Pancreatic cancer cells show lower oleic acid oxidation and their conditioned medium inhibits oleic acid oxidation in human myotubes.

BACKGROUND: /Objectives: We aimed to metabolically compare healthy primary human pancreatic epithelial cells (hPEC) to a pancreatic cancer cell line (PANC-1) and explore the effect on energy metabolism of exposing primary human myotubes to conditioned medium from hPEC and PANC-1 cells. METHODS: Differences in metabolism were examined with radiolabeled glucose, oleic acid and lactic acid, and by qPCR. Mass spectrometry-based proteomics was used to study global protein secretion from the two cell types. Pathway analyses were performed. RESULTS: PANC-1 cells tended to have higher glucose uptake, production of lactic acid, and glucose oxidation compared to hPEC cells. PANC-1 cells had higher uptake but lower oxidation of oleic acid, and mitochondrial reserve capacity from oleic acid was lower in PANC-1 cells. These differences in energy metabolism were reflected by differences in gene expressions and pathway analyses of the secretome. Conditioned medium from PANC-1 cells attenuated oleic acid oxidation in primary human myotubes. CONCLUSIONS: Metabolic characterization of the PANC-1 cells revealed a glycolytic phenotype since they had an active glucose oxidation. Furthermore, PANC-1 cells showed a lower oleic acid oxidation and secreted a high amount of proteins into conditioned medium that also induced a reduced oleic acid oxidation in myotubes.

Communication skills training enhances nurses' ability to respond with empathy to parents' emotions in a neonatal intensive care unit.

AIM: We quantitatively analysed the effect of a course in communication on the content of nurse-parent encounters and the ability of nurses to respond to the empathic needs of parents in a level III neonatal intensive care unit. METHODS: We evaluated 36 and 45 nurse-parent encounters audio recorded before and after 13 neonatal nurses attended a communication course. The number of empathic opportunities, the nurses' responses to these and the ways they involved parents in their infants' care were studied. RESULTS: Both before and after the course, the nurses talked more than the parents during the conversations. This nurse-centredness decreased after the course. The use of empathic or exploring responses to empathic opportunities increased from 19.9 ± 9.0% to 53.8 ± 8.9% (p = 0.027), whereas ignoring the feelings of the parents or giving inadequate advice decreased from 63.0 ± 10.0% to 27.5 ± 8.4% (p = 0.043) after the course. Use of statements expressing caring for the parents and encouragement for parents to participate in the care of their infant increased after the course (p = 0.0034 and p = 0.043, respectively). The nurses felt the course was very useful for their profession. CONCLUSION: A course in communication techniques improved nurses' ability to respond to parents' feelings with empathy.

Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice.

BACKGROUND: Neutralizing antibodies (NAbs) against interferon beta (IFNß) lead to loss of treatment efficacy in multiple sclerosis patients. The seroprevalence of NAbs in multiple sclerosis patients treated with IFNß during 2003-2004 was 32% in a cross-sectional analysis of routine data. OBJECTIVES: The aim of this study was to investigate whether the seroprevalence of NAbs, the levels of NAb titres and the IFNß preparations used for treatment of multiple sclerosis patients had changed in 2009-2010. METHODS: This study included 1296 patients, analysed for NAbs with the myxovirus resistance protein A gene expression assay in 2009-2010. RESULTS: The seroprevalence of NAbs had decreased to 19% in 2009-2010, which is significantly lower compared with the previous study in 2003-2004 (p<0.0001). This decrease was attributed to the IFNß-1a preparations only, not to IFNß-1b. The frequency of patients with high positive titres decreased the most, from 16% to 7% (p<0.0001). CONCLUSIONS: NAb seroprevalence has decreased since NAb monitoring became clinical practice in 2003, especially for patients with high NAb titres. This might be due to the stricter monitoring of NAb titres that prompt NAb positive patients to stop treatment, to preferential use of less immunogenic drugs and to alteration of drug formulations.

Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab.

BACKGROUND: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. OBJECTIVE: The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. METHODS: We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. RESULTS: Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0-5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0-4.0%) and transient in 1.0% (95% CI: 0.7-1.3%) of the patients. The frequencies of permanently antibody positive patients did not show statistically significant differences between the four centres, whereas the frequencies of transiently antibody positive patients showed some variations. CONCLUSION: The frequencies of antibodies appeared to be of the same magnitude in the four centres, but might be less than in the pivotal studies of natalizumab.

A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis.

BACKGROUND: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. METHODS: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. RESULTS: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing-remitting MS patients (n=901), mean Expanded Disability Status Scale (EDSS, -10.7%), Multiple Sclerosis Severity Scale (MSSS, -20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical -9.9%, psychological -13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. CONCLUSIONS: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

Inhibition of endogenous interferon beta by neutralizing antibodies against recombinant interferon beta.

OBJECTIVE: To determine if neutralizing antibodies (NAbs) against interferon beta from patients with multiple sclerosis (MS) cross-react with other type 1 interferons, especially endogenous interferon beta, and thus might impede the immune systems of affected patients. DESIGN: Masked serum samples from MS patients were challenged in vitro against recombinant interferon beta-1a and interferon beta-1b, as well as human leukocyte interferon and fibroblast interferon, the latter representing endogenous interferon. The neutralizing capacity of serum samples on these type 1 interferons was assessed using a luciferase reporter gene assay. Randomly selected samples were titrated to further delineate the cross-reactivity of antibodies. SETTING: University medical center in Düsseldorf, Germany. PATIENTS: We randomly selected 150 samples from interferon beta-treated MS patients who had previously been tested for the presence of binding antibodies and NAbs. MAIN OUTCOME MEASURES: Neutralization of interferon beta bioactivity and cross-reactivity of anti-interferon beta antibodies. RESULTS: Antibody-mediated neutralization of interferon beta bioactivity in vitro against recombinant interferon beta was observed in all serum samples that had previously tested positive for binding antibodies and NAbs. A neutralizing pattern comparable to that of recombinant interferon beta was observed when endogenous interferon was assessed, reflecting cross-reactivity of NAbs. No differences in neutralization between recombinant and endogenous interferon were observed with respect to the interferon beta preparation used for treatment. Furthermore, no neutralization of other type 1interferons by NAbs could be detected. CONCLUSIONS: A proportion of MS patients who are treated with recombinant interferon beta develop NAbs that also neutralize endogenous interferon. Because NAbs at high titers can persist for years, these antibodies may impede the immune system in affected MS patients regardless of their current treatment regimen.