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Galactose clearance, measured during low galactose infusion and calculated as infusion rate divided by peripheral galactose concentration (systemic clearance), has been proposed as a measure of liver blood flow. This requires nearly complete hepatic extraction as well as negligible extrahepatic elimination. The purpose of the study was to examine if these assumptions are fulfilled in subjects with no liver disease, and to compare the galactose clearance measurement with an independent measurement of liver blood flow. Liver blood flow was measured in 6 subjects by means of a constant indocyanine green infusion, indocyanine green concentration measurements in a peripheral artery and a hepatic vein, and calculation according to Fick's principle. The mean (+/- SEM) blood flow rate was 1.2 +/- 0.1 L/min. Galactose was given at a constant infusion rate of 142 +/- 10 mumol/min, and steady-state concentrations were measured in the peripheral artery (A) and the hepatic vein (V). The hepatic extraction fraction [(A - V)/A] was 0.91 +/- 0.03. The hepatic galactose elimination rate [(A - V) X flow] was 101 +/- 12 mumol/min; this is about two-thirds of the total elimination rate (viz., infusion rate). Urinary excretion was negligible. This indicates an extrahepatic galactose elimination of approximately 41 mumol/min. Systemic galactose clearance, calculated as mentioned above, was 1.5 +/- 0.1 L blood/min. It was significantly higher than the liver blood flow in each subject (paired t-test, each p less than 0.02), on average 133% of the flow. Thus the systemic galactose clearance value overestimates liver blood flow, probably due to a small, but in this context quantitatively important, extrahepatic galactose elimination.
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PMID:Galactose clearance measurements and liver blood flow. 333 19

Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy-6-(5-tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.38 +/- 0.47, 3.44 +/- 0.25, and 1.20 +/- 0.10 mM +/- SEM on day 7; 1.16 +/- 0.13, 1.52 +/- 0.37, and 0.16 +/- 0.02 mM on day 21; and 0.67 +/- 0.09, 0.61 +/- 0.08, and 0.06 +/- 0.006 mM on day 42. Red cell adenine triphosphate levels at the same time intervals were 1.84 +/- 0.09, 1.46 +/- 0.18, and 2.11 +/- 0.04 mM; 2.10 +/- 0.05, 2.07 +/- 0.17, and 2.13 +/- 0.05 mM; and 1.42 +/- 0.13, 1.37 +/- 0.13, and 1.38 +/- 0.06 mM, respectively. The degree of hemolysis was less with the addition of the compounds, and the methemoglobin formation, plasma Na+ and K+, and lactate production were unaffected by the compounds.
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PMID:Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate-phosphate-dextrose-adenine (CPDA-1) blood. 334 Oct 63

Gastric stasis and duodenogastric reflux have each been implicated in the pathogenesis of various upper gastrointestinal disorders. However, the relationship between intragastric bile and gastric emptying has not been explored. In each of nine healthy volunteers (seven men and two women, ages 22-47 years), gastric emptying of 300 ml 10% dextrose labeled with [99mTc]DTPA was measured twice using gamma camera imaging. During one study, 20 min after ingestion of the test meal, 525 mg of freeze-dried, sterilized human T-tube bile dissolved in 20 ml water was introduced into the stomach via a previously sited fine-bore nasogastric tube. Intragastric bile salt concentrations were calculated to be within the range 1.7-2.9 mM. In control studies, 20 ml of water alone was similarly introduced. Emptying at 20 min was comparable for both groups of studies (38 +/- 3% vs 39 +/- 4%; mean values +/- SEM). For each individual study, emptying from 20 to 60 min was well represented by a single exponential function (r = 0.81-0.99). Half-emptying times for curves fitted over this period were similar in the two groups (bile: T1/2 = 18.8 +/- 2.6 min; control T1/2 = 18.8 +/- 1.9 min). These results indicate that intragastric bile, in concentrations similar to those found in patients with gastric ulcer, has no effect on gastric emptying of dextrose in normal subjects.
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PMID:Intragastric bile does not perturb gastric emptying of liquids in humans. 334 20

Thin sheets of mucosa from small intestine of neonatal calves were mounted in incubation chambers for in vitro studies. These mucosal sheets generated a potential difference (PD) of 2.05 +/- 0.02 mV (mean +/- SEM), short-circuit current (SCC) of 23.32 +/- 3.81 microA x cm2, and tissue resistance of 86.22 +/- 4.41 ohms x cm2 (n = 6). Ouabain in the serosal bathing solution caused a sharp decrease in the SCC (P less than 0.01) and PD (P less than 0.005), a decrease in tissue K content (P less than 0.05), and an increase in tissue Na content (P less than 0.05). The mucosa responded to D-glucose by an increase in PD (P less than 0.001) and SCC (P less than 0.001). In vitro methods used in the calf were validated in similar experiments on rabbit ileum.
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PMID:Effect of D-glucose on in vitro short-circuit current in neonatal calf jejunum and rabbit ileum. 339 17

1. Osmotically stimulated thirst and vasopressin release were studied during infusions of hypertonic sodium chloride and hypertonic D-glucose in euglycaemic clamped diabetic patients and healthy controls. 2. Infusion of hypertonic sodium chloride caused similar elevations of plasma osmolality in diabetic patients (288.0 +/- 1.0 to 304.1 +/- 1.6 mosmol/kg, mean +/- SEM, P less than 0.001) and controls (288.6 +/- 0.9 to 305.7 +/- 0.6 mosmol/kg, P less than 0.001), accompanied by progressive increases in plasma vasopressin (diabetic patients, 0.9 +/- 0.3 to 7.7 +/- 1.5 pmol/l, P less than 0.001; controls 0.5 +/- 0.1 to 6.5 +/- 1.0 pmol/l, P less than 0.001) and thirst ratings (diabetic patients 1.0 +/- 0.2 to 7.1 +/- 0.5 cm, P less than 0.001; controls 1.8 +/- 0.4 to 8.0 +/- 0.5 cm, P less than 0.001) in both groups. 3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both diabetic patients and healthy controls. 4. There were close and significant correlations between plasma vasopressin and plasma osmolality (diabetic patients, r = +0.89, controls r = +0.93) and between thirst and plasma osmolality (diabetic patients r = +0.95, controls r = +0.97) in both diabetic patients and healthy controls during hypertonic saline infusion. 5. Hypertonic D-glucose infusion caused similar elevations in blood glucose in diabetic patients (4.0 +/- 0.2 to 20.1 +/- 1.2 mmol/l, P less than 0.001) and healthy controls (4.3 +/- 0.1 to 19.3 +/- 1.2 mmol/l, P less than 0.001) but did not change plasma vasopressin or thirst ratings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus. 339 97

We previously reported that in insulin-treated diabetic subjects the time course of action of regular insulin injected sc is different from that reported in standard textbooks. The present studies evaluated the role of insulin antibodies (Abs) in the altered pharmacokinetics of regular insulin by comparing the time course of insulin action in 10 patients receiving chronic insulin therapy and having insulin Abs with that in 15 previously untreated patients without detectable Abs. After an overnight fast, the patients were given an infusion of 5% dextrose in water at 100 ml/h. Regular insulin (15 U) was then injected sc in the deltoid region of the arm. The onset of action of sc insulin, as indicated by a 10% fall in serum glucose, was similar in both patient groups [1.9 +/- 0.1 (+/- SEM) hour in Ab-negative and 1.8 +/- 0.1 h in Ab-positive patients]. The peak effect of insulin action, as determined by the nadir of serum glucose, was 4.6 +/- 0.2 h in the previously untreated patients, not significantly different from the value in the diabetic patients with insulin Abs (5.2 +/- 0.4 h). The duration of action of insulin was also similar in both groups (14.7 +/- 0.7 vs. 14.4 +/- 1.0 h). No significant correlations were found between insulin Ab levels and any of these 3 parameters of insulin action. However, the peak effect and total duration of insulin action were significantly correlated with the baseline serum glucose levels. A possible role of insulin Abs was evaluated in these patients by repeating the studies over a 2-year period. During this time, the previously untreated patients were treated with highly purified pork insulin, to which they developed low titers of insulin Abs. The diabetic patients who had been chronically treated with insulin were changed from less purified insulin to highly purified pork insulin, and all had a significant reduction in their Ab titers. No changes in insulin pharmacokinetics were found in either group. These studies demonstrate that the prolonged action of sc injected regular insulin in diabetic patients is not related to the effect of circulating insulin Abs.
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PMID:Prolonged action of regular insulin in diabetic patients: lack of relationship to circulating insulin antibodies. 351 90

We recently reported that the peak effect and duration of action of regular insulin injected sc were prolonged in diabetic patients and were not related to the presence of insulin antibodies. The results suggested that the ambient level of plasma glucose might be an important factor in determining the pharmacokinetics of regular insulin. In the present study we used a glucose clamp technique, which minimizes interference by counterregulatory phenomena, to study the pharmacokinetics of regular insulin injected sc at 2 different blood glucose concentrations [276 +/- 7 (+/- SEM) and 130 +/- 5 mg/dl] in 10 insulin-dependent diabetic patients. The patient's blood glucose concentration was maintained constant by means of a variable rate iv infusion of 20% dextrose in water after sc injection of regular insulin (0.2 U/kg) in the deltoid region of the arm. The onset of insulin action occurred at similar times at both glucose concentrations (0.6 +/- 0.1 h at 276 mg/dl vs. 0.5 +/- 0.1 h at 130 mg/dl; P greater than 0.05). Peak insulin action (determined from the time of the maximal glucose infusion rate) was delayed in the studies done at 276 mg/dl (4.7 +/- 0.2 h) compared to that in studies done at mean glucose concentrations of 130 mg/dl (4.3 +/- 0.2 h; P less than 0.05). The duration of insulin action was also significantly prolonged in the studies done at the higher glucose concentrations (9.1 +/- 0.3 h at 276 mg/dl vs. 7.7 +/- 0.2 h at 130 mg/dl; P less than 0.01). These results confirm previous reports of prolonged insulin action in diabetic patients, especially in the presence of hyperglycemia.
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PMID:The pharmacokinetics of subcutaneous regular insulin in type I diabetic patients: assessment using a glucose clamp technique. 352

To evaluate whether the viscera contribute to the system of membranes used in peritoneal dialysis, dialysis rate studies were performed comparing control rats (n = 9, mean peritoneal area 509 +/- 38 cm2) with eviscerated rats (n = 12, mean peritoneal area 200 +/- 123 cm2). The mass transfer coefficient (MTC) and absorption from the peritoneal cavity were calculated for urea, creatinine, and inulin, which had been added to commercially available 1.5% hydrous dextrose dialysate. Rates of peritoneal blood flow to the peritoneal membranes remaining after evisceration were similar for both groups. Urea, creatinine, glucose, and inulin were used as markers to compare control and eviscerated animals. The MTC results were (in milliliters per minute, mean +/- SEM): urea 3.0 +/- 0.3, 4.1 +/- 0.5 (P less than 0.01); creatinine 1.4 +/- 0.2, 2.0 +/- 0.2 (P less than 0.05); glucose 1.2 +/- 0.3, 1.7 +/- 0.2 (P less than 0.09); inulin 0.3 +/- 0.02, 0.6 +/- 0.1 (P less than 0.01); and MTC inulin/MTC urea 0.16 +/- 0.01, 0.14 +/- 0.01. Absorption of urea, creatinine, glucose, and inulin from the peritoneal cavity was only 10% to 23% greater among control animals. Whether the results were caused by nonparticipation of the intestinal viscera or other mechanisms, such as improved contact between dialysate and membrane, awaits further study.
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PMID:Systems of membranes involved in peritoneal dialysis. 365 24

Osmoreceptors in the upper small bowel may delay gastric emptying by inhibiting fundal tone and/or by increasing outflow resistances. In this study we examined the contribution of postpyloric resistances to this braking system. Seven dogs had gastric emptying of 250 ml 15% dextrose, labelled with 99mTc-DTPA, measured by gamma camera imaging (preoperative studies: n = 21). A proximal duodenal cannula was inserted and studies repeated in four modes: with the cannula closed (n = 14); with total diversion of gastric effluent through the cannula (n = 7); with diversion and downstream reinstillation of effluent at a constant rate (n = 14) equivalent to emptying calculated from studies without diversion; and with diversion and total reinstillation of effluent (n = 14). Gastric emptying at 90 minutes was similar in preoperative studies (48 +/- 5% - mean +/- SEM) and in those with the cannula closed (50 +/- 3%). By comparison 'total diversion' produced rapid emptying over 90 minutes (97 +/- 1%; p less than 0.001). Reinstillation of effluent at a constant rate reduced the 90 minute emptying to 59 +/- 6%, and total reinstillation slowed emptying further to 37 +/- 4% (p less than 0.05). Neither reinstillation protocol yielded gastric emptying rates that were significantly different from those in studies without diversion. With total reinstillation, emptying and hence reinstillation rates were more variable, proceeding in a step and plateau fashion. We conclude that canine jejunal osmoreceptor activity is mediated through the stomach, with postpyloric resistances playing little or no role. Gastric emptying curve analysis suggested that increments of rapid small bowel filling provoke exaggerated braking responses.
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PMID:Small bowel resistances and the gastroduodenal brake. 366 63

The effect of temperature changes (36-40 degrees C) on the liver function was studied in the isolated perfused pig liver. When compared with control studies no effect was observed on lactate, glucose, bile flow, ATP and energy charge, and the recovery after the changes in temperature was complete. The only significant changes observed regarded the hepatic oxygen uptake and galactose elimination capacity. The increase of 1 degree C resulted in an increase in galactose elimination of 6%, corresponding to a Q10 of 1.98 (SEM 0.12) with an energy of activation of 48 kJ/mol (SEM 4.7). Oxygen uptake was linearly related to galactose elimination (1.75 mol for 1 mole change in galactose elimination). These results indicate that circulatory changes are unimportant within physiological temperature changes. It is concluded that temperature effects on galactose elimination are too small to warrant a correction when used as a clinical test of quantitative liver function.
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PMID:The effect of physiological temperature changes on the galactose elimination capacity of the isolated perfused pig liver. 374 57


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