Thermodynamic temperature assignment to the point of inflection of the melting curve of high-temperature fixed points.

The thermodynamic temperature of the point of inflection of the melting transition of Re-C, Pt-C and Co-C eutectics has been determined to be 2747.84 ± 0.35 K, 2011.43 ± 0.18 K and 1597.39 ± 0.13 K, respectively, and the thermodynamic temperature of the freezing transition of Cu has been determined to be 1357.80 ± 0.08 K, where the ± symbol represents 95% coverage. These results are the best consensus estimates obtained from measurements made using various spectroradiometric primary thermometry techniques by nine different national metrology institutes. The good agreement between the institutes suggests that spectroradiometric thermometry techniques are sufficiently mature (at least in those institutes) to allow the direct realization of thermodynamic temperature above 1234 K (rather than the use of a temperature scale) and that metal-carbon eutectics can be used as high-temperature fixed points for thermodynamic temperature dissemination. The results directly support the developing mise en pratique for the definition of the kelvin to include direct measurement of thermodynamic temperature.

Experimental pancreatitis disturbs gastrointestinal and colonic motility in mice: effect of the prokinetic agent tegaserod.

Acute pancreatitis remains a potentially life-threatening disease associated with gastrointestinal motility disturbances. Prokinetic agents may be useful to overcome these motility disturbances. In this study, we investigated the effect of acute necrotizing pancreatitis (ANP) on gastrointestinal motility in female mice and evaluated the effect of tegaserod, a prokinetic 5-hydroxytryptamine-4 (5HT4) receptor agonist. ANP was induced by feeding mice a choline-deficient ethionine-supplemented diet during 72 h. In vivo intestinal motility was measured as the geometric centre (GC) of 25 glass beads 30-120-360 min after gavage. Colonic peristaltic activity was studied using a modified Trendelenburg set-up. ANP significantly decreased GC 30-120-360 min after bead gavage, associated with a significant increase of myeloperoxidase in the proximal small intestine and colon, but not in the stomach or distal small intestine. Tegaserod significantly ameliorated GC 360 min after bead gavage in control and pancreatitis mice. In isolated colonic segments, ANP significantly decreased the amplitude of peristaltic waves and increased the interval between peristaltic contractions. Tegaserod normalized the disturbed interval. In conclusion, ANP impairs gastric, small intestinal and colonic motility in mice. Tegaserod improves ANP-induced motility disturbances in vivo and in vitro, suggesting a therapeutic benefit of prokinetic 5HT4 receptor agonists in the treatment of pancreatitis-induced ileus.

Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment.

CONTEXT: Recently, several cases of sudden death in GH-treated and non-GH-treated, mainly young Prader-Willi syndrome (PWS), patients were reported. GH treatment in PWS results in a remarkable growth response and an improvement of body composition and muscle strength. Data concerning effects on respiratory parameters, are however, limited. OBJECTIVE: The objective of the study was to evaluate effects of GH on respiratory parameters in prepubertal PWS children. DESIGN: Polysomnography was performed before GH in 53 children and repeated after 6 months of GH treatment in 35 of them. PATIENTS: Fifty-three prepubertal PWS children (30 boys), with median (interquartile range) age of 5.4 (2.1-7.2) yr and body mass index of +1.0 sd score (-0.1-1.7). INTERVENTION: Intervention included treatment with GH 1 mg/m2.d. RESULTS: Apnea hypopnea index (AHI) was 5.1 per hour (2.8-8.7) (normal 0-1 per hour). Of these, 2.8 per hour (1.5-5.4) were central apneas and the rest mainly hypopneas. Duration of apneas was 15.0 sec (13.0-28.0). AHI did not correlate with age and body mass index, but central apneas decreased with age (r = -0.34, P = 0.01). During 6 months of GH treatment, AHI did not significantly change from 4.8 (2.6-7.9) at baseline to 4.0 (2.7-6.2; P = 0.36). One patient died unexpectedly during a mild upper respiratory tract infection, although he had a nearly normal polysomnography. CONCLUSIONS: PWS children have a high AHI, mainly due to central apneas. Six months of GH treatment does not aggravate the sleep-related breathing disorders in young PWS children. Our study also shows that monitoring during upper respiratory tract infection in PWS children should be considered.

Regional differences in gastrointestinal motility disturbances during acute necrotising pancreatitis.

Patients with acute pancreatitis often suffer from intestinal motility disturbances but the mechanism of this dysfunction is largely unknown. We studied the effect of acute necrotising pancreatitis (ANP) on in vivo gastrointestinal motility and in vitro intestinal contractility in mice. ANP was induced non-invasively by feeding young female mice a choline-deficient ethionine-supplemented (CDE) diet during 72 h. Gastric emptying and intestinal transit were measured in vivo 15 min after intragastric gavage of a semiliquid Evans blue bolus. Gastric and intestinal neuromuscular function was determined in vitro on isolated muscle strips. ANP significantly decreased gastric emptying from 61.2 +/- 9.8 to 34.9 +/- 7.1% and intestinal transit from 63.4 +/- 5.6 to 32.5 +/- 5.4%. ANP did not affect receptor-dependent and receptor-independent gastric muscle contractions except the contractions to substance P, which were slightly inhibited. In intestinal muscle strips, ANP significantly decreased contractions to EFS, carbachol, PGF(2alpha), substance P and KCl. Our results show that ANP delays gastric emptying in vivo, associated with a specific reduction in substance P contractility in vitro. ANP also impairs intestinal transit in vivo, associated with a non-specific reduction of intestinal contractility in vitro. We conclude that ANP impairs gastrointestinal motility in mice with underlying regional differences in the pathogenic mechanisms.

[The teenager who finds it difficult to wake up in the morning: aberrant behavior, misperception or an underlying sleep disorder?]. / 's Morgens moeilijk wakker worden bij tieners: gedragsprobleem, misperceptie of slaapstoornis?

Three teenagers, two girls aged 14 years and one boy aged 10 years, had had difficulty with getting to sleep in the evening and waking up in the morning from a very early age. These difficulties led to underperformance at school and/or tension in the household. The anamneses and a sleep study led to the following conclusions: 'delayed sleep phase syndrome', 'sleep state misperception' and 'aberrant interaction between the child and its parents'. Treatment with phototherapy and regulation of the bedtimes, information and regulation of the bedtimes, and pedagogic advice, respectively, was successful within a few months. Teenagers often complain about problems with sleeping, in particular about late onset of sleep and difficulties with awakening. These problems are self-limiting in most cases, but can have a disastrous influence on social life and education.

Regression of cholesterol induced venous plaques after cholesterol withdrawal in rabbits.

Rabbits receiving a dietary cholesterol supplement of 0.5% develop atheromatous plaques in the systemic arteries, the pulmonary artery, the pulmonary veins and the venous cavities of the plexus pampiniformis in the funiculus spermaticus. Six months after the withdrawal of the cholesterol supplement the arterial lesions are still present, and show a fibrous transformation. This study is the first report of the total regression of the lesions in the particular venous localizations of the lungs and the plexus pampiniformis. The level of intraluminal pressure is discussed as the possible mechanism responsible for the diverging vascular reactivity.

Destruction of lacis cells of the juxtaglomerular apparatus in the hypercholesterolemic rabbit.

During a study of experimentally induced atheromatosis in hypercholesterolemic rabbits we found a heavy infiltration of the lacis cell field (G field) by lipids in the kidney. A systematic study was done in 12 rabbits receiving a dietary cholesterol supplement of 0.3% for 26 weeks and in 8 animals receiving a supplement of 2% for 8 weeks. Standard histology, immunohistochemistry for a-smooth muscle cell actin and with the macrophage specific antibody RAM 11, and transmission electron microscopy were performed. In the low cholesterol, long duration group, 90% of the G fields were involved. The lipid accumulation was mainly extracellular. The lacis cells contained moderate numbers of medium sized lipid vacuoles and showed signs of cytoplasmic damage leading to disintegration. The mesangial cells contained few dipid droplets and the matrix was normal. The arterioles were not involved. The lesion suggests an impairment of the clearance of lipids, leading to interstitial accumulation and cellular damage.

The influence of collapse of the lung parenchyma on the morphology of pulmonary blood vessels in the rat.

During a search for resident subendothelial smooth muscle cells in pulmonary vessels of the rat we found that in expanded lungs the muscular pads in the veins, considered by some authors as sphincters, were hardly visible whereas in collapsed lungs they were very conspicuous. In a separate study intended to quantify the degree of collapse or expansion the left lung was examined in 5 rats with a collapsed and in 5 rats with an expanded lung: the expansion was produced by filling the airways by gravity with Methacarn fixative. The degree of expansion was determined by morphometry measuring the volume density of the tissue fraction of the pulmonary parenchyma in the microscopic sections: in the expanded lung the mean value was 8.5% (range 6.7-12.6%), in the collapsed lung 20.1% (range 18.7-22.3%), a highly significant difference (p < 0.000). Serial sections generally 60-100, 6-microns-thick, were stained by PAS, Sirius red hematoxylin and Verhoeff's elastic stains. Immunohistochemical staining was done with monoclonal antibody against alpha smooth muscle cell actin and desmin. Graphic reconstructions of representative vessels were performed. It was shown that the muscular media of the veins was interrupted and that the muscular pads corresponded to the contracted smooth muscle cell segments alternating with the noncontracted segments devoid of muscle. In the expanded lungs muscular pads were flattened and often hardly detectable. This indicates that the structures considered as sphincters are postmortem contraction rings in collapsed lungs.

Sephadex induced granulomatous reaction in rats.

Granuloma formation in the rat lung after single or repeated i.v. injections, intratracheal instillation and intradermal implantation of Sephadex beads was studied over a time period from 3 h to 3 mo. Macrophages were identified with the mAB ED1, vascular smooth muscle cells with an mAB against alpha SMC-actin, endothelial cells with a polyclonal AB against factor VIII and cyclic activity with an mAB against PCNA. The morphology and the time course of the development of the granulomas is identical in the different experimental conditions. The macrophages form the bulk of the cellular infiltrates, giant cells appear after 24 h. Cyclic activity is early and marked in the interstitially located macrophages, it is delayed and slight around the beads, suggesting a biphasic pattern. The macrophage reaction is markedly enhanced after a second i.v. injection, indicating the development of a hypersensitivity state. Numerous eosinophils are located in the interstitium, but only few are in direct contact with the beads. Their number doesn't increase after a second i.v. injection. Intradermal implantations show only macrophages and lymphocytes. A special feature is the disappearance of the arterial wall around the beads resulting in extrusion without haemorrhages or thromboses.

The relationship between pre-existing subendothelial smooth muscle cell accumulations and foam cell lesions in cholesterol-fed rabbits.

We investigated whether pre-existing subendothelial smooth muscle cell (SMC) accumulations in cholesterol-fed rabbits are transformed into foam cell plaques. Twenty-four rabbits received a standard diet supplemented with 2% cholesterol for 4 or 8 weeks. Six rabbits received a supplement of 0.3% cholesterol for 35 weeks. The aorta and other systemic and pulmonary vessels were studied by immunohistochemistry for smooth muscle cells SMC (alpha-SMC actin), macrophages (RAM11), cell replication (proliferating cell nuclear antigen) and endothelial cells (von Willebrand factor; vWF). Initially the foam cell plaques were composed exclusively of foam cells of macrophage origin (MFC). In more advanced lesions SMC and collagen fibres were also present, leading to a fibrous transformation of the plaque. Cell replication was mainly located in the MFC. The endothelial cells covering the plaques showed an increased immunoreactivity for vWF which was also deposited in the interstitium between the FC. Pre-existing subendothelial SMC did not transform into FC. The newly formed FC plaques remained clearly separated from the pre-existing subendothelial SMC. The development of the plaques can be attributed not only to monocyte recruitment but also to macrophage multiplication.

Longitudinally oriented smooth muscle cells in rabbit arteries.

Intima formation in vessels, spontaneous or experimentally induced, is generally characterized by the presence of longitudinally oriented smooth muscle cells (LSMC). During an experiment of neo-intima induction in carotid arteries in rabbits, by application of a non-constrictive silastic cuff, a study was performed to investigate the presence of LSMC in the systemic and pulmonary circulations, in both elastic and muscular arteries. Three patterns could be distinguished: intimal cushions in muscular arteries, single or small groups of LSMC in the intima in elastic and larger muscular arteries, and intra-medially located layers or columns of LSMC in the aorta, the pulmonary artery, at the bifurcation of the aorta and around orifices of branches. In order to understand this peculiar orientation a biomechanical approach was used: this showed that near the lumen the circumferential stress is 4.5 times higher than the longitudinal. Because the cell surface of the smooth muscle cells exposed to this stress per unit vessel length is much less in the longitudinal than in the circular direction we conclude that the LSMC align in the direction which allows them to cope most effectively with the mechanical stresses.

Thromboxane and prostacyclin production in the perfused rabbit lung.

We investigated whether prostacyclin formation by the isolated rabbit lung can serve as a measure of pulmonary distress. The basal TXA2 and PGI2 formation was very low, and depended on the preperfusion history of the lung (low or high flow, use of dextran or artificial perfusate). The basal prostanoid production remained unchanged over a time period of 2 h. Neither was it influenced by the serotonin uptake inhibitor chlorimipramine and by small changes in temperature (33 degrees C vs 39 degrees C). The PGI2 formation was almost independent of hemodynamic alterations such as embolism or vasoconstriction. An enhanced production was only seen after a dramatic increase in flow (from 1.7-5 ml/sec), and a transient 3-fold increase was observed after administration of 1 mM H2O2. A substantial (up to 40-fold) but transient increase in TXA2 production was measured after 1 mM of H2O2, and the TXA2 production was positively correlated to the increase in pulmonary arterial pressure. However, thromboxane production was also dramatically augmented by hemodynamic alterations such as embolism, increased flow and--to a lesser extent--vasoconstriction. We conclude that the determination of the prostanoid production (and particularly the TXA2 formation) by the rabbit lung cannot be used as a direct measure of endothelial distress. To this end it is excessively biased by hemodynamic alterations such as recruitment and shear stress.

Platelet inhibition by endothelium-derived relaxing factor from the rabbit perfused aorta.

1. The platelet inhibiting activity of endothelium-derived relaxing factor (EDRF) released by the perfused thoracic aorta of the rabbit was investigated. 2. The aortic effluent superfused a ring of the abdominal aorta without endothelium in order to bioassay EDRF. Aliquots of effluent were collected on rabbit washed platelets and aggregation induced by U-46619 was measured after 1 min. Prostacyclin (PGI2) was monitored by radioimmunoassay of 6-oxo-prostaglandin F1 alpha. 3. Acetylcholine (ACh) caused a dose-dependent secretion of EDRF, PGI2 and anti-aggregating activity. Plasma and methylene blue suppressed the platelet inhibition by the effluent. 4. The PGI2 content of the effluent was not sufficient to account for all the anti-aggregating activity. However, the platelet inhibition disappeared when PGI2 formation was blocked with indomethacin. 5. Compression of the thoracic aorta increased the EDRF content in the effluent. A transient secretion of anti-aggregating activity was then observed in aortic effluent in the absence of PGI2. This activity coincided with the presumed EDRF peak in the effluent. 6. Superoxide dismutase enhanced the ACh-induced EDRF content and revealed secretion of an anti-aggregating substance when PGI2 formation was blocked. Pretreatment of the platelets with subthreshold concentrations of PGI2, or the cyclic GMP phosphodiesterase inhibitor RX-RE 56, also revealed the release of a labile platelet inhibitor in response to ACh. 7. The results indicate that EDRF released by fresh aortic endothelium may suppress platelet aggregation, particularly when PGI2 is present.

Modulation of prostacyclin biosynthesis by calcium entry blockers and extracellular calcium.

The influence of variations in the availability of extracellular Ca2+ and of Ca2+-entry blockers on prostacyclin production by mesothelial cells in culture was studied. The Ca2+-entry blockers nifedipine and verapamil suppressed the basal, as well as the thrombin-, bradykinin-, and ionophore A23187-stimulated biosynthesis by about 50-60%, but high concentrations were required and the inhibition was never complete. Basal prostacyclin formation was unaffected by a Ca2+-poor buffer, but showed 50% reduction in the Ca2+-free buffer. Although the thrombin-stimulated prostacyclin formation was not significantly influenced by a Ca2+-poor or a Ca2+-free buffer, prostacyclin release stimulated by A23187 and bradykinin was diminished in the presence of these modified incubation media; the reduction of bradykinin stimulated biosynthesis was rather small (30%). These results suggest that the Ca2+ from intracellular stores is sufficient for half maximal stimulation of the phospholipases involved in the biosynthetic pathway of prostacyclin and that--depending on the nature of the stimulus--different phospholipases are activated with varying requirements for free Ca2+.