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Biomedical subjects

M Petek

Publications and source records attributed to M Petek.

At least 37 records · Page 2Linked to original sources

Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats.

The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 microg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutory effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.

Acute Disease↗

The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promotors and gut peptides.

The protection of stomach and duodenum in conjecture with anti-inflammatory effect was demonstrated for a novel 15 amino acid peptide, coded BPC 157, a fragment of the recently discovered gastric juice peptide BPC. BPC 157 (i.p./i.g.) was investigated in rats in comparison with several reference standards in three experimental ulcer models (48 h-restraint stress, subcutaneous cysteamine, intragastrical 96% ethanol ulcer tests) (pre-/co-/post-treatment). Only BPC 157 regimens were consistently effective in all of the tested models. On the other hand, bromocriptine, amantadine, famotidine, cimetidine and somatostatin were ineffective (restraint stress). A dose-dependent protection (cysteamine) and/or partial positive effect (related to treatment conditions) (ethanol), was obtained with glucagon, NPY and secretin whereas CCK/26-30/was not effective. Based on Monastral blue studies BPC 157 beneficial effect appears to be related to a strong endothelial protection.

Amino Acid Sequence↗

Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin.

The hepatoprotective effects of a newly synthesized 15 amino acid fragment code named BPC 157 was evaluated in comparison with the reference standards (bromocriptine, amantadine and somatostatin) in various experimental models of liver injury in rats: 24 h-bile duct+hepatic artery ligation 48 h-restraint stress and CCl4 administration. BPC 157 administered either intragastrically or intraperitoneally, significantly prevented the development of liver necrosis or fatty changes in rats subjected to 24 h bile duct + hepatic artery ligation, 48 h-restraint stress, CCl4 treatment (1 ml/kg i.p., sacrifice 48 h thereafter). The other reference drugs had either little or no protective actions in these models. Noteworthy, the laboratory test results for bilirubin, SGOT, SGPT fully correlated with the macro/microscopical findings. Thus, on the basis of consistent protective effect of BPC 157, possible clinical application in liver diseases is now warranted.

Amino Acid Sequence↗

A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC.

The possibility that the stomach, affected by general stress, might initiate a counter-response has not until recently been considered in theories of stress. We suggest that the stomach, as the most sensitive part of the gastrointestinal tract and the largest neuroendocrine organ in the body, is crucial for the initiation of a full stress response against all noxious stress pathology. The end result would be a strong protection of all organs invaded by 'stress'. Consistent with this assumption, this coping response is best explained in terms of 'organoprotection'. Endogenous organoprotectors (eg prostaglandins, somatostatin, dopamine) are proposed as mediators. Such an endogenous counteraction could even be afforded by their suitable application. A new gastric juice peptide, M(r) 40,000, named BPC, was recently isolated. Herein, a 15 amino acid fragment (BPC 157), thought to be essential for its activity, has been fully characterized and investigated. As has been demonstrated for many organoprotective agents using different models of various tissue lesions, despite the poorly understood final mechanism, practically all organ systems appear to benefit from BPC activity. These effects have been achieved in many species using very low dosages (mostly microgram and ng/kg range) after ip, ig, and intramucosal (local) application. The effect was apparent already after one application. Long lasting activity was also demonstrated. BPC was highly effective when applied simultaneously with noxious agents or in already pathological, as well as chronical, conditions. Therefore, it seems that BPC treatment does not share any of the so far known limitations for 'conventional organoprotectors'. No influence on different basal parameters and no toxicity were observed. These findings provide a breakthrough in stress theory. BPC, as a possible endogenous free radical scavenger and organoprotection mediator, could be a useful prototype of a new class of drugs, organoprotective agents.

Adrenal Glands↗

The significance of the gastroprotective effect of body protection compound (BPC): modulation by different procedures.

To elucidate any mechanism of a body protecting effect the observed events should be investigated also by the way of their modulations induced by ablation of particular organs. For Body Protection Compound (BPC), a newly partially characterized gastric juice peptide, the gastroprotection has largely been studied in basal and modified conditions of 48 h-restraint stress. Ablations or sham operations have been performed before restraint as follows: 60 min vagotomy, 24 h ovaria, testes, spleen, 48 h medulla of adrenal glands, 40 days thyroid + parathyroid glands. BPC (10 micrograms/kg) or saline (5 ml/kg) have been regularly applied (after surgery, 1 h before restraint) intraperitoneally. The group subjected to thyroparathyroidectomy received also once-daily BPC/saline treatment. A very strong gastroprotective effect in basal conditions has been modulated by ovariectomy and demedullation (abolishment), thyroparathyroidectomy (decrease), and no change occurred in case of vagotomy, splenectomy or orchidectomy. Sham operated rats did not differ from corresponding controls. Thus, seeing from point of view a wide range of organoprotective effects of BPC (intestinum, kidney, liver, pancreas, inflammation, diabetes mellitus, delayed type of hypersensitivity), the gastroprotection has been supposed a) to be of crucial pattern in the general concept of organo-protection and b) to be responsible for the mediation of the suggested "stomach stress organoprotective response". Therefore, the obtained modulations suggest a complex and specifical, sex-related action of the overall beneficial effects of BPC.

Adrenalectomy↗

Dopamine agonists prevent duodenal ulcer relapse. A comparative study with famotidine and cimetidine.

The present study investigated both the healing rate (after four weeks) and the relapse rate (during six months) following treatment with the dopamine-like drugs bromocriptine (2.5 mg twice daily), amantadine (100 mg nocte), or with the H2 blockers cimetidine (800 mg nocte), and famotidine (40 mg nocte) in 124 patients with endoscopically proven duodenal ulcer (DU). The ulcer was completely healed in 27 (amantadine), 26 (bromocriptine), 23 (cimetidine), and in 24 (famotidine) patients. Relapse was noted in 34.7% (cimetidine) and 25% (famotidine) versus 11.7% (amantadine) and 7.7% (bromocriptine) DU patients. No significant difference was found in initial healing rates. However, the relapse rate in the cimetidine-treated group was significantly higher than in all the other test groups. Additional comparisons between all the treatment categories showed a significantly lower relapse rate with the dopamine-like agents. These important new results indicate that dopamine-like compounds are equally effective as H2 blockers in inducing DU healing and may offer a promising advantage over H2 blockers concerning their efficacy in preventing ulcer relapse in DU patients.

Adult↗

Thyroid hormone economy in response to extreme cold exposure in healthy factory workers.

The effects of cold exposure on serum total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), rT3, TSH, T4-binding globulin (TBG), and T3 resin uptake were investigated in 82 euthyroid factory workers. Twenty-five workers (group 1) were exposed intermittently (approximately 3.5 h daily) to extreme cold (-40 to -20 C) during the 8-h work shift, and 47 (group 2) were exposed to moderate cold (-10 to 8 C) for the entire 8 h. Ten individuals working at room temperature for the same period also were studied. After cold exposure, serum TT4 decreased in group 1 and did not change in group 2, whereas FT4 did not change in group 1 and increased in group 2. After exposure, serum TT3 and rT3 decreased significantly in both groups, while FT3 did not change in either. The basal serum TT4 levels in groups 1 and 2 were significantly lower than those in the control group, whereas those of FT4 and FT3 were higher. Thus, cold exposure had opposite effects on total thyroid hormones and their free fractions, consistent with a cold-induced decrease in thyroid hormone-binding capacity. A postexposure decrease in serum TBG was found in women in group 2, but not in men in either group 2 or group 1, suggesting that factors other than decreased TBG are also involved. The results suggest the possibilities that 1) decreased thyroid hormone-binding capacity is an adaptive response to cold exposure, and/or 2) increased free thyroid hormone levels in response to cold exposure result in a new higher equilibrium between extracellular and intracellular FT4 and FT3.

Adaptation, Physiological↗

The influence of dopamine agonists and antagonists on indomethacin lesions in stomach and small intestine in rats.

Dopamine agents (saline in control groups) were coadministered with indomethacin by either single or repeated application. The ulcerogenic effect (erosions and/or ulcers) of repeated given indomethacin on gastric mucosa differed clearly from that on intestinal mucosa. The effect on intestinal mucosa was markedly greater than after a single dose. The effects of dopamine agents appeared to be more consistent. Domperidone and haloperidol, given as single or repeated doses, strongly aggravated both the gastric and intestinal lesions. Bromocriptine and amantadine had a protective effect. The adverse effects of both dopamine antagonists (increased after repeated administration) were strongly inhibited by the simultaneous administration of either bromocriptine or amantadine. The involvement of the dopamine system (central or peripheral) in the mechanisms that maintain gastric (probably related to cytoprotection also) and intestinal mucosa integrity is therefore suggested.

Animals↗

The influence of dopamine receptor agonists and an antagonist on acute pancreatitis in rats.

The influence of the dopamine receptor-stimulating agent, bromocriptine, the dopamine-releasing drug, amantadine, and the dopamine antagonist, domperidone, on acute pancreatitis was studied in rats. Acute pancreatitis was induced by ligation of the bile duct at its point of entry into the duodenum. Each drug was applied intraperitoneally 1 h before induction of acute pancreatitis and all the surviving animals were killed 24 h thereafter. The control, saline-pretreated animals exhibited the mortality rate, macroscopical and histological changes, as well as increase of serum amylase levels that were consistent with acute pancreatitis. Domperidone induced a large increase in serum amylase which was significantly reduced by the simultaneous administration of bromocriptine. However, both bromocriptine and amantadine, when given separately did not prevent the increase of serum amylase levels to the control levels. Statistical analysis showed that the difference between the mortality rate in the control and treated groups did not reach the level of significance probably due to the rather limited number of animals used. On the other hand, application of bromocriptine as well as amantadine successfully reduced the onset of acute pancreatitis whereas domperidone, a rather specific peripheral dopamine receptor blocker, had the opposite effect. Both bromocriptine and amantadine significantly reduced the mortality rate from acute pancreatitis in domperidone-pretreated rats. Since the aggravating effect of domperidone was successfully reduced by simultaneous application of bromocriptine, we think that these effects are mediated by peripheral dopamine receptors. However, the mechanisms whereby dopamine receptor-stimulating and dopamine-releasing drugs produce their beneficial effects remain to be elucidated.

Acute Disease↗

The influence of dopamine agonists and antagonists on gastric lesions in mice.

The dopamine agonist bromocriptine and L-dopa significantly inhibited whereas dopamine antagonist haloperidol aggravated the gastric lesions induced by pylorus ligation in mice as found earlier for rats. Furthermore, the successful use of a dopamine antagonist alone for the induction of gastric lesions also in mice was demonstrated, since the gastric lesions were induced by a single dose of haloperidol without any additional noxious treatment. Bromocriptine successfully inhibited both the gastric lesion-potentiating as well as the gastric lesion-inducing effect of haloperidol.

Animals↗

The urinary iodide excretion in subjects on different diets.

The urinary iodide excretion in hospital subjects on regular and different restrictive diets was investigated. In subjects on a regular diet the average urinary iodide (microgram I-/g creatinine; mean +/- SD) was 104.7 +/- 36.7. In subjects on a low caloric diet the urinary iodide content was 101.1 +/- 24.2; in subjects starving for weight-reduction the mean value was 63.2 +/- 23.9, significantly different from the controls (p less than 0.005). In subjects on a high-caloric diet the urinary iodide was 145 +/- 45.4, in those on a hepatoprotective diet 96.8 +/- 18.8, respectively. The iodide excretion in subjects on an ulcer-protective diet was on the average 76.4 +/- 22.3 which was significantly different from those on a regular diet (p less than 0.01).

Diet↗

Thyroidal thyroxine and triiodothyronine in autonomously functioning thyroid nodule and paranodular tissue.

Thyroidal thyroxine (T4), triiodothyronine (T3), thyroglobulin (Tg) and T4/T3 ratio were investigated in nodular and paranodular tissue from 16 patients with autonomously functioning thyroid adenomas. The concentration of T4 and T3 in the nodule were 97.7 +/- 20.5 (Mean +/- SE) and 10.2 +/- 2.4 micrograms/g wet weight (w.w.). Both iodothyronines were significantly lower in paranodular tissue (22.6 +/- 4.8 and 1.45 +/- 0.32 micrograms/g w.w., respectively), but with disproportionately decreased T3 which resulted in T4/T3 ratio (25.4 +/- 6.4) higher than in adenoma tissue (11.2 +/- 1.6). In patients with high normal or supranormal serum T3 concentration, thyroidal concentration of T3 in adenoma tissue was higher (15.6 +/- 5.0 vs. 6.3 +/- 1.2 micrograms/g w.w.) and T4/T3 ratio lower (8.05 +/- 2.1 vs. 13.2 +/- 1.9) than in patients with normal serum T3. The results suggest that thyroid release of T3 from adenoma is relatively higher than T4 in patients with autonomously functioning thyroid nodules and increased peripheral T3.

Adenoma↗

Elevated levels of substances immunologically cross-reactive with insulin in blood of patients with malignant and nonmalignant pulmonary tissue proliferation.

Results of a survey of concentrations of substances immunologically cross-reactive with insulin (SICRI), glucose and growth hormone in preprandially drawn blood of 84 patients suffering from bronchial epidermoid, microcellular and adenocarcinomas and 22 patients from sarcoidosis, tuberculosis and obstructive bronchitis are presented. In all these diseases, tissue proliferation takes place. Supranormal SICRI concentrations were frequently associated with these diseases, whereas concentrations of glucose and growth hormone remained unaffected; this shows that physiological effects of SICRI in these diseases differ from the effects in patients suffering from some lympho-proliferative and solid tumors. These results indicate that elevated levels of circulating substances detectable by insulin-specific radioimmunoassay can accompany both malignant and nonmalignant proliferation in lungs.

Adult↗

Somatostatin suppresses growth of murine myeloid leukemia in vivo.

Daily injections of somatostatin into mice with myeloid leukemia retarded the tumor growth. This myeloid leukemia is an insulin-dependent tumor (in that it grows more slowly in hypoinsulinemic diabetic mice than in nondiabetic animals). Since somatostatin decreased the level of immunoreactive insulin in mice with myeloid leukemia, and since the treatment with insulin abrogated the antileukemic effect of somatostatin, we attribute retarded growth of this leukemia to decreased secretion of insulin, caused by somatostatin.

Animals↗

Competitive ligand - binding assay for thyroxine binding globulin. Comparison with TBG radioimmunoassay and T3 uptake test.

A simple and reproducible competitive ligand binding assay has been utilized to measure serum TBG concentration. In euthyroid subjects TBG concentration (mean +/- SD, mg/l) was 33.7 +/- 4; hyperthyroid 24 -/+ 6; T3-thyrotoxicosis 20 +/- 7; hypothyroid 37 -/+ 7; pregnant 67 -/+ 18; post-partum period 59.8 -/+ 17; oral contraceptives 45 -/+ 7. The correlation of CLBA with RIA measurement of TBG was significant (p less than 0.001). The estimations of serum TBG by CLBA correlated significantly with T3 uptake test (p less than 0.001), but at higher concentration of TBG correlation was non-linear. T4 : TBG ration according to serum T4 and TBG concentration provided a reliable index in the assessment of thyroid function.

Contraceptives, Oral↗