Supersensitivity induced by the toxin of Brazilian scorpion venom (Tityus serrulatus Lutz e Mello)

The purified toxin of the Brazilian scorpion venom (TsTX) enhances the pharmacological actions of directly and indirectly acting substances on several preparations. The enhancing action of TsTX is more pronounced for the indirectly acting drugs, which is highly suggestive of a prejunctional site of action. Secondarily, TsTX does also produce an unspecific increase of sensitivity at the level of the pharmacological receptor itself. The mechanism by which these changes are brought about remains to be determined.     

Tityus serrulatus scorpion venom toxins display a complex pattern of antigenic reactivity

The antigenic properties of alpha-type and beta-type toxins purified from Tityus serrulatus (Ts) venom were analysed by radioimmunoassay, using rabbit antibodies raised against Ts VII, the main beta-type toxin in the venom, and against Ts IV, an alpha-type toxin. The anti-Ts VII serum did not recognize either the other beta-toxins Ts I and Ts II or the alpha-toxin Ts IV; the anti-Ts IV serum did not bind any of the three beta-toxins Ts I, Ts II or Ts VII. Thus, Tityus toxins display at least three distinct antigenic reactivity patterns.     

Biochemical and histopathological alterations induced in rats by Tityus serrulatus scorpion venom and its major neurotoxin tityustoxin-I

Intravenous injection into the rat of sublethal doses of Tityus serrulatus scorpion venom (100 micrograms protein/kg) or its major neurotoxin tityustoxin-I (TsTX-I, 20 micrograms/kg) caused, 30-180 min after injection, statistically significant increases in the serum levels of aspartate aminotransferase, amylase, creatine kinase and lactate dehydrogenase, as well as hyperglycemia, a high level of plasma free fatty acids and a low level of liver glycogen. The in vitro serum levels of the above enzymes did not change. For alanine aminotransferase, gamma-glutamyl transferase and alkaline phosphatase, neither in vitro nor in vivo alterations were observed. The whole venom and TsTX-I caused hepatic congestion with hemolysis and hydropic degeneration. Other histological lesions included edema and congestion with subpleural hemorrhage in the lungs, hypertrophy of fibers with degeneration areas in the heart, and congestion and hemorrhage in the kidneys. In the salivary glands, alterations to the acini and ductules were visible. In the adrenal glands no morphological alterations could be detected at the studied doses. The results suggest that the in vivo enzymatic and histopathological alterations are due to tissue lesions evoked by the whole venom and TsTX-I. An indirect effect, however, induced by stimulation of acetylcholine and catecholamine release in the postganglionic nerve terminals, cannot be excluded.     

Isolation and properties of a new kallikrein inhibitor from Tityus serrulatus venom

BACKGROUND: Most dyspeptic patients in primary care are managed without confirmatory investigations. In this study the reliability of the unaided clinical diagnosis and the diagnostic value of dyspepsia subgrouping are evaluated in unselected dyspeptic patients in primary care. METHODS: Six hundred and twelve unselected dyspeptic patients were referred for interview and endoscopy. General practitioners stated a provisional diagnosis and a proposed management strategy. Before endoscopy, patients were classified on the basis of predominant symptoms as reflux-, ulcer-, or dysmotility-like or as unclassifiable RESULTS: The sensitivity and the positive predictive value of the diagnosis of ulcer were 0.58 and 0.29, respectively, and those for esophagitis 0.30 and 0.43. The predictive value of a clinical diagnosis of functional dyspepsia was high, but, considering the high prevalence of the condition, the chance-corrected validity was at the same level as for the other diagnoses (0.18-0.22). Classification of patients by predominant symptoms increased the a priori probability of ulcer and esophagitis in the respective subgroups. However, more than one-third of the patients with ulcer or esophagitis were classified in inappropriate subgroups. CONCLUSIONS: It is difficult to select an appropriate management strategy for dyspeptic patients on the basis of symptoms and history alone. Dyspepsia subgroups are of limited help in the decision process because of the low predictive value of the endoscopic diagnosis.     

Gastric morphology and serum gastrin levels in pernicious anaemia

Mucosal biopsies from multiple sites in the stomachs of 21 patients with pernicious anaemia have been examined. The histological changes almost always involved the entire gastric mucosa, including that of the pyloric antrum. Metaplastic changes were almost universal and consisted of intestinal metaplasia in the body and antrum and pyloric metaplasia in the body. The severity of the pyloric metaplasia was such as to make the distinction between body and antrum on biopsy impossible. No relationship was found between serum gastrin activity and the histological appearances of the gastric antrum or body.     

Exocrine pancreatic response to the venom of the scorpion, Tityus trinitatis

This paper records for the first time the exocrine pancreatic response to scorpion venom, in this case that of Tityus trinitatis, a scorpion endemic in Trinidad. The crude venom injected intravenously into fasting anaesthetised dogs induced a secretion of the exocrine pancreas. The secretion evoked was rich in enzymes.     

Effect of aging on gastrin receptor gene expression in rat stomach

Broiler chickens were raised in separate rooms kept at temperatures of either 27 C or 16 C from 28 through 39 days of age. At the high temperature mouth breathing was recorded, but it was absent at the lower temperature. The number of dust particles in the air was greater in the warm rooms. More than 50% of the chickens in warm rooms had microscopic lesions in the bronchi of their lungs, whereas fewer than 5% of chickens in cold rooms had such lesions. Large dust particles were visible in some of the lesions. It was postulated that the increased incidence of lung lesions in chickens from warm rooms was due to mouth breathing rather than the higher dust levels in the air of these rooms.     

Lower esophageal sphincter pressures and serum gastrin levels after cholinergic stimulation

To define the role of gastrin, if any, in the response of the lower esophageal sphincter (LES) to bethanechol, serum gastrin determinations and LES pressure measurements were made in controls, patients with vagotomy and antrectomy (V&A), and patients with vagotomy and pyloroplasty (V&P). Despite significant differences in mean basal serum gastrin levels no differences were found in mean resting LES pressures among these groups. In controls significant increases in LES pressure occurred after subcutaneous bethanechol, but serum gastrin levels did not change from basal values. Subcutaneous injections of bethanechol produced significantly greater increases in LES pressures in V&P patients than in V&A patients. Serum gastrin levels did not change in either group; however, background serum gastrin concentrations were significantly greater for V&P patients than V&A patients throughout the study. Intravenous infusion of human gastrin I heptadecapeptide in controls significantly increased sphincter responses to bethanechol. Thus, these studies provide evidence to suggest that the LES response to bethanechol is affected by background serum gastrin levels.     

Gastric ulcer: effect of healing on gastric acid secretion and fasting serum gastrin levels

In 15 patients with uncomplicated gastric ulcers, basal and peak gastric acid outputs and fasting serum gastrin levels were studied before and after healing. The mean basal acid output [4.0 +/- 1.3 (SEM) mEq H+/hr], the mean peak acid output (29.5 +/- 5.1 mEq H+/hr), and the mean fasting serum gastrin level (80.3 +/- 16.7 pg/ml) in these patients did not change significantly with healing. Failure of gastric secretory function to change with healing suggests that mucosal resistance factors are more important than gastric acid secretion in the pathogenesis of a gastric ulcer.     

Effect of experimental diabetes mellitus on gentamicin-induced acute renal functional changes in the anaesthetized rat

1. Rats with streptozotocin (STZ) diabetes are protected from gentamicin (GEN) nephrotoxicity. Because the chronic renal damage from GEN is preceded by acute renal functional changes (notably hypercalciuria), the present study aims to determine whether diabetes may also protect against the acute effects of the drug. If there is a link between the rapid physiological actions of GEN and its subsequent nephrotoxicity, the former may also be affected by the diabetic condition. 2. Standard renal clearance techniques were performed on anaesthetized rats that had been injected with STZ or vehicle 2 weeks previously. All animals were infused with 0.9% NaCl for 5 h and then either GEN (0.28 mg/kg per min) or 0.9% NaCl alone for 2 h. 3. Baseline fractional calcium excretion (FE(Ca)) of diabetic rats was three-fold that of control animals (6.6+/-0.2 vs 2.2+/-0.2%, respectively; P<0.01, MANOVA). Following GEN infusion, a comparable increase in FE(Ca) occurred in control and diabetic rats (5.3+/-0.6 vs 5.3+/-0.8%, respectively; NS). 4. Streptozotocin diabetes, therefore, does not alter the acute hypercalciuric response to GEN. This may suggest that the acute effects of GEN on renal calcium handling do not contribute to the subsequent nephrotoxicity. However, the higher baseline FE(Ca) seen in diabetic rats may afford protection against the renal injury caused by gentamicin.     

Effect of flosequinan on ischaemia-induced arrhythmias and on ventricular cyclic nucleotide content in the anaesthetized rat

1. Flosequinan, milrinone, isoprenaline and forskolin given intravenously at similarly hypotensive doses have been evaluated in separate studies for their effect on ischaemia-induced arrhythmias and on ventricular cyclic nucleotide content following coronary artery ligation in the pentobarbitone anaesthetized rat. 2. Flosequinan did not affect mortality or arrhythmias following coronary artery ligation in either study and no change in ventricular cyclic nucleotide content was observed. 3. Isoprenaline caused a significant increase in mortality (P < 0.05) in both studies whereas milrinone and forskolin caused a significant increase in mortality in only one of the two studies conducted. All three agents caused significant increases in cyclic AMP which were associated with increased incidence of arrhythmias. 4. When compared at similarly hypotensive doses, flosequinan, in contrast to milrinone, isoprenaline and forskolin, did not influence ischaemia-induced arrhythmias or raise ventricular cyclic nucleotide levels in the anesthetized rat.     

Association between serum gastrin levels, gastric acid secretion and age in early gastric cancer

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.     

Effect of varying alloxan concentration on serum levels of glucose, calcium and alkaline phosphatase in the rat

Two groups of rats were injected intravenously 20 and 40 mg alloxan/kg of body weight respectively. It was shown that different doses of alloxan induced the increase of glucose concentration, activity of alkaline phosphatase and decrease of calcium level in the rat serum. The above changes more expressed in the groups of rats that received the higher dose of alloxan.     

Site of peptic ulcer. comparison of hydrochloric acid output, pepsinogen and gastrin serum levels

BACKGROUND/AIMS: Basal (BAO) and maximum (PAO) hydrochloric acid output after Histalog stimulation, basal pepsinogen (SPL-B), at 60 (SPL-60) and at 90 minutes (SPL-90), and basal gastrin (BG) levels were measured and compared in different gastric (GU) and duodenal (DU) ulcer sites. MATERIAL AND METHODS: Fifty nine patients with peptic ulcer were grouped according to Johnson's classification for gastric ulcers: type I (15), type II (16) type III (12) GU and (16) DU. Fifteen normal subjects were studied as controls. RESULTS: The BAO was greater in the DU than in the control or GU groups. No significant difference was noted in the production of hydrochloric acid after stimulation with Histalog. The SPL-B, at 60 and at 90 minutes was higher in type II GU than in the DU group and controls. The SPL-60 was higher in type II GU patients than in type III GU. Basal gastrin was higher in group DU and types II and III GU compared to the type I GU patients and controls. CONCLUSION: The topographic criteria for differentiating peptic ulcers has low discrimination capacity based on comparison of mean values of HCl acid production, pepsinogen and gastrin serum levels both basal and after stimulation with Histalog due to heterogeneity of these variables in group studies. In these studies, peptic ulcers from different sites should not be grouped as distinct entities except for type II gastric ulcers.     

Effects of carbamylcholine chloride on human antral gastrin mRNA levels

The effects of the muscarinic receptor agonist, carbamylcholine chloride (carbachol), on gastrin release and gastrin mRNA levels in human antral mucosa (n = 15) were determined. During a-2-h incubation period, carbachol (10(-6)-10(-4) M) decreased gastrin mRNA levels to 71 +/- 8% (10(-6) M), 40 +/- 8% (10(-5) M), and 33 +/- 5% (10(-4) M) of control levels. Carbachol (10(-5) M) decreased intracellular gastrin (from 1634 +/- 103 to 1272 +/- 126 pg/mg tissue protein), while it increased gastrin release into the medium (from 609 +/- 48 to 918 +/- 68 pg/ml per mg tissue protein). After 6- and 9-h culture, carbachol gradually increased gastrin mRNA levels, by 96 +/- 12% and 126 +/- 23%, respectively. Atropine sulfate (10(-5) M) completely inhibited the carbachol-induced changes. Cycloheximide markedly decreased tissue gastrin concentration, but increased gastrin mRNA levels, whereas it had no effects on gastrin release. These findings suggested that carbachol may have a time-related biphasic action on human antral gastrin biosynthesis.     

High performance liquid chromatography purification and amino acid sequence of toxins from the muscarinic fraction of Tityus discrepans scorpion venom

In this study, pH metry was simultaneously applied with a new technique, the intraluminal multiple electrical impedance (IMP) procedure, for measuring gastrointestinal motility for gastroesophageal reflux (GER) detection. Seventeen infants with clinical symptoms of GER disease such as recurrent apnea, aspiration pneumonia, wheezing, and failure to thrive were investigated during two feeding periods. A single catheter combining a pH electrode with seven electrodes for impedance measurements over a distance of 8.5 cm was used for the investigation. In all patients, 185 acid episodes were detected by pH metry. In 106 of these 185 acid episodes, a unique pattern in the IMP readings was noted, indicated by a retrograde esophageal volume flow. These episodes were regarded as acid GER episodes. Seventy-one of the 185 acid episodes occurred during the clearance process of a preceding acid GER characterized by typical IMP readings of an anterograde bolus transport. Eight of 185 acid episodes were missed in the IMP readings for technical reasons. The IMP pattern described as characteristic for a GER was observed in 490 other episodes not detected by pH metry. More than 75% of all GER detected by IMP reached the pharyngeal space; 73% of all GER occurred during feeding and the first 2 postprandial hours and 27% occurred during the remaining time until the next feeding. Even during the latter period, 34% of GER were detected by IMP only; they were missed by pH metry. Volume clearance indicated by IMP was always completed earlier than acidity clearance. The results show that IMP technique facilitates the detection of all GER, whereas pH metry is confined to the measurement of acid GER. Therefore, this technique might improve the evaluation of GER disease and detection of GER in conditions with gastric hypoacidity.