|
|
|
|
| LEADER |
10405cam a2200469 i 4500 |
| 001 |
NSK01000172485 |
| 003 |
HR-ZaNSK |
| 005 |
20070917114255.0 |
| 008 |
960917s1996 ci a m 000 0 hrv |
| 035 |
|
|
|9 (HR-ZaNSK)172687
|
| 035 |
|
|
|9 (HR-ZaNSK)960917049
|
| 035 |
|
|
|a (HR-ZaNSK)000172485
|
| 040 |
|
|
|a HR-ZaNSK
|b hrv
|c HR-ZaNSK
|e ppiak
|
| 041 |
0 |
|
|a hrv
|
| 044 |
|
|
|a ci
|c hr
|
| 080 |
|
|
|a 615.22.099
|
| 100 |
1 |
|
|a Šeparović-Hanževački, Jadranka
|
| 245 |
1 |
0 |
|a Učinak novog peptida BPC na eksperimentalne modele kardiotoksičnosti :
|b doktorska disertacija /
|c Jadranka Šeparović.
|
| 260 |
|
|
|a Zagreb :
|b J. Šeparović,
|c 1996
|e ([s. l. :
|f s. n.])
|
| 300 |
|
|
|a 154 lista :
|b table, graf. prikazi, ilustr. djelomično u bojama ;
|c 30 cm.
|
| 500 |
|
|
|a mentor: Predrag Sikirić; Komisija za ocjenu: Želimir Bradamante, Zijad Duraković, Stjepan Gamulin, Ante Svetina, Predrag Sikirić; Komisija za obranu: Želimir Bradamante, Zijad Duraković, Stjepan Gamulin, Ante Svetina, Predrag Sikirić; datum obrane: 04.07.1996; datum promocije:
|
| 502 |
|
|
|a Sveučilište u Zagrebu, Medicinski fakultet, Zagreb, 1996
|
| 504 |
|
|
|a Bibliografija: str. 130-153
|
| 504 |
|
|
|a Summary
|
| 520 |
|
|
|a Sažetak: U ovoj disertaciji opisani su rezultati istraživanja o učincima novog pentadekapeptida BPC-157 na eksperimentalnim modelima kardiotoksičnosti, s ciljem otkrivanja njegovog djelovanja u kardiovaskularnom sustavu. Pokusi su izvedeni na albino štakorima soja Wistar i zamorčićima soja Hartley. Kardiotoksičnost smo izazivali primjenom otopine barijevog klorida (10mg/kg t.t.), dezipramina (10 mg/kg), digitalisa (ukupna doza 6.5 mg/kg) i izoprenalina (15 mg/kg) kroz vensku kanilu na jugularnoj poziciji. Višekratnom (3 mg/kg subkutano, jednom tjedno 13 tjedana) i jednokratnom (7 mg/kg intravenski) primjenom doksorubicina izazivali smo kardiomiopatiju. Kardiotoksičnost smo izazvali i imobilizacijskim stresom, kao nefarmakološkim oštećenjem miokarda.
|
| 520 |
|
|
|a Ispitani pentadekapeptid primijenjen je ovisno o modelu: 1. barijev klorid - a) pretretman (jedan sat prije): BPC-157 50 [mikro)g/kg 10 [mikro]g/kg i 10 [nano]g/kg intraperitonealno, b) posttretman (nakon 60 sekundi): BPC-157 10 [mikro]g/kg i 10[nano]g/kg intravenski; 2. dezipramin: BPC-157 50 [mikro]g/kg i 50 [nano]g/kg intraperitonealno sat vremena prije, 3. digitalis: BPC-157 50 [mikro]g/kg i 50 [nano]g/kg intravenski svakih 15 minuta, 4. izoprenalin: BPC-157 50 [mikro]g/kg i 50 [nano]g/kg intravenski 15 minuta prije, 5. imobilizacijski stres: BPC-157 10 [mikro]g/kg i 10 [nano]g/kg intraperitonealno sat prije i neposredno prije vezivanja, te u 24. i 48. satu imobilizacije.
|
| 520 |
|
|
|a 6. a) doksorubicin kronična toksičnost: BPC-157 10 [mikro]g/kg i 10 [nano]g/kg intraperitonealno istodobno s doksorubicinom, b) doksorubicin akutna toksičnost: BPC-157 10 [mikro]g/kg i 10 [nano]g/kg intraperitonealno sat prije doksorubicina. U modelima aritmija anesteziranoj životinji elektrokardiogram je bilježen kontinuirano brzinom 1mm/s, a svakih 15 s ili kod poremećaja ritma učinjeni su duži odsječci zapisa brzinom 25 mm/s, 50 mm/s ili 100 mm/s. U ostalim modelima elektrokardiogram je bilježen jednokratno ili višekratno, na dužim odsječcima brzinom 50 mm/s, pri čemu je životinja kratkotrajno anestezirana. Doksorubicinska kardiotoksičnost utvrđivana je makroskopskom i mikroskopskom analizom srca i ostalih organa, te biokemijskim pretragama. Sličan postupak primijenjen je i kod imobilizacijskog stresa.
|
| 520 |
|
|
|a Rezultati našeg istraživanja u modelu izazivanja aritmija barijevim kloridom pokazuju antiaritmički učinak ispitivanog pentadekapeptida. U pretretmanu ispitivani pentadekapeptid odgađa nastup i prevenira pojavu aritmija i skraćuje i prevenira nastajanje ishemije. U posttretmanu dovodi do brže konverzije u sinus ritam i prevenira ponovno javljanje aritmija. U potpunosti prevenira naglo usporavanje frekvencije i smetnje provođenja izazvane dezipraminom (PQ-produljenje i širenje QRS-kompleksa), kao i pojavu ventrikulske tahikardije u sklopu proaritmičkog učinka dezipramina i teže oblike atrioventrikulskog bloka. Učinak je ovisan o dozi. Ispitivani pentadekapeptid BPC-157 ima djelomičan učinak na kardiotoksičnost izazvanu digitalisom.
|
| 520 |
|
|
|a Pozitivan učinak pokazuje kod naglih usporavanja frekvencije i poremećaja ritma (ventrikulske ekstrasistolije, ventrikulsku tahikardiju i atrioventrikulski blok) koje prevenira ili umanjuje, dok nema značajnog djelovanja na usporavanje intraventrikulskog provođenja izazvanog toksičnom dozom digitalisa. Učinak je jače izražen kod primjene mikrogramske doze pentadekapeptida. Nismo registrirali sigurno pozitivno djelovanje na tahikardiju uzrokovanu izoprenalinom. Međutim, ispitivani pentadekapeptid BPC-157 pokazao je jasno preveniranje ishemije i razvoj infarkta miokarda. Učinak je izraženiji u mikrogramskoj dozi. Isto tako ishemija (utvrđena elektrokardiografski) kao i histološka oštećenja miokarda izazvana imobilizacijskim stresom jasno se preveniraju jednokratnom intraperitonealnom primjenom pentadekapeptida BPC-157 sat prije.
|
| 520 |
|
|
|a Ishemija se gubi i primjenom pentadekapeptida kod već izraženih elektrokardiografskih promjena nakon 24 sata mobilizacije štakora. Primjena mikrogramske doze pentadekapeptida izaziva povećanje visine QRS-kompleksa. Ispitivani pentadekapeptid BPC-157 značajno je umanjio i patomorfološki nalaz antraciklinske kardiomiopatije (teško oštećenje miocita i stijenki krvnih žila i vakuolizaciju) nakon jednokratne i još više nakon višekratne primjene doksorubicina. Aktivnost enzima LDH značajno je niža, iako su apsolutne vrijednosti vrlo visoke.
|
| 520 |
|
|
|a Summary: The dissertation describes the study results on the effects of a new pentadecapeptide BPC-157 in the experimental models of cardiotoxicity. Experiments were conducted on albino Wistar rats and Hartley guinea pigs. Cardiotoxicity was induced by administration of barium chloride solution (10 mg/kg b.w.), dezipramin (10 mg/kg), digitalis (total dose 6.5 mg/kg) and isoprenaline (15 mg/kg), through jugular venous cannula. Doxorubicin in multiple (3 mg/kg subcutaneously, once weeklx through 13 weeks) and single (7 mg/kg intravenously) dosage provoked cardiomyopathy. Cardiotoxicity was also induced by immobilization stress, as nonpharmacological myocardial damage.
|
| 520 |
|
|
|a The studied pentadecapeptide was administered according to the model: 1. barium chloride - a) pre-treatment (one hour before): BPC-157 50[mikro]g/kg, 10 [mikro]g/kg and 10[nano]g/kg intraperitoneally, b) post-treatment (after 60 seconds): BPC-157 10 [mikro]g/kg and 10[nano]g/kg intravenously; 2. dezipramin: BPC-157 50[mikro] g/kg and 50 [nano]g/kg intraperitoneally one hour before; 3. digitalis: BPC-157 50 [mikro]g/kg and 50[nano]g/kg intravenously at 15-minute intervals; 4. isoprenaline: BPC-157 50 [mikro]g/kg, and 50 [nano]g/kg intravenously 15 minutes before; 5. immobilization stress: BPC-157 10 [mikro]g/kg and 10 [nano]g/kg intraperitoneally one hour before and immediately after the tying, and at 24 and 48 hours of immobilization;
|
| 520 |
|
|
|a 6.a) chronic doxorubicine toxicity: BPC-157 10[mikro]g/kg and 10 [nano]g/kg intraperitoneally concomitantly with doxorubicin, b) acute doxorubicin toxicity: BPC-157 10[mikro]g/kg and 10 [nano]g/kg intraperitoneally one hour before doxorubicine. In arrhythmia models, electrocardiogram was continously recorded on anesthetized animals, and each 15 second or when rythm disturbances occured extended recordings were made at 50 mm/s or 100 mm/s. In other models electrocardiogram was recorded once or repetedly with animals briefly anesthetized, at the paper speed of 50 mm/s in extended recordings. Doxorubicin toxicity was evaluated by macroscopic and microscopic examination of the heart and other organs and by biochemical analyses. A similar procedure was applied in immobilization stress.
|
| 520 |
|
|
|a Our results show antiarrhythmic effect of the studied peptide in the model of barium chloride-induced arhythmieas. In pretreatment, this peptide delays and prevents arrhythmia occurrence, reduces and prevents ischemia. In posttreatment it causes rapid conversion to sinus rhythm and prevents arrhythmia recurrence. It completely prevents sudden decrease in heart rate and conduction disturbances induced by desipramin (PQ prolongation and QRS widening). It also prevents ventricular tachycardia associated with proarrhythmic effect of desipramin, and severe atrioventricular block. The effect is dose-dependent. The studed pentadecapeptide BPC-157 has selective effect on digitalis-induced cardiotoxicity.
|
| 520 |
|
|
|a It demonstrates positive effect on sudden decrease in heart rate and rhythm disturbances (ventricular extrasystole, ventricular tachycardia and atrioventricular block) by means of preventing or attenuating them. However, its effect on the slowing of conduction induced by toxic dose of digitalis is not significant. The effect is more pronounced with microgram dose of the pentadecapeptide. We have not observed definitive positive effect on isoprenaline-induced tachycardia. However, the studied pentadecapeptide BPC-157 clearly prevented ischemia and myocardial infarction. The effect is more pronounced with microgram dosage.
|
| 520 |
|
|
|a Single intraperitoneal administration of the pentadecapeptide BPC-157 in pretreatment resulted in prevention of electrocardiographically demonstrated ischemia and histological myocardial damage during immobilization stress. Posttreatment peptide administration in already overt electrocardiographic changes also relieves ischemia. Microgram dosage of the peptide results in increased in voltage of QRS complex, particularly in pretreatment. The studied pentadecapeptide BPC-157 has significantly reduced pathomorphological findings of antracyclin cardiomyopathy (severe damage of myocytes and vessel walls, and vacuolisation) after single, and in greater extent after multiple doxorubicin administration. LDH activity is significantly decreased, in spite of markedly elevated absolute values.
|
| 650 |
|
7 |
|a Kardiovaskularni agensi
|x Kardiotoksičnost
|2 nskps
|
| 981 |
|
|
|p CRO
|r HRB1996
|
| 998 |
|
|
|n DCD
|c sbn, 199703
|c rjkp9803
|
| 852 |
4 |
|
|j DCD-ZG-135/96
|
| 876 |
|
|
|e DCR
|a 135/1996
|
| 886 |
0 |
|
|2 unimarc
|b 10082iam0 2200397 450
|