Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.

Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel disease and multiple sclerosis, and thereby, shown to equally counteract the models of both of those diseases. For colitis, cysteamine (400 mg/kg intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7, and 14) were used. BPC 157 (10 µg/kg, 10 ng/kg) was applied either intraperitoneally once time daily (first application immediately after surgery, last at 24 hours before sacrifice) or per-orally in drinking water (0.16 µg/ml/12 ml/day till the sacrifice) while controls simultaneously received an equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12 ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) was combined with BPC 157 (in drinking water 0.16 µg or 0.16 ng/ml/12 ml/day/rat + 10 µg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. In general, the controls could not heal cysteamine colitis and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently less nerve damage in all damaged areas, especially in those areas that otherwise were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and impaired forelimb function. Thereby, this experimental evidence advocates BPC 157 in both inflammatory bowel disease and multiple sclerosis therapy.

Advantages of new materials in fascia transversalis reinforcement for inguinal hernia repair.

PURPOSE: We investigated whether new absorbable materials can be used in the treatment of inguinal hernia with the same efficacy as the traditionally used polypropylene. METHODS: We compared local tissue inflammation and fibrous reaction, postoperative complications (bleeding, wound haematoma, wound infection) and postoperative recovery time (time of mobilisation) in rats (Fischer strain) after implantation of a polypropylene mesh (PPM) (Prolene, Ethicon, Bracknell, UK) or a dual component fibrin mesh (DCFM) (Tachosil, Nycomed, Marlow, UK), between the muscle layer and the fascia transversalis defect. We further compared direct hernia repair methods using Lichtenstein's operation in humans after implantation of either PPM or DCFM for fascia transversalis reinforcement regarding postoperative pain and complications, time needed for patient mobilisation, and recurrence. RESULTS: The results show that implantation of DCFM in rats resulted in milder inflammatory response and thicker fibrous tissue formation. Patients implanted with DCFM had significantly lower postoperative pain scores on a visual-analogue scale and lower analgesic use. The overall incidence of postoperative complications was significantly reduced with the use of DCFM. The incidence of recurrence after 24-month follow-up was the same in both groups. CONCLUSION: This study has shown that DCFM has the same short-term efficacy in hernia treatment as the standard PPM, with a reduction in postoperative pain and analgesic use, and a decrease in overall postoperative complications. In the rat model, DCFM resulted in milder inflammatory response and thicker fibrous plate than the PPM. Further biomechanical testing and longer follow-up is necessary, but initial results are promising.

Serum cytokine changes after gastric resection or gastrectomy for gastric cancer.

BACKGROUND/AIMS: Although essential for postoperative recovery, excessive surgical stress response leads to higher rate of serious postoperative complications, such as sepsis and multiple organ disorder syndrome. Exact regulation of surgical stress response is not yet known. Still, our ability to modify surgical stress response severity has led to diminished postoperative morbidity and mortality rates and development of fast-track surgery. In this study we tried to further clarify the roles of several cytokines in surgical stress response regulation. METHODOLOGY: We measured leukocyte count and serum concentrations of C-reactive protein, IL-2, IL-6, IL-10, TNF-alpha, IFN-gamma and cortisol in patients undergoing gastrectomy or gastric resection for gastric cancer. Blood samples were collected preoperatively, 3 hours, 24 hours and 48 hours postoperatively. We also grouped our patients according to operation type and duration and then compared measured values between groups. RESULTS: Elevated postoperative leukocyte count and serum concentrations of IL-4, IL-6, IL-10 and cortisol were measured, all peaking at 3 hours postoperatively. Also, serum IL-6 concentration was higher after longer operations, and leukocyte count was higher after gastrectomy. CONCLUSIONS: The synchronicity of postoperative elevation of IL-4, IL-6 and IL-10 concentrations, each having different role in surgical stress response regulation, might indicate that, in order to determine surgical stress response severity, several cytokines should be measured simultaneously.

Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth.

In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-beta, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157+HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE+BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.

Fibrin glue-antibiotic mixture in the treatment of anal fistulae: experience with 69 cases.

BACKGROUND/AIMS: To investigate the potential value of the use of the fibrin glue-antibiotic mixture in the treatment of anal fistulae. MATERIALS AND METHODS: 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. 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. RESULTS: 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 in 5 (11%). CONCLUSION: 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

Percutaneous autologous bone marrow grafting on the site of tibial delayed union.

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.

Pancreatic head cystadenoma: a case report.

An 18 year-old resident of Zagreb was admitted to our hospital with intermittent pain in the right subcostal region. On examination, a palpable resistance was found in the upper abdomen. After extensive clinical and laboratory tests, a tumor of the pancreatic head, 80-85 mm in diameter, was verified. Cytologically, a diagnosis of microcystic adenoma of the pancreas was established. The patient underwent a cephalic pancreatoduodenectomy with preservation of the pylorus. Six months later the patient was no longer on a diet and, at follow-up, 3 years after surgery, she is symptom-free and feeling well.

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

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.

Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

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.

[Surgical prevention and treatment of cerebral ischemia]. / Kirurska prevencija i lijecenje ishemickog mozdanog udara.

Cerebral ischemic attack is a common disease and a major health, social and economic problem. The authors discuss the diagnostics of cerebrovascular insufficiency, and the indications for a surgical intervention. They analyse the frequency of surgical and early postoperative complications in patients undergoing surgery for stenotic changes in the arteries of the aortic arch. In 625 reconstructive procedures performed, operative and early postoperative neurologic deficits were observed in 16 (2.5%) patients. In 5 patients (0.8%), neurologic deficit disappeared during the early postoperative period, while in 11 (1.7%) patients persisted after the patient's discharge from the hospital. This paper also reports the late results of surgical treatment in a group of 62 patients followed up at 4 to 6 years or approximately for five years after operation. The authors also investigate the results of pharmacotherapy in a group of 32 patients who were not willing to accept the recommended surgery and who were followed up for a period of 3 to 6 years or approximately for 4.5 years postangiography. The results of surgical treatment were correlated with the pharmacotherapy results. There is a statistically significant difference to the advantage of surgically treated patients (P less than 0.001). It is concluded that reconstructive interventions on the cervical part of cerebral arteries indicated in the case of obliterative arteriosclerosis seem to prevent or considerably decrease the incidence of recurrent cerebral attack. In addition, the incidence of neurologic surgical deficit is considerably decreased by the routine application of a temporary intraluminal bypass.