Evaluation of a new immunochromatographic test for Helicobacter pylori IgG antibodies in elderly symptomatic patients.

AIM: To determine the diagnostic value of a new serum and whole blood serological IgG antibody test, FlexPack HP, for the diagnosis of Helicobacter pylori in elderly symptomatic patients. METHODS: 94 consecutive symptomatic patients who underwent upper endoscopy were studied (mean age, 62.6 years). On endoscopy, the presence of H. pylori infection was examined by biopsies from gastric antrum and body for rapid urease test and histologic examination. Blood was drawn prior to endoscopy and both blood and serum were immediately analyzed for human IgG antibodies to H. pylori by a new commercially available qualitative immunochromatographic method, FlexPack HP. This test incorporates high-molecular weight cell-associated proteins (HM-CAP), which are highly specific for H. pylori IgG antibodies. RESULTS: Overall agreement for FlexPack HP whole blood vs FlexPack HP serum was 100%, and agreement with biopsy results was 71%. The gold standard (detection of H. pylori by histology or urease test) identified H. pylori in 61 patients (65%). Complete agreement was observed between the gold standard test and the serology kit in 72% (68/94) of sera (51 positive and 17 negative). Disagreement was found in sera of 26 patients; 16 sera were negative by the gold standard and positive by FlexPack HP and 10 patients were found negative by serology. The sensitivity of FlexPack HP was 84% and the specificity 52% when compared with the gold standard. CONCLUSIONS: FlexPack HP serum and whole blood test is a simple and reliable method for the detection of H. pylori antibodies, with 100% agreement between the serum and blood results. In the elderly symptomatic patients the sensitivity of FlexPack HP was similar to that of other serologic tests, but the specificity was relatively low, limiting its use in this population.

Vanadate has no effect on insulin-extraction by the rat liver.

The mechanism(s) responsible for the insulin-like effects of vanadate are still unclear, although several possible explanations have been raised. However, the possibility that vanadate induces inhibition of insulin degradation in the liver was not examined yet. Therefore, in the present study we examined the effect of vanadate on the extraction of insulin by the perfused rat liver using an open, non-recycling system. Baseline insulin extraction (44 +/- 2% and 37 +/- 3%) was not affected by the administration of 1 and 5 microM vanadate (decreased to 42 +/- 2% and 36 +/- 1, respectively, p = NS). Vanadate had no adverse effects on liver viability, and the bile flow remained stable during and after vanadate administration (0.87 +/- 0.08 microliter/min/g liver prior to Vs. 0.084 +/- 0.11 microliter/min/g liver following vanadate administration). This study shows that vanadate does not inhibit insulin extraction by the perfused liver, and that does of vanadate that effectively inhibit hepatic glucose production possess no adverse effects on liver viability.

Alpha interferon has no effect on lidocaine metabolism in the rat.

Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine elimination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blood was drawn from the arterial catheter for lidocaine determination every 3 min for 20 min. 7 rats were pre-treated with intramuscular rat alpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rats were given saline i.m. The lidocaine elimination rate constant was unchanged, 0.065 min-1 and 0.063 min-1 for the control and IFN groups, respectively. To investigate lidocaine extraction, the isolated perfused rat liver was used. Perfusate samples from the portal and hepatic veins were drawn at 2 min intervals for 20 min, and lidocaine extraction determined. Extraction was determined in two groups of 6 rats each. The first group served as control and these rats were injected with saline only, while in the second group, the rats were pre-treated with rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated perfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded that the rat alpha-IFN affects neither the elimination nor the extraction of lidocaine.

Famotidine has no effect on cardiac performance and liver blood flow in the rat.

Conflicting results have been reported on the effect of famotidine on cardiac performance and visceral hemodynamics, studied by non-invasive techniques. It is for that reason that we used the radioactive microsphere technique to study the effect of famotidine on cardiac performance in the rat. Hepatic blood flow (HBF) and portal blood flow (PBF) were measured during the same experiment. Rats were either given famotidine (2.0 mg/kg per day) or drinking water for 7 days through an orogastric tube. Administration of famotidine had no effect on cardiac output (CO), HBF, PBF, or liver blood flow (LBF), which is the sum of HBF and PBF. In both groups, LBF consisted of a similar fraction of CO, 14.5 +/- 3.9% and 15.7 +/- 4.38%, in the control and the famotidine groups, respectively. Pulse rate, systolic pressure and left ventricular contractility were not affected by famotidine. It is concluded that in the rat, administration of famotidine for 7 days has no effect on systemic, hepatic or portal hemodynamics.

Cimetidine and omeprazole do not affect cyclosporine disposition by the rat liver.

Cyclosporine has been used with increased frequency, occasionally in conjunction with cimetidine and omeprazole. The present study was undertaken to study a possible interaction between either of the two drugs and cyclosporine in the liver. The isolated perfused rat liver was used with recirculation of perfusate for 150 min. 6 experiments were performed with each of the following: cyclosporine alone, cyclosporine with cimetidine, and cyclosporine with omeprazole. Initial concentrations of cyclosporine, cimetidine and omeprazole were 600 micrograms/ml, 12.5 micrograms/ml, and 4.5 micrograms/ml, respectively. At 1 and 2 h of perfusion 1 micrograms of omeprazole was added to perfusate. Cyclosporine concentration was determined at 30 min intervals. Results at 150 min expressed as percentage of the initial concentration of cyclosporine were 59 +/- 3%, 55 +/- 6%, and 60 +/- 9% for cyclosporine alone, with cimetidine and with omeprazole, respectively. The elimination rate of cyclosporine by the liver did not change during the entire experiment with the addition of cimetidine or omeprazole. Thus, it is concluded that short administration of cimetidine or omeprazole will not affect cyclosporine metabolism by the liver.

Recovery of pressor response to norepinephrine following relief of the obstructed common bile duct in the rat.

Jaundice caused by common bile duct (CBD) obstruction is associated with a blunted pressor response to norepinephrine (NE). We studied the rate and extent of recovery of the pressor response in the rat following relief of the obstruction. Three groups of male Wistar rats underwent CBD ligation. In the first and second group blood pressure measurements were obtained at 72 and 144 h after CBD ligation, respectively. In the third group pressure measurements were recorded 72 h after the relief of a 72-h obstruction. A fourth group served as control, and measurements were obtained 72 h after a sham operation. In all four groups measurements included basal blood pressure and pressure change following escalating doses of NE, ranging from 0.5 to 10 micrograms/kg. Basal blood pressure was similar in all four groups. In the control group the change of blood pressure was 23.4% +/- 6.7% in response to the lowest dose of NE, and 83.5% +/- 24.9% in response to the highest dose. A blunted pressor response to NE was recorded in all three groups with CBD obstruction. The duration of CBD ligation (72 or 144 h) did not affect this blunded response. Re-establishment of bile flow for 72 h made only a slight improvement in the response to NE. Obstruction of the CBD was associated with hyperbilirubinemia which disappeared following the re-anastomosis of the CBD to the duodenum. This most significant decrease in serum bilirubin was not associated with a similar improvement in pressor response to NE. We conclude that in the rat CBD obstruction is associated with a blunted pressor response to NE, that relief of CBD obstruction for 72 h is insufficient to abolish this response, and that there is no full correlation between serum bilirubin and pressor response.

Recovery of hepatic clearance and extraction following a release of common bile duct obstruction in the rat.

The rate of recovery for hepatic clearance and extraction following release of common-duct obstruction was investigated in the rat. Male Wistar rats underwent ligation of a cannulated common bile duct. Two weeks later, the cannula was opened and implanted into the duodenum, thus re-establishing enterohepatic circulation. Hepatic extraction and indocyanine green clearance were determined in three groups of six rats each, which differed by the time elapsed from the re-establishment of communication between the common bile duct and duodenum, i.e., 1, 48 and 168 h, respectively. A fourth group, in which a sham operation was performed, served as a control. Clearance was reduced from 16.9 +/- 2.5 ml/min per kg in the control group to 2.9 +/- 0.8, 5.4 +/- 2.4, and 8.5 +/- 3.3 ml/min per kg 1, 48, and 168 h, respectively, after release of common-bile-duct obstruction. Extraction rate was reduced from 37.3 +/- 5.9% to 17.5 +/- 2.7% in the 1st hour and recovered completely at 1 week. Thus, in the rat, release of a 2-week common-bile-duct obstruction is associated with complete recovery of the extraction capacity of the liver within a week, but only incomplete recovery of clearance. This decrease in clearance seems to be due to a decrease in effective hepatic blood flow, mostly probably due to the development of porto-systemic shunts.

Vanadate inhibits glucose output from isolated perfused rat liver.

Previous studies have demonstrated that vanadate ions mimic many of the actions of insulin in in vitro systems. Also, vanadate administered to diabetic hyperglycemic rats lowers their blood glucose levels to normal values. In this study we demonstrate that vanadate inhibits glucose output in the isolated perfused rat liver. Glucose production was suppressed maximally (about 50% to 60%), on addition of extremely low vanadate ion concentrations (0.5 to 1 mumol/L). This concentration is about two log units lower than the vanadate ion concentrations that are required to activate hexose uptake and glucose metabolism in vitro and is within the range of endogenous intracellular vanadium concentration. Insulin had little or no effect in inhibiting hepatic glucose output in this experimental system. The effect of vanadate ions is rapid in onset and is not accompanied by any signs of liver toxicity as assessed by various criteria. In conclusion, the study indicates that (a) vanadate ions inhibits hepatic glucose output, maximally and at extremely low, nontoxic concentrations (ID50 = 0.7 +/- 0.1 mumol/L). (b) The modulation action of the ion is fast and probably occurs at point(s) distal to the insulin receptor itself. (c) The liver participates in the process of maintaining euglycemia in diabetic rats receiving optimal doses of vanadate orally.

Cimetidine and omeprazole have different effects on hepatic extraction of lidocaine in rats.

The effect of two antisecretory drugs, omeprazole and cimetidine, on the hepatic extraction of indocyanine green and lidocaine was studied in the isolated perfused rat liver. Both indocyanine green and lidocaine are removed by the liver with high extraction efficiency in a flow-dependent manner. The elimination of lidocaine, but not indocyanine green, involves metabolism by the mixed-function oxidase in the liver. A selective effect on the hepatic extraction of lidocaine, but not indocyanine green, may therefore indicate an inhibition of hepatic mixed-function oxidase. To test this hypothesis, a nonrecycling system at a fixed perfusion flow rate was used to measure the extraction of lidocaine. Under control conditions, the extraction rate of lidocaine was 83% +/- 8%. In the presence of omeprazole at concentrations of 0.9, 2.0, and 4.5 micrograms/mL, the extraction rates were 81% +/- 9%, 82% +/- 7%, and 75% +/- 7%, respectively. These changes were not significantly different than control rates. In contrast, the increasing concentrations of cimetidine caused significant decreases in the hepatic extraction of lidocaine to values of 78% +/- 8%, 63% +/- 14%, and 48% +/- 14% at concentrations of 0.25, 0.50 and 1.25 micrograms/mL, respectively. The hepatic extraction of indocyanine green, 39% +/- 6%, was not affected by the administration of either omeprazole or cimetidine. Thus, in the rat, omeprazole seems to be a less potent inhibitor of cytochrome P-450 than cimetidine.

The effect of chronic captopril administration on hepatic blood flow of the rat.

The effect of chronic captopril administration on indocyanine green (ICG) clearance and hepatic extraction has been studied in the rat using the intact liver for ICG clearance and the isolated perfused liver for ICG extraction. The captopril was added to the drinking water to give a calculated daily intake from 0-45 mg kg-1. Hepatic clearance of ICG was dose related from 16.5 +/- 2.4 (control) to 7.2 +/- 1.6 mL min-1 kg-1, respectively. The hepatic extraction of ICG was not significantly different (37 +/- 6%) from the control value in groups on 4 and 45 mg kg-1 daily. Since ICG clearance and extraction are dependent on hepatic blood, a change in ICG clearance without a change in the extraction reflects a similar change in the hepatic blood flow. This remained unchanged at daily captopril intakes of 1 and 4 mg kg-1 and decreased when the daily intake was 10 mg kg-1 or higher. If these results in the rat are applicable to man, the chronic administration of therapeutic doses of captopril (0.5-2 mg kg-1) will not affect the hepatic blood flow.

The effect of PGE2 on hepatic blood flow and bile indocyanin green in the rat.

The effect of Prostaglandin E2 (PGE2) on hepatic blood flow and bile excretion has been only partially investigated. We studied in the rat the effect of PGE2 on indocyanine green (ICG) clearance, bile flow and ICG recovery in the bile. PGE2 administered to rats at a rate of 2 micrograms/kg/min had no effect on ICG clearance as compared to vehicle-treated rats (14.6 +/- 2.5 Vs, 16.9 +/- 2.5 ml/min/kg) and on bile flow (1.23 +/- 0.15 Vs. 1.24 +/- 0.11 microliters/min/gm liver). However, ICG excretion in bile was significantly increased as compared to a vehicle-treated group, 0.48 +/- 0.09 and 0.25 +/- 0.02 micrograms/microliters bile, respectively (P less than 0.005). This effect of PGE2 on ICG recovery in bile was found to be dose-dependent, and when PGE2 was administered at a rate of 1 microgram/kg/min, bile ICG decreased to 0.33 +/- 0.10 microgram/microliter bile. The effect of PGE2 on bile ICG is not due to an increased extraction of ICG by the liver since using the isolated perfused rat liver, the mean ICG extraction rate over a 20 minute period, with and without PGE2 infusion, was very similar, 33 +/- 3.5 and 37 +/- 6.2 percent, respectively. The lack of effect of PGE2 on ICG clearance and extraction and on bile flow, with an increase in biliary excretion of ICG, suggests a decreased hepatic storage of ICG induced by PGE2 possibly due to an accelerated rate of ICG excretion from the hepatocytes to the bile canaliculi.