Is there a relationship between gastric acid secretion and plasma catecholamines in duodenal ulcer disease?

Plasma adrenaline, noradrenaline and dopamine concentrations have been analyzed in three different groups of duodenal ulcer (DU) patients under various regimens of acid reduction in an attempt to find out if acidity per se has any influence on plasma catecholamine concentrations. Treatment with cimetidine in patients with asymptomatic chronic DU disease, reduced gastric acidity to the same level as after highly selective vagotomy (HSV), but increased plasma noradrenaline concentrations insignificantly. In a group of DU patients subjected to HSV, plasma noradrenaline levels were significantly higher 1 year after surgery than 6 weeks thereafter despite the fact that the basal acid output was the same. In a third group of DU patients, plasma noradrenaline and dopamine levels were found to be 20% higher during the active, untreated ulceration than after 4 weeks of ranitidine treatment when the ulcer had healed. It is concluded that the elevated plasma noradrenaline levels found in DU patients are not caused by the hypersecretion of acid per se, nor does there seem to be any general correlation between acidity and the catecholamine levels in peripheral plasma.     

Genetic and clinical characterization of sporadic cystic parathyroid tumours

objective The hyperparathyroidism–jaw tumour (HPT–JT) syndrome is one of the familial disorders characterized by primary hyperparathyroidism and has been linked to the chromosomal region of 1q32–q21. The parathyroid tumours related to this syndrome have shown loss of wild‐type alleles at this locus suggesting that inactivation of a tumour suppressor gene might be responsible for the disease. In the majority of these tumours cysts are a prominent feature. By loss of heterozygosity (LOH) studies, we investigated the region of interest in an attempt to clarify its possible role in a series of cystic sporadic parathyroid adenomas. design and subjects A total of 30 patients diagnosed with sporadic hyperparathyroidism were included in the study, genotyped with 17 polymorphic microsatellite markers at chromosome 1q, and additional markers from 1p and 11q13 which are commonly involved in sporadic parathyroid tumours. The cystic parathyroid tumours were characterized clinically, and immunohistochemistry against PTH was carried out to confirm the parathyroid origin of the cysts. results LOH was found in six of 30 tumours (20%) on 1q, six of 30 tumours (20%) on 1p and five of 30 tumours (17%) on 11q13. We found a significant correlation between allelic alterations and the clinical parameters, tumour weight and PTH. Furthermore, we found a significant difference between tumour weight and PTH in cases of cystic parathyroid tumours compared with unselected sporadic cases. conclusions These results suggest that cystic parathyroid tumours might represent a new subgroup among parathyroid tumours based on the genetic and clinical findings. Loss of heterozygosity at 1q further supports the presence of a tumour suppressor gene at this locus.     

The rational of forehead lifting in patients with chronic facial paralysis

Background

The incidence of permanent facial sequels in patients with Bell’s palsy is about 30 % and results in impaired mimic expression of both midface and forehead in varying degrees. Even at rest, most patients experience an imbalance of their facial features. In this article, static correction of brow imbalance was evaluated in patients with sequels after unilateral facial palsy.

Methods

Thirty-one patients with sequels of Bell’s palsy underwent surgery with endoscopic forehead lift. Brow position was geometrically assessed pre- and postoperatively. The validated self-assessment instrument for quality of life [Short Form 36(SF-36)] was completed prior to and after surgery. The follow-up period was 12 months.

Results

A notable improvement in the position of the brows was demonstrated over time with lasting results. All patients experienced an improvement in facial symmetry and balance at rest. However, no significant difference could be shown using SF-36 pre- and postoperatively.

Conclusion

Endoscopic forehead lift combined or as an isolated procedure is a valuable instrument to correct sequels of Bell’s palsy. Level of Evidence: Level IV, therapeutic study.     

Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.     

Internalization and signal transduction of PrP106−126 in neuronal cells

Invasion of the nervous system and neuronal spread of infection are critical, but poorly understood steps in the pathogenesis of prion diseases. We have thus analyzed the internalization and signal transduction of the neurotoxic fragment of the prion protein PrP_106–126 in the rat neuroblastoma cell line B104 by fluorescence microscopy and quantification by ELISA and in primary neuronal cells from mice. Phospholipase D (PLD) is known to be an enzyme involved in the regulation of secretion, endocytosis and receptor signalling. We determined the PLD activity using a transphosphatidylation assay and could show that PLD is involved in PrP_106–126 internalization. The determination of receptor activity via quantification of ERK1/2 phosphorylation and cAMP level measurement verified the PrP_106–126-induced signal transduction in B104 cells and primary neuronal cells. PrP_106−126-induced a decrease in cAMP level in neuronal cells. These studies indicate the involvement of PLD in PrP_106–126-endocytosis and mediated cellular signalling by an unidentified inhibitory G-protein-coupled receptor and may allow the development of therapeutic agents interfering with prion uptake and/or PLD function using PLD as a possible pharmaceutical target.     

Noradrenergic mechanisms in hemorrhagic shock of the rat.

The effects of hemorrhagic shock on the noradrenergic nerves of the rat were studied. Fluorescence microscopy of these nerves combined with biochemical determination of noradrenaline revealed a highly selective activation of certain adrenergic nerves, especially the nerves of the arterioli. Under the present experimental conditions transmitter mechanisms such as uptake and release of noradrenaline were not severely impaired by shock.     

Receptor endocytosis counteracts the development of opioid tolerance

In contrast to endogenous opioids, the highly addictive drug morphine activates the mu-opioid receptor without causing its rapid endocytosis. It has recently been reported that coapplication of low concentrations of [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) facilitates the ability of morphine to stimulate mu-opioid receptor endocytosis and prevents the development of morphine tolerance in rats. To investigate the clinical relevance of this finding for analgesic therapy, the endocytotic efficacies of a series of clinically used opioids were determined, and the effect of a combination of these drugs with morphine on the mu-opioid receptor endocytosis in receptor-expressing human embryonic kidney (HEK) 293 cells was quantified. The combination of morphine and opioid drugs with high endocytotic efficacies (e.g., DAMGO, etonitazene, sufentanil, beta-endorphin, piritramide, or methadone) did not result in a facilitation of morphine-mediated endocytosis but rather in a decrease of the receptor endocytosis mediated by the tested opioid drugs. These findings demonstrate a partial agonistic effect of morphine on the agonist-induced receptor endocytosis. Moreover, we demonstrated that the endocytotic potencies of opioid drugs are negatively correlated with their ability to cause receptor desensitization and opioid tolerance in HEK 293 cells. These results strongly support the hypothesis that mu-opioid receptor endocytosis counteracts receptor desensitization and opioid tolerance by inducing fast receptor reactivation and recycling. In addition, it is shown that agonist-induced receptor endocytosis facilitates the compensatory up-regulation of the cAMP pathway, a cellular hallmark of opioid withdrawal. Our findings suggest that opioids with high endocytotic efficacies might cause reduced opioid tolerance but can facilitate compensatory mechanisms, resulting in an enhanced opioid dependence.