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Notes: Abstract Histamine concentrations in canine whole blood and plasma were determined under several pharmacological, pathophysiological, and clinical conditions, using fluorometric methods. The specificity of the assay for whole-blood histamine was investigated by comparing 3 purification procedures for the isolation of histamine from whole blood including butanol extraction (Shore), ion-exchange chromatography on Dowex 50 W-X 8, and the combination of these 2 methods (Lorenz). Histamine in whole blood was identified in analytical and preparative samples by fluorescence spectra, thin-layer chromatography, degradation by diamine oxidase from pig kidney and inactivation by histamine methyltransferase from guinea-pig brain as well as by biological tests on the isolated guinea-pig ileum. Since butanol extraction resulted in significantly higher ‘histamine’ values than the other two purification procedures, ion-exchange chromatography on Dowex 50 was recommended as the method of choice for the specific determination of histamine in dog's whole blood. Normal values of histamine concentrations in canine plasma were tentatively estimated. They depended on the time between pretreatment of the animals (anaesthesia, operation) and the collection of blood and showed an approximately logarithmic normal distribution. The median, the lower/upper quartiles and the range of the plasma histamine levels obtained 30 minutes after the end of pretreatment were 0.2, 0–0.4 and 0–1.2 ng/ml, respectively. Nearly 50% of the values were zero (below 0.1 ng according to the sensitivity of the method), only 1% of them exceeded slightly 1 ng/ml. Thus histamine release by drugs or by other medical treatments was only stated, when plasma histamine levels exceeded 1 ng/ml and decreased in a way to give an elimination curve of approximately first-order kinetics (Bateman function). Histamine concentrations in dog's whole blood showed approximately a logarithmic normal distribution. The median, lower/upper quartiles and range were 47, 34/75 and 13–209 ng/ml respectively. The histamine levels in the whole blood of four circulatory regions did not show any significant differences. The plasma histamine concentrations in the portal vein were slightly higher than in the hepatic veins. The injection of exogenous histamine and the concomitant determination of plasma and whole-blood histamine levels in four circulatory regions showed that the plasma histamine determination was the more sensitive method for measuring histamine elimination curves than the whole-blood histamine assay. The elimination of exogenous histamine administered intravenously was influenced by several drugs including inhibitors of histamine inactivation and histamine receptor antagonists. Aminoguanidine and the H2-receptor antagonist burimamide slowed down the disappearance of histamine from the plasma, the H1-receptor antagonist dimethpyrindene enhanced it, but amodiaquine had no significant effects. Dimethpyrindene and burimamide were capable of releasing histamine in dogs, in some cases to a considerable extent. The plasma substitute Haemaccel®, a chemically modified gelatin, released histamine in dogs. Using batch 3000, from 27 animals investigated, 15 animals showed elevated plasma histamine levels and a hypotensive blood pressure response, whereas in 12 of the dogs it did not show an effect on these parameters. The plasma histamine levels at the time of maximum hypotension showed an approximately logarithmic normal distribution. This frequency distribution in combination with the varying incidence of anaphylactoid reactions depending on the batches used seemed very important for the interpretation of clinical reactions to Haemaccel in human test persons and patients. By histamine determinations in plasma and whole blood of several circulatory regions and in various tissues before and after infusion of Haemaccel it could be demonstrated that the sites of histamine release by Haemaccel in dogs were especially the skin of the upper hemisphere of the body and the liver, whereas the gastro-intestinal tract took up histamine from the circulation. These numerous results under various experimental conditions may be considered as an evidence for the high quality and reliability of the method to study histamine release in the whole animal or in human subjects by evaluating histamine elimination curves in plasma.

Notes: Summary Regulatory effects of insulin, somatostatin and cholecystokinin on amino acid transport in the isolated perfused rat pancreas have been studied using a rapid dual isotope dilution technique. Uni-directional L-serine transport (15 s) was quantified relative to an extracellular tracer D-mannitol over a wide range of substrate concentrations. In pancreata perfused with 2.5 mmol/l D-glucose, a weighted nonlinear regression analysis of overall transport indicated an apparent Km=14.4±1.6 mmol/l and Vmax=25.9±1.4 μmol ·min−1·g−1 (n=6). Although L-serine transport was stimulated during perfusion with 100 μU/ml bovine insulin, endogenous insulin (7–25 ng·min−1·g−1) released during continuous perfusion with either 8.8 mmol/l or 16.8 mmol/l D-glucose had no such effect. Exogenous somatostatin-14 (250 pg/ml) or cholecystokinin octapeptide (CCK-8, 3 × 10−11mol/l) appeared to increase only the Km for transport. Only CCK-8 evoked a notable protein output (2.9±0.3 mg·30min−1·g−1) and juice flow (68±10μl·30min−1·g −1, n=3) from the exocrine pancreas. When pancreata were perfused with bovine insulin (100 μU/ml) and somatostatin-14 (250 pg/ml), the stimulatory action of exogenous insulin on L-serine transport was abolished. If endogenous insulin and somatostatin, released concurrently in response to 16.8 mmol/l D-glucose, were conveyed to the exocrine epithelium via an islet-acinar portalaxis, it is conceivable that somatostatin modulates the stimulatory action of insulin on basolateral amino acid transport in the exocrine pancreas.

Notes: Summary Histamine concentrations in plasma, whole blood and various tissues of human subjects, monkeys, pigs and dogs were determined by fluorometric methods before, during and after surgical operations. Following intraabdominal surgery in 6 of 22 patients elevated plasma histamine levels were found several hours after the end of operation. Some of the causes of histamine release in surgery were found to be premedication by atropine, intravenously administered anaesthetics, infusion of plasma substitutes and manipulation on the gut. Acute blood losses were without effect on the plasma histamine levels. Clinical symptoms and pathophysiological reactions, such as tachycardia, hypotension, increased gastric secretion and anaphylactoid reactions could be related to the release of histamine in some circumstances.

Notes: Summary Rapid unidirectional transport (15 sec) ofl-serine and 2-methylaminoisobutyric acid (MeAIB) was studied in the isolated perfused rat pancreas using a dual-tracer dilution technique. Time-course experiments in the presence of normal cation gradients revealed a time-dependent transstimulation ofl-serine influx and transinhibition of MeAIB influx. Transport of the model nonmetabolized System A analog MeAIB was Na+ dependent and significantly inhibited during perfusion with 1mm ouabain. Although transport ofl-serine was largely Na+ independent, ouabain caused a time-dependent inhibition of transport. Influx of both amino acids appeared to be inhibited by the ionophore monensin but unaffected by a lowered extracellular potassium concentration. Removal of extracellular calcium had no effect on influx of the natural substratel-serine, whereas stimulation of transport by exogenous insulin (100 μU/ml) was entirely dependent upon extracellular calcium and unaffected by ouabain. Paradoxically, exogenous insulin had no effect on the time-course of MeAIB influx. The characteristics ofl-serine influx described in earlier studies together with our present findings suggest that insulin may modulate the activity of System asc in the exocrine pancreatic epithelium by a calcium-dependent mechanism.

Notes: Two recently reported pseudopotentials, an ab initio and a semiempirical one, both simulating the Ar-like core of the Ca atom, are compared in calculations for CaO. While the former pseudopotential leads to a collapse of the molecule in the X 1Σ+ ground state, such a collapse does not occur with the latter one. The reasons for this discrepancy are discussed and are attributed mainly to differences in the treatment of the higher l components of the pseudopotentials.

Notes: In recent SCF calculations for M5CO clusters (M=Cu, Ni, Al), Bagus et al. found that serious errors arise when pseudopotentials are introduced for the Cu and Ni atoms. Using the Cu pseudopotential and basis set given by Bagus et al., in SCF/CI calculations for Cu2, we find that serious errors arise indeed, but that the bulk of these errors can be eliminated by (i) a proper account of core–core interaction and (ii) enlargement of the basis set.