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C Löser

Publications and source records attributed to C Löser.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of neurotensin on pancreatic growth and pancreatic polyamine metabolism in rats.

The neuropeptide neurotensin is known to play a role in the regulation of exocrine pancreatic secretion, but actually there are conflicting results as to whether or not neurotensin exerts a trophic response on the pancreas and there are no data concerning its effect on pancreatic polyamine metabolism. In the present study, acute and long-term effects of various intraperitoneal dosages of neurotensin that resulted in mildly supraphysiological and even unphysiological high plasma concentrations of neurotensin were studied. Furthermore, neurotensin was simultaneously administered with cholecystokinin (1 microgram CCK-8/kg body wt ip every 8 h) for five days. The administration of neurotensin resulted in an acute significant decrease of pancreatic amylase and trypsinogen concentrations (p < 0.001), which indirectly confirms the potent effect of neurotensin on pancreatic exocrine secretion. In contrast to that, neither during the short-term study (100 micrograms neurotensin/kg body wt ip every 8 h for 2, 4, 6, 8, 16, and 24 h) nor during the long-term study (1 microgram, 100 micrograms, or 200 micrograms neurotensin/kg body wt ip three or eight times daily for 10 d) did neurotensin administration result in any increase of the various parameters of pancreatic growth and polyamine metabolism. Simultaneous administration of neurotensin and CCK failed to alter or further increase the known stimulatory effect of CCK on pancreatic polyamine metabolism and pancreatic growth after 5 d of treatment. These data indicate that neither alone nor in combination with cholecystokinin did various dosages of neurotensin exert any significant stimulation on pancreatic growth or the parameters of pancreatic polyamine metabolism.

Animals↗
PubMed1995

Dissimilar effect of the carcinogenic agent azaserine on pancreatic and hepatic polyamine metabolism in rats.

The present study was designed to investigate the effects of the carcinogenic agent azaserine on the induction of pancreatic and hepatic polyamine metabolism in rats. One single injection of 30 mg azaserine/kg body weight i.p. is known to induce adenoma and subsequently carcinoma, predominantly in the pancreas, after several months. Male Lewis rats were treated with either azaserine (30 mg/kg body weight i.p.) or saline and 5-10 animals per group were sacrificed 2, 6, 9, 12, 18, 24, and 48 h later. Furthermore, animals were simultaneously treated with the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) or the polyamine oxidase inhibitor MDL 72527 and killed 6 and 12 h after azaserine injection. The azaserine-induced significant increase in pancreatic putrescine concentrations was accompanied by an increase in spermidine/spermine N1-acetyltransferase but unchanged ODC and was significantly inhibited by N, N'-bis(2,3-butadienyl)putrescine (MDL 72527) but not by DFMO. S-Adenosylmethionine decarboxylase (SAM-DC) activity was significantly decreased in the pancreata of azaserine-treated animals compared to controls. In contrast, the azaserine-induced significant increase in hepatic putrescine was lower and transient, was accompanied by an increase in ODC and SAM-DC, and was completely inhibited by simultaneous DFMO treatment but not by MDL 72527. These data show completely different patterns of activation of polyamine metabolism in the pancreas and in the liver: Azaserine treatment forms putrescine in the liver by de novo synthesis via ODC only, while azaserine-induced pancreatic putrescine is exclusively produced by the interconversion pathway via oxidation of N1-acetylspermidine.

Animals↗
PubMed1995

[Differential therapy of exocrine pancreatic insufficiency--current aspects and future prospects of substitution therapy with pancreatic enzymes].

The indication for initiation of a replacement therapy with pancreatic enzymes in the course of ongoing exocrine pancreatic insufficiency is clinically given with the appearance of loss of body weight, steatorrhea with stool fat excretion of more than 15 g per day, dyspeptic symptoms with strong meteorism, diarrhoea, and subjective misbehaviour caused by chronic pancreatitis, in rare cases with the appearance of maldigestion of proteins and carbohydrates and--under certain circumstances--for the treatment of pain in chronic pancreatitis. Due to the increase of chronic pancreatitis in recent years, the number of patients who necessarily have to be treated with enzyme replacement therapy has increased, too. The adequate replacement therapy with pancreatic enzymes, especially in patients with severe exocrine pancreatic insufficiency, is still a serious problem--requiring sufficient knowledge of the individual pathophysiological circumstances of the patient as well as the various pharmacological aspects of the different types of enzyme drugs. The most important clinical aim of the replacement therapy is the necessity to achieve a sufficient lipase activity in the duodenum. Accordingly the achievement of this aim is the main problem in clinical practice, since the acid-instable lipase is predominantly inactivated by gastric acid and proteases. Furthermore, in many cases an asynchronous gastroduodenal transport of the administered enzyme drug and food is found as a result of inadequate size of the drug or drug particles. In general, the necessary doses of administered enzymes does not follow general rules, but has to be adjusted individually. Recent scientific developments, as the characterization of an acid-stable bacterial lipase, the cloning of human acid-stable lipase, the transfection of human lipase genes by virus-mediated gene transfer as well as the development of very small acid-stable mini microspheres, present interesting new perspectives to further optimize the efficacy of the therapy of exocrine pancreatic insufficiency in the near future.

Exocrine Pancreatic Insufficiency↗
PubMed1994

Progesterone-induced acrosome reaction: potential role for sperm acrosome antigen-1 in fertilization.

We have established a monoclonal antibody (mAb) AG7 defining a sperm acrosome antigen-1 (SAA-1) on spermatozoa from the human and several mammalian species. MAb AG7 inhibits fertilization of mouse eggs in vitro and in vivo. An important characteristic of mAb AG7 is its inhibition of the rise in intracellular calcium induced by progesterone in human spermatozoa. Here we show that, following the acrosome reaction, SAA-1 is lost from the cap of human spermatozoa but remains detectable in the equatorial region. Acrosome reaction assays demonstrated a clear difference between progesterone- and A23187-induced acrosome reactions. For induction of the acrosome reaction with progesterone, a minimum capacitation time of 6 h was required. A23187 induced the acrosome reaction regardless of capacitation time. MAb AG7 completely inhibited the progesterone-induced acrosome reaction, but not the A23187-induced acrosome reaction in human spermatozoa. Differences in the pattern of calcium flux induced by the two agents might account for this phenomenon. The inhibition of the progesterone-induced acrosome reaction by mAb AG7 implies a regulatory function of SAA-1 during the human sperm acrosome reaction.

Acrosome↗
PubMed1994

Epidermal growth factor (EGF) fails to stimulate pancreatic growth and pancreatic polyamine metabolism in rats.

Epidermal growth factor (EGF) is a potent mitogen exerting a variety of biologic effects. While the growth stimulatory effect of EGF is well investigated in the gut, there are conflicting results concerning the growth stimulatory effect of EGF in the pancreas and no data concerning its effect on pancreatic polyamine metabolism in vivo. In the present study male Wistar rats (180 g) were either treated with EGF (20 micrograms/kg b. wt. i.p. every 8 hours) alone, EGF plus the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethyl-ornithine (DFMO), DFMO alone or saline as controls and 9-10 rats per group were killed after 8 hours, 1, and 5 days. To prove the biologic activity of EGF (> 97% purity; HPLC) rats were i.p. injected with 150 micrograms EGF/kg b. wt. and five animals were killed after 2, 4, or 6 hours, respectively and ODC and S-adenosylmethionine decarboxylase (SAM-DC) activities were calculated in the duodenum, ileum, and pancreas. In contrast to the gut neither acute high-dose nor long-term administration of EGF resulted in any stimulation of pancreatic growth or pancreatic polyamine metabolism of rats in vivo.

Adenosylmethionine Decarboxylase↗
PubMed1994

[The effect of ranitidine and famotidine on the intragastric pH profile of healthy subjects. Randomized cross-over trial with ranitidine effervescent tablets (300 mg) versus famotidine film tablets (40 mg) ].

Influence of Ranitidine and Famotidine on the Intragastric pH-profile in Healthy Volunteers/Randomised cross-over study of ranitidine effervescent tablets (300 mg) versus famotidine film coated tablets (40 mg). A controlled cross-over trial was carried out to compare the duration of time until the onset of action and its intensity following administration of ranitidine (R, Sostril, CAS 76824-35-6) effervescent tablets (300 mg) and famotidine (F, CAS 76824-35-6) film coated tablets (40 mg). Twelve volunteers (4 female, 8 male) participated in the study. The efficacy of the test medications was assessed by pH-metry during 12 h. The evaluation of the measurements showed that a pH-value 3.5 was reached 100 s after administration of R and 3,392 s (56.5 min) after F (p < 0.01). The median pH-values were significantly higher after R during the first 2 h. The AUC-values (area under the curve; pH-time) for 1, 2 and 4 h were calculated by the trapezoid rule. The intake of R resulted in significantly higher areas than that of F. After reaching the pH-value of 3.5 this value remained stable during the complete period of measurement (R = 12 h, F = 11 h). The faster onset of pH-value elevation could correspond clinically with a faster onset of pain relief.

Adult↗
PubMed1993

Importance of various intracellular regulatory mechanisms of polyamine metabolism in camostate-induced pancreatic growth in rats.

Aim of the present study was to evaluate the relevance of various intracellular regulatory mechanisms of polyamine metabolism in normal and camostate (FOY 305)-induced pancreatic growth in rats. Furthermore it was investigated whether the simultaneous inhibition of the polyamine interconversion pathway by the potent polyamine oxidase inhibitor MDL-72527 together with the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) is able to enhance and prolong the only initial and transient inhibitory effects of DFMO on camostate-induced pancreatic growth. Simultaneous administration of DFMO and MDL-72527 resulted in a significant inhibition of the camostate-induced increases in pancreatic putrescine, ODC and DNA over 5 days, while the initial significant inhibition of pancreatic weight, protein content, DNA-polymerase and especially spermidine was absent after 5 days and spermine as well as N1-acetylspermidine were even increased. Diamine oxidase (DAO) activity in pancreas is very low and the potent DAO inhibitor aminoguanidine failed to alter any of the measured parameters except DAO. Therefore, oxidative degradation of putrescine by DAO--which is essential in the gut--is irrelevant in the pancreas. Simultaneous inhibition of the pancreatic polyamine interconversion pathway extended the initial inhibitory effects of DFMO only slightly and failed to exert a potent long-lasting inhibitory effect on spermidine and pancreatic growth.

Amine Oxidase (Copper-Containing)↗
PubMed1993

A concept of treatment in acute pancreatitis--results of controlled trials, and future developments.

The prognostic assessment, as well as the individual therapy especially of acute necrotizing pancreatitis, still remains a common clinical problem. Today, conservative intensive care is widely accepted as the most important initial therapeutic measure. Despite various attempts based on different underlying pathophysiological mechanisms, advances in conservative therapeutic concepts over the last few years have remained small. The aim of the following review is to present current concepts of treatment of acute pancreatitis, summarizing the established guidelines for conservative and operative surgical therapy as discussed in further articles of this issue. Furthermore, important recent attempts at therapeutic innovation are discussed, and the prospects for future development presented.

Acute Disease↗
PubMed1991

[Acupuncture to alleviate pain during colonoscopy].

36 patients (18 males and 18 females, mean age 51 [21-76] years) were prepared for colonoscopy with acupuncture (points: Hegu, Neiguan, Zusanli and Gongsun bilaterally), without acupuncture or pretend acupuncture at points not expected to bring about pain relief. In the 12 acupuncture patients mean pain sensitivity, estimated during the examination by means of a visual analog scale, was significantly (P = 0.003) lower (1.4 +/- 0.4) than in the groups without acupuncture (n = 12; 2.7 +/- 0.3) or pretend acupuncture (n = 12; 3.0 +/- 0.3). In addition, analgesics and sedatives needed to be given significantly less to those with acupuncture (one patient each; P = 0.005) than those without (analgesics to five, sedatives to eight patients) or with pretend acupuncture (analgesics to four, sedatives to five patients). These data demonstrate that pain connected with colonoscopy can be reduced by preceding acupuncture.

Acupuncture Analgesia↗
PubMed1991

[Clinical and pharmacological aspects of pancreatic enzyme substitution therapy].

The adequate therapy of pancreatic enzyme replacement in patients with exocrine pancreatic insufficiency is still a difficult clinical problem especially in patients following pancreatectomys, with chronic alcoholic pancreatitis or cystic fibrosis. The substitution of lipase to eliminate steatorrhoea is the most important aim but due to its acid lability even the most serious problem in pancreatic enzyme replacement therapy. Various different medications are meanwhile available: conventional preparations from porcine pancreatin or fungal enzymes as rizolipase, enteric-coated tablets or even enteric-coated microspheres or adjunctive therapy with H2-receptor antagonists. While dosage requirements vary widely and therefore have to be tried out individually, the choice of the adequate preparation should be influenced by the realization of the physiological and pathophysiological characteristics of the individual patient and the pharmaceutical characteristics of the different supplements. The advantages and disadvantages of the various medications for enzyme replacement therapy in patients with exocrine pancreatic insufficiency are reviewed in this article.

Alcoholism↗
PubMed1991

[Value of imaging procedures in diagnosis of cystic pancreatic tumors].

Cystadenoma and cystadenocarcinoma are rare tumors of the pancreas. While these cystic neoplasms neither present any typical clinical symptoms nor cause any specific changes in laboratory parameters, great emphasis is laid on imaging procedures for the diagnosis of these pancreatic tumors. Tumor size, localization and the typical cystic character are well-documented by ultrasound and contrast-enhanced computed tomography. Furthermore, CT could contribute to distinguish between serous and mucinous cystadenoma of the pancreas because of typical features of both tumors. Angiography presents a further suitable diagnostic method, while ERCP findings are rather unspecific and non-homogenous. Furthermore, ultrasound guided fine-needle biopsy should be carried out in unclear cases to confirm the diagnosis.

Biopsy, Needle↗
PubMed1990

Cystic neoplasms of the pancreas: a clinical and radiological study of eight cases.

Four patients with benign serous cystadenoma, one with mucinous cystadenoma, and three with mucinous cystadenocarcinoma treated in the university hospital of Göttingen between 1985 and 1988 were investigated. The main initial symptoms of these cystic tumors were abdominal pain (7/8), weight loss (3/8), maldigestion (3/8), and palpable abdominal mass (3/8), while laboratory investigations revealed nonspecific alterations (elevated ESR, mild hypochromic anemia). CA 19-9 was elevated in two patients, one of whom had cystadenocarcinoma; CEA also was elevated in this patient only. In all cases size, localization, and cystic character of the tumors were shown clearly by sonography and computed tomography; fine needle biopsy helped to distinguish between serous and mucinous cystadenoma in four of six cases. Because of their malignant potential, total extirpation of mucinous cystic tumors is the treatment of choice, while serous cystadenomas are benign and therefore may be treated conservatively in uncomplicated cases or high-risk patients.

Adult↗
PubMed1990

Polyamines in colorectal cancer. Evaluation of polyamine concentrations in the colon tissue, serum, and urine of 50 patients with colorectal cancer.

Total, free, and acetylated polyamine concentrations were measured simultaneously in colon tissue, serum, and urine of 50 patients with histologically proven colorectal cancer, 40 patients with nonmalignant gastrointestinal diseases, and 30 healthy volunteers. Compared with histologically unaffected colon tissue, concentrations were significantly (P less than 0.001) higher for putrescine, elevated for cadaverine, and nearly identical for spermidine and spermine in colon carcinoma, whereas N1-acetylated and N8-acetylated spermidine were detectable in cancer tissue only. Serum and urine concentrations of all polyamines except total cadaverine and spermine in serum and free spermine in urine were significantly elevated compared with healthy controls and highest sensitivity for colon cancer was found for total spermidine (89.15%) in serum and acetylputrescine (84.5%), total putrescine (84.0%), N1-acetylspermidine (79.3%), and total spermidine (92.1%) in urine. However, nonmalignant gastrointestinal diseases partly showed similar elevations which resulted in a low specificity for polyamines in colorectal cancer. Therefore, polyamines are of little value only as diagnostic markers in colorectal carcinoma. Since polyamine concentrations in serum and urine normalized in patients after curative operation while they were further elevated in patients with proven tumor relapse or metastases, these substances might play a clinical role in predicting therapeutic success or indicating relapse of the tumor. Although a significant dependency of polyamine concentrations in serum or urine to Dukes' classification, tumor localization, CEA, CA 19-9, or CA 125 did not exist, a significant linear correlation was found for tumor size.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Dissimilar trophic effects of cerulein and xenopsin on the rat pancreas.

Cholecystokinin (CCK), gastrin, cerulein, and other analogs are known to stimulate the growth of the rat pancreas. In the present study, we compared the trophic action of a member of this gastrin/CCK family, the amphibian peptide cerulein, with a member of the structurally unrelated neurotensin/xenopsin group, the amphibian peptide xenopsin. For this purpose, 0.56 nmols/kg cerulein, 1.0 nmols/kg xenopsin, or normal saline were injected intraperitoneally three times a day in 28 rats for 3 d. Pancreatic weight, DNA, and incorporation of 3H-thymidine into DNA were determined. In another study, pancreatic weight, DNA, and the polyamines, putrescine, spermidine, and spermine, were determined after a single dose of 2.7 nmol/kg cerulein, 4.5 nmol/kg xenopsin, or saline. The polyamines were measured by reverse-phase HPLC and post-column derivatization. Cerulein increased pancreatic weight, stimulated 3H-thymidine incorporation into DNA, and raised putrescine concentrations significantly, but led to a significant reduction of pancreatic DNA concentration. Xenopsin also stimulated 3H-thymidine incorporation into DNA, but did not affect pancreatic weight, DNA concentration, or the polyamines during the 4 h of the experiment. These findings suggest that cerulein, in the dose and intervals applied, initiated hyperplasia and induced hypertrophy of the pancreas, whereas xenopsin only initiated hyperplasia. These results, together with the dissimilar secretory effects of the two peptide families, may be the expression of a dissimilar mode of action. However, it cannot be excluded that, since cerulein is more potent than xenopsin, the differences also are owing to dosage. We conclude that cerulein and xenopsin, which both have trophic effects on the pancreas, may act by different mechanisms.

Animals↗
PubMed1990

Polyamine concentrations in pancreatic tissue, serum, and urine of patients with pancreatic cancer.

We investigated the total, free, and acetylated polyamine concentrations in pancreatic tissue, serum, and urine of 20 patients with pancreatic cancer, 30 healthy volunteers, and 40 patients with nonmalignant, gastrointestinal diseases by reversed-phase liquid chromatography. Tissue concentrations in carcinoma compared to histologically unaffected pancreas were significantly higher for putrescine, elevated for cadaverine, and nearly identical for spermidine and spermine, while N1-acetylspermidine was detectable in cancer tissue only. With the exception of free spermine in urine and total spermine in serum, all other polyamines were significantly elevated in the urine and serum of cancer patients compared to healthy controls. These data support the concept that polyamines play an important role in rapidly growing tissues. However, nonmalignant gastrointestinal diseases partly showed similar elevations. Because of this low specificity, polyamines are of little value only as diagnostic markers of pancreatic carcinoma. Since polyamine concentrations normalized in patients after curative operation while they were further elevated in patients with tumor relapse or metastases, polyamines might play a clinical role in predicting therapeutic success or indicating relapse of the tumor. A significant linear correlation of polyamine concentrations and the size of the tumor was found while a significant correlation to CEA, CA 19-9, and CA 125 or the presence of organ metastases did not exist.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Polyamines in pancreatic growth.

This chapter reviews available data concerning the role of polyamines in pancreatic growth. Like in many other mammalian cells stimulation of pancreatic proliferation by trophic factors is associated with an early increase in ornithine decarboxylase (ODC) activity with consequent putrescine formation. ODC and putrescine play probably an important role in the initiation but not maintenance of pancreatic growth. The application of the specific ODC inhibitor alpha-difluoromethylornithine (DFMO) alone is not sufficient to judge the role of polyamines in pancreatic growth. For that purpose a combination of substances which inhibit ODC (DFMO) and polyamine oxidase (N1,N4-bisallenylputrescine) and/or S-adenosylmethionine-decarboxylase (SAM-DC) simultaneously has to be investigated. Ideally polyamines from dietary sources and intestinal bacterial flora should be abolished. The uptake of polyamines from the circulation has still to be considered. Studies will be presented proving that though ODC is completely inhibited by DFMO putrescine is still formed via spermidine/spermine N1-acetyltransferase (SAT). The fast increase of ODC in response to growth stimulating factors like cholecystokinin (CCK) is regulated at a pretranslational level by increasing ODC mRNA.

Animals↗
PubMed1990

Acute and chronic effects of cyclosporine A on pancreatic polyamine metabolism and pancreatic adaptation.

The present study was designed to investigate the effects of acute and chronic application of the immunosuppressive agent cyclosporine A (CsA) on pancreatic polyamine metabolism as well as pancreatic growth of rats in vivo. Seven to ten animals per group were treated with either the synthetic trypsin inhibitor camostate (FOY-305, 200 mg/kg b.wt. p.o. twice a day), CsA (10 mg/kg b.wt. p.o. once a day), camostate plus CsA, or oil as control, and animals were killed after 8 h, 1, 5 and 14 days. Feeding of camostate resulted in a significant increase of the measured parameters in the following time-course: cholecystokinin (CCK), 8 h; ornithine decarboxylase (ODC), 8 h: putrescine, 8 h; S-adenosylmethionine decarboxylase (SAM-DC), 1 day; pancreatic weight, 1 day; protein content, 5 days; spermidine, 5 days; RNA, 5 days; and DNA, 14 days. Simultaneous treatment with CsA resulted in a significant inhibition of camostate-induced increases in ODC, SAM-DC as well as putrescine and spermidine and furthermore caused a nearly complete inhibition of the increase of all trophic parameters, while CCK plasma levels were not altered. Counterregulatory mechanisms to maintain the intracellular polyamine pool as known after application of specific inhibitors of enzymes of the polyamine metabolism (i.e. DFMO) were not observed. Therefore we conclude that CsA does not directly interact with the polyamine metabolism, but rather with the second messenger system or any other intracellular mechanism, that is activated after stimulation with CCK before the polyamine metabolism is induced.

Acetyltransferases↗