Comparison of plasma bismuth levels after oral dosing with basic bismuth carbonate or tripotassium dicitrato bismuthate.

In 20 healthy subjects plasma bismuth concentration was measured after single oral doses of basic bismuth carbonate or tripotassium dicitrato bismuthate. The drugs were administered in the fasted state or immediately after ingestion of a standard breakfast. After basic bismuth carbonate, plasma bismuth rose to concentrations between 0.7 and 2.6 micrograms/L in the fasted state, while after the meal the maximal level was only 1.3 micrograms/L. In contrast to these very low levels after basic bismuth carbonate, the administration of tripotassium dicitrato bismuthate was paralleled by an increase of plasma bismuth to concentrations between 15 and 232 micrograms/L with a mean peak value of 64 +/- 15.3 (S.E.M.) micrograms/L in the fasted state. Postprandial ingestion of tripotassium dicitrato bismuthate attenuated the peak concentrations to 10.9 +/- 6.3 micrograms/L. One subject, however, had a value of 120 micrograms/L. This study demonstrates that basic bismuth carbonate leads to very low plasma bismuth concentrations, which are far below the critical range that might eventually be associated with bismuth neurotoxicity. Therefore this compound can be considered potentially useful for bismuth therapy of gastrointestinal disorders.

Effect of endogenous opioids on vagally induced release of gastrin, somatostatin and bombesin-like immunoreactivity from the perfused rat stomach.

The aim of the present study was to evaluate the effect of the opiate receptor antagonist naloxone on vagally stimulated secretion of bombesin-like immunoreactivity (BLI), somatostatin and gastrin from the isolated rat stomach, which was perfused via the celiac artery with Krebs-Ringer buffer. Vagal stimulation was performed for 10 min with 1 ms, 10 V and 2, 5, 10 or 20 Hz, respectively. In control experiments BLI release increased significantly above basal secretion during a stimulation frequency of 10 Hz (1367 +/- 357 pg/10 min; P < 0.001) and 20 Hz (996 +/- 202 pg/10 min; P < 0.01), but not at 2 and 5 Hz. In comparison to the controls naloxone (10(-6) M) significantly increased BLI secretion at 5 Hz by 573 +/- 150 pg/10 min (P < 0.05), but attenuated the BLI response to higher stimulation frequencies of 10 and 20 Hz to 284 +/- 143 pg/10 min (P < 0.001) and 490 +/- 114 pg/10 min (P < 0.01), respectively. At 2 Hz naloxone had no effect on BLI release. As shown previously the cholinergic blocker atropine (10(-7) M) induced a significant BLI release during vagal stimulation at 2 Hz (680 +/- 233 pg/10 min; P < 0.01) and 5 Hz (935 +/- 324 pg/10 min; P < 0.05), but was without effect at 10 and 20 Hz compared to the controls. The effects of the combination of naloxone and atropine were similar to naloxone and atropine alone. Naloxone had no effect on vagal or GRP-induced regulation of gastrin and somatostatin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Vagally induced release of gastrin, somatostatin and bombesin-like immunoreactivity from perfused rat stomach. Effect of stimulation frequency and cholinergic mechanisms.

The isolated stomach of rats was vascularly perfused to measure the secretion of gastrin, somatostatin (SLI) and bombesin-like immunoreactivity (BLI). The gastric lumen was perfused with saline pH 7 or pH 2, and electrical vagal stimulation was performed with 1 ms, 10 V and 2, 5 or 10 Hz, respectively. Atropine was added in concentrations of 10(-9) or 10(-7) M to evaluate the role of cholinergic mechanisms. In control experiments, vagal stimulation during luminal pH 2 elicited a significant increase of BLI secretion only at 10 Hz but not at 2 and 5 Hz. Somatostatin release was inhibited independent of the stimulation frequency employed. Gastrin secretion at 2 Hz was twice the secretion rates observed at 5 and 10 Hz, respectively. At luminal pH 7 BLI rose significantly at 5 and 10 Hz. SLI secretion was decreased by all frequencies. Gastrin secretion at 2 and 5 Hz was twice as high as during stimulation with 10 Hz. Atropine at doses of 10(-9), 10(-8), 10(-7) and 10(-6) M had no effect on basal secretion of BLI, SLI and gastrin. At luminal pH 2, atropine increased dose-dependently the BLI response at 2 and 5 but not at 10 Hz. The decrease of SLI during 2 and 5 Hz but not 10 Hz was abolished by atropine 10(-9) M. SLI was reversed to stimulation during atropine 10(-7) M at all frequencies. The rise of gastrin at 2 Hz was reduced by 50%. At luminal pH 7, atropine had comparable effects with a few differences: the BLI response at 10 Hz was augmented and the gastrin response to 2 and 5 Hz was reduced. In conclusion the present data demonstrate a frequency and pH-dependent stimulation of BLI and gastrin release. The stimulation of BLI is predominantly due to atropine-insensitive mechanisms while muscarinic cholinergic mechanisms exert an inhibitory effect on BLI release during lower stimulation frequencies (2 and 5 Hz) independent of the intragastric pH and also during higher frequencies at neutral pH. Both, atropine sensitive and insensitive mechanisms are activated frequency dependent. The atropine-sensitive cholinergic mechanisms but not the noncholinergic mechanisms involved in regulation of G-cell function are pH and frequency dependent. Somatostatin is regulated largely independent of stimulation frequency and pH by at least two pathways involving cholinergic mechanisms of different sensitivity to atropine. These data suggest a highly differentiated regulation of BLI, gastrin and SLI secretion and the interaction between these systems awaits further elucidation.

The effect of glucose and insulin on vagally induced gastrin, bombesin-like immunoreactivity and somatostatin secretion from the perfused rat stomach.

Previous studies in the isolated perfused rat stomach have shown that elevated glucose and insulin concentrations modulate BLI and somatostatin release during arterially administered peptidergic stimuli. In the present study the effect of elevated levels of glucose or insulin was examined on vagally induced changes of gastrin, somatostatin and BLI secretion. The lumen of the stomach was perfused with saline pH 7 or pH 2. Vagal stimulation (5 Hz, 1 msec, 10V) increased gastrin and BLI secretion and inhibited somatostatin release. The increase of the perfusate glucose concentration from 100 mg/dl to 150 or 300 mg/dl or the addition of insulin (100 microU/ml) augmented vagally stimulated gastrin release at luminal pH 7 but not pH2. Vagally induced inhibition of somatostatin was attenuated by both concentrations of glucose at either luminal pH while insulin had no effect. BLI secretion was affected neither by elevated glucose nor by insulin. On the other hand, the noncholinergic component of vagally induced BLI secretion in the presence of atropine was augmented by insulin. These data demonstrate that glucose and insulin can modulate vagally activated gastric neuroendocrine functions which could be of relevance during the ingestion of carbohydrate containing meals.

Effect of galanin on gastrin and somatostatin release from the rat stomach.

Galanin has been shown to be present in the gastrointestinal tract, pancreas and CNS. In the rat stomach, immunohistochemical studies have revealed the presence of galanin in the intrinsic nervous system suggesting a function as putative neurotransmitter or neuromodulator which could affect neighbouring exo- or endocrine cells. Therefore this study was performed to determine the effect of galanin on the secretion of gastrin and somatostatin-like immunoreactivity (SLI) from the isolated perfused rat stomach. The stomach was perfused via the celiac artery and the venous effluent was collected from the portal vein. The luminal content was kept at pH 2 or 7 Galanin at a concentration of 10(-10), 10(-9) and 10(-8) M inhibited basal gastrin release by 60-70% (60-100 pg/min; p less than 0.05) at luminal pH 7. At luminal pH 2 higher concentrations of galanin (10(-9) and 10(-8) M) decreased basal gastrin secretion by 60-70% (60-100 pg/min; p less than 0.05). This inhibitory effect was also present during infusion of neuromedin-C, a mammalian bombesin-like peptide that stimulates gastrin release. SLI secretion remained unchanged during galanin administration. The inhibitory action of galanin on gastrin secretion was also present during the infusion of tetrodotoxin suggesting that this effect is not mediated via neural pathways. The present data demonstrate that galanin is an inhibitor of basal and stimulated gastrin secretion and has to be considered as an inhibitory neurotransmitter which could participate in the regulation of gastric G-cell function.

Effect of bombesin antagonist D-Phe6-BN(6-13)OMe on vagally induced gastrin release from perfused rat stomach.

The aim of the present study was to evaluate the effect of the bombesin antagonist D-Phe6-BN(6-13)OMe (BN-antagonist) on vagally stimulated gastrin release from the isolated rat stomach, which was perfused via the celiac artery with Krebs-Ringer buffer. Vagal stimulation was performed for 10 minutes with 1 ms, 10 V and 10 or 2 Hz, respectively. Gastrin secretion increased significantly during stimulation with 10 and 2 Hz. BN-antagonist was added to the perfusate at the concentration of 10(-6) M, which induced a significant reduction of vagally stimulated gastrin release at 10 Hz (619 +/- 65 vs. 252 +/- 62 pg/10 min, p < 0.05), but not at 2 Hz (564 +/- 117 vs. 493 +/- 113 pg/10 min, p > 0.05). In contrast, atropine (10(-7) M) reduced significantly the gastrin response at 2 Hz (270 +/- 78 pg/10 min, p < 0.01), but not at 10 Hz (446 +/- 87 pg/10 min, p > 0.05). The combination of BN-antagonist and atropine elicited an inhibition of vagally stimulated gastrin release similar to each substance when given alone. Basal gastrin release was not changed by the BN-antagonist. The present data suggest, that in the rat stomach endogenously released bombesin-related peptides contribute to the noncholinergic stimulation of gastrin release at higher stimulation frequencies (10 Hz), however, bombesin-related peptides are not involved, when lower stimulation frequencies (2 Hz) are employed. At both stimulation frequencies additional mechanisms are activated which are noncholinergic and not related to bombesin peptides.

Effect of met-enkephalin and met-enkephalin-Arg6-Phe7 on bombesin-like immunoreactivity (BLI), somatostatin and gastrin secretion from the perfused rat stomach.

In the present study we examined the effect of the two endogenous opioids met-enkephalin and met-enkephalin Arg6Phe7 on gastric bombesin-like immunoreactivity, gastrin and somatostatin release. At doses of 10(-11), 10(-9), 10(-8) and 10(-6) M both peptides elicited a significant stimulation of bombesin-like immunoreactivity secretion, while the same doses of morphine were ineffective. The stimulatory effect was abolished by naloxone. Met-enkephalin and met-enkephalin Arg6Phe7 stimulated somatostatin secretion at a dose of 10(-8) M, and this effect was reversible by naloxone. Neither peptide had any effect on gastrin secretion. In conclusion, the data demonstrate that both enkephalins must be considered potential regulators of bombesin-like immunoreactivity secretion in the rat stomach.

A rare source of occult gastrointestinal bleeding: jejunal filiae secondary to metastatic lung carcinoma.

A case of occult gastrointestinal bleeding due to jejunal metastases of a primary lung carcinoma in a 53-year-old man is reported. When after healing of a large gastric ulcer melena persisted, a subsequently performed double contrast enema of the small bowel revealed evidence of several jejunal tumors. This was confirmed by angiography of the superior mesenteric artery and computed tomography of the abdomen. After resection of the tumor-bearing jejunal loop, histological evaluation revealed metastases secondary to a large-cell bronchogenic carcinoma which had been resected 1 year previously.

Effect of gastrin-releasing peptide (GRP1-27), neuromedin-C (GRP18-27), and neuromedin-B on gastrin and somatostatin secretion from the rat stomach.

In the present study the effects of gastrin-releasing peptide (GRP1-27), its C-terminal decapeptide neuromedin-C (GRP18-27) and the related peptide neuromedin-B were examined on the secretion of gastrin and somatostatin-like immunoreactivity (SLI) from the isolated perfused rat stomach at intraluminal pH 7 or pH 2. GRP1-27 and GRP18-27 stimulated gastrin secretion equally effective at concentrations of 10(-10), 10(-9), 10(-8), 10(-7) and 10(6)M at luminal pH 7. In addition neuromedin-B was tested at 10(-11), 10(-10), 10(-8) and 10(-6)M and it increased gastrin release similar to equimolar doses of GRP18-27. At luminal pH 2 GRP1-27 stimulated gastrin secretion at 10(-9), 10(-8), 10(-7) and 10(-6)M while GRP18-27 was only effective at 10(-8) and 10(-7)M. Neuromedin-B elicited a gastrin increase at 10(-8)M similar to GRP18-27 and also at 10(-6)M. All three peptides had no significant effect on SLI release at luminal pH 7. At luminal pH 2 GRP1-27 at 10(-9)M and 10(-6)M and GRP18-27 and neuromedin-B at 10(-10)M elicited a significant stimulation of SLI secretion. These data demonstrate that all three bombesin-like peptides GRP1-27, GRP18-27 and neuromedin-B can stimulate gastrin release at either a neutral or an acidic luminal pH, while SLI release is affected only at an acidic intragastric milieu. This suggests that all three forms of bombesin-like peptides are good candidates for the peptidergic regulation of gastrin release in the rat stomach, while their role in somatostatin release seems to be more restricted.

IgA nephropathy--Groote Schuur Hospital experience.

The prevalence of IgA nephropathy among 872 renal biopsies performed at Groote Schuur Hospital over a period of 7 years was retrospectively examined. Only 34 cases were shown to have IgA nephropathy. The features of these biopsies were compared with clinical and biochemical findings at the time of biopsy. The average age at histological diagnosis was 28.5 years (range 13-61 years); there were 25 males and 9 females. All patients had hematuria and in 44% it was macroscopic at some stage. Five of 25 patients in whom 24-hour urinary protein excretion was measured excreted more than 3.5 g/day. Histological changes ranged from mild proliferative changes (grade 1) to crescents and sclerosis (grades 4 and 5). There was a significant correlation between histological grade and serum creatinine (p less than 0.004) and proteinuria (p less than 0.005). The low prevalence of the disease in our total renal biopsy experience (3.8%) is similar to that reported from the United States (1.5) and England (4%). The age and clinical findings at the time of diagnosis were similar to most other series. The sex ratio was equal in the mixed-origin race group, while amongst the whites, males predominated. No IgA nephropathy was found in biopsies from blacks, which supports the observation of others that this condition is rare in the black population.