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Biomedical subjects

U Leonhardt

Publications and source records attributed to U Leonhardt.

At least 55 records · Page 3Linked to original sources
PubMed1993

The effect of different solutions for organ preservation on immediate postischemic pancreatic function in vitro.

The present study compares the effect of organ preservation with Euro-Collins solution, cardioplegic histidine-tryptophan-ketoglutarate solution, and University of Wisconsin solution on immediate pancreatic function after cold storage at 4 degrees C for 24 hr. Postischemic organ quality of a porcine pancreas preparation was tested by quantification of physiological and biomedical parameters in a one-line reperfusion system. During reperfusion with a constant arterial pressure the arteriovenous flow rate was significantly higher for HTK (5.7 +/- 0.91 ml/min, n = 8; P < 0.05 vs. EC) and UW (7.4 +/- 0.81 ml/min, n = 8; P < 0.05 vs. EC) than for EC (3.0 +/- 0.26 ml/min, n = 6). The lowest lactate content in the reperfusate was found after HTK protection (HTK, 64.0 +/- 7.2 mumol/50 ml, n = 8; versus EC, 114.2 +/- 1.7 mumol/50 ml, n = 6, P < 0.001; versus UW, 148.0 +/- 28.6 mumol/50 ml, n = 8, P < 0.05). Amylase in the venous effluent was significantly lower (P < 0.05) for HTK or UW protection than for EC (HTK, 189 +/- 72.6 U/ml; UW, 188 +/- 39.4 U/ml; EC, 416 +/- 71.7 U/ml). Oxygen consumption during reperfusion was significantly higher for HTK (2.15 +/- 0.22 microliters/g/min, P < 0.001) and UW (1.80 +/- 0.52 microliters/g/min, P < 0.05) than for EC (0.47 +/- 0.13 microliters/g/min). We conclude that immediate postischemic organ quality and pancreatic function after protection with HTK is not inferior to preservation with UW.

Adenosine↗
PubMed1992

[Diagnostic and therapeutic problems in Lamblia infections].

A 28-year-old woman complained of chronic diarrhoea of about one year's duration, made worse by taking food. As a lactose tolerance test showed evidence of severe intolerance she was given a lactose-free diet, but this brought no improvement. Duodenal biopsy showed villous atrophy, and in the duodenal juice there were numerous flagellated lamblia. After a single oral dose of 2 g tinidazole the diarrhoea stopped, the lamblia disappeared, and the lactose intolerance and villous atrophy cleared up. Lamblia were also detected in the duodenal juice of a 50-year-old woman, but her infection was much more difficult to treat. Tinidazole (single dose of 2 g), metronidazole (800 mg twice daily for 6 days), ornidazole orally 500 mg twice daily for 10 days and ornidazole intravenously 500 mg twice daily for four days all proved ineffective. However, after a 5-day course of epsilon-9-aminacridine (100 mg three times daily by mouth) the diarrhoea ceased and both vegetative forms and lamblia cysts disappeared. These cases emphasize that lambliasis should be considered as a possible cause of severe chronic diarrhoea even when there is no history of travel abroad and when the symptoms are atypical. Conventional chemotherapeutic agents may be ineffective.

Adult↗
PubMed1992

Influence of a platelet-activating factor antagonist on severe pancreatitis in two experimental models.

This study investigates the role of platelet-activating factor (PAF) in experimental pancreatitis. The concentration of PAF quantified in ascites of bile-induced pancreatitis by radioimmunoassay (RIA) ranged from 3.67 +/- 0.39 pmol/mL 2 h to 0.954 +/- 0.39 pmol/mL 10 h after injection of taurocholate. Administration of a potent PAF antagonist, WEB-2170, prior to injection of taurocholate prolonged mean survival time in rats receiving i.v. camostate and albumin (46.4 h, n = 15, vs controls 38.3 h, n = 13). However, the survival rate after 72 h was not improved. The histologically estimated severity of pancreatitis and pancreatic enzymes in blood, tissue, or ascites was not affected. WEB-2170 had no effect on survival when injected simultaneously with taurocholate into the pancreatic duct or given i.v. after induction of pancreatitis (1, 0.1, or 0.01 mg/kg WEB-2170 vs controls). Subcutaneous injection of 10 mg/kg WEB-2170 also did not improve survival in pancreatitis induced by choline-deficient, ethionine-supplemented diet in mice. It is concluded that administration of a PAF antagonist after the onset of severe experimental pancreatitis does not influence its outcome, although activation of PAF may play a role in the pathogenesis of pancreatitis.

Animals↗
PubMed1991

Influence of the CCK-antagonist loxiglumide on bile-induced experimental pancreatitis.

The present study investigates the effect of CCK-receptor blockade on taurocholate-induced pancreatitis in rats using the potent antagonist loxiglumide. Intraperitoneal administration (50 mg/kg) of loxiglumide began 3 h before, or 10 min or 3 h after induction of pancreatitis. Mean survival times of the experimental groups were 31.2, 23.6, and 20.5 h, respectively, compared to 18.2 h for controls. Survival for 24 h after induction of pancreatitis was significantly improved when the antagonist was given 3 h before, but not in the time periods after induction. After 72 h, survival time was not significantly altered in any of the groups. Furthermore, amylase and lipase levels quantified 10 h after induction of pancreatitis in ascites, blood, or tissue did not indicate a significant difference, nor was improvement in survival seen when the CCK-antagonist was tested in rats receiving a basal treatment with intravenous volume substitution, peritoneal lavage, and protease inhibition. We conclude that CCK-receptor blockade does not improve the final outcome of bile-induced pancreatitis in the rat, even if treatment is started before induction of pancreatitis.

Animals↗
PubMed1990

Preservation of the porcine pancreas with HTK and Euro-Collins solution: studies in a reperfusion system.

The present study compares the preservation of the porcine pancreas by the standard Euro-Collins solution or the cardioplegic histidine-tryptophan-ketoglutarate solution (HTK). The explanted pancreas was stored at 4 degrees C for 6 and 24 h respectively, following which organ quality was assessed in a reperfusion chamber measuring physiological and biomedical parameters. After 6 h ischaemia, the amount of lactate was significantly lower when HTK was used for protection. Other parameters like insulin release, amylase release, vascular resistance and oxygen consumption of the pancreas did not indicate a significant difference. Protection with HTK significantly improved pancreas preservation after 24 h ischaemia: lactate content in the reperfusate was lower (HTK: 64.0 +/- 7.2 mumol 50 ml-1 n = 8, v. EC: 114.2 +/- 1.7 mumol 50 ml-1, n = 6), the arteriovenous flow rate was higher (HTK: 5.7 +/- 0.91 ml min-1 v. EC: 3.0 +/- 0.26 ml min-1), and the pancreatic oxygen consumption was increased (HTK: 2.15 +/- 0.22 microliter O2 min-1 g-1 v. 0.47 +/- 0.08 microliter O2 min-1 g-1). We conclude that pancreas preservation can be improved in vitro by protection with HTK solution.

Amylases↗
PubMed1990

Camostate (FOY-305) improves the therapeutic effect of peritoneal lavage on taurocholate induced pancreatitis.

The effect of peritoneal lavage with the addition of camostate to the lavage fluid on the outcome of taurocholate pancreatitis in rats was studied. Camostate is a low molecular weight protease inhibitor which has been developed recently. Peritoneal lavage was performed for 12 hours and camostate was added to the lavage fluid in five concentrations. At 0.1 mg/ml the survival rate increased significantly (11 of 20 v controls 4 of 20, p less than 0.05); the maximal effect was observed at 0.2 mg/ml, and no effect was seen at 0.01 and 0.05 mg/ml. Adverse effects occurred at 0.5 mg/ml. The addition of 0.1 mg/ml camostate significantly reduced the acidosis in arterial blood: mean (SD) pH 7.30 (0.035) v controls 7.23 (0.054) (n = 9, p less than 0.01) and arterial base excess: -15.4 (1.26) mmol/l v controls: -17.4 (2.51) mmol/l (n = 9, p less than 0.05). There was no difference, however, in plasma amylase activity and in the histological degree of specific tissue damage to the pancreas. A combination of intravenous camostate and lavage with the addition of camostate to the lavage fluid yielded a significantly improved survival compared with treatment with intravenous camostate alone (10 out of 16 animals v intravenous camostate alone, two out of 16, p greater than 0.01). We conclude that lavage with camostate significantly improves the prognosis of severe necrotising pancreatitis in rats.

Acute Disease↗
PubMed1989

The perfused porcine pancreas as a model for testing organ protective solutions.

The present study was designed to establish an in vitro perfused porcine pancreas preparation as a model for testing the effect of organ protective solutions on stimulated pancreatic endocrine and exocrine secretion. The pancreas was prepared and perfused for 10 min with Euro Collins solution, thereafter it was stored in the cold (4 degrees C) for various times. After 3-h and 6-h ischemia pancreatic insulin release in response to glucose was not significantly affected. After 12-h ischemia reduced pancreatic insulin secretin, increased perfusion pressure, and increased amylase and lipase release indicated pancreatic damage. Complete pancreatic dysfunction was seen after 24-h and 48-h ischemia with massive increase in perfusion pressure and low insulin secretion which did not follow a glucose-dependent release pattern, while amylase and lipase concentrations in the perfusion medium increased. Stimulated exocrine pancreatic secretion was significantly decreased already after 3-h ischemia and completely lost after 12 h.

Amylases↗
PubMed1989

Evidence for neuropeptide Y synthesis in the rat anterior pituitary and the influence of thyroid hormone status: comparison with vasoactive intestinal peptide, substance P, and neurotensin.

Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.

Animals↗
PubMed1989

A new pituitary protein 7B2 is increased in patients with high alpha- or beta-hCG.

The presence of 7B2 (a 180 amino acid peptide first extracted from the porcine pituitary) was investigated by a specific radioimmunoassay and gel filtration chromatography in the plasma of three groups of patients known to have increased levels of alpha- and beta-hCG subunits. Plasma 7B2 immunoreactive equivalents (7B2-IE) were increased in postmenopausal women (range 67-143 pmol/l, median: 94 pmol/l, N = 20, P less than 0.05), in patients with Klinefelter's syndrome (range 195-230 pmol/l), median 213 pmol/l, N = 4, P less than 0.01) and in 17 patients with malignant endocrine gastrointestinal tumours (range 66-20,000 pmol/l, N = 32) compared with healthy controls (range 23.6-98.2 pmol/l, median 41.5 pmol/l, N = 40). Tumour tissue from 4 patients with endocrine pancreatic tumours had significantly higher 7B2-IE concentrations than normal pancreatic tissue, with the highest concentration in an insulinoma (449 pmol/g, normal: 28 pmol/g). During therapy almost parallel changes in plasma 7B2 and other hormones were noted and 7B2-IE therefore might be an additional marker for cancers of the APUD system.

Adolescent↗
PubMed1989

The anterior pituitary content of neuromedin U-like immunoreactivity is altered by thyrotrophin-releasing hormone and thyroid hormone status in the rat.

In this study we have examined the effects of TRH, thyroid hormones and dopamine on the rat anterior pituitary content of neuromedin U-like immunoreactivity. Oral administration of TRH (20 mg/100 g per day) to euthyroid animals evoked a fivefold increase in peptide content after 12 days of treatment. This effect was found to be dependent upon circulating levels of thyroid hormone, since administration of TRH to thyroidectomized animals failed to show a similar effect without simultaneous treatment with tri-iodothyronine. The possibility that the TRH-induced increase in anterior lobe neuromedin U content reflected alterations in prolactin secretion or synthetic rate was also examined. Treatment of euthyroid animals with a dopamine agonist and antagonist was, however, without effect. These results demonstrate a unique relationship between TRH and thyroid hormone levels in increasing the anterior lobe content of neuromedin U immunoreactivity.

Animals↗
PubMed1988

Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse, and human pituitary, in rat hypothalamus, and in 30 human pituitary and extrapituitary tumors.

The distributions of three novel peptides, 7B2, neuromedin B, and neuromedin U, in rat, mouse, and human pituitaries, rat hypothalamus, and 30 human pituitary tumors were investigated with immunocytochemistry. Immunoreactivity for 7B2 was present in rat, mouse, and human gonadotropes, in intermediate lobe cells and posterior lobe nerve fibers in rats and mice, in rat hypothalamus (particularly in the median eminence), and in eight human pituitary gonadotropinomas. In gonadectomized rats, larger, more numerous LH beta- and 7B2-immunoreactive gonadotropes were seen than in controls. Extractable 7B2-like immunoreactivity was elevated but not significantly so in gonadectomized rat pituitaries [males: castrated, 37.4 +/- 4.3 (mean +/- SE); controls, 26.9 +/- 4.3; females: ovariectomized, 27.2 +/- 2.7; controls, 19.1 +/- 2.2 pmol/gland]. Neuromedin B immunoreactivity was found in normal rat and mouse thyrotropes and weakly in "thyroidectomy" cells in hypothyroid rats, in which extractable pituitary neuromedin B was significantly depleted (thyroidectomized, 87.0 +/- 14.0; methimazole-treated, 82.0 +/- 11.4; control, 230.7 +/- 25.6 fmol/gland). Hyperthyroid rat pituitaries showed increased TSH beta and neuromedin B immunoreactivities and neuromedin B content (TRH-treated, 385.2 +/- 30.2; T4-treated, 352.6 +/- 20.2; control, 230.7 +/- 25.6 fmol/gland). Neuromedin U immunoreactivity occurred in corticotropes of all species, in rat and mouse intermediate lobe, and throughout the rat hypothalamus, with immunoreactive cell bodies in the arcuate nucleus. Neuromedin U-immunoreactive cells were present in six of six human pituitary and five of six human extrapituitary corticotropinomas. In adrenalectomized rats, corticotropes were larger and more numerous than in controls, but extractable anterior pituitary neuromedin U-like immunoreactivity was not raised (adrenalectomized, 3.30 +/- 0.45; control, 3.32 +/- 0.27 pmol/gland). Our findings suggest that 7B2, neuromedin B, and neuromedin U may be involved in pituitary function.

Animals↗
PubMed1987

Size heterogeneity of immunoreactive prolactin in patients with prolactinoma.

We investigated the chromatographic pattern of serum prolactin in 41 patients with prolactinoma and correlated the distribution of immunoreactive prolactin with the clinical variables sex, tumour size, age, and response to bromocriptine therapy. In addition, the effect of long-term storage and repeated freezing and thawing on the different molecular weight forms of prolactin was evaluated. Gel chromatography (column 100 cm X 1.5 cm) was performed in 0.1 mol/l phosphate buffer, pH 7.5, using Ultrogel ACA 54 (LKB). No correlation of age or the response to drug therapy to the elution pattern of prolactin was found. Females showed a higher percentage of big prolactin than males (10.4 +/- 1.2% vs 6.8 +/- 0.7%, mean +/- SEM, P less than 0.05) and patients with microprolactinomas too had a higher percentage of big prolactin than those with macroprolactinomas (11.3 +/- 1.8% vs 7.7 +/- 0.7%, P less than 0.05). Serum samples kept frozen for more than 2 years showed a higher percentage of bigbig prolactin (P less than 0.01) than samples stored for less than 12 months suggesting formation in vitro. However, examination of fresh samples prior to freezing also demonstrated bigbig prolactin, indicating that bigbig prolactin circulates in vivo. Repeated freezing and thawing of bigbig prolactin led to almost complete interconversion to little prolactin without any increase in immunoreactivity. This finding supports the concept that bigbig prolactin represents little prolactin loosely associated to a carrier molecule.

Adult↗