The role of adrenergic innervation in the regulation of lacrimal gland (LG) ductal fluid secretion is unknown. The Aim of the present study was to investigate the effect of adrenergic stimulation on fluid secretion in isolated LG duct segments and to study the underlying intracellular mechanisms. METHODS. Fluid secretion of isolated mouse LG ducts was measured using videomicroscopy. Effect of various adrenergic agonists (norepinephrine, phenylephrine, and isoproterenol) on fluid secretion as well as inhibitory effects of specific antagonists on adrenergic agonist-stimulated secretory response were analyzed. Changes in intracellular Ca 2+ level [Ca 2+ i ] were investigated with microfluorometry. RESULTS. Both norepinephrine and phenylephrine initiated a rapid and robust fluid secretory response, whereas isoproterenol did not cause any secretion. Phenylephrine-induced secretion was completely blocked by α 1D-adrenergic receptor blocker BMY-7378. The endothelial nitric oxide synthase (eNOS) inhibitor L-NAME or guanylyl cyclase inhibitor ODQ reduced but not completely abolished the phenylephrine-induced fluid secretion, whereas co-administration of Ca 2+-chelator BAPTA-AM resulted in a complete blockade. Phenylephrine stimulation induced a small, but statistically significant elevation in [Ca 2+ i ]. CONCLUSIONS. Our results prove the direct role of α 1-adrenergic stimulation on LG ductal fluid secretion. Lack of isoproterenol-induced fluid secretory response suggests the absence of β-receptor mediated pathway in mouse LG ducts. Complete blockade of phenylephrine-induced fluid secretion by BMY-7378 and predominant inhibition of the secretory response either by L-NAME or ODQ suggest that α-adrenergic agonists use the NO/cGMP pathway through α 1D receptor. Ca 2+ signaling independent from NO/cGMP pathway may also play an at least partial role in α-adrenergic induced ductal fluid secretion.

The aim of this study is to describe four new cases of trepanation from the Great Hungarian Plain and complement two other previously published cases with new results from the 9th to 16th c. CE. Sex determination and age-at-death estimation were performed using classical macromorphological methods. In certain cases, radiographic imaging, 3D scanning, and radiocarbon dating were also performed. Our cases fit the formerly established understanding of trepanations, with a male majority and signs of trauma as accompanying symptoms. The cause of intervention was mostly therapeutic, i.e., trauma, in most cases. In order to simplify the currently confusing nomenclature in trepanation categories (complete–incomplete vs. surgical–symbolic), we propose the use of “trepanation” exclusively to all forms of intentional, non-violent removals of all three layers of the cranial vault. On the other hand, the phenomena widely known in Eastern Europe as symbolic trepanations should be designated as “cranioglyphs,” referring to all forms of superficial interventions administered to the cranial vault that do not penetrate all three layers of the bone. In case the data are insufficient to properly categorize the phenomenon at hand, one should refrain from it, and simply describe the lesion as intentional cranial intervention. In order to bring spotlight to the wide range of cranial interventions in the early medieval Carpathian Basin, our team is conducting several research projects, in order to contribute to a better understanding of these traditions in the future.

Background Anti-tumour necrosis factor (TNF) therapy has dramatically changed the treatment of inflammatory bowel disease (IBD). The relationship between clinical outcomes and serum anti-TNF levels is controversial. This study aimed to perform simultaneous analyses of the serum, mucosal and faecal infliximab and adalimumab levels to determine the mucosal expression of TNF-α and assess the relationship of the anti-TNF-α levels in these biological samples with the endoscopic and clinical activities and body composition in IBD patients. Methods Consecutive IBD patients who received maintenance anti-TNF-α therapy and underwent colonoscopy were enrolled. We assessed the clinical disease activity, collected the blood, faecal and biopsy samples. The number of TNF-α positive cells in the mucosa was detected using immunofluorescent labelling. Serum, mucosal and faecal anti-TNF-α levels, anti-drug antibody level in the serum and faecal calprotectin were determined using ELISA. Each patient underwent body composition analysis. Results Fifty consecutive patients have been analysed in the study. The number TNF-α positive cells was significantly higher in the inflamed than in the un-inflamed part of the colon (p = 0.01); however, such a difference was not detected in case of tissue drug levels. Tissue drug level did not correlate with the serum drug level. Nevertheless, tissue drug levels of the samples obtained from the un-inflamed part of the colon were significantly higher in patients who were in remission (p = 0.03467). The presence of the drug in the faeces was significantly different according to disease activity (p = 0.0022). Drug levels in the biological samples did not show any association with the presence of anti-drug antibodies. Body composition parameters had no significant impact on the serum and tissue drug levels. Faecal calprotectin showed significant correlation with faecal drug concentration (p = 0.0162) and clinical and endoscopic activity (p < 0.001). Conclusion To the best our knowledge, this is the first study to measure drug concentrations in all the relevant biological samples. Our findings highlight the importance of faecal drug monitoring because active disease may be present in spite of normal serum anti-TNF levels. Simultaneous determination of faecal drug concentration and faecal calprotectin may be more accurate for evaluating therapeutic responses in the future.

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