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Biomedical subjects

L Varga

Publications and source records attributed to L Varga.

At least 145 records · Page 8Linked to original sources

Pentagastrin analogues containing alpha-aminooxy acids. VII. Catabolism in vivo and in vitro of a pentagastrin analogue containing N-terminal aminooxyacetyl residue.

In rat, BOC-NHO-1-14C-Ac-Trp-Met-Asp-Phe-NH2 (14C-I) is metabolised more slowly than BOC-1-14C-Gly-Trp-Met-Asp-Phe-NH2 (14C-II). Of the cytosol fractions of the rat organs the lung and pancreas exhibited a lower activity in the catabolism of BOC-NHOAc-Trp-Met-Asp-Phe-NH2 (I) than in that of BOC-Gly-Trp-Met-Asp-Phe-NH2 (II). In contrast, the cytosol fractions of the dog's lung, small intestine and pancreas hydrolysed I at a faster rate than they hydrolysed II.

Acetates↗

[Addition of albumin to solutions of cholecystokinin (CCK)--effect on pancreatic secretion, plasma CCK level and release of pancreatic polypeptide (PP)].

Dissolving basic peptides such as insulin, secretin, and somatostatin in albumin-containing solutions increases the biologic potency. As CCK-33 also constitutes a basic peptide, it should have similar qualities. In four conscious dogs with chronic gastric and pancreatic Thomas fistulas, we studied the effect of CCK-33 solutions with and without addition of albumin on pancreatic secretin, plasma PP concentration, CCK-like immunoreactivity in plasma and infusion lines. The response of pancreatic protein output (mg/15 min) to increasing doses of 99% pure CCK-33 (0.5; 1; 2; 4 IDU/kg/h) was significantly higher (p less than 0.05) when CCK was dissolved in 0.154 M NaCl with albumin than in NaCl alone. These results were confirmed by measuring plasma CCK-immunoreactivity by CCK-RIA and CCK-immunoreactivity in samples from tips of infusion lines by gastrin-RIA. CCK evoked PP release at increasing doses of CCK-33, which was significantly (p less than 0.05) higher when CCK was dissolved in an albumin-containing solution. There was a significant (p less than 0.02) correlation between plasma PP concentration and pancreatic protein output. Our study shows addition of albumin to solutions of CCK-33 to cause an increase of CCK-33 activity, probably by preventing adsorption of the peptide to glass and plastic surfaces. This is valid for its effect on pancreatic protein secretion as well as PP release.

Albumins↗

Effect of adding albumin to solutions of cholecystokinin on pancreatic protein output and pancreatic polypeptide release.

In four conscious dogs with chronic gastric and pancreatic Thomas fistulas we studied the effect of 99% pure cholecystokinin-33 (CCK-33) solutions on pancreatic secretion and PP release. CCK-33 was dissolved in 0.154 M NaCl alone or in the same solution containing 1 g per 100 ml dog albumin. The response of pancreatic protein output to increasing doses of CCK-33 (0.5, 1, 2, 4 IDU/kg per h) was significantly (P less than 0.05) higher when CCK was dissolved in NaCl with albumin than in NaCl alone. These results were confirmed by measuring CCK immunoreactivity in samples from tips of infusion lines by a gastrin radioimmunoassay. Release of pancreatic polypeptide (PP) following increasing doses of CCK-33 was also significantly (P less than 0.05) elevated when CCK was dissolved in an albumin-containing solution. There was a significant (P less than 0.02) correlation between plasma concentrations of PP and pancreatic protein output. This study suggests that albumin should be added to CCK-33 solutions to preserve biological activity. The biological effect of CCK-33 may be substantially underestimated if albumin is omitted.

Animals↗

Effect of food on antacid neutralizing capacity in man.

In order to estimate their in-vivo reactivity two antacids of equal theoretical neutralizing capacity (approximately 3.9 mol/l at pH 3.5) but of different chemical composition were employed as intragastric titrant (pH 3.5) following a liquid protein meal (oxo) in two groups of five volunteers each. The two antacids chosen (alucol and Camalox) contain different amounts of aluminium hydroxide, magnesium hydroxide and Camalox in addition contains calcium carbonate. The intragastric consumption of these two antacids was much higher than their respective theoretically available neutralizing capacity (Alucol 3.9 times, Camalox 2.4 times). In-vitro studies demonstrated that interaction with oxo reduced the neutralizing capacity of the two antacids at pH 3.5 from 3.9 mol/l to 1.7 mol/l (Alucol) and 2.5 mol/l (Camalox). This potency loss was related to the aluminium hydroxide content of the two antacids. This study indicates that the neutralizing capacity of antacids is not predictable from their reactivity in aqueous solution and is markedly reduced by protein-containing foods.

Adult↗

Sensitivity of the parietal cell to pentagastrin in health and duodenal ulcer disease: a reappraisal.

In view of the conflicting results on whether pentagastrin sensitivity is genuinely increased in duodenal ulcer (DU) patients, the pentagastrin-gastric acid relationship was restudied in 17 normal subjects and 15 DU patients. In a reproducibility study performed on nine healthy subjects the mean pentagastrin responses obtained on 2 different study days, using a step technique (range, 0.025-6.4 micrograms kg-1h-1), were congruent at each of the five measuring points. Analysis of variance revealed no significant overall differences. However, ED50 values showed a large within- and between-subject variation and failed to correlate significantly, this because a plateau response was not regularly obtained with the top dose. Consequently, ED50 values in normal subjects and DU patients showed a large scatter and were not significantly different, although the potency ratio calculated from the linear parts of the respective dose-response curves was significantly different (2.6; 95% confidence limits, 1.8-3.9). This study thus supplies further evidence that the parietal cell of DU patients has a higher sensitivity to pentagastrin and demonstrates that the reliability of individual ED50 estimations obtained in pentagastrin dose-response studied should not be overrated.

Adult↗

Importance of cell-to-cell contact and transfer in white cell activity.

Formation of cell junctions and the occurrence of cell-to-cell transfer through these was examined in mixed cultures of PK 15 pig kidney and mouse peritoneal cells. Under standardized conditions of experiment, a close contact developed between peritoneal and target cells within 90 min. Light and scanning electron microscopic examinations of the area of close contact indicated extension of cytoplasmic processes from peritoneal cells towards the nucleoli of target cells. The size and localization of the nucleolus and the incorporation of a considerable amount of label by the nucleolar associated chromatin also indicated the decisive role of the nucleolus in the events following upon the establishment of close contact. Autoradiographic examinations showed that part of the 6-3H-thymidine labelled material migrated from the nucleus of target cells into the cytoplasm of peritoneal cells within 30 min. A greater cytoplasmic accumulation of label took place in peritoneal cells exclusively in the presence of actinomycin-D, indicating a rapid breakdown of transferred material under normal conditions. The development of cell-to-cell contact and transfer was found to depend greatly on the composition of the nutrient medium.

Animals↗

The release of pancreatic polypeptide by CCK-octapeptide and some analogues in the dog.

In dogs with gastric and pancreatic Thomas fistulas the effect of different cholecystokinin-like peptides upon pancreatic polypeptide (PP) release was studied in three ways: (a) Plasma PP concentrations were determined by radioimmunoassay in response to 135 pmol/kg/h of the synthetic C-terminal octapeptide of cholecystokinin (CCK-OP) (A), of three of its analogues (B, C, D) where methionine has been replaced by methoxinine, and in response to 45 pmol/kg/h of caerulein. The greatest rise in plasma PP concentration expressed as delta PP was achieved with caerulein (327 +/- 37 pM), when taking into account the threefold smaller dose used, followed by CCK-OP (536 +/- 67 pM) and analogues B (343 +/- 51 pM), C (87 +/- 46 pM), and D (32 +/- 15 pM). The order of potency with respect to stimulation of exocrine pancreatic secretion was the same: E and A precede B, C, and D. delta PP correlated linearly with the pancreatic protein output (r = 0.98, p less than 0.01). (b) CCK-OP was infused in four doses of 35, 70, 135, and 270 pmol/kg/h, and plasma PP concentrations and exocrine pancreatic secretion were monitored. The correlation between pancreatic protein output and delta PP was very close (r = 0.98, p less than 0.01). (c) Atropine sulfate (0.1 mg/kg, i.v.) reduced the PP response to the 135 pmol/kg/h dose of CCK-OP by 61%. We conclude from this that CCK-OP and related peptides do release PP and that their effect on exocrine pancreatic secretion is closely correlated with their PP-releasing capacity. The PP release may therefore be used as an indicator of the CCK-like activity of CCK fragments and analogues. CCK-OP may well represent one of the humoral stimulatory factors contributing to the release of PP, but this action appears to depend on a cholinergic background.

Animals↗

Morphine-like action of enkephalin analog FK 33-824 on motility of the isolated rat colon.

Actions of the synthetic met-enkephalin analog FK 33-824 were compared to normorphine on intraluminal pressure of the isolated rat colon. Phasic and tonic contractions of isolated colonic segments in Ringer-Tyrode's solution under standard conditions were measured by intraluminal perfusion manometry. FK 33-824 or normorphine induced substantial tonic contractions of colonic muscles which lasted about 6 min. The maximum tonic contraction occurred at 10(-5) M normorphine or 10(-6) M FK 33-824. Naloxone (10(-6) M) and Mr 2266 alone or in combination inhibited competitively the tonic contraction induced by FK 33-824 with a similar potency ratio, whereas 10(-6) M norepinephrine or 10(-8) M isoproterenol inhibited it noncompetitively. Tetrodotoxin (10(-6) M) counteracted tonic contractions due to FK 33-824 or normorphine in all parts of the undissected colon but only in the proximal segment of the dissected colon and enhanced it in the middle and distal colonic segment. Neither 10(-5) M atropine sulfate nor 10(-6) M methysergide interfered with the action of FK 33-824 or normorphine. FK 33-824 produced morphine-like motor actions in the isolated rat colon evidently by stimulation of opiate receptors, suggested to be located in nervous and muscular tissue in the proximal and solely in muscular tissue in the mid and distal colonic segment. The neural pathway stimulated by FK 33-824 or normorphine is not identified. The data suggest it to be noncholinergic, nonadrenergic and nonserotoninergic.

Animals↗

The effect of DDVP, an organophosphorus pesticide on the humoral and cell-mediated immunity of rabbits.

The effect of daily oral administration of LD50 1/40, 1/20 and 1/10 of an organophosphate pesticide DDVP (Dichlorvos) was studied in rabbits for its effect on the humoral immune response after vaccination with Salmonella typhi, as well as on cell-mediated immunity. Serum antibody titers of treated animals showed a dose-dependent fall compared with the controls. The skin redness measured in the tuberculin test showed the same dose-dependent tendency.

Animals↗

Laser-nephelometric detection of soluble immune complexes.

A new method for the detection of soluble immune complexes has been worked out by combining the polyethylene glycol (PEG) precipitation method with laser nephelometry. Experiences achieved by measurements on in vitro immune complexes are presented. The method was found suitable for the detection of immune complexes development in vivo. The optimum concentration of PEG was found to be 3.51%. Results were compared to those achieved by the traditional PEG precipitation technique in 88 cases. The laser nephelometric method was found to be more sensitive and is recommended for use in clinical laboratories.

Antigen-Antibody Complex↗

BOC-14C-glycine pentapeptide metabolism in vitro in rat organ homogenates.

BOC-14C-glycine pentapeptide undergoes hydrolysis on incubation with tissue homogenates. The enzyme activities responsible for hydrolysis have the pancreas, lung and small intestine as their sites. No enzyme activity is demonstrable in liver, kidney and muscle. While intrapulmonary enzyme activity is marked by thermolability, the activities of the pancreatic and intestinal tissues are scarcely affected by heat. The optimum pH is 7.1 for the pulmonary, 7.1 and 10 for the pancreatic and small intestinal enzyme activity. EDTA has proved inhibitory to the enzyme activities of all three organs, in contrast to Gordox and to soybean trypsin inhibitor which leave these activities unaltered.

Animals↗

An assay for serum vitamin-B12 and for intrinsic factor antibody type I by means of hog intrinsic factor.

A method of assay for the circulating intrinsic factor antibody type I (IFA1) and for the serum vitamin-B12 level by the use of hog intrinsic factor has been developed. The results, the sources of error being taken into consideration, are in agreement with the values obtained by the generally accepted methods of ARDEMAN--CHANARIN for IFA1 and of WIDE--KILLANDER for the serum vitamin-B12 level. Parallel with the increase in the frequency of circulating IFA1, the serum vitamin-B12 level was found to decline in normal individuals as well as in patients with atrophic gastritis or pernicious anaemia. The method is suitable for the assessment of vitamin-B12 deficiency and lends itself to screening of patients tending to pernicious anaemia.

Adult↗