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Biomedical subjects

C Bruns

Publications and source records attributed to C Bruns.

103 records · Page 6Linked to original sources
PubMed1991

Inhibition of the growth of transplanted rat pancreatic acinar carcinoma with octreotide.

The effects of octreotide on transplanted azaserine-induced pancreatic acinar tumours were investigated in the rat. When tumours became palpable, rats were treated either with octreotide (40 micrograms/kg per day, by infusion) or NaCl 0.9% (controls) for 14 days. Tumours were then analysed for their size, composition and somatostatin receptors. Octreotide induced a 80% reduction in tumour growth rate during the first 2 days of treatment. This rate was less marked from day 4 to day 15. The tumour weight, protein, DNA, RNA and enzyme content were reduced in parallel by 50 to 60%. A homogeneous distribution density and a high affinity of somatostatin receptors were found by receptor autoradiography and in vitro binding assays in tumours of both groups. These findings indicate that octreotide reduces the growth rate of the transplanted pancreatic acinar tumour and may exert its inhibitory effect directly via specific somatostatin receptors on tumour cells.

Animals↗
PubMed1990

Identification and characterization of somatostatin receptors in neonatal rat long bones.

Somatostatin (somatotropin release inhibiting factor; SRIF) has widespread functions as a modulator of neural activity as well as of endocrine and exocrine secretion. In the present paper, the binding characteristics of somatostatin receptors have been investigated in rat long bones using the stable analogue, 125I-SDZ 204-090, as a ligand. Binding studies revealed the presence of a single class of high-affinity binding sites for 125I-SDZ 204-090 on cells prepared from neonatal rat long bones with an equilibrium dissociation constant (KD) of 70.1 +/- 8.2 pM (n = 3). An excellent correlation was found between the ability of various somatostatin analogues to inhibit growth hormone in pituitary cells and to displace the binding of 125I-SDZ 204-090 to the bone cell preparation, indicating that the receptors are very similar, if not identical. The localization of the somatostatin-binding sites was examined by autoradiography after labelling in vitro and in vivo. The binding sites were shown by both procedures to be selectively localized to the metaphysis of rat long bones. The labelling experiments in vivo indicate that these receptors can be reached in the living animal by circulating somatostatin analogues. In addition, the analogue SMS 201-995 inhibited the forskolin-stimulated adenylate cyclase activity in bone cell suspensions. These results suggest that somatostatin could be an important regulatory factor in bone metabolism.

Adenylyl Cyclases↗
PubMed1990

Somatostatin receptors are restricted to a subpopulation of osteoblast-like cells during endochondral bone formation.

Specific binding sites for the peptide hormone somatostatin have previously been demonstrated in long bones from neonatal rats. In the present study, the distribution of somatostatin receptors during embryonic bone formation has been investigated using the stable radioiodinated somatostatin analogue, SDZ 204-090. Somatostatin receptors in rat long bones were first detectable at the time of invasion of the cartilage model by osteogenic cells. Initially, receptors were detectable throughout the region occupied by osteogenic cells. As bone growth proceeded, however, receptors were restricted to the region of most recent invasion of the hypertrophic cartilage, where osteoid had not yet been deposited. In vivo labelling studies in neonatal rats were carried out to identify the cells bearing somatostatin receptors. Receptors were present in a restricted region of the metaphysis, immediately adjacent to the hypertrophic cartilage. Chondrocytes, osteoclasts, and mature osteoblasts were not labelled by the radioligand. The labelled cells were often apposed to remnants of cartilage matrix and stained positively for the osteoblast marker, alkaline phosphatase. Thus the cells with specific somatostatin-binding sites were probably osteoblast precursor cells. Specific binding was detectable in all endochondral bones examined, including those of the skull, but no specific binding was found in the membrane bones of the skull. These data suggest that somatostatin is involved in the regulation of osteoblast differentiation during endochondral bone formation.

Animals↗
PubMed1987

Synthetic diacylglycerols induce a rise of quin2-detectable free intracellular calcium in human platelets.

The two activators of protein kinase C, oleoylacetylglycerol (OAG) and dioctanoylglycerol (DOG), are able to induce a concentration-dependent rise in cytoplasmic free Ca2+ concentration in gel-filtered human platelets, detected as an increase in quin2 fluorescence. The phorbol ester phorbol-12-myristate-13-acetate (PMA) has no effect. The OAG-induced increase of intracellular Ca2+ is not influenced by forskolin, in contrast to the effect of the diterpene on the thrombin-stimulated increase in cytoplasmic Ca2+. It is concluded that the increase in intracellular free Ca2+ concentration induced by synthetic diacylglycerols and their activation of protein kinase C are two different and independent processes.

Aminoquinolines↗
PubMed1987

Pertussis toxin inhibits the angiotensin II and serotonin-induced rise of free cytoplasmic calcium in cultured smooth muscle cells from rat aorta.

Angiotensin II, serotonin and K+-depolarization cause an increase in free cytoplasmic Ca2+ in cultured smooth muscle cells. The involvement of a guanine nucleotide-binding protein has been investigated by using pertussis toxin. When smooth muscle cells were pretreated with pertussis toxin angiotensin II and serotonin-induced rise of cytosolic Ca2+ was found to be significantly reduced whereas the Ca2+ influx mediated by K+-depolarization remained unchanged. These results suggest the participation of a guanine nucleotide-binding protein in the receptor-mediated rise of intracellular Ca2+.

Angiotensin II↗
PubMed1986

[Hepatitis A outbreak in a shelter for the homeless in Vienna].

An outbreak of hepatitis A was observed in a shelter for the homeless in Vienna with about 200 inhabitants. Twenty-two cases occurred within a period of 6 months. The outbreak could not be brought under control by measures of general hygiene. However, after the administration of hepatitis A immunoglobulin (120 IU/ml), at a dosage of 0.05 ml/kg body weight, to 102 of the 105 seronegative inhabitants and members of staff, no further clinical cases of hepatitis A were reported from this group. Nevertheless, 8 of these 102 "protected" persons showed signs of subclinical infection at subsequent follow up. Apart from these, 2 further cases of hepatitis A occurred among the non-immunised children at risk, whose parents had refused permission for serological investigation or immunoglobulin administration.

Adolescent↗
PubMed1986

Stereospecific inhibition of 5-HT-induced increase of intracellular free calcium by (+)- and (-)-desmethoxyverapamil in human platelets.

The concentration of intracellular free calcium [Ca2+]i in human platelets was measured by the quin-2 method. 5-Hydroxytryptamine (5-HT) at 10(-5) M induced a rapid transient increase of [Ca2+]i which was antagonized by 10(-7) M ketanserin or cyproheptadine. The verapamil derivative, desmethoxyverapamil (D888), showed stereospecific inhibition of the 5-HT-induced [Ca2+]i increase. The IC50 for (-)-D888 was approx. 2 X 10(-8) M; (+)-D888 was almost 50 times less potent.

Blood Platelets↗
PubMed1984

Stressful life events and drug use among adolescents.

The authors investigated the hypothesis that increased amounts of stress during and/or prior to adolescence would be associated with elevated use or abuse of drug substances by adolescents. Through the study the authors also provided further information regarding the usefulness of various techniques of life event surveying in the measurement of presumptive stress among adolescents. Using a multivariate analysis of the data, a number of conclusions were drawn with the overall conclusion that increased life stress levels are significantly associated with elevated drug use.

Adolescent↗
PubMedDate not supplied

Somatostatin analog sandostatin and inhibition of tumor growth in patients with metastatic endocrine gastroenteropancreatic tumors.

A prospective study was performed to determine the efficacy of octreotide (Sandostatin; SMS 201-995) 200 micrograms tid in controlling tumor growth. The study included 21 patients with metastasized endocrine GEP tumors: 6 gastrinomas, 8 carcinoid syndromes, 7 nonfunctioning tumors. Treatment was performed for 3 to 59 months (median 15 months). Evaluation of the response to octreotide was facilitated in 12 patients by a pretreatment observation period of 3 to 47 months (median 17 months) during which the natural growth behavior was determined. Based on the presence or absence of a control period prior to treatment, 5 patients were considered to be responders, 7 as questionable responders (no pretreatment phase available), and 9 as nonresponders. None of the 21 patients had documented shrinkage of the tumor mass. The most favorable response was tumor standstill. In all but one responder an escape to an initially favorable response occurred after 6 to 28 months (median 14 months). Proved inhibition of growth was paralleled by a reduction of serum and urine hormone parameters, whereas unaltered progression of tumor growth was observed also in the presence of hormone suppression. Tumor growth and hormone release was inhibited in the absence and presence of somatostatin receptors on the tumor. It is concluded that octreotide exerts a limited effect on metastatic GEP tumor growth. The evaluation of a response to octreotide is facilitated by an observation period prior to the drug that provides information on growth characteristics of the tumor. The presence of octreotide receptors does not predict the success of therapy.

Adenoma, Islet Cell↗
PubMedDate not supplied

Dissimilar associations of two secretory peptides with a neurosecretory granule-enriched fraction from the bag cells.

The bag cell neurons of Aplysia californica synthesize and secrete several neuropeptides. To gain more detailed information about their posttranslational routing and transport, we have undertaken isolation of the neurosecretory granules (NSG). Extracts of radiolabeled cells were subjected to discontinuous, isosmotic density-gradient centrifugation. Radiolabeled peptides likely to be contained in NSG were found to relocate from the starting zone and to be associated with particulate structures. Assay of enzyme markers for lysosomes and endoplasmic reticulum disclosed gradient distributions that differed from that shown by the peptides. Hence, it is probable that the position of peak concentrations of particulate peptides represents the location of NSG. Of particular interest is the further observation that the known secretory peptides ELH and AP do not evidence strict covariance across the gradient. This deviation from covariance is consistent with hypotheses that the peptides are in different associations with the NSG cores or that more than one type of neurosecretory granule is produced in the bag cells.

Animals↗
PubMedDate not supplied

Synthesis, biological activity and conformational study of a somatostatin hexapeptide analogue containing a reduced peptide bond.

The cyclic hexapeptide analogue of somatostatin, c[Phe psi(CH2-N)Pro-Phe-D-Trp-Lys-Thr], was prepared by solid-phase synthesis of the linear precursor, followed by cyclization using diphenylphosphoryl azide. The inhibition of GH release, as well as receptor affinity, is greatly decreased. Conformational analysis by NMR in DMSO/H2O (1/1) revealed the presence of a type II' beta-turn in the core tetrapeptide region and a delta-turn over the reduced peptide bond.

Amino Acid Sequence↗
PubMedDate not supplied

Indirect antiproliferative effect of the somatostatin analog octreotide on MIA PaCa-2 human pancreatic carcinoma in nude mice.

Analogs of somatostatin (SRIF) such as octreotide exert antiproliferative effects that are mediated directly by tumoral SRIF receptors or indirectly by down-modulation of factors that stimulate tumor growth. Direct and indirect antiproliferative effects have been demonstrated in certain SRIF receptor-positive and -negative human breast cancer models in nude mice, respectively. These antiproliferative mechanisms are also being explored in other cancer types including pancreatic cancer. While clinical pilot studies have indicated that a fraction of pancreatic adenocarcinomas respond to high-dose octreotide treatment, it is known from receptor autoradiographic and scintigraphic studies that human pancreatic carcinomas fail to express SRIF receptors, in contrast to rat pancreatic carcinomas or human endocrine pancreatic cancer. Studies on the potential anticancer effect of octreotide on the growth of experimental human pancreatic cancer and its SRIF receptor status have been controversial. Therefore, we investigated in vivo the effects of octreotide on the growth of MIA PaCa-2 human pancreatic carcinomas raised from cultured cells with a low passage number after receipt from the American Type Culture Collection. Nude mice bearing MIA PaCa-2 tumors were treated with a single injection of the recently developed octreotide long-acting release formulation, "SMS pa LAR." This treatment was well tolerated and resulted in a highly significant inhibition of tumor growth during weeks three and eight after administration. MIA PaCa-2 tumors were removed after eight weeks and processed for RT-PCR analysis using probes specific for each of the five somatostatin receptor subtypes sst1-sst5. This analysis revealed that MIA PaCa-2 tumors, like human pancreatic adenocarcinomas, do not express any of the five SRIF receptor subtypes, suggesting an indirect mode of tumor growth inhibition. In summary, the depot formulation SMS pa LAR exerted long-lasting antiproliferative effects in SRIF receptor-negative human pancreatic carcinomas in nude mice.

Animals↗