Clinical trial: efficacy and safety of dexlansoprazole MR 60 and 90 mg in healed erosive oesophagitis - maintenance of healing and symptom relief.

BACKGROUND: Dexlansoprazole MR, a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, effectively heals erosive oesophagitis. AIM: To assess dexlansoprazole MR in maintaining healed erosive oesophagitis. METHODS: Patients (n = 451) with erosive oesophagitis healed in either of two dexlansoprazole MR healing trials randomly received dexlansoprazole MR 60 or 90 mg or placebo once daily in this double-blind trial. The percentage of patients who maintained healing at month 6 was analysed using life table and crude rate methods. Secondary endpoints were percentages of nights and of 24-h days without heartburn based on daily diaries. RESULTS: Dexlansoprazole MR 60 and 90 mg were superior to placebo for maintaining healing (P < 0.0025). Maintenance rates were 87% and 82% for the 60 and 90 mg doses, respectively, vs. 26% for placebo (life table), and 66% and 65% vs. 14%, respectively (crude rate). Both doses were superior to placebo for the percentage of 24-h heartburn-free days (60 mg, 96%; 90 mg, 94%; placebo, 19%) and nights (98%, 97%, and 50%, respectively). Diarrhoea, flatulence, gastritis (symptoms) and abdominal pain occurred more frequently with dexlansoprazole MR than placebo, but were not dose-related. CONCLUSION: Dexlansoprazole MR effectively maintained healed erosive oesophagitis and symptom relief compared with placebo, and was well tolerated.

Effect of added µ-calpain and post-mortem storage on the mechanical properties of bovine single muscle fibres extended to fracture.

The effects of µ-calpain and post-mortem storage on the strength of single muscle fibres were investigated. During the 10 min of incubation at pH 7.5, µ-calpain became evenly distributed throughout the fibre. µ-Calpain-incubation resulted in thinner (P <0.001) Z-lines and reduced (P <0.001) the strength of the fibres compared to controls. These results demonstrate that µ-calpain is capable of mechanically weakening the muscle fibres. Post-mortem storage of meat for 10 days at 2 °C weakened (P <0.001) the muscle fibres compared to 24-h fibres. The presence or absence of Ca(2+) affected fibre stiffness. Fibres incubated at pH 7.5 in 100 µM Ca(2+) were less stiff than fibres incubated in 200 µM EGTA. Breaking stress and strain were not affected by Ca(2+). We hypothesise that Ca(2+) causes conformational changes in some of the load-bearing proteins, which alters their initial resistance to extension, but does not affect the breaking strength of the fibres.

Effect of proteolytic enzyme activity and heating on the mechanical properties of bovine single muscle fibres.

The effect of proteolysis and heating on the mechanical properties of single muscle fibres isolated from bovine M. semitendinosus was investigated. Short incubations with µ-calpain (pH 7.5) and cathepsin B (pH 5.6) at room temperature reduced (P<0.01) the raw fibre strength by 50%. After subsequent heating, µ-calpain-incubated fibres were 20% weaker and cathepsin B-incubated fibres 50% weaker than heated controls. Fibres were incubated for 8 days at 2 °C under post-mortem like pH conditions (pH 5.6) or pH conditions optimal for the calpains (pH 7.5). At pH 5.6 no significant weakening of the fibres was observed when incubations were performed in 0.1, 1 or 10 mM Ca(2+). In contrast, incubation in 1 or 10 mM Ca(2+) at pH 7.5 decreased the strength of the fibres. Addition of the protease inhibitors E-64 or PD150,606 prevented this weakening, suggesting that the weakening is caused by proteolyses and not directly by Ca(2+).

[Measurement of quality of care and the "soft values" at a pediatric department]. / Måling af den faglige kvalitet og de "bløde vaerdier" på en børneafdeling.

INTRODUCTION: Medical care must be provided in accordance with high professional standards and patients' needs and priorities. MATERIALS AND METHODS: In this study, interviews with parents and focus group interviews with the health care staff (doctors and nurses) were conducted in order to set quality standards and define related indicators for emergency admittance to a paediatric department. According to the standards, the quality of care was measured with the indicators developed. One hundred and fifty episodes of care were assessed by questionnaires covering parent satisfaction, registration of waiting times, and investigation of case records. RESULTS: In 17% of the episodes, there were waiting times of more than 2 hours before seeing a doctor. Various quality problems were identified. Thirty-one medical standards of the episodes of care were assessed in a structured audit process. The results of the clinical audit showed that some standards were met only in 50% of the episodes. DISCUSSION: Quality development must be implemented on a documented basis. Improvements have been implemented according to the results.

Tenderization of beef by lactic acid injected at different times post mortem.

The potential to tenderize beef muscles by the injection of lactic acid (0.5 M, 10% w/w) was studied using the pectoralis profundus muscle from cull cows. The injection was performed either 1 h (pre rigor) or 24 h (post rigor) post mortem, and the meat was stored for 2 or 14 days post mortem. Both treatments caused a rapid pH drop to around 5.0 within 4 h of injection. Other effects were: (1) an accelerated release of lysosomal enzymes into the cytosol; (2) a greater degradation of myosin heavy chains; (3) ultrastructural alterations of the myofibrils which included a general weakening or rupture in the M-lines and, to a lesser extent, in the I-bands; (4) a decreased heat stability of perimysial collagen indicated by a lower insoluble collagen content, lower differential scanning calorimetry transition temperature, and lower transition temperatures in isometric tension tests on muscle strips. The lactic acid injections improved significantly the textural traits of the meat (shear value, tensile strength, sensory scores) at 2 days post mortem with little further improvement when storage was extended to 14 days post mortem. Changes in texture were of similar amplitude at both post mortem injection times. The tenderization mechanisms of lactic acid injection are discussed.

The effect of cooking temperature on mechanical properties of whole meat, single muscle fibres and perimysial connective tissue.

The structural changes in beef semitendinosus caused by cooking were studied by performing tensile tests of the isolated meat components (i.e. single muscle fibres and perimysial connective tissue) and related to the toughness of the whole meat. Whole meat toughness was found to increase in two separate phases upon cooking from 40-50°C, and again from 60 to 80°C with a decrease in meat toughness between 50 and 60°C, in agreement with previous studies. The changes in whole meat toughness at temperatures below 60°C were found to correspond to changes in the mechanical properties of the perimysial connective tissue, whereas changes of whole meat toughness at temperatures above 60°C were found to correspond to increased breaking strength of single muscle fibres. The myofibrillar component explained approximately 47% of the variation in whole meat toughness upon cooking whereas inclusion of the connective tissue component increased the goodness of fit.

Combined effect of epinephrine and exercise on calpain/calpastatin and cathepsin B and L activity in porcine longissimus muscle.

The objective of the study was to improve the understanding of the relationship between the effect of epinephrine plus exercise and meat tenderness. The calpain, calpastatin, and cathepsin B + L activities and postmortem proteolysis in porcine longissimus muscle were studied. The muscle glycogen stores were depleted in five pigs by s.c. injection of epinephrine (.3 mg/kg) at 15 h antemortem and exercise on a treadmill (5 min, 3.8 km/h) immediately before slaughter. Antemortem injection of epinephrine and treadmill exercise resulted in higher ultimate pH (6.32 vs 5.66 in control) and decreased (P < .05) thaw loss, cooking loss, and shear force values. The muscle energy depletion treatment increased (P < .05) the muscle mu-calpain activity measured 42 min postmortem, and at 24 h mu-calpain activity was still approximately 50% greater in the high ultimate pH group. Also, as the ratio of mu-calpain to calpastatin increased (P < .01), the overall proteolytic potential of the calpain system were greater. These observations suggest that the muscle energy level may influence the activity of the calpain system in the living animal. The high ultimate pH group showed lower (P < .001) cathepsin B + L activity in the myofibrillar and the soluble fractions after 8 d of storage, suggesting that the increased ultimate pH increased the stability of the lysosomal membrane and thereby reduced the release of cathepsins from the lysosomes during storage. The SDS-PAGE showed increased (P < .001) degradation of a 39-kDa band in the epinephrine and exercise-treated samples. Degradation products at 30, 31, and 32 kDa were labeled by troponin-T antibody in western blot. An appearing 24-kDa band was identified as a troponin-I degradation product in western blot. The proteolytic degradation pattern of myofibrillar proteins during storage differed in control and treated samples, supporting the hypothesis that calpain-mediated proteolysis was affected after treatment, resulting in meat with high ultimate pH.

Convulsions, ataxia and hallucinations following propofol.

A 6-year-old fit girl experienced convulsions 44 h after an otherwise uneventful anaesthesia with propofol, alfentanil and nitrous oxide. As an underlying pathology was suspected, the child was kept sedated for 6.5 h for further investigations. During this period she received a continuous infusion of propofol amounting in total to 1600 mg. After having regained consciousness, she was strikingly ataxic and remained so for 5 days. During this period she also experienced two episodes of hallucinations lasting about 2 h. Investigations including lumbar puncture, EEG, cerebral CT and MR scan could not explain the neurological symptoms. She recovered without long-term sequelae.

Tenderisation of pork as affected by degree of cold-induced shortening.

Porcine M. longissimus dorsi from 12 carcasses were used to study the effect of ante mortem exercise treatment, time of boning and different ageing periods on tenderness and tenderisation in pork. The pigs were randomly allocated into three groups, of which the pigs (in two of them) were exposed to work on a treadmill: (1) 30 min rest after work, then slaughtered; (2) slaughtered without rest after work; and (3) controls, which were not exposed to work before slaughter. At 1 and 6 h post-stunning, samples from right side of each carcass were excised and immediately chilled in icewater until 24 h post-stunning. The left side loins were used as controls and were chilled on the carcasses at 12-14°C for 90 min and then at 2°C before boning at 24 h post-stunning. The effect of ageing, 0 or 7 days at 2°C, was studied. No parameter in this study was significantly affected by ante mortem treatment. WB shear force decreased significantly with increasing boning time and was correlated to the degree of muscle shortening in unaged excised samples. Muscle shortening for the 1 h excised cuts showed an average value of 27·4%, while an average value of only 6·1% was obtained for 6 h excised cuts. Ageing for 7 days resulted in only minor (7·3%) tenderness improvement for the 1 h excised cuts as compared to the 24·5% decrease in WB shear force obtained from the 6 h excised, less cold-shortened cuts. These differences in ageing rate, however, did not result in detectable changes in the degradation profile of myofibrillar proteins as analysed by SDS-PAGE.

Production of histamine and tyramine by lactic acid bacteria isolated from vacuum-packed sugar-salted fish.

The incidence of histamine- or tyramine-producing lactic acid bacteria was examined in several products of vacuum-packed sugar-salted fish (salmon, halibut, mackerel). No histamine-producing isolates were observed, whereas the majority of tyramine-producing isolates were identified as Carnobacterium spp. These organisms were shown to be important members of the microbial flora during storage of vacuum-packed sugar-salted salmon at 5 degrees C. The amount of tyramine produced was reduced by lowering the temperature from 9 degrees C to 4 degrees C for all of five strains of carnobacteria or lactobacilli. The majority of tyramine was produced during the exponential growth phase for Carnobacterium piscicola N 5 and Lactobacillus viridescens N 69. The ability of these bacteria to produce tyramine may be used as an index of microbial quality/acceptability of stored vacuum-packed sugar-salted fish.

An FPLC method for determination of calpains and calpastatin in porcine m longissimus dorsi.

Using a rapid FPLC procedure for the separation of calpain I, calpain II and the inhibitor calpastatin from pork meat, results of proteolytic and inhibitory activity were obtained. Duplicate measurements showed variation coefficients less than 0.13. Compared to others we found lower calpain I activity 1 h post-mortem. Three groups of pigs were randomly selected. One group was exposed to work immediately before slaughter, another group was exposed to work but allowed 30 min rest before slaughter, while the third group was a control group. Samples were taken from m longissimus dorsi 1 h and 6 h post-mortem. Work had no influence on the calpain/calpastatin activity, but a significant decrease in the calpain and calpastatin activity 6 h post-mortem was found. It should be noted that the results are preliminary and are part of an ongoing study. The method described allows separation of three extracts per instrument per day followed by activity determinations of calpains and calpastatin by the casein assay.

Purification and characterisation of tyrosine decarboxylase and aromatic-L-amino-acid decarboxylase.

Microbial tyrosine decarboxylase (EC 4.1.1.25) and mammalian aromatic-L-amino-acid decarboxylase (EC 4.1.1.28) catalyse the formation of tyramine from L-tyrosine. These enzymes were characterised after isolation to purity by methods including fast polymer liquid chromatography (FPLC). Tyrosine decarboxylase was isolated from Streptococcus faecalis by FPLC anion exchange chromatography (11-times purification; 72% recovery; 23.2 U/mg protein). FPLC on Phenyl-Superose resulted in purification to 115 U/mg protein. Aromatic-L-amino-acid decarboxylase was isolated from pig kidney by ammonium sulfate fractionation, DEAE chromatography, and FPLC anion exchange chromatography (21-times purification; 22% recovery; 0.71 U/mg protein). By FPLC chromatofocusing, tyrosine decarboxylase eluted at pH 4.3 and aromatic-L-amino-acid decarboxylase at pH 5.0. Isoelectric focusing of tyrosine decarboxylase gave two bands (pI 4.4 and 4.5). With pyridoxal 5'-phosphate removed by ultrafiltration, only one band (pI 4.4) appeared, and SDS polyacrylamide electrophoresis confirmed the purity. FPLC gel filtration resulted in molecular weights 143,000 and 86,000, respectively, for tyrosine decarboxylase and aromatic-L-amino-acid decarboxylase. In SDS electrophoresis, tyrosine decarboxylase had the monomer molecular weight 75,000, showing a dimer structure for the enzyme.

Adenosine 3',5'-monophosphate in plasma, urine, and native and isoproterenol-stimulated leukocytes of dogs.

Adenosine 3',5'-monophosphate (cAMP) was determined by means of a commercial kit in urine and plasma from 40 hospitalized dogs and in native and isoproternol-stimulated leukocytes from 30 of these animals. Mean urine and plasma concentrations were 6.1 micron and 14 nM, with 95% tolerance limits ("normal values") ranging from 0.0 to 12 micron and 0.21 to 27 nM, respectively. The plasma concentration was approximately half the value previously reported for experimental dogs. The median cAMP content in native leukocytes was 5.9 pmol/10(7) cells. The mean response to isoproterenol was 0.85 pmol/10(7) cells, much less than in human leukocytes. The response was statistically significant (P less than 0.01), but was so small that it is unlikely to be measurably affected in atopic dogs.