Assessment of vestibulo-ocular reflex with video head impulse test in epilepsy patients undergoing carbamazepine monotherapy.

OBJECTIVE: Carbamazepine may cause clinical effects such as dizziness and nystagmus. This may depend on the duration of use. The aim of this study is to measure the effect of carbamazepine monotherapy on the vestibular system electrophysiologically by using Video Head Impulse Test (VHIT) and to compare the numerical and objective data obtained between the groups. PATIENTS AND METHODS: In this study, in which 55 people (110 ears) participated, Video Head Impulse Test (VHIT) was performed to evaluate the vestibulo-ocular reflex (VOR) in the epilepsy patients and a healthy control group consisting of healthy individuals. In addition, patients were analyzed in two groups to demonstrate the long-term effects of carbamazepine (<10 years and >10 years). Right/left lateral, anterior, posterior semi-circular canals (SCCs) VOR gains, lateral, left anterior right posterior, and right anterior right posterior gain asymmetries were measured between groups. RESULTS: Lateral SCCs VOR gains were 0.878±0.057 and 0.921±0.045 between the patient and healthy control groups, respectively (p=0.024). A decrease in the right and left lateral SCCs VOR gains (0.885±0.062 and 0.868±0.063) was detected in the patients (p=0.011 and p=0.001). Those using carbamazepine for >10 years had a decrease in lateral SSCs VOR gains (0.843±0.055) compared to those using the drug for <10 years (0.902±0.046) (p=0.008). CONCLUSIONS: A relative reduction in lateral (right/left) SCCs VOR gains was found in epilepsy patients using carbamazepine and in the group of patients using this drug for a long time (>10 years).

A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism.

Circadian Clock Protein PERIOD 3 (PER-3) is situated on chromosome 1p36.23 and has a polymorphic domain that expresses 4 or 5 copies of the 54-bp tandem repeat sequence. PER-3 gene polymorphisms play a role in the dysregulation of the immune system. This study intended to investigate the distributions and clinical effectiveness of the PER-3 gene polymorphism in multiple myeloma (MM) patients. One hundred fifty patients diagnosed between January 2007-2009 and 100 healthy individuals were included in this study. All patients were suitable for autologous stem cell transplantation (ASCT) at first evaluation, and after 4 courses of VCD at least partial remission, ASCT was carried out. Later, LD was used as maintenance. Genotypes of PER-3 gene of patients and healthy controls were statistically compared before treatment. In addition, these genotypes' effects on overall and progression free survival (OS and PFS) were investigated. Median PFS in the 5R/5R genotype was found to be significantly longer, albeit low, at 86% (p = 0.046). In the statistical analysis performed between the 4R/4R genotype and others, the PFS of patients with 4R/4R was found to be significantly shorter at 40.4 months (p = 0.026). Patients with the 4R/4R genotype would have a risk of 2.049 times of a shorter PFS (p=0.009). With this first study investigating the effect of a circadian gene in MM, the net effect of PER-3 gene polymorphism on PFS was revealed, and it will be a guide for future studies.

Effects of COVID-19 Pandemic on the Treatment of Pancreatic Cancer: A Perspective from Central Europe.

BACKGROUND: This survey aimed to register changes determined by the COVID-19 pandemic on pancreatic surgery in a specific geographic area (Germany, Austria, and Switzerland) to evaluate the impact of the pandemic and obtain interesting cues for the future. METHODS: An online survey was designed using Google Forms focusing on the local impact of the pandemic on pancreatic surgery. The survey was conducted at 2 different time points, during and after the lockdown. RESULTS: Twenty-five respondents (25/56) completed the survey. Many aspects of oncological care have been affected with restrictions and delays: staging, tumor board, treatment selection, postoperative course, adjuvant treatments, outpatient care, and follow-up. Overall, 60% of respondents have prioritized pancreatic cancer patients according to stage, age, and comorbidities, and 40% opted not to operate high-risk patients. However, for 96% of participants, the standards of care were guaranteed. DISCUSSION/CONCLUSIONS: The first wave of the COVID-19 pandemic had an important impact on pancreatic cancer surgery in central Europe. Guidelines for prompt interventions and prevention of the spread of viral infections in the surgical environment are needed to avoid a deterioration of care in cancer patients in the event of a second wave or a new pandemic. High-volume centers for pancreatic surgery should be preferred and their activity maintained. Virtual conferences have proven to be efficient during this pandemic and should be implemented in the near future.

Disorders of the enteric nervous system - a holistic view.

The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A 'leaky gut' represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.

Association of bacteria in pancreatic fistula fluid with complications after pancreatic surgery.

BACKGROUND: Pancreatic fistula (PF) is a common complication after pancreatic surgery. It is unclear how microbes in PF fluid affect outcomes and which microbes are present after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). The aim of this study was to compare the microbiological spectrum of PF fluid after PD versus DP, and its association with postoperative complications. METHODS: Bacterial strains and antibiotic resistance rates of bacterial swabs obtained from the PF fluid of patients who underwent DP or PD were analysed. Cultured bacteria were classified as Enterobacterales and as 'other intestinal and non-intestinal microorganisms' based on whether they are typically part of the normal human intestinal flora. RESULTS: A total of 847 patients had a pancreatic resection (PD 600; DP 247) between July 2007 and December 2016. Clinically relevant PF was detected in 131 patients (15·5 per cent). Bacterial swabs were obtained from 108 patients (DP 47; PD 61), of which 19 (17·6 per cent) were sterile. Enterobacterales were detected in 74 per cent of PF fluid swabs after PD, and in 34 per cent after DP. Infected, polymicrobial or multidrug-resistant PF fluid was more common after PD (rates of 95, 50 and 48 per cent respectively) than after DP (66, 26 and 6 per cent respectively). Patients with higher grade complications (Clavien-Dindo grade IV-V) or grade C PF had more Enterobacterales and multidrug-resistant Enterobacterales in the PF fluid after DP. CONCLUSION: Enterobacterales and multidrug-resistant bacteria are detected frequently after PD and DP, and are associated with more severe complications and PF in patients undergoing DP.

ANTECEDENTES: La fístula pancreática (pancreatic fistula, PF) es una complicación frecuente de la cirugía pancreática. No está claro cómo los microorganismos que se encuentran en el líquido de la PF (pancreatic fistula fluid, PFF) afectan los resultados y qué microbios están presentes después de la duodenopancreatectomía (pancreaticoduodenectomy, PD) y de la pancreatectomía distal (distal pancreatectomy, DP). El objetivo de este estudio fue comparar el espectro microbiológico del PFF después de PD versus DP y su asociación con las complicaciones postoperatorias. MÉTODOS: Se analizaron las cepas bacterianas y las tasas de resistencia a los antibióticos de las muestras bacterianas obtenidas del PFF de pacientes de nuestra institución que se sometieron a DP o PD. Las bacterias identificadas en los cultivos se clasificaron en "enterobacterias" y "otros microorganismos intestinales y no intestinales" en función de si típicamente forman parte de la flora intestinal humana normal o no. RESULTADOS: Un total de 847 pacientes se sometieron a resección pancreática (PD: 600, DP: 247) entre julio de 2007 y diciembre de 2016, y se detectó FP clínicamente relevante en 131 pacientes (15,5%). Se obtuvieron muestras bacterianas de 108 pacientes (DP n = 47, PD N = 61), de los cuales 19 (18%) eran estériles. Se detectaron enterobacterias en el 74% del PFF después de PD y en el 34% después de DP. El PFF infectado, con flora polimicrobiana o flora multirresistente fue más frecuente después de la PD (95,1%, 50%, 47,5%, respectivamente) que después de la DP (66,0%, 25,8%, 6,4%, respectivamente). Los pacientes con complicaciones de grado superior (Clavien-Dindo 4/5) o PF grado C presentaron más enterobacterias y enterobacterias multirresistentes en el PFF después de DP. CONCLUSIÓN: Las enterobacterias y las bacterias multirresistentes se detectaron con frecuencia después de la PD y la DP, y se asociaron a complicaciones más graves y PF en pacientes sometidos a DP.

Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome.

PURPOSE: Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS. METHODS: We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case-control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method. RESULTS: We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 ± 1.91 vs. 3.72 ± 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels. CONCLUSIONS: Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS.

Outcomes of arterial switch operation for Taussig-Bing anomaly versus transposition of great arteries and ventricular septal defect.

BACKGROUND: This study aims to present the outcomes of arterial switch operation for Taussig-Bing anomaly versus transposition of the great arteries and ventricular septal defect. METHODS: Between November 2010 and December 2016, a total of 100 consecutive arterial switch operations in 42 pediatric patients (25 males, 17 females; median age 17 days; range, 2 to 210 days) were performed in two centers. Among them, 42 patients had associated ventricular septal defect and were diagnosed with Taussig-Bing anomaly (n=15) or transposition of the great arteries and ventricular septal defect (n=27). Aortic arch anomalies were present in six patients (40%) with Taussig-Bing anomaly and two patients (7.4%) with transposition of the great arteries and ventricular septal defect (p=0.016). Coronary anomaly was observed in five (33.3%) and six (22.2%) patients, respectively. All patient had a large defect (multiple n=4), except for eight patients who had moderate defect in the transposition of the great arteries group. RESULTS: Early mortality was 13.3% in the Taussig-Bing anomaly group and 7.4% in the other group. Extracorporeal membrane oxygenation support was needed in three patients. Delayed sternal closure was used in most of the patients (92.9%). The median length of intensive care unit and hospital stays were similar between the groups. The median follow-up was 16 (range, 1 to 50) months. Two patients including one planned (debanding and multiple defect closure) and one unplanned (residual defect closure) were reoperated. Three patients needed aortic balloon angioplasty due to recoarctation and one patient underwent pulmonary balloon angioplasty. Overall reintervention rate was 18.4%. CONCLUSION: Although the incidence of aortic arch and coronary anomalies were higher in patients with Taussig-Bing anomaly, early and mid-term results were similar. Based on these results, primary arterial switch operation seems to be successfully performed for both pathologies.

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma.

BACKGROUND: Neoadjuvant therapy may increase the rate of radical tumour resection in patients with pancreatic cancer. Its impact on tumour recurrence has not been investigated fully. This study aimed to assess the impact of neoadjuvant therapy on patterns of recurrence. METHODS: A systematic review was performed of articles identified through the PubMed, Scopus, Embase, Ovid and Google Scholar databases that analysed the relationship between neoadjuvant therapy and recurrence published to January 2016. The main endpoint was overall tumour recurrence. Other endpoints included local recurrence, any kind of distant, hepatic, pulmonary or peritoneal metastasis. RESULTS: A total of 4257 citations were reviewed. Twelve observational studies comprising 1365 patients were analysed. Neoadjuvant therapy significantly reduced the risk of overall (risk ratio (RR) 0·82, 95 per cent c.i. 0·74 to 0·90; P < 0·001) and local (RR 0·42, 0·32 to 0·55; P < 0·001) recurrence. Neoadjuvant therapy did not reduce the risk of any kind of distant (RR 1·02, 0·91 to 1·14; P = 0·78), hepatic (RR 0·86, 0·68 to 1·10; P = 0·23), pulmonary (RR 0·99, 0·37 to 2·66; P = 0·98) or peritoneal (RR 0·88, 0·57 to 1·38; P = 0·58) metastasis. CONCLUSION: Neoadjuvant therapy reduced the risk of local recurrence but not that of distant metastasis.

bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM)-the active metabolite of the laxatives bisacodyl and sodium picosulfate-enhances contractility and secretion in human intestine in vitro.

BACKGROUND: Stimulant laxatives are widely used to treat constipation. We investigated in human small and large intestinal preparations the effects of bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), the active metabolite of the laxatives bisacodyl and sodium picosulfate on smooth muscle tone and epithelial secretion. METHODS: Circular and longitudinal muscle tone of small or large intestinal preparations were recorded with isometric force transducers. Epithelial ion flux (ISC ) and tissue resistance was measured with Ussing chamber technique after apical and basolateral BHPM application to large intestinal mucosa/submucosa preparations. Studies were performed in macroscopically normal specimens from 79 patients. KEY RESULTS: BHPM concentration-dependently (0.5-5 µM) increased the tone of circular and longitudinal muscle from small to large intestine. The effect was strongest in large intestinal longitudinal muscle and smallest in small intestinal circular muscle. Increase in muscle tone was prevented by the L-type Ca++ channel blocker nifedipine but insensitive to the nerve blocker tetrodotoxin. Apical or basolateral BHPM concentration-dependently decreased or increased ISC, respectively. The KCa 1.1 (BK) channel blocker iberiotoxin reversed apical ISC decrease whereas tetrodotoxin reversed basolateral ISC increase. BHPM had no effect on tissue resistance or nerve-mediated secretory or muscle response with one exception: at the highest concentration basolateral BHPM reduced nerve-mediated secretion. CONCLUSIONS AND INTERFERENCES: BHPM enhanced mucosal secretion and muscle contractility. Results suggested that the laxative effect of BHPM was a consequence of the increase in muscle tone as well as an increased K+ secretion when acting luminally and a nerve-driven Cl- and HCO3- secretion once acting basolaterally after absorption.

Tryptase potentiates enteric nerve activation by histamine and serotonin: Relevance for the effects of mucosal biopsy supernatants from irritable bowel syndrome patients.

BACKGROUND: We previously showed that mucosal biopsy supernatants from irritable bowel syndrome patients activated neurons despite low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We studied the potentiating responses between these mediators on excitability of enteric neurons. METHODS: Calcium-imaging was performed using the calcium-sensitive dye Fluo-4 AM in human submucous plexus preparations from 45 individuals. Histamine, serotonin, and tryptase were applied alone and in combinations to evaluate nerve activation which was assessed by analyzing increase in intracellular Ca2+ ([Ca2+ ]i ), the proportion of responding neurons and the product of both defined as Ca-neuroindex (NI). Protease activated receptor (PAR) 2 activating peptide, PAR2 antagonist and the serine protease-inhibitor FUT-175 were used to particularly investigate the role of proteases. KEY RESULTS: Histamine or serotonin (1 µmol/L each) evoked only few small responses (median NI [25%/75%]: 0 [0/148]; 85 [0/705] respectively). Their combined application evoked statistically similar responses (216 [21/651]). Addition of the PAR2 activator tryptase induced a significantly higher Ca-NI (1401 [867/4075]) compared to individual application of tryptase or to coapplied histamine and serotonin. This synergistic potentiation was neither mimicked by PAR2 activating peptide nor reversed by the PAR2 antagonist GB83, but abolished by FUT-175. CONCLUSIONS & INFERENCES: We observed synergistic potentiation between histamine, serotonin, and tryptase in enteric neurons, which is mediated by proteolytic activity rather than PAR2 activation. This explained neuronal activation by a cocktail of these mediators despite their low concentrations and despite a relatively small PAR2-mediated response in human submucous neurons.

Effect of preoperative biliary drainage on bacterial flora in bile of patients with periampullary cancer.

BACKGROUND: Patients with obstructive jaundice due to periampullary tumours may undergo preoperative biliary drainage (PBD). The effect of PBD on the microbiome of the biliary system and on postoperative outcome remains unclear. METHODS: A single-centre retrospective study of patients with obstructive jaundice due to periampullary cancer, treated between July 2007 and July 2015, was undertaken. Intraoperative bile samples were obtained for microbiological analysis after transection of the common bile duct. Postoperative complications were registered. RESULTS: Of 290 patients treated, intraoperative bile samples were present for 172 patients (59·3 per cent) who had PBD and 118 (40·7 per cent) who did not. Contamination of bile was increased significantly in patients who underwent stenting (97·1 per cent versus 18·6 per cent in those without stenting; P < 0·001). PBD resulted in a shift in the biliary microbiome from Escherichia coli in non-stented patients (45 per cent versus 19·2 per cent in stented patients; P = 0·009) towards increased contamination with Enterococcus faecalis (9 versus 37·7 per cent respectively; P = 0·008) and Enterobacter cloacae (0 versus 20·4 per cent; P = 0·033). This shift was associated with a high incidence of bacterial resistance against ampicillin-sulbactam (63·6 per cent versus 18 per cent in patients with no PBD; P < 0·001), piperacillin-tazobactam (30·1 versus 0 per cent respectively; P = 0·003), ciprofloxacin (28·5 versus 5 per cent; P = 0·047) and imipenem (26·6 versus 0 per cent; P = 0·011). The rate of wound infection was higher in patients with a positive bile culture (21·0 per cent versus 6 per cent in patients with sterile bile; P = 0·002). Regression analysis revealed the presence of Enterococcus faecium (odds ratio 2·83, 95 per cent c.i. 1·17 to 6·84; P = 0·021) and Citrobacter species (odds ratio 5·09, 1·65 to 15·71; P = 0·005) as independent risk factors for postoperative wound infection. CONCLUSION: There are fundamental differences in the biliary microbiome of patients with periampullary cancer who undergo PBD and those who do not. PBD induces a shift of the biliary microbiome towards a more aggressive and resistant spectrum, which requires a differentiated perioperative antibiotic treatment strategy.

Effect of hyoscine butylbromide (Buscopan®) on cholinergic pathways in the human intestine.

BACKGROUND: Hyoscine butylbromide (HBB, Buscopan(®) ) is clinically used to treat intestinal cramps and visceral pain. Various studies, mainly on animal tissues, suggested that its antimuscarinic action is responsible for its spasmolytic effect. However, functional in vitro studies with human tissue have not been performed so far. METHODS: We wanted to provide a comprehensive study on the mode of action of HBB in human intestinal samples and investigated HBB (1 nmol L(-1) -10 µmol L(-1)) effects on muscle activity with isometric force transducers and calcium imaging, on epithelial secretion with Ussing chamber technique and on enteric neurons using fast neuroimaging. KEY RESULTS: Hyoscine butylbromide concentration dependently reduced muscle contractions, calcium mobilization, and epithelial secretion induced by the muscarinic agonist bethanechol with IC50 values of 429, 121, and 224 nmol L(-1), respectively. Forskolin-induced secretion was not altered by HBB. Cholinergic muscarinic muscle and epithelial responses evoked by electrical nerve stimulation were inhibited by 1-10 µmol L(-1) HBB. Moreover, HBB significantly reduced the bethanechol-induced action potential discharge in enteric neurons. Interestingly, we observed that high concentrations of HBB (10 µmol L(-1)) moderately decreased nicotinic receptor-mediated secretion, motility, and nerve activity. CONCLUSIONS & INFERENCES: The results demonstrated the strong antimuscarinic action of HBB whereas the nicotinic antagonism at higher concentrations plays at most a moderate modulatory role. The muscle relaxing effect of HBB and its inhibition of muscarinic nerve activation likely explain its clinical use as an antispasmodic drug. Our results further highlight a so far unknown antisecretory action of HBB which warrants further clinical studies on its use in secretory disorders.

Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons.

BACKGROUND: Beneficial effects of ginger in the treatment of gastrointestinal (GI) problems and chemotherapy-induced nausea and vomiting are well accepted. In rodents, the action of ginger seems to be mediated by the inhibition of 5-HT3 receptors, which are established targets to combat emesis and irritable bowel syndrome. METHODS: Heterologously expressed human 5-HT3 A or 5-HT3 AB receptors were characterized by means of Ca(2+) influx studies using HEK293 cells. Complementing Ca(2+) measurements in Fluo-4-AM-stained whole-mount preparations of the human submucous plexus were carried out. Furthermore, [3H]GR65630 binding assays were performed to reveal the mode of action of ginger and its pungent compounds. KEY RESULTS: We show for the first time that ginger extracts and its pungent arylalkane constituents concentration-dependently inhibit activation of human 5-HT3 receptors. Ginger extracts inhibited both receptors with increasing content of pungent compounds, confirming that these are part of ginger's active principle. Inhibition potencies of the arylalkanes 6-gingerol and 6-shogaol on both receptors were in the low micromolar range. A lipophilic ginger extract and 6-gingerol had no influence on 5-HT potency, but reduced the 5-HT maximum effect, indicating non-competitive inhibition. The non-competitive action was confirmed by [(3) H]GR65630 binding, showing that the ginger extract did not displace the radioligand from 5-HT3 A and 5-HT3 AB receptors. The potential relevance of the inhibitory action of ginger on native 5-HT3 receptors in the gut was confirmed in whole-mount preparations of the human submucous plexus. While a general neurotoxic effect of 6-gingerol was ruled out, it inhibited the 2-methyl-5-HT-mediated activation of 5-HT3 receptors residing on enteric neurons. CONCLUSIONS & INFERENCES: Our findings may encourage the use of ginger extracts to alleviate nausea in cancer patients receiving chemotherapy and to treat functional GI disorders.

N-acetylcysteine prevents doxorubucine-induced cardiotoxicity in rats.

This study is designed to observe the effects of N-acetylcysteine (NAC) on doxorubucine-induced cardiac toxicity in rats both histologically and biochemically. Totally 32 rats divided equally into four groups were studied. The first group received only 200 mg/kg NAC intraperitoneal (i.p.) once every 24 h for 5 days (group 1); the second group received 20 mg/kg doxorubucine (DOX) i.p. single dose plus NAC 200 mg/kg i.p. once every 24 h for 5 days (group 2); the third group received DOX 20 mg/kg DOX i.p. single dose (group 3) and the fourth group, which is also the control group, received saline (group 4). Following 24 h of the final dose, blood samples were drawn from a portal vein and heart tissue were obtained. Tissue thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) levels were highest in the DOX group. In the DOX-treated rats, serum TBARS, NO, aspartate transaminase, lactate dehydrogenase and creatine kinase levels were highest when compared with other groups. Except for serum superoxide dismutase levels, all other parameters differed significantly between the DOX plus NAC group and the DOX group. In the DOX plus NAC group, general architecture was preserved better than the DOX group and myofibril loss was minimal compared with the DOX group. NAC demonstrated, both biochemically and histologically, to be effective in the prevention of DOX-induced cardiotoxicity in rat models. Evaluation of NAC's effect on DOX toxicity warrants further clinical trials on cancer patients.

Securing the data economy: translating privacy and enacting security in the development of DataSHIELD.

Contemporary bioscience is seeing the emergence of a new data economy: with data as its fundamental unit of exchange. While sharing data within this new 'economy' provides many potential advantages, the sharing of individual data raises important social and ethical concerns. We examine ongoing development of one technology, DataSHIELD, which appears to elide privacy concerns about sharing data by enabling shared analysis while not actually sharing any individual-level data. We combine presentation of the development of DataSHIELD with presentation of an ethnographic study of a workshop to test the technology. DataSHIELD produced an application of the norm of privacy that was practical, flexible and operationalizable in researchers' everyday activities, and one which fulfilled the requirements of ethics committees. We demonstrated that an analysis run via DataSHIELD could precisely replicate results produced by a standard analysis where all data are physically pooled and analyzed together. In developing DataSHIELD, the ethical concept of privacy was transformed into an issue of security. Development of DataSHIELD was based on social practices as well as scientific and ethical motivations. Therefore, the 'success' of DataSHIELD would, likewise, be dependent on more than just the mathematics and the security of the technology.

Prophylactic glycine administration attenuates pancreatic damage and inflammation in experimental acute pancreatitis.

BACKGROUND/AIMS: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. METHODS: To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. RESULTS: Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. CONCLUSIONS: Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP. and IAP.

The microenvironment in chronic pancreatitis and pancreatic cancer induces neuronal plasticity.

BACKGROUND: Pancreatic neuropathy in chronic pancreatitis (CP) and pancreatic cancer (PCa) is characterized by pancreatic neuropathy, i.e. increased neural density and hypertrophy, which are associated with neuropathic pain. To better understand the mechanism of these neuropathic alterations, we aimed at achieving an in-vitro simulation of the intrapancreatic neuroplasticity. METHODS: Dissociated myenteric plexus (MP) and dorsal root ganglia (DRG) neurons of newborn rats were treated with normal human pancreas (NP), CP or PCa tissue extracts. Furthermore, MP and DRG neurons were cultured in supernatants from different pancreatic cancer cell lines (PCC) and human pancreatic stellate cells (hPSC) obtained from either CP or PCa tissues. For analysis, the neurite density, outgrowth, neuronal branching capacity and perikaryonal size were quantified. KEY RESULTS: Myenteric plexus and DRG neurons grown in CP and PCa tissue extracts built denser networks than in NP extracts. Both neuronal types showed a strong neurite outgrowth, more complex branching pattern and a somatic hypertrophy in CP and PCa extracts. Pancreatic cancer cell supernatants induced a prominent neurite outgrowth, increased neurite density and perikaryonal hypertrophy in MP and DRG neurons. Supernatants of CP-derived hPSC strongly stimulated neurite outgrowth. Glial density in MP cultures was strikingly increased by PCa tissue extracts. CONCLUSIONS & INFERENCES: Intrapancreatic microenvironment in CP and PCa induces neuroplastic alterations under in-vitro conditions, leading to increased neural density and hypertrophy. Thus, due to its neurotrophic attributes, the intrapancreatic microenviroment in CP and PCa seems to be a key player in the generation of pancreatic neuropathy and neuroplasticity.

Nanoplankton population dynamics and dissolved oxygen change across the Bay of Izmir by neural networks.

The bay of Izmir, which is the biggest harbor on the Aegean Sea, is of upmost economical importance for Izmir, the third largest city in Turkey. Most of the studies carried out focused on the effects of intensive industrial activity and agricultural production on the bay pollution within the region. These studies, most of the time, are limited to monitoring the level of pollution. However, it is believed that these studies should be supported with models and statistical analysis techniques, as the models, especially the prediction ones, provide an important approach to assessing risk and assessment. In this study, neural network analysis was used to construct prediction models for nanoplankton population change with nutrients and other environmentally important parameters. The results indicated that, using data over a 52 week period, it is possible to predict nanoplankton population dynamics and dissolved oxygen change for the future.