Plasma impurities observed by a pulse height analysis diagnostic during the divertor campaign of the Wendelstein 7-X stellarator.

The paper reports on the optimization process of the soft X-ray pulse height analyzer installed on the Wendelstein 7-X (W7-X) stellarator. It is a 3-channel system that records X-ray spectra in the range from 0.6 to 19.6 keV. X-ray spectra, with a temporal and spatial resolution of 100 ms and 2.5 cm (depending on selected slit sizes), respectively, are line integrated along a line-of-sight that crosses near to the plasma center. In the second W7-X operation phase with a carbon test divertor unit, light impurities, e.g., carbon and oxygen, were observed as well as mid- to high-Z elements, e.g., sulfur, chlorine, chromium, manganese, iron, and nickel. In addition, X-ray lines from several tracer elements have been observed after the laser blow-off injection of different impurities, e.g., silicon, titanium, and iron, and during discharges with prefill or a gas puff of neon or argon. These measurements were achieved by optimizing light absorber-foil selection, which defines the detected energy range, and remotely controlled pinhole size, which defines photon flux. The identification of X-ray lines was confirmed by other spectroscopic diagnostics, e.g., by the High-Efficiency XUV Overview Spectrometer, HEXOS, and high-resolution X-ray imaging spectrometer, HR-XIS.

The bone-protective effect of the phytoestrogen genistein is mediated via ER alpha-dependent mechanisms and strongly enhanced by physical activity.

Reduced estrogen levels occurring during menopause in women are accompanied by a variety of disorders, e.g. hot flushes, depressions, osteoporosis, increase in body weight and reduced movement drive. The phytoestrogen genistein (GEN) has been demonstrated to have a significant bone-protective potency. In order to study the ER subtype-specific effects of this phytoestrogen on bone in an animal model, ovariectomized (OVX) female Wistar rats were either treated with 17beta-estradiol (E(2)) (4 microg/kg/day), the ER alpha-specific agonist (ALPHA) 16 alpha-LE(2) (10 microg/kg/day), the ER beta-specific agonist (BETA) 8 beta-VE(2) (100 microg/kg/day) or GEN (10 mg/kg/day) for 3 weeks. Vehicle-treated OVX animals served as controls. All animals had the opportunity of voluntary wheel running. Movement activity, changes of body weight and trabecular bone mineral density (BMD) in the tibia were analyzed. E(2) and ALPHA treatment, but not treatment with BETA, significantly increased the movement activity of OVX rats. Treatment with GEN resulted in a significant decrease of movement activity as compared to OVX animals. Bone mineral density in the trabecular area of the tibia and the expression of bone morphogenetic protein-2 (BMP-2) were significantly reduced in OVX- and BETA-treated rats as compared to rats substituted with E(2), ALPHA and GEN. The bone-protective effect of ALPHA was antagonized by co-treatment with the pure antiestrogen Faslodex (ICI). In order to distinguish hormone-dependent effects from those of exercise, we performed an additional experiment where the animals had no opportunity of wheel running. The results demonstrate that physically inactive rats have a stronger decrease of bone mineral density than physically active animals. Very surprisingly, our data demonstrate that GEN has no bone-protective activity in the absence of physical activity. In contrast, ALPHA and E(2) are bone-protective in the presence and absence of physical activity. In conclusion, our data provide evidence that the effects of E(2) on body weight, movement drive and protection of bone mineral density are mediated via ER alpha, whereas activation of ER beta has only a limited effect. Our data also indicate that the bone-protective effects of GEN may be mediated via ER alpha-dependent mechanisms and that physical activity has a strong impact on the bone-protective potency of this phytoestrogen.

Resting energy expenditure in females with cystic fibrosis: is it affected by puberty?

OBJECTIVE: The aims of this study were to determine the effect of puberty and the menstrual cycle on resting energy expenditure (REE) in females with cystic fibrosis (CF). DESIGN: Cross-sectional study. All participants had measurements of REE, anthropometry and pubertal staging. The measurements in the postmenarche group were carried out both in the follicular and luteal phases of their menstrual cycle. SETTING: CF outpatient clinic at the Children's Hospital at Westmead. SUBJECTS: Fifty-six females with CF and pancreatic insufficiency (13 postmenarche) were recruited from the hospital clinic and 63 controls (21 postmenarche) were recruited through families and friends of hospital staff. RESULTS: Females with CF had a higher REE than controls (111.6+/-12.8% of predicted from controls P<0.001). There was a significant effect of menarche on REE with a decrease in the postmenarche -470 kJ/24 h compared with premenarche after adjustment for fat-free mass, fat mass and group (control or CF). There was no difference in REE between the follicular and luteal phases for either CF or controls. CONCLUSIONS: Females with CF had raised REE that appeared to be independent of menarche. This study implies all females with CF and pancreatic insufficiency may need more intensive dietary management, owing to raised REE, to maintain growth and nutritional status, and possibly improve survival.

Parallel secretion of pancreatic phospholipase A(2), phospholipase A(1), lipase, and colipase in children with exocrine pancreatic dysfunction.

The cosecretion of pancreatic lipase and colipase are important in normal fat digestion. As adsorption of phosphatidylcholine to the lipid substrate interferes with lipase activity, hydrolysis to lysophosphatidylcholine with subsequent desorption is also essential for fat digestion. There are some data regarding the secretion of pancreatic phospholipases in normal adults but none in children or patients with pancreatic disease. In the present study, we aimed a) to develop an accurate fast assay method to measure phospholipase A(2) and b) to determine the secretion rate of pancreatic phospholipase A(2) and whether it is cosecreted with lipase and colipase in children with exocrine pancreatic dysfunction. Nine male patients aged 0.5 to 16 y (seven with cystic fibrosis, two with malabsorption) underwent pancreatic stimulation tests. Their colipase and lipase secretion rates were measured by titrimetric methods and phospholipase A(2) and A(1) by phosphorus magnetic resonance spectroscopy ((31)P NMR). It was found that the phospholipases, colipase, and lipase were absent in the two patients with pancreatic insufficiency. In patients with normal absorption, there were marked inter-and intrasubject variations of lipase, colipase, and phospholipase secretion rates that were consistent with the degree of exocrine pancreatic dysfunction. However, in the three 20-min stimulation periods of the pancreatic function test, pancreatic phospholipase is cosecreted with lipase and colipase, and average colipase and phospholipase A(2) secretion rates follow a similar or parallel pattern. These findings are consistent with the important role of pancreatic phospholipases in intestinal phospholipid hydrolysis leading to the desorption of phospholipids from the lipid substrate and enhancing lipid hydrolysis and phospholipid absorption.

Pancreatic function and extended mutation analysis in DeltaF508 heterozygous infants with an elevated immunoreactive trypsinogen but normal sweat electrolyte levels.

BACKGROUND: Newborn screening for cystic fibrosis (CF) with immunoreactive trypsinogen (IRT) and DeltaF508 analysis followed by sweat testing misses some infants with CF and detects more DeltaF508 carriers than expected. Some of the apparent DeltaF508 carriers may be DeltaF508 compound heterozygotes with normal sweat electrolyte levels. METHODS: Infants identified by newborn screening with an elevated IRT level, one DeltaF508 allele, and a sweat chloride level <60 mmol/L underwent CF mutation analysis, pancreatic stimulation testing, and repeat IRT analysis followed by clinical review and repeat sweat test at 12 months. RESULTS: Over a 24-month period we identified 122 DeltaF508 heterozygotes and recruited 57; 4 had borderline sweat chloride levels (40 to 60 mmol/L), 5 (8.8%, 95% CI 1.4, 16.2) had a second CF mutation (R117H), and 11 (20%, 95% CI 10, 30) had the intron 8 5T allele. Three had clinical CF at 12 months (initial sweat chloride levels: 53, 51, and 32 mmol/L). Pancreatic electrolyte secretion in the subjects with a borderline sweat chloride level was similar to that in patients with known CF. CONCLUSION: The excess of DeltaF508 heterozygotes detected by IRT/DNA screening is associated with the presence of a second mutation or the 5T allele in some infants. Screened infants with borderline sweat chloride levels almost certainly have CF, but long-term follow-up of the infants with the genotype DeltaF508/R117H and DeltaF508/5T is required to determine their outcome. In the meantime, newborn screening should be confined to severe mutations associated with classic CF.

Phospholipid changes in children with pancreatic sufficiency and insufficiency.

The phospholipid secretion rates and phospholipase A1 and phospholipase A2 activities in biliary-pancreatic secretions of patients with pancreatic sufficiency and insufficiency were measured using 31P-NMR spectroscopy. It was possible to quantify conveniently the individual phospholipids without prior extraction of lipids or treatment of the samples with detergent. The reciprocal nature of the decrease in phosphatidylcholine concentration, compared with the increase in the concentration of 1-lysophosphatidylcholine and 2-lysophosphatidylcholine, suggested a substrate/product relationship consistent with the activities of phospholipase A1 and phospholipase A2, respectively. Although the secretion rates of total biliary phospholipids among the patients with pancreatic sufficiency were similar, the phospholipase A1 and phospholipase A2 activities varied considerably. The latter differences were similar to their pancreatic lipase and colipase secretion levels and hence their degree of pancreatic dysfunction. The biliary-pancreatic secretions from patients with pancreatic insufficiency showed no enzyme activities. Total biliary phospholipid secretions in patients with pancreatic insufficiency with common bile duct stenosis were significantly lower than those in patients with pancreatic sufficiency, and pancreatic insufficiency without common bile duct stenosis.

Hepatobiliary disease in cystic fibrosis patients with pancreatic sufficiency.

Focal and multilobular biliary cirrhosis are considered pathognomonic of cystic fibrosis (CF) and almost invariably have been reported in patients with steatorrhea. In contrast, patients with pancreatic sufficiency and normal absorption are considered less likely to develop liver or biliary tract problems. The authors report three patients with CF and pancreatic sufficiency, presenting with recurrent abdominal pain (unrelated to pancreatitis). All had common bile duct disease, one with multilobular cirrhosis and portal hypertension. Pancreatic sufficiency was proven by quantitative pancreatic stimulation tests, 3-day fecal fat analyses, and serum pancreatic isoamylases. All three patients had mild lung disease. Two were homozygous for the common delta F508 mutation, and the other, a delta F508 compound heterozygote. Hepatobiliary structure and function were determined by serial hepatobiliary scintigraphy, percutaneous transhepatic cholecystography, and biochemical liver function tests. Patients 1 and 3 had mild hepatomegaly, normal liver biochemistry, and distal common bile duct strictures. Patient 2 had a firm nodular liver with splenomegaly, abnormal liver biochemistry, and a cholangiographic appearance of sclerosing cholangitis. All have undergone operative treatment for persistent abdominal pain. These cases confirm the occurrence of common bile duct pathology and liver disease in patients with CF and pancreatic sufficiency. They demonstrate that liver and biliary tract disease can occur independently of the underlying disease severity and the presence of steatorrhea. Further, they suggest that obstruction of the biliary tract may be an additional factor in the evolution of liver disease in CF.

Determination of conjugated and unconjugated serum 3 alpha-OH bile acids by high-performance liquid chromatography.

A simple reverse-phase liquid chromatographic method has been developed for the quantitative measurement of 11 3 alpha-OH bile acids in paediatric serum samples. Bile acids are enzymatically reduced to the corresponding 3-keto compound and then derivatized with the fluorophore dansyl hydrazine. Preliminary fractionation of bile acids is not required. The limit of detection is 0.1 mumol/L using a sample size of 200 microL. One hundred and twenty-three serum samples were analysed by the high-performance liquid chromatography (HPLC) method and the results compared with a commercial kit method (Enzabile) presently used in many laboratories for the measurement of total bile acids. There was a good correlation between the two methods (r = 0.96). The method is suitable for use in a clinical laboratory for the further investigation of those patients with abnormally high total bile acid levels where quantification of bile acid fractions is required.

Assessment of pancreatic function in screened infants with cystic fibrosis.

Previously we have reported that 37% of infants with cystic fibrosis diagnosed by neonatal screening with the dried blood spot immunoreactive trypsin assay have pancreatic sufficiency. However, 34 of the 78 infants had pancreatic function tests an average 2.3 years after diagnosis, thus it was possible that the percentage with neonatal pancreatic sufficiency was underestimated, due to the loss of pancreatic function with time in some infants. To assess this hypothesis we have assessed pancreatic function at the time of diagnosis in a further 20 infants since the completion of the previous study. Results of fecal fat determinations and/or pancreatic stimulation tests indicate that 10 (50%) of these infants have pancreatic sufficiency. Combining these results with those of the previous study, 31 of 64 patients (48%) have pancreatic sufficiency at this early age. We have also monitored the progression of pancreatic disease in the 39 patients with pancreatic sufficiency recognized to date. Eleven have developed pancreatic insufficiency and require enzyme replacement therapy. Five others have shown further improvement of colipase secretion with age. We conclude that the dried blood immunoreactive trypsin screening program for cystic fibrosis does recognize patients with pancreatic sufficiency, and at diagnosis nearly half the patients are in this category. To date, 28% of patients with pancreatic sufficiency have demonstrated a variable decline in pancreatic function with age.

Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program.

The use of the dried-blood immunoreactive-trypsin assay for the detection of cystic fibrosis in newborns has been questioned on the grounds that it may fail to identify patients with enough pancreatic function to have normal fat absorption. To investigate this possibility, we assessed pancreatic function in 78 patients identified in a neonatal screening program as having cystic fibrosis. The diagnosis of cystic fibrosis was confirmed by abnormal results on a sweat chloride test. The results of measurements of fecal fat excretion, pancreatic-stimulation tests, and estimations of the serum level of pancreatic isoamylase indicated that 29 of the 78 children (37 percent) had substantial preservation of pancreatic function. These children (median age, four years) had growth that was close to normal and comparable to growth in children with severe pancreatic insufficiency who received oral enzyme therapy. Pancreatic insufficiency subsequently developed in 6 of the 29 patients, at 3 to 36 months of age. We conclude that the serum immunoreactive-trypsin assay used in neonatal screening programs identifies patients with cystic fibrosis who have sufficient pancreatic function to have normal fat absorption and that a substantial proportion of infants identified as having cystic fibrosis are in this category.

Nutritional status, growth and development in children undergoing intensive treatment for cystic fibrosis.

Dietary intakes were measured over a period of 5 days in 36 malnourished and 36 well-nourished patients with cystic fibrosis. Both energy and protein intakes were significantly less in the malnourished patients for the two age groups studied: 4-9.99 years (p less than 0.01 for both parameters), and 10-16 years (p less than 0.05 and p less than 0.01, respectively). In both age groups and both patient groups, average protein intakes were well in excess of the recommended daily intake, but energy intake in the malnourished patients was below the recommended daily intake. Nutritional supplementation of 10 malnourished patients with a polymeric formula, infused overnight via a gastrostomy tube, resulted in a seven-fold increase in weight gain (p less than 0.001) and a doubling of linear growth velocity (p less than 0.01) over a period of 18 months, compared to the 18 months prior to gastrostomy feeding. Measurements of total body nitrogen in eight of these patients demonstrated a 38% increase in body nitrogen content over 12 months, indicating a replenishment of the protein deficit.

Chronic undernutrition/growth retardation in cystic fibrosis.

There is now sufficient evidence to prove that the maintenance of a high energy normally balanced diet prevents malnutrition/growth retardation and may well enhance prognosis in patients with CF. Most patients are able to tolerate the normal to high fat content without undue problems with steatorrhoea and with the recent advent of more effective enzyme replacement therapy, this should be even less of a problem. Conversely, there is an equally large bulk of evidence to indicate that the maintenance of a low fat diet, while controlling symptoms from steatorrhoea in some patients, is energy depriving and produces growth failure. In children or teenagers who are presently growth retarded, installation of a high energy intake may improve growth in some, but not in others. Further investigation of the latter patients is required to evaluate their persistent anorexia and advantages and disadvantages of nutritional supplementation by invasive techniques. Certainly growth and wellbeing can be vastly improved. However, such studies may well have to be multicentered to obtain sufficient patients to control for the many variables involved, in order to demonstrate the effects on pulmonary function.

Methemoglobin reduction in crocodile blood: are high levels of MetHb typical of healthy reptiles?

In 82 wild-caught Crocodylus porosus, levels of NADH-MetHb reductase and GSH seem adequate to maintain hemoglobin in its reduced functional state. Studies of C. porosus erythrocytes in vitro show reduction of metHb in the presence of lactate, glucose and plasma, but not pyruvate. These findings, together with recent data which show low metHb in a variety of reptiles, cast doubt on the accepted view that high levels of MetHb are typical of healthy reptiles. One explanation for the sharp contrast between earlier and more recent data could be technical. We found low metHb in Crocodylus johnstoni, Chelodina longicollis and Sphenomorphus quoyi. However, high and variable vales reminiscent of many of the earlier data were obtained by omitting final centrifugation prior to spectrophotometry. Interestingly, this step is not part of the standard clinical method but is necessary in analyses of blood with nucleated red cells. These observations suggest that high metHb may not be typical of reptiles after all.

Levels of glycolytic enzymes in the red blood cells of Australian Aborigines.

Blood samples wer collected from three populations of full-blood Aborigines, and twelve different enzymes were assayed in red blood cells. These results were compared with those of Caucasian controls. In the majority of enzymes studied significant differences were observed between the Aboriginal populations and also between individual Aboriginal populations and the Caucasian controls.

Effect of other drugs and chemicals on the degradation of aspirin in vitro: possible extrapolation to in vivo metabolism of aspirin.

To assess the possible influence of other drugs and chemicals on the metabolic degradation of aspirin in man, their effect on the serum aspirin esterase activity was determined in vitro. The activation or inhibition of the enzyme as observed with these compounds suggest the possibility that simultaneous ingestion of these drugs with aspirin may influence the pharmacology and toxicity of the analgesic.

PIP: The action of various drugs and chemicals on the serum aspirin esterase activity was tested as a measure of their possible effect on the metabolic degradation of aspirin in order to elucidate how the interaction between drugs and aspirin may influence aspirin's pharmacology and toxicity. The in vitro test used serum as the source of the enzyme which was incubated with soluble aspirin as substrate followed by treatment with an acidic reagent of mercuric chloride and ferric nitrate, which precipitates the serum proteins. The following drugs were found to act as inhibitors of serum aspirin esterase activity: codeine phosphate (50%), dextropropoxyphene (Doloxen and Digestic both 50%), morphine, methadone, pethidine, papaveretum (all 50%), hydroxychloroquine (Plaquenil 50%), heparin (50%), propanolol (Inderal 50%), cimetidien (Tagamet 50%), alcohol (50%), and ascorbic acid (50%). The following drugs were activators of aspirin esterase: calcium (50%) and magnesium (50%). The following drugs were found inactive: paracetamol, caffeine, phenacetin, phyenylbutazone (Butazolidine), indomethacin (Indocid), cortisone acetate, flufenamic acid (Arlef), mefenamic acid (Ponstan), Ibuprofen (Brufen), dipyridamole (Persantin), warfarin (Coumadin), clofibrate (Atromid), sulphinpyrazone (Anturan), colchincine, allopurinol, diazepam (Valium), oral contraceptives, and sodium cromoglycate (Intal).

A kindred with red cell pyruvate kinase deficiency.

A case is described of mild haemolytic anaemia in a female homozygous for pyruvate kinase deficiency, with 20% of normal enzyme activity and with the unexplained associations that she suffers from angina pectoris and that three of her children died in childhood from a muscular dystrophy presumed to be Werdnig-Hoffman disease.

Red blood cell glycolysis and potassium type in sheep.

Based on the observations made on human and dog red blood cells, it was recently proposed that the response of red cell glycolysis to variations in the levels of specific cations in an evolutionary adaptation in response to a specific cellular environment. We have now examined the effect of K+ and Na+ on the activity of pyruvate kinase (PK) in the red blood cells from 2 genetically different types of sheep high potassium (HK) and low potassium (LK). The results indicate that K+ stimulate glucose consumption and the activity of PK in both types of sheep. It thus appears that red cell PK from LK sheep does not fit into the concept of cellular environment and PK activity.

Erythrocyte 2,3-diphosphoglycerate in anaemic sheep.

Experimental anaemia resulted in an increase of red cell 2,3-DPG from 0.11 micronM/g Hb to 0.99 micronM in haemoglobin A sheep and from 0.21 micronM in haemoglobin B sheep. Production of haemoblobin Cas a result of anaemia was confined to haemoblobin A only. The results, therefore, appear to suggest that the rise in 2,3-DPG in the red blood cells of different haemoblobin types is independent of haemoblobin C.