RESUMEN

BACKGROUND: Prions are renowned for their distinct resistance to chemical or physical inactivation, including steam sterilization. Impaired efficacy of inactivation poses a risk to patients for iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) via contaminated surgical instruments. AIMS: Most established prion inactivation methods were validated against scrapie agents, although those were found to be generally less thermostable than human prions. Thus, knowledge gaps regarding steam-sterilization kinetics of CJD prions should be filled and current guidelines reviewed accordingly. METHODS: Prion inactivation through widely recommended steam sterilization at 134°C was assessed for several holding times by analysing the residual prion seeding activity using protein misfolding cyclic amplification (PMCA). FINDINGS: Scrapie 263K was found to be the least thermoresistant prion strain showing no seeding activity after 1.5 min at 134°C, while variant CJD was the most stable one demonstrating some seeding activity even after 18 min of steam sterilization. Sporadic CJD subtype VV2 exhibited residual seeding activity after 3 min, but no detectable activity after 5 min at 134°C. CONCLUSION: Validated steam sterilization for 5 min at 134°C as previously recommended for the routine reprocessing of surgical instruments in contact with high-risk tissues is able to substantially reduce the seeding activity of CJD agents, provided that no fixating chemical disinfection has been performed prior to sterilization and that thorough cleaning has reduced the protein load on the surface to less than 100 µg per instrument.

Asunto(s)

RESUMEN

Test strips are convenient tools for rapid, semi-quantitative analysis of a variety of parameters by dipping them for a few seconds in a sample solution followed by a simple colorimetric read-out. Their sensitivity is mainly determined by the reactivity of the test dyes on the reaction zone and is not sufficient for some applications. The detection limit of commercially available free chlorine test strips, for example, is at present not low enough to confirm the absence of this analyte as disinfectant in rinsing solutions after disinfection or to control required residual amounts of chlorine in drinking water. Therefore, we developed a user-friendly lateral flow test which is capable to detect very low amounts of free chlorine. The latter relies on a larger sample volume passing the reaction zone as compared to simple dip test strips. An amount of as low as 0.05 ppm chlorine can, however, only be detected if oxidation stable flow test substrates are used. The eventually developed flow test reaches a 10x higher sensitivity than a commercial dip test. The result is obtained within 4-5 min flow time, whereby no action is required by the user during this analysis time.

RESUMEN

This noninterventional, prospective study investigated the administration of tapentadol prolonged release (PR; the dosage form described in this article is commercially available in Germany as Palexia retard; Grünenthal GmbH, Aachen) for severe chronic pain in routine clinical practice over a 3-month period. Effectiveness analyses included data from 3134 patients; 1331 received World Health Organization (WHO) Step III pretreatment. A total of 97.8% of patients received long-term analgesic pretreatment (42.5% with strong opioids). Switching to tapentadol PR produced a 3.9-point mean pain reduction (baseline, 7.0 ± 1.5; end of observation, 3.1 ± 1.8; 11-point numerical rating scale; descriptive P value ≤.001); 72.1% of patients experienced clinically relevant pain relief (≥50%) at the end of observation. Significant decreases in pain-related impairment of daily activities and improvements in quality of life (descriptive P value ≤.001) were observed with tapentadol PR with good tolerability. Tapentadol PR was effective for various pain indications in patients previously receiving strong opioids (67.2% achieved clinically relevant pain relief). Tapentadol PR can be considered an alternative therapy to classical opioids for treatment of severe chronic pain.

Asunto(s)

RESUMEN

The instability of currently used electrolyte solutions and of the carbon support during charge-discharge in non-aqueous lithium-oxygen cells can lead to discharge products other than the desired Li2O2, such as Li2CO3, which is believed to reduce cycle-life. Similarly, discharge in an O2 atmosphere which contains H2O and CO2 impurities would lead to LiOH and Li2CO3 discharge products. In this work we therefore investigate the rechargeability of model cathodes pre-filled with four possible Li-air cell discharge products, namely Li2O2, Li2CO3, LiOH, and Li2O. Using Online Electrochemical Mass Spectrometry (OEMS), we determined the charge voltages and the gases evolved upon charge of pre-filled electrodes, thus determining the reversibility of the formation/electrooxidation reactions. We show that Li2O2 is the only reversible discharge product in ether-based electrolyte solutions, and that the formation of Li2CO3, LiOH, or Li2O is either irreversible and/or reacts with the electrolyte solution or the carbon during its oxidation.

Asunto(s)

RESUMEN

Glyme-based electrolytes were studied for the use in lithium-air batteries because of their greater stability towards oxygen reduction reaction intermediates (e.g., superoxide anion radicals (O2˙(-))) produced upon discharge at the cathode compared to previously employed carbonate-based electrolytes. However, contradictory results of glyme stability tests employing KO2 as an O2˙(-) source were reported in the literature. For clarification, we investigated the reaction of KO2 with glymes of various chain lengths qualitatively using (1)H NMR and FTIR spectroscopy as well as more quantitatively using UV-Vis spectroscopy. During our experiments we found a huge impact of small quantities of impurities on the stability of the solvents. Therefore, we studied further the influence of impurities in the glymes on the cycling behavior of Li-O2 cells, demonstrating the large effect of electrolyte impurities on Li-O2 cell performance.

RESUMEN

BACKGROUND: Chronic pain in the elderly is common. Especially in the elderly inadequate treatment of pain can cause significant functional impairmentand deterioration of qualityof life. METHODS: Theaim of this post-marketing surveillance study was to collect data from clinical practice on the analgesic efficacy and safety of the 7-day transdermal buprenorphine patch in patients with chronic non-malignant pain pre-treated with opioids. A total of 2713 elderly multimorbid patients were switched to 7-day transdermal buprenorphine patch from previous opioid treatment mainly due to inadequate analgesia. 83% of patients received a 7-day transdermal buprenorphine patch dosage > or = 10 microg/h. During the 8-weekobservation period, data on pain intensity, quality of sleep/life (NRS-11 point scales) and safety wererecorded. RESULTS: Mean pain intensity decreased by 4 points with 7-day transdermal buprenorphine patch (p < or = 0.001). Quality of sleep and life as well as social activities and self-reliance improved significantly. Compliance and tolerability were assessed as very good/good in > 90% of patients. Adverse drug reactions (ADRs) occurred in 3% of patients and corresponded to 90.1% to the already-known spectrum of ADRs of 7-daytransdermal buprenorphinepatch. CONCLUSIONS: The results confirm that elderly patients with opioid pre-treatment benefit from a switch to 7-day transdermal buprenorphine patch with regard to reduction of pain and improved quality of life.

Asunto(s)

RESUMEN

BACKGROUND: A patient-orientated therapy management for patients with severe chronic pain includes effective analgesia, improvement of health related quality of life and improvement of functionality. PATIENTS AND METHOD: In this prospective, non-interventional trial in 630 patients with severe chronic pain mostly due to chronic low back pain or gonarthrosis, treatment with tapentadol retard was evaluated with respect to its effects on analgesia, functionality and quality of life. Collected data included pain intensity, painDETECT,SF-12, FFbH-R and FFbH-OA. RESULTS: Mean pain intensity decreased significantly (NRS-3: -3.2 points, p < or = 0.001) and in 47.9% of the patients the mean pain intensity was reduced by at least 50%. Health-related quality of life and functionality improved significantly. Tolerability was good. The known tolerability profile of tapentadol retard could be confirmed. CONCLUSION: In this study in real-life-setting tapentadol was effective in terms of analgesic effect but also in terms of improvementof health-related quality of life and functionality, leading to a benefit for the patient in daily life.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: This prospective, non-interventional study involving general practitioners and internists in Germany investigated the administration of tapentadol prolonged release (Palexia retard) for the treatment of severe chronic pain in routineclinical practice over a 3-month observation period. METHODS: Collected data included tapentadol PR dosage, previous and concomitant analgesic treatment, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. Effectiveness was analyzed for 3134 patients; additionally, a subgroup analysis was performed in 1331 patients with WHO III pretreatment. RESULTS: A total of 97.8% of all patients received analgesic long-term pretreatment, 42.5% of those strong opioids. Switching to tapentadol PR resulted in a mean pain reduction of 3.9 points from 7.0 +/- 1.5 at baseline to 3.1 +/- 1.8 at end of observation (NRS-11, 11-point pain scale; descriptive p value < or = 0.001); 72.1% of patients experienced a clinically relevant pain relief of > or = 50% at end of observation. A total of 89.4% of the patients attained either their intended pain reduction and/or an additional individual treatment goal at end of observation; both were established at start of tapentadol PR treatment. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life (descriptive p value < or = 0.001) with an overall good tolerability of tapentadol PR. In particular, good effectiveness of tapentadol PR treatment was reported for various pain indications in patients who had already previously been treated with strong opioids. A clinically relevant pain reduction > or = 50% was achieved in 67.2% of these patients. CONCLUSIONS: Tapentadol PR can be considered an alternative therapy to classical opioids for the treatment of severe chronic pain. Particularly for severe chronic pain requiring long-term medication, a reduction of common opioid side-effects with tapentadol PR therapy could contribute to better patient compliance.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: This subgroup analysis of a non-interventional study involving general practitioners and internists investigated the administration of tapentadol prolonged release (Palexia retard) for the treatment of severe chronic tumor pain in routine clinical practice in Germany. METHODS: Data of all patients in the study cohort who were exclusively diagnosed with tumor pain (n = 143) were included in this analysis. Data collection during the 3-month observation period included previous and concomitant analgesic treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. RESULTS: A total of 96.5% of all patients with tumor pain had already received analgesic long-term treatment prior to initiation of tapentadol PR therapy, 49.0% of those strong opioids. Switching to tapentadol PR resulted in a mean pain reduction of 3.8 points from 7.1 +/- 1.4 at baseline to 3.3 +/- 1.9 at end of observation (NRS-11, 11-point pain scale; descriptive pvalue < or = 0.001). At end of observation, 67.4% of the patients had experienced a clinically relevant pain relief of > or = 50%, and 89.9% of the patients attained either their intended pain reduction and/or an additional individual treatment goal; both goals had been predefined at start of tapentadol PR treatment. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life (descriptive p value < or = 0.001) with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. CONCLUSIONS: Treatment with tapentadol PR resulted in marked effective and well tolerated relief of severe tumor pain accompanied by an improvement of pain-related impairments of daily activities and quality of life in this routine clinical practice non-interventional study. Tapentadol PR--an innovative effective analgesic--might thus provide an alternative treatment option in the management of tumor pain.

Asunto(s)

RESUMEN

During cancer therapy with DNA-damaging drug-agents, the development of secondary resistance to apoptosis can be observed. In the search for novel therapeutic approaches that can be used in these cases, we monitored chemotherapy-induced apoptosis resistance in a syngenic mouse tumor model. For this, syngenic murine colorectal carcinoma cells, which stably expressed a FRET-based caspase-3 activity sensor, were introduced into animals to induce peritoneal carcinomatosis or disseminated hepatic metastases. This syngenic system allowed in vitro, in vivo and ex vivo analysis of chemotherapy induced apoptosis induction by optically monitoring the caspase-3 sensor state in the tumor cells. Tumor tissue analysis of 5-FU treated mice showed the selection of 5-FU-induced apoptosis resistant tumor cells. These and chemo-naive fluorescent tumor cells could be re-isolated from treated and untreated mice and propagated in cell culture. Re-exposure to 5-FU and second line treatment modalities in this ex-vivo setting showed that 5-FU induced apoptosis resistance could be alleviated by imatinib mesylate (Gleevec). We thus show that syngenic mouse systems that stably express a FRET-based caspase-3 sensor can be employed to analyse the therapeutic efficiency of apoptosis inducing chemotherapy.

Asunto(s)

RESUMEN

We describe a surgical emergency due to GI-bleeding caused by gastrointestinal autonomic nerve tumours (GANT s) in a patient with von Recklinghausen s disease. A 72 year old female patient with von Recklinghausen s disease was admitted with maelena. Endoscopy showed no active bleeding in the stomach and the colon. Therefore an angio-CT-scan was performed which revealed masses of the proximal jejunum as source of bleeding. Laparotomy was indicated and a 20 cm segment of jejunum which carried multiple extraluminal tumours was resected. The source of the bleeding was a 2 cm tumour which had eroded the mucosal surface. Immunohistologically, evidence of neuronal differentiation could be shown in the spindle-formed cells with positive staining for C-Kit (CD 117), CD 34, and a locally positive staining for synaptophysine and S100. This case report illustrates the association between neurofibromatosis and stromal tumours and should alert surgeons and gastroenterologist about gastrointestinal manifestations in patients with von Recklinghausen s disease.

Asunto(s)

RESUMEN

Se describe una urgencia quirúrgica por sangrado intestinal debidoa tumor gastrointestinal de nervios autónomos (GANT) asociadoa enfermedad de von Recklinghausen.Una mujer de 72 años con neurofibromatosis fue ingresadacon signos de melena. La endoscopia digestiva alta y baja fue negativa.Se indicó TAC con contraste que advirtió tumores yeyunalescomo causa del sangrado. Se realizó laparotomía y resecciónde un segmento de 20 cm de yeyuno que incluía varios tumores.La causa del sangrado activo fue lesión en mucosa intestinalpor erosión tumoral. El análisis por inmunohistoquímica de la piezamostró diferenciación neuronal, con células fusiformes con tinciónpositiva para el C-Kit (CD 117), CD 34.Esta nota clínica pone de manifiesto la asociación entre la neurofibromatosisy los tumores estromales y debe alertar a gastroenterólogosy cirujanos sobre las posibles manifestaciones intestinalesen pacientes con enfermedad de von Recklinghausen

We describe a surgical emergency due to GI-bleeding causedby gastrointestinal autonomic nerve tumours (GANT’s) in a patientwith von Recklinghausen’s disease.A 72 year old female patient with von Recklinghausen’s diseasewas admitted with maelena. Endoscopy showed no activebleeding in the stomach and the colon. Therefore an angio-CTscanwas performed which revealed masses of the proximal jejunumas source of bleeding. Laparotomy was indicated and a 20cm segment of jejunum which carried multiple extraluminal tumourswas resected.The source of the bleeding was a 2 cm tumour which haderoded the mucosal surface. Immunohistologically, evidence ofneuronal differentiation could be shown in the spindle-formedcells with positive staining for C-Kit (CD 117), CD 34, and a locallypositive staining for synaptophysine and S100.This case report illustrates the association between neurofibromatosisand stromal tumours and should alert surgeons and gastroenterologistabout gastrointestinal manifestations in patientswith von Recklinghausen’s disease

Asunto(s)

RESUMEN

Characteristics of thermal denaturation of pea legumin and a product of its limited proteolysis with trypsin - legumin-T, in a wide range of NaCl concentrations have bean measured by means of differential scanning microcalorimetry. By the increase of NaCl concentration, the number of cooperative units (domains) increases from 1 per one polypeptide chain to 2 for legumin and 1.8 for legumin-T. Deconvolution of denaturation peaks have revealed up to three peaks, which were ascribed to the dissociation of protein macromolecules to subunits and the unfolding of alpha- and beta-polypeptide chains. The analysis of experimental data based on some assumptions showed that the splitting of C-termini of alpha-chains, which are not constituents of cooperative domains, in the course of limited trypsinolysis results in destabilization of the quaternary structure of legumin and loosening of alpha-chains, as well as decrease of the temperatures of their maximum stability.

Asunto(s)

Asunto(s)

RESUMEN

The term "functional potential" was introduced to better approach to the understanding of the relationships between the structure and the functional properties of food proteins. Although in practice the complex of structural features of a protein contributes to its functionality, it is very useful to regard the functional potential of the protein surface on the one side and to look on special effects of protein conformation (role of compact or unfolded state) on the functionality on the other side. This point of view may help to design the best strategy of modification of the protein structure and functionality. The special situation of the oligomeric legume storage protein, i.e. legumin-like 11 S globulins and vicilin-like 7 S globulin, and the structural and functional modification of 11 S globulin by limited tryptic hydrolysis and by acylation are discussed in this paper.

Asunto(s)

RESUMEN

Associative interactions between proteins and polysaccharides, both coulombic and non-coulombic, lead to the formation of interpolymer complexes. Complex formation with charged polysaccharides, either anionic or cationic, imparts solubility to seed globulins in the vicinity of their isoelectric points. This has been shown for the complexes "sunflower 11 S globulin (helianthinin)--sodium alginate" and "faba bean legumin (or the product of its limited proteolysis with trypsin--legumin-T)--chitosan". Hysteresis effects allow to control the solubility of seed globulins in weakly acid or weakly basic media. Formation of soluble complexes of faba bean legumin or legumin-T with chitosan substantially increases the emulsion stability of the both proteins.

Asunto(s)

RESUMEN

The properties of acetylated, succinylated and phosphorylated protein isolates extracted from the flour of yellow lupins (L. luteus) were studied by means of oscillatory rheology. The flow behaviour of protein dispersions (15% w/w) and the properties of thermotropic gels were distinctly influenced by the modification. Succinylation increased the viscosity of the dispersions of unmodified protein isolate (LPI) from 99 mPas to 515 mPas and results in the lowest gel point (T = 30.5 degrees C). Acetylation and phosphorylation enhance the pseudoplastic flow behaviour of the dispersions. Acylated lupin samples formed the strongest gels with a small visco-elastic range while phosphorylation leads to weak and "rubber-like" gels.

Asunto(s)

RESUMEN

The behaviour of a rapeseed protein isolate (RI) and its main protein components - globulin (RG) and albumin (RA) - in adsorbed and spread monolayers, as well as in emulsions was investigated. Tensiometry, film-pressure area and Langmuir-Blodgett-techniques, and emulsion parameters were used to characterise the behaviour of the rapeseed proteins at various interfaces. The adsorption isotherms for albumin showed a plateau value for the surface pressure (Pi(e)) of 11.6 mN/m at the low critical association concentration (CAC) of 5.6x10(-8) g/ml. Both values were found to be distinctly higher for the globulin and the protein isolate. The isotherms of a mixture of RG and RA, which corresponds to the composition of RI, seems to be a superimposition of the isotherms of RA and RG. Contact angle measurements showed that all samples used were able to form LB-layers and to make hydrophilic glass surfaces more hydrophobic and vice versa. The changes in contact angle were more pronounced on hydrophobic glass surfaces. Monolayer and emulsion characteristics are dominated by the interfacial properties of albumin. The maximum film pressure reached by globulin was only about 8 mN/m. The globulin also possesses the lowest emulsifying activity. From the mean molecular area calculated for spread globulin, it is concluded that the globulin maintains its globular conformation at surfaces, which explains the low surface activity. Albumin and the protein isolate were highly surface active in monolayers and emulsion formation. The slightly different interfacial behaviour of the protein isolate compared with the corresponding mixture is probably due to additional effects of non-protein components and a partially denatured state of the protein.

RESUMEN

The investigation of hydrodynamic and thermodynamic properties and the determination of the molecular mass of legumin-T, the product of limited tryptic hydrolysis of the 11-S-globulin from pea seeds, was carried out to ascertain the structural relationship to globulin-T's from other legumin-like proteins. The obtained legumin-T preparation has a molecular mass M(W)=260+/-10 kDa and M(S,D)=270+/-20 kDa. The secondary structure of legumin-T is characterised by a high percentage of beta-sheet conformation, comparable to that of native legumin and a reduced percentage of helical conformation. The conformational stability of legumin-T evaluated by equilibrium unfolding in the presence of guanidinium chloride was only slightly reduced in comparison to the native legumin, whereas the calorimetrically determined denaturation enthalpy and Gibbs energy of denaturation were found to be increased for legumin-T. These physicochemical properties are very similar to those of faba bean legumin-T.

Asunto(s)

RESUMEN

The effect of progressive phosphorylation by phosphorous oxychloride upon the conformation of the 300 kDa storage protein (cruciferin) from rapeseed has been studied using chemical analysis, SDS-PAGE, HPLC, analytical ultracentrifugation, viscometry, fluorescence spectroscopy, and hydrophobicity measurement. The amount of phosphorous in the protein increased with the excess of phosphorous oxychloride and the pH of reaction. The bulk of phosphorus was only loosely bound to the protein and was removed by washing with cold perchloric acid. The more stably bound phosphorus groups after reaction at pH 8 were found to be nearly equally attached to amino and hydroxyl groups, whereas phosphorylation at pH 10-11 led to predominant O-phosphorylation as detected by studying the acid- and alkali-lability of the protein-phosphorous bonds. A 50 kDa component appeared as a product of covalent cross-linking of the constituent alpha- and beta-polypeptide chains. A 2.5S fraction appeared as the main product of dissociation, which takes place after a critical step of modification. The higher the extent of phosphorylation, the larger was the percentage of higher molecular weight products, the percentage of which was most significant after modification under strongly alkaline conditions. They may be attributed both to products of chemical cross-linking and to noncovalently linked aggregates formed by interactions of partially unfolded derivatives exhibiting an increased surface hydrophobicity.

Asunto(s)