T Sosa

University Hospital Merkur, Zagrabia, Grad Zagreb, Croatia

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Publications (9)19.36 Total impact

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    ABSTRACT: We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders.
    Journal of Orthopaedic Research 06/2006; 24(5):1109-17. · 2.88 Impact Factor
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    ABSTRACT: Gastrointestinal stromal tumors (GISTs) are characterized with diverse clinical presentations, including acute and chronic gastrointestinal bleeding, abdominal pain, presence of an intra-abdominal mass, anorexia, and intestinal obstruction. A 60-year-old obese woman presented as an acute abdominal emergency with right lower quadrant (RLQ) pain and tenderness, nausea and leukocytosis, all mimicking acute appendicitis. Laparotomy revealed a spontaneously ruptured GIST of the jejunum, which was localized to the RLQ due to postoperative adhesions following previous two cesarean sections and cholecystectomy. Complete surgical resection was performed, followed by an uneventful early postoperative course.
    Collegium antropologicum 01/2005; 28(2):937-41. · 0.61 Impact Factor
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    ABSTRACT: Achilles tendon unilateral transection (ATT) in the rat was attenuated by a beneficial effect of a stable gastric pentadecapeptide, shown to heal a non-union fracture and deep thickness skin burns, and to reduce adjuvant arthritis, without special carrier, named BPC 157 (GEPPPGKPADDAGLV, M.W.1419). Assessed 4,7,10,14 days after surgery, tensiometry and microscopical investigation showed a steady healing improvement in saline treated controls, i.e. failure load (N) (1.71, 5.14, 10.42, 9.97), Yang elasticity module (2.14, 4.66, 6.46, 6.68), fibroblast number (1303, 1763, 1978, 1873) and collagen proportion per visual fields (0.32, 0.40). BPC 157 10 microg, 10 ng or 10 pg /kg b.w. dissolved in saline were given intraperitoneally immediately after the surgery, and thereafter once daily, last application 24 h before sacrifice. With respect to control values (P<0.05 / P<0.017) in pentadecapeptide BPC 157 rats we noted the increased failure load (13.4 (ng), 13.0 (microg), 14 day), Yang elasticity module (9.43 (microg), 10 day; 10.51 (microg), 14 day), fibroblast number (2019 (ng), 2023 (microg), 7 day; 2364 (ng), 2245 (microg), 10 day), collagen proportion per visual fields (0.49 (ng), 0.50 (microg), 10 day; 0.54 (ng), 0.52 (microg), 14 day). Therefore, pentadecapeptide BPC 157 may positively influence formation and differentiation (maturation), and strength of tissues during Achilles tendon healing after surgical transection. The significance of this advanced healing was especially supported by structural characteristics of pentadecapeptide BPC 157 shown by a computational investigation. Numerous BPC 157 motifs are clustered in collagens and proteoglycans, essential for the healing process, such as collagen a-1 (I), collagen a-1 (IX), aggrecan, fibromodulin precursor, chondroitin sulfate proteoglycan NG2 precursor and cartilage oligomeric matrix protein precursor. Likewise, a special relation over BMP-6 molecule is postulated.
    1st Joint Meeting of the International Bone and Mineral Society and the European Calcified Tissue Society, Madrid, Spain; 06/2001
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    ABSTRACT: To investigate the potential value of the use of the fibrin glue-antibiotic mixture in the treatment of anal fistulae. This study included 69 patients with idiopathic nonspecific anal fistulae. Patients with IBD (inflammatory bowel disease), TBC, actinomycosis, and cancer were excluded from the study. The microbiological analysis of the discharge of the fistula was done routinely. If there was any doubt about vertical classification of the fistulous tract MR of anal canal was necessary. As regards the vertical disposition, 39 fistulae were classified as intersphincteric and 30 as transsphincteric, and as to the length of the fistulous tract, 24 fistulas had tracts </=3.5 cm long, and 45 fistulas had tracts >3.5 cm long. All fistulae were first treated with the lavage of the fistulous tract with antibiotic solution until a sterile microbiological finding was obtained. This was followed by electrocoagulation of the fistulous tract with a special probe for the eradication of granulomatous tissue. Finally the fibrin glue-antibiotic mixture (Tisseel, Immuno Ltd., Vienna, Austria) was applied. After a follow-up of 18-36 months (median 28) 18 patients (26%) had a recurrence; among these, intersphincteric fistula recurred in 9 patients (23%) and transsphincteric also in 9 (30%). Regarding the length of the fistulous tract, a fistula with a </=3.5 cm long tract recurred in 13 patients (54%) and a fistula with a >3.5 cm long tract in 5 (11%). The analysis showed that the success of the treatment of anal fistulae with fibrin glue-antibiotic mixture was independent of the vertical disposition of the fistula, and was dependent on the length of the fistulous tract. Surgical treatment remains a golden standard for simple fistulae with a tract </=3.5 cm. Anal fistulae with a longer tract usually present a more complex problem and are often more difficult to treat surgically, the use of the fibrin glue-antibiotic complex proved to be a feasible method for those cases. It is a safe, cheap, reproducible, pain-free procedure, which eliminates the possibility of anal incontinence and can be performed under local anesthesia.
    Digestive Surgery 01/2000; 17(1):77-80. · 1.47 Impact Factor
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    ABSTRACT: Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called 'direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells - polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC 157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL x kg(-1) water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control values, BPC 157-treated groups consistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated groups showed no difference compared with control values. Thus, despite limitations, a generalization supporting a direct importance of a common cytoprotective approach, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions.
    Journal of Physiology-Paris 01/2000; 93(6):467-77. · 0.82 Impact Factor
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    ABSTRACT: Six months after injury, 150 mL of autogenous bone marrow was applied percutaneously at the site of delayed union to stimulate the healing of a tibial delayed union fracture in a 44 year-old man. Five months following the procedure, the fracture gaps and bone defects were completely filled with callus, the external fixator was removed, and the patient started using normal leg loading.
    Croatian Medical Journal 10/1999; 40(3):429-32. · 1.25 Impact Factor
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    ABSTRACT: Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.
    Bone 04/1999; 24(3):195-202. · 4.46 Impact Factor
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    ABSTRACT: Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their 'cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minor lesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96% ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs. endogenous (e.g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple 'cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 microg or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events preceding the late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essential link between the various reactions in cytoprotection/adaptive cytoprotection.
    European Journal of Pharmacology 02/1999; 364(1):23-31. · 2.59 Impact Factor
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    ABSTRACT: Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called `direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells – polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL.kg–1 water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control values, BPC 157-treated groups consistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated groups showed no difference compared with control values. Thus, despite limitations, a generalization supporting a direct importance of a common cytoprotective approach, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions.
    Journal of Physiology-Paris 01/1999; 93(6):467-477. · 0.82 Impact Factor