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This study was designed to determine the effect of acute hyperventilation on distal nephron hydrogen ion secretion. The blood PCO2 declined and stabilized rapidly when bicarbonate loaded rats were hyperventilated. In contrast, the urine PCO2 declined slowly, resulting in an early increase in the urine minus blood (U-B) PCO2 which could not be obliterated by carbonic anhydrase infusion. Within approximately 50 min, the U-B PCO2 in the hyperventilated and carbonic anhydrase infused rats approached zero. Consequently, equilibrium between collecting duct urine and arterial blood PCO2 was then presumed to exist. This provided the basis for the subsequent studies on a series of rats. The U-B PCO2 decreased from a control of 22+/-1 mm Hg (mean+/-SEM) to 11+/-2 mm Hg (mean+/-SEM) with hypocapnia, and rose again to its control value when the blood PCO2 returned to prehyperventilation values. This decline in U-B PCO2 with acute hyperventilation could not be attributed to changes in urine flow, phosphate, or bicarbonate excretion, suggesting, therefore, a decrease in distal nephron (probably collecting duct) hydrogen ion secretion with acute hyperventilation. Possible pitfalls in the interpretation of the UB PCO2 are illustrated.
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PMID:The effect of hyperventilation on distal nephron hydrogen ion secretion. 0 92

At present, a practical method for continuous monitoring of the state of tissue metabolism in the individual patient's heart during cardiac operations is not available. We have explored the use of miniature electrode measurements of myocardial interstitial pH to provide this monitoring capability, making comparisons with intracellular pH in left ventricular biopsy specimens and with tissue PCO2 measured by mass spectrometry. The electrode system consisted of a hydrogen ion-sensitive glass miniature electrode, housed in the beveled end of a 21 gauge (0.8 mm diameter) hypodermic needle, and a 2 mm diameter reference electrode, with an internal silver-silver chloride electrode coupled to tissue through a saline bridge (150 mM/L sodium chloride) saturated with silver chloride. Accuracy in blood at 37 degrees C was compared with conventional instrumentation (Radiometer BMS-3 MK-2 Blood Micro System) over a pH range of 7.4 to 6.4 with linear regression analysis (n = 26) revealing a high correlation (r = 0.997) and a mean difference in paired observations of only 0.01 +/- 0.004 (mean +/- SEM) pH units. In two groups of dogs on cardiopulmonary bypass, the pH needle and reference electrodes were inserted into the anterior wall of the left ventricle. Ischemic arrest of the heart at 37 degrees C was used to vary myocardial pH. In Group 1 (n = 8), intracellular pH was estimated from left ventricular biopsy specimens (400 mg each) taken over a microelectrode pH range of 7.37 to 6.37, snap frozen, and homogenized. In Group II (n = 6), tissue PCO2 in the anterior wall of the left ventricle was determined by mass spectrometry (sampling catheter 1.3 mm diameter). Miniaturized electrode (interstitial) pH exceeded biopsy (intracellular) pH under control conditions by 0.28 +/- 0.025 pH units (p less than 0.001), but below an electrode pH of 6.8 the results of the two techniques did not differ significantly. The tissue PCO2 rose from 69 +/- 2 mm Hg to a final plateau of 419 +/- 25 mm Hg, which was similar to the predicted value of 427 +/- 28 mm Hg calculated from the pH change (7.37 +/- 0.01 to 6.01 +/- 0.07), providing a further independent check on the pH electrode technique. These data indicate that our intramyocardial pH measurements do reflect intracellular metabolism during elective arrest of the heart and may have potential for clinical use.
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PMID:Intramyocardial pH as an index of myocardial metabolism during cardiac surgery. 3 64

We measured free calcium and related variables before and after the subject changed from the upright to the supine posture, doing 15 separate such experiments on 11 healthy men. After such a change, free calcium (1.7 +/- 0.4%), total calcium (4.6 +/- 0.7%), total protein (11.5 +/- 1.4%), albumin (12.2 +/- 2.0%), total magnesium (3.8 +/- 0.9%), and the activity of hydrogen ion (2.9 +/- 1.0%) decreased significantly (values are means +/- SEM), but promptly reverted when three subjects assumed the alternative posture. Changes in lactate values were not rapidly reversible; sodium and potassium showed no significant change. The mechanism of the changes in free calcium is unclear, but they correlated only with the changes in total calcium and were notably less than the changes in total calcium, indicating that posture will have less effect on the interpretation of free calcium values than on values for total calcium.
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PMID:Influence of posture on free calcium and related variables. 3 19

Renal cortical blood flow of rats with postischemic, myohemoglobinuric, and mercury-induced acute renal failure was measured by the hydrogen washout technique using implanted platinum electrodes. Total renal blood flow was determined by venous cannulation in separate series of rats. The values obtained with the two methods were in excellent qualitative agreement (r=0.99, P less than 0.001), although venous cannulation gave values that were constantly lower than those calculated for whole kidney from the cortical flow rate and assumed cortical mass. Myohemoglobinuria produced by glycerol injection caused cortical blood flow to fall from a control value of 7.37+/-0.23 (SEM) ml/min X g of cortex to approximately one-half that value for four hours after injection (P less than 0.001). Flow rates 12 and 24 hr after glycerol injection were 85% (P less than 0.001) and 90% (P less than 0.05) of control, respectively. Cortical flow was reduced to 5.49+/-0.39 (SEM) ml/min X g of cortex four hours after release of one hour's total bilateral renal arterial occlusion (P less than 0.001), but rose to normal within 24 hr. Poisoning with 4.7 mg/kg of body wt of mercuric chloride produced a cortical blood flow value that was 30% higher than control 24 hr after injection (P less than 0.01), while a 12 mg/kg of body wt dose gave a normal flow value. Inulin clearance was severely depressed in all models at all study times. Thus, in contrast to human acute renal failure, marked renal cortical ischemia is not an essential feature of these different forms of murine acute renal failure.
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PMID:Normal renocortical blood flow in experimental acute renal failure. 85 3

The quantity of lactose not absorbed by 4 normal and 6 lactase-deficient subjects was determined by three indirect methods which involved: (1) measurement of pulmonary hydrogen (H2) excretion, (2) pulmonary (14)CO2 excretion, and (3) stool (14)C excretion, after ingestion of 12.5 g of 1-(14)C-lactose and 4 g of polyethylene glycol (PEG). Results were compared with absorption determined directly from the (14)C:PEG ratio of multiple terminal ileal aspirates. The fraction of lactose not absorbed determined by ileal aspiration ranged from 0 to 8% in normals and 42 to 75% in mild-intolerant subjects. Whereas all three indirect methods were useful in qualitatively separating normal from deficient subjects, the quantity of lactose absorbed as determined by H2 excretion correlated most closely with ileal measurements (r = 0.94). Pulmonary (14)CO2 excretion for 24 hr after (14)C-lactose ingestion did not distinguish normal (17 +/- 4% (SEM) of ingested (14)C per 24 hr) from lactase-deficient subjects (21.1 +/- 3%). Likewise, stool (14)C:PEG ratios grossly underestimated malabsorption with less than one-quarter of the nonabsorbed (14)C appearing in the stool. This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon. Analysis of ileal fluid collected during passage of the lactose meal indicated that about two-thirds of the osmotic load delivered to the colon consists of endogenous electrolytes. Thus the water load delivered to the colon is about 3 times that calculated to be osmotically held by the nonabsorbed sugar.
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PMID:Quantitative measurement of lactose absorption. 126 65

To determine alpha-fetoprotein (AFP) in human saliva, a highly sensitive sandwich enzyme immunoassay for saliva AFP was developed. AFP standards and saliva samples were added into the wells of a polystyrene plate coated with goat IgG antibody against human AFP. After incubation, the wells were washed and horseradish peroxidase-labelled antibody was added. The enzyme activity specifically bound to the well was assayed using 3,3',5,5'-tetramethylbenzidine and hydrogen peroxide as substrate. The reaction was stopped by addition of 2 M sulphuric acid and the AFP concentration was determined from the absorbance at 450 nm. The minimum detectable concentration was 8 ng/L. The recovery of AFP mixed with human saliva was 91.1-102.4%. The within-assay and between-assay coefficients of variation were 6.5-8.9% and 7.6-10.8%, respectively. The assay correlated well with a radioimmunoassay for human AFP (r = 0.985, n = 13, P less than 0.001). The mean concentration of AFP in normal human saliva was 14.3 ng/L (SEM = 4.9 ng/L, n = 10) and significantly higher levels of saliva AFP were observed in hepatocellular carcinoma patients with positive serum AFP (mean 1367.8 ng/L, SEM 595.4 ng/L, n = 6; P less than 0.001). Strong correlation was observed between saliva AFP and serum AFP (r = 0.978, P less than 0.01, n = 13).
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PMID:Highly sensitive sandwich enzyme immunoassay for alpha-fetoprotein in human saliva. 128 27

Different types of dietary fiber are fermented to various extents in vitro, but little is known about the effects of fiber on breath hydrogen and methane levels in vivo. Therefore, we studied the effects on breath hydrogen and methane of 15 g of guar, pectin, psyllium, soy polysaccharide, or cellulose in eight healthy subjects over a 12-h period. None of the fibers had a significant effect on breath hydrogen or methane concentrations, compared with the control (fasting). The four methane producers had lower breath hydrogen levels than the nonproducers 1 h after 15 g of lactulose (3 +/- 1 vs. 42 +/- 9, p less than 0.005) and 5-12 h after the different fibers (3.3 vs. 4.8 ppm; pooled SEM = 0.8; p less than 0.025). When the methane responses of the methane producers were expressed as increments relative to the control, there were small differences between treatments, with guar producing a larger response, 8.2 +/- 3.3 ppm, than cellulose, -2.9 +/- 2.3 ppm (p less than 0.05). The incremental methane responses of the different fibers in vivo were related to the previously reported production of propionic acid (r = 0.94, n = 5, p less than 0.02) and methane (r = 0.93, n = 4, NS) from in vitro fermentation of the same fibers. We conclude that methane producers have lower breath hydrogen levels than nonproducers. Purified fermentable and nonfermentable dietary fibers have no effect on breath hydrogen levels over 12 h in subjects previously consuming a normal diet. However, fermentable fibers may produce small increases in breath methane in methane-producing subjects.
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PMID:Effect of guar, pectin, psyllium, soy polysaccharide, and cellulose on breath hydrogen and methane in healthy subjects. 131 94

The potential of hydrogen peroxide to reduce the levels of salivary thiol precursors of oral malodor was investigated in-vitro and in-vivo. In both cases the concentration of thiol groups was determined colorimetrically by quantitative reaction with 4,4'-bis (dimethylamino) diphenyl carbinol. Addition of volumes of hydrogen peroxide solution (containing between 0.18 and 0.90 mmol) to premeasured aliquots of saliva in-vitro, resulted in reductions in salivary thiol levels of between 53% and 75% compared to controls. This positive indication prompted an in-vivo investigation. The efficacy of a fluoride-containing test toothpaste also containing 0.67% hydrogen peroxide and 5.48% sodium bicarbonate was evaluated in a crossover study using ten male and female subjects (non-smokers). All subjects used the test product and a control fluoride dentifrice, in a random order. For the duration of the study subjects used a standard silica based toothpaste containing 1500 ppm F (as sodium monofluorophosphate) exclusively for their normal oral hygiene. On each sampling morning they refrained from oral hygiene and eating and drinking on rising. At the test facility they generated a background saliva sample stimulated by chewing unflavored, unsweetened gum. Subjects brushed for 1 minute with 1.50 (+/- 0.05) g test or control paste and generated another saliva sample as before, 30 minutes after product application. Using the same analytical procedures the mean (+/- SEM) percent reduction in salivary thiol levels post treatment compared to baseline was found to be 59.0 (+/- 7.0)% for the test product compared with 12.5 (+/- 5.2)% for the fluoride control paste.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction in the levels of oral malodor precursors by hydrogen peroxide: in-vitro and in-vivo assessments. 133 26

The alpha 2-adrenergic receptor agonist dexmedetomidine produces an anesthetic state in a variety of species. Although its effects on cerebral blood flow and the electroencephalogram have been investigated, the effect of this drug on intracranial pressure (ICP) has not been reported previously. Dexmedetomidine therefore was intravenously administered to 24 New Zealand white rabbits that had been anesthetized with halothane and mechanically ventilated to maintain a constant arterial CO2 tension (PaCO2) between 34 and 39 mm Hg. After placement of an arterial catheter and ventricular cannula, baseline measurements of monitored variables, including heart rate, mean arterial blood pressure, ICP, end-tidal CO2, body temperature, and arterial blood gases, were recorded. Dexmedetomidine (20, 80, or 320 micrograms/kg IV) or saline solution was then infused over a 10-min period. The ICP transiently decreased by 31% in the 20-micrograms/kg group (from a mean value of 9.4 +/- 1.3 [SEM] to 6.5 +/- 1.0 mm Hg, P less than 0.05). In the 320-micrograms/kg group, ICP remained unchanged over the course of the study despite a significant increase in arterial blood pressure (32 mm Hg). The effects of dexmedetomidine on ICP were next investigated in the presence of intracranial hypertension produced by a cryogenic lesion (mean baseline ICP 16.8 mm Hg). In addition to the previously monitored variables, sagittal sinus blood flow was measured by the hydrogen clearance technique before and after the administration of dexmedetomidine (320 micrograms/kg IV). In these experiments, dexmedetomidine was associated with a 14% decrease in sagittal sinus blood flow that was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracranial pressure effects of dexmedetomidine in rabbits. 135 50

U74006F, a novel 21-aminosteroid, is an inhibitor of iron-dependent lipid peroxidation that is devoid of glucocorticoid and mineralocorticoid side effects. The efficacy of U74006F in reducing cerebral infarct size was investigated in a rabbit model of thromboembolic stroke. Each animal received either U74006F (3.0 mg/kg immediately before and 2 hr after embolization, n = 8) or vehicle control (n = 10). Hematocrit, mean arterial pressure, PCO2, PO2, and pH were measured and controlled both before and after the administration of an autologous clot into one internal carotid artery. Regional cerebral blood flow (in ml/100 g/min, mean +/- SEM) measured by hydrogen clearance was similar in both groups, being reduced from 68.2 +/- 9.6 to 5.2 +/- 1.9 in the control group immediately after clot embolization and from 73.3 +/- 14.9 to 7.0 +/- 1.7 in the U74006F group. Four hours after embolization the brain was harvested and cerebral infarct size was determined using the triphenyl-tetrazolium chloride technique (% hemisphere, mean +/- SEM). In the U74006F-treated group, the infarct size was significantly reduced (P < 0.05) to 14.8 +/- 6.4 from a control value of 36.0 +/- 6.4. Additionally, cerebral blood flow values after embolization were consistently higher in the U74006F group, although the differences were not statistically significant. This data suggests that the 21-aminosteroid U74006F may have a protective effect in cerebral ischemia.
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PMID:The effect of the 21-aminosteroid U74006F in a rabbit model of thromboembolic stroke. 143 19


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