Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.

The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.

Plasma noradrenaline in cirrhosis: a study of kinetics and temporal relationship to ascites formation.

The kinetics of plasma noradrenaline (NA) were studied in 14 patients with cirrhosis and ascites and 13 normal subjects. [3H]noradrenaline ([3H] NA) was infused intravenously to steady state and the spillover of NA into plasma and its clearance from plasma calculated. The increase in plasma NA in the cirrhotic patients was due to an increase in NA spillover (14.5 vs 3.9 nmol min-1m-2; P less than 0.001). NA plasma clearance was also increased in the cirrhotic patients (3.5 vs 2.11 min-1m-2; P less than 0.01). Plasma NA and dihydroxyphenylglycol (DHPG), a metabolite of NA of which a portion is formed after re-uptake of NA into sympathetic nerve endings, were then measured in 23 patients with cirrhosis and ascites, 17 patients with cirrhosis who had never had ascites, and 34 normal subjects. Both plasma NA and DHPG were significantly increased in the patients with ascites (NA 4.7, DHPG 14.7 nmol l-1 and in the patients with cirrhosis but no ascites (NA 3.8, DHPG 12.0 nmol l-1) compared with normal subjects (NA 1.9, DHPG 8.8 nmol 1-1). Therefore, the increase in plasma NA in cirrhosis is due to increased activity of the sympathetic nervous system rather than interference with the metabolism of NA or impaired neuronal uptake of NA. This increase appears to precede the development of ascites.

Rise in plasma noradrenaline with age results from an increase in spillover rate.

Venous plasma noradrenaline (NA) kinetics, determined using steady-state intravenous infusions of subpressor doses of [3H] NA, were measured in 8 young, 13 middle-aged and 8 elderly subjects. Plasma NA concentrations were 0.71 nmol/l (0.25-0.98) in the young, 1.90 nmol/l (0.98-3.65) in the middle-aged and 3.03 nmol/l (1.15-3.85) in the elderly (young vs. elderly, p less than 0.001). NA spillover rates were 2.07 nmol/l/m2 (1.05-4.91) in the young, 3.91 nmol/l/m2 (1.62-9.44) in the middle-aged and 7.57 nmol/l/m2 (4.38-24.0) in the elderly (young vs. elderly, p less than 0.001). Plasma NA clearance was similar in young and elderly subjects. NA spillover was positively correlated with age (r = 0.58; p less than 0.01) and was not independently related to blood pressure. The rise in plasma NA with age results from an increase in spillover rate rather than any alteration in clearance.

Plasma [3H]-noradrenaline kinetics and blood pressure following regular, moderate ethanol consumption.

Normotensive male volunteers (n = 8) either abstained from ethanol for 4 days or consumed 66 g of ethanol per day in an open, crossed, random order study. Mean arterial pressures rose by an average of 5.4 mmHg following the ethanol phase of the study (P less than 0.001). Plasma noradrenaline (NA) concentration was higher during ethanol ingestion (P less than 0.01), principally because of a significant reduction in NA clearance of -1.51 l min-1 m-2 (P less than 0.05). In contrast, NA spillover or release rates did not significantly differ between the two study periods. Total plasma calcium levels were significantly lower (P less than 0.05) following the ethanol compared to the control period. These data do not appear to support the proposition that regular alcohol consumption raises blood pressure by producing a generalised increase in sympathetic activity.

An improved approach for the determination of plasma [3H]noradrenaline kinetics using high-performance liquid chromatography.

An improved approach for the determination of plasma [3H]noradrenaline ([3H]NA) kinetics in man is described, incorporating the extraction of plasma [3H]catechols on alumina and separation of [3H]NA from [3H]dihydroxymetabolites by high-performance liquid chromatography (HPLC). After a 30 min intravenous infusion, [3H]NA accounted for 57.2 +/- 13.2% of the radioactivity recovered by the procedure, while the dihydroxy-metabolites 3,4-[3H]dihydroxyphenylethylene. glycol ([3H]DHPG) and 3,4-[3H]dihydroxymandelic acid ([3H]DOMA) accounted for 32.3 +/- 11.5% and 4.9 +/- 6.0% respectively. After 90 min of constant infusion the proportion due to [3H]NA fell to 44.4 +/- 10.4%, while that due to [3H]DHPG rose to 45.9 +/- 9.5% because of an increase in the amount of [3H]DHPG at the later time. Plasma [3H]NA radioactivity rose rapidly during the constant infusion and usually reached a plateau by 30 min. However, in individual subjects large variations in plasma [3H]NA radioactivity occurred during the course of the infusion, implying rapid and variable changes in plasma [3H]NA clearance. The inclusion of a step to separate [3H]NA from [3H]dihydroxymetabolites is necessary if the aim is to determine plasma [3H]NA kinetics, as a large proportion of the radioactivity recovered from plasma on alumina is due to the presence of these metabolites.

Comparison of plasma 3,4-dihydroxyphenylethylene glycol (DHPG) and norepinephrine levels as indices of sympathetic activity in man.

Plasma levels of norepinephrine (NE) and the NE metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) were measured simultaneously following sympathetic activation induced by standing, cold pressor testing and bicycle exercise at progressively increasing workloads in normal volunteers. Free DHPG and NE levels both increased with sympathetic activation, but free NE levels were a more sensitive index of change. In addition, plasma free NE levels more closely reflected the fall in heart rate following exercise than free DHPG. In contrast to free levels, conjugated DHPG and NE levels did not change significantly after exercise. Supine resting free DHPG/NE ratios were always greater than 2.0, but fell progressively with increasing sympathetic activation because of a proportionately greater rise in NE than DHPG. The simultaneous measurement of plasma free DHPG and NE does not offer advantages over free NE levels as an index of sympathetic activity in man, but may be of use in the diagnosis of pheochromocytoma and in studies of NE metabolism.