV was purified by nickel-chelation chromatography and characterized by its reactivity with different N-specific monoclonal antibodies.

Protease-activated receptor 2 expression in trigeminal neurons innervating the rat nasal mucosa.

Protease-activated receptor 2 (PAR2) is activated by trypsin and mast cell tryptase to induce widespread inflammation by unknown mechanisms. Trypsin and tryptase were shown to activate sensory neurons to release substance-P and related peptides to mediate neurogenic inflammation. In the present study, the expression of PAR2 and tachykinins were investigated in rat trigeminal neurons that were identified by retrograde labeling with rhodamine dye from the nasal mucosa by using neuronal tracing in combination with immunohistochemistry.

Peroxisome proliferator-activated receptor-gamma ligands for the treatment of breast cancer.

Pioglitazone and rosiglitazone are thiazolidinediones used for the treatment of Type 2 diabetes mellitus. They modulate glucose and fat metabolism, mainly by binding to the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma signalling is involved in a number of other disease conditions including cancer.

Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats.

Background And Aims: Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity.

Gene expression and regulation of transcription factor activator protein-2 alpha in human mast cells.

Background: The transcription factor activator protein (AP)-2 regulates cell-type specific gene expression during development and differentiation, but its role in mast cell development has so far not been explored.

Methods: Gene expression and regulation of AP2 was assessed in normal skin, diseases with increased mast cell numbers, and in vitro models of mast cell differentiation.

Results: AP-2alpha-protein was not detectable in normal skin but in mastocytoma lesional mast cells.

Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airways.

Background: Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways.

Objective: The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular-nodose ganglion neurons innervating the murine airways.

Methods: Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation.

Central European Dobrava Hantavirus isolate from a striped field mouse (Apodemus agrarius).

Dobrava virus (DOBV) is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS) in Europe. It is hosted by at least two rodent species, Apodemus flavicollis and A. agrarius.

Development and evaluation of serological assays for detection of human hantavirus infections caused by Sin Nombre virus.

Background: The hantavirus cardiopulmonary syndrome (HCPS) was first recognized in 1993 after a cluster of acute respiratory distress syndrome deaths in the southwestern of the United States. The major causative agent of HCPS in North America is the Sin Nombre virus (SNV) carried by the deer mouse Peromyscus maniculatus. The first HCPS case imported to Europe was reported in 2002.

Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells.

Coenzyme Q10 is an essential cofactor in the electron transport chain and serves as an important antioxidant in both mitochondria and lipid membranes. CoQ10 is also an obligatory cofactor for the function of uncoupling proteins. Furthermore, dietary supplementation affecting CoQ10 levels has been shown in a number of organisms to cause multiple phenotypic effects.

Gene expression and regulation of nerve growth factor in atopic dermatitis mast cells and the human mast cell line-1.

The gene expression and regulation of nerve growth factor (NGF) in atopic dermatitis (AD) and the human mast cell line (HMC)-1 was investigated at the molecular level. NGF-stimulation of HMC-1 cells resulted in increases in tryptase activity and histamine contents, paralleled by an increase of tryptase and histamine at the transcriptional level. Also, an increased expression of NGF was found in AD lesions, in association with increased systemic NGF plasma levels.

Expression of substance P and nitric oxide synthase in vagal sensory neurons innervating the mouse airways.

Introduction: Airway sensory nerves have the capacity to release neuromediators such as substance P and nitric oxide to control airway functions. The aim of the present study was to investigate substance P and neuronal nitric oxide synthase (NOS-1) expression in airway-specific sensory neurons.

Methods: Airway-projecting neurons in the jugular-nodose ganglia were investigated for NOS-1 and substance P expression by neuronal tracing and double-labelling immunoreactivity.

Expression of tyrosine hydroxylase and neuropeptide tyrosine in mouse sympathetic airway-specific neurons under normal situation and allergic airway inflammation.

Background: The traditional neurotransmitter catecholamine and the neuropeptide tyrosine in sympathetic airway nerves have been proposed to be involved in the pathogenesis of airway diseases.

Objective: The aim of the present study was to investigate the effect of allergic airway inflammation on the expression of catecholamine enzyme tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and tachykinins in mouse sympathetic airway ganglia.

Methods: Using neuronal tracing in combination with immunohistochemistry, the present study was designed to characterize TH, NPY and tachykinin profiles of superior cervical (SCG) and stellate ganglia after allergen challenge.

Molecular mechanisms of severe acute respiratory syndrome (SARS).

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network.

Neuronal plasticity in persistent perennial allergic rhinitis.

Objective: Persistent perennial allergic rhinitis belongs to the most frequent diseases in occupational and environmental medicine. Because the innervation may play a role in the pathogenesis of the disease, the present study analyzed nasal mucosal nerve profiles.

Methods: Neuropeptide-containing nerve fibers were examined using immunohistochemistry and related to eosinophil and mast cell numbers.

Mast cells and vasculature in atopic dermatitis--potential stimulus of neoangiogenesis.

Background: Atopic dermatitis skin lesions are characterized by inflammatory changes and epithelial hyperplasia requiring angiogenesis. As mast cells may participate in this process via bidirectional secretion of tissue-damaging enzymes and pro-angiogenic factors, the present study aimed to assess the occurrence and possible function of mast cells in the papillary dermis and in epidermal layers of atopic dermatitis lesions.

Methods: Semi-thin and serial sections in combination with immunohistochemistry, histochemistry and proliferating cell nuclear antigen (PCNA)-activity assays were used and related to epidermal thickness and targeted gene expression studies.

Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis.

Substance P and neurokinin A are regulatory peptides of the tachykinin family that influence many aspects of human airway function in health and diseases such as bronchial asthma or chronic obstructive pulmonary disease (COPD). Tachykinin-induced mucus secretion has been regarded as sensory nerve-dependent so far. We studied the distribution of tachykinin-mRNA and -peptide and its relation to NK-1 subtype-positive cells in human airway glands to assess if tachykinins may also be expressed in inflammatory cells.

Models of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level.

Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers.

Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate.