Biochemistry and pharmacology of diethylaminoethyl-dextran (DEAE-D).
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Biomedical subjects
Publications and source records attributed to G Mengozzi.
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The effects of three types of white wine (10% ethanol; pH 2.84-3.26), Coke (pH 2.45) and water (pH 8.03) on basal and food-stimulated gastric acid secretion in dogs were investigated. Water and Coke did not significantly modify acid secretion and gastrin release under basal conditions. By contrast, white wine or water +10% ethanol significantly increased acid secretion, with a tendency to elevate plasma gastrin concentrations. Acid secretion and gastrin release induced by a standard meal were not significantly modified by previous administration of Coke and water. In contrast, white wine and water +10% ethanol significantly increased food-stimulated total acid output, without changing plasma gastrin levels. It is concluded that Coke and water have only trivial effects on basal and on food-stimulated gastric acid secretion and gastrin release in the dog. The gastric stimulant effect of white wine is mainly related to its percentage of alcohol regardless of the slight differences in pH of the solutions.
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The effects of dermorphin and morphine on gastric acid secretion were studied in conscious dogs with both gastric fistulas (GF) and Heidenhain pouches (HP). Under basal conditions dermorphin and morphine, infused systemically at graded doses, produced a significant increase in acid secretion from both GF and HP. This increase was significantly inhibited by naloxone, naltrexone methylbromide and N-methyl-levallorphan methanesulphonate. Dermorphin did not modify the acid output stimulated by 2-deoxy-D-glucose from GF, while morphine significantly inhibited it; on the contrary acid secretion from HP was increased in this test by both dermorphin and morphine. Acid secretion from GF stimulated by pentagastrin was unaffected by morphine and significantly enhanced by dermorphin. Under these conditions a significant increase in acid secretion from HP was recorded with dermorphin and morphine. Naloxone and N-methyl-levallorphan methanesulphonate, given during pentagastrin-stimulated secretion, significantly inhibited acid output 'per se' from GF and HP and prevented the stimulatory effect of dermorphin and morphine. Bethanechol-induced secretion from GF and HP was significantly increased by both dermorphin and morphine. The present results demonstrate that opioids have simultaneous yet opposite effects on acid secretion in the dog and that mu receptors are involved in both the excitatory and inhibitory effects. Excitatory effects do not seem to be mediated via a vagal pathway (peripheral ?), in contrast to the inhibitory effects (central ?). The inhibitory effects of opiate antagonists on pentagastrin-stimulated secretion suggest a physiological role of peripheral opioid receptors in gastric acid secretion.
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Sixteen patients affected by congestive cardiomyopathy were studied by means of right and left cardiac catheterization and cineangiocardiography. Cardiac output and mean pulmonary circulation time were determined by the radiocardiographic method. Left ventriculograms were obtained in all the patients in the 45 degrees RAO projection; the left ventricular end diastolic and end systolic volumes were calculated both by the area-length and by the slice method. Among the several hemodynamic data (stroke index, mean pulmonary circulation time, left ventricular end diastolic pressure, left ventricular volumes and ejection fraction) the most early impaired and therefore usefull for an early diagnosis, were: the left ventricular end-systolic volume, the left ventricular end-diastolic volume and the left ventricular ejection fraction.
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The mediator for the action of ethanol on the parietal cell of the stomach is not known. However, because the action of ethanol on gastric acid secretion was proposed to involve the release of histamine, we decided to investigate the effects of ethanol and some alcoholic beverages (red wine and beer) on histamine release from the dog stomach. After performing a splenectomy in anaesthetized beagle dogs, the gastrosplenic vein draining the corpus of the stomach was cannulated for blood withdrawal to evaluate the local release of gastrin and histamine by RIA. Intragastric administration of 200 ml of beer (4.8% ethanol) or red wine (12.5% ethanol) caused a significant enhancement in gastrin and histamine concentrations in venous blood from the stomach. By contrast, intragastric administration of pure ethanol in distilled water at the same concentrations of wine or beer did not significantly modify gastrin and histamine release. Integrated histamine responses for 20 min to beer and wine paralleled gastrin concentrations and were of the same magnitude of those induced by intravenous infusion of pentagastrin at 1 and 6 micrograms/ kg/h, respectively. We conclude that: 1) beer and red wine, but not pure ethanol, are potent releasers of histamine; 2) histamine release seems to be related to the gastrin response and probably occurs at the level of enterochromaffin-like (ECL) cells; 3) the ethanol content of these drinks is not important for their stimulant effect, indicating that some other components of beer and wine are responsible for gastrin and histamine release from the dog stomach.
We studied the changes in some cardiovascular risk (CVR) factors in 24 maintenance hemodialysis patients treated for 1 year with recombinant human erythropoietin (rHuEPO) either intravenously (12 cases) or subcutaneously (12 cases). In order to clarify whether changes in some parameters were due to direct action of rHuEPO or to changes in food intake, we divided the patients into two groups: group A was formed by 14 patients who showed an increase in their food intake during rHuEPO therapy and group B by 10 patients without or with slight changes in their food intake. rHuEPO induced an improvement in well-being in 20 of 24 patients and in physical working capacity in 14 of 24, an increase in mean blood pressure in all patients, and hypertension in 4 of 24 patients. The incidence of hypertension was slightly higher after intravenous (3/12) than after subcutaneous (1/12) treatment. The rate of dialysis treatment with symptomatic hypertension significantly decreased from 44.0 +/- 8.0 to 12.1 +/- 2.2% after intravenous and from 41.3 +/- 6.8 to 10.0 +/- 3.8% after subcutaneous treatment. Evaluation of glucose metabolism (intravenous glucose tolerance test) before and after 3 months of rHuEPO therapy showed an improvement in glucose utilization (insulin resistance reduction). Cholesterol (CH), low-density lipoprotein CH, triglycerides, and apolipoprotein B significantly increased in group A, but not in group B. Both in groups A and B, high-density lipoprotein CH significantly decreased during the first 6 months and returned to basal values during the following months, and the apolipoprotein A1 level significantly decreased during the first 4 months and increased to levels higher than basal values during the following months. Changes in CH and apolipoprotein B were also positively correlated with changes in the protein catabolic rate. We infer that rHuEPO has opposite effects on CVR, but subcutaneous administration, dietary control, and antihypertensive treatment may produce a net decrease in CVR of maintenance hemodialysis patients on rHuEPO therapy.
The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.
BACKGROUND: Parathyroid hormone (PTH) has important applications in the nephrological clinical practice. Because assays of Intact PTH (I-PTH) are liable to interferences by N-truncated fragments, a novel method for whole-(1-84) PTH has been proposed. This study is aimed at comparing the latter with some of the previous I-PTH assays. For each method the results are referred to pertinent markers of mineral metabolism. METHODS: We enrolled 171 subjects, including 56 healthy controls (C), 65 calcium stone- formers (CaSF), 40 haemodialysis patients (HD), 10 with primary hyperparathyroidism (PHP). On blood samples we measured: I-PTH by four methods (N-Tact, Advantage, Elecsys, Scantibodies), whole-(1-84) PTH, defined as CAP (Cyclase Activating PTH), total and ionised calcium, phosphate, vitamin D, osteocalcin and Crosslaps. The difference between I-PTH and CAP Scantibodies is defined as CIP (Cyclase Inhibiting PTH). RESULTS: Despite relating to each other (r>0.97) PTH values varied remarkably among methods. For all methods, the reference intervals differed from those provided by the producer. Assuming these new ranges, 10 CaSF had over-range values not always associated with abnormalities of mineral metabolism. One of the PHP patients was normal for I-PTH with 2/4 methods. In HD the differences among methods were even greater, there were inverse (p<0.05) and direct (p<0.001) relationships with ionised calcium and osteocalcin-crosslaps, respectively. The CAP/CIP ratio was lower in low bone turnover patients, but the two subgroups widely overlapped. CONCLUSIONS: This study indicates that the reliability of I-PTH assays is still unsatisfactory, and none of the four methods emerged as the best. Assay for CAP only improves diagnostic efficiency, whereas the CAP/CIP ratio does not exhibit powerful discriminating capacity. Our suggestion is that each Centre should establish its own reference ranges. PTH assay should always be coupled with measurements of other markers of mineral metabolism as well as renal function.