Therapy for Unhealed Gastrocutaneous Fistulas in Rats as a Model for Analogous Healing of Persistent Skin Wounds and Persistent Gastric Ulcers: Stable Gastric Pentadecapeptide BPC 157, Atropine, Ranitidine, and Omeprazole

Objective This study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers. Methods The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 μg/kg) (12 ml/rat/day) or intraperitoneally (10 μg/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)]. Results Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine). Conclusion We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.     

Gastric Pentadecapeptide BPC 157 and Short Bowel Syndrome in Rats

The gastric pentadecapeptide BPC 157, which was shown to be safe as an antiulcer peptide in trials for inflammatory bowel disease (PL14736, Pliva), successfully healed intestinal anastomosis and fistula in rat. Therefore, we studied for 4 weeks rats with escalating short bowel syndrome and progressive weight loss after small bowel resection from fourth ileal artery cranially of ileocecal valve to 5 cm beneath pylorus. BPC 157 (10 μg/kg or 10 ng/kg) was given perorally, in drinking water (12 ml/rat/day) or intraperitoneally (once daily, first application 30 min following surgery, last 24 h before sacrifice). Postoperatively, features of increasingly exhausted presentation were: weight loss appearing immediately regardless of villus height, twofold increase in crypt depth and fourfold increase in muscle thickness within the first week, jejunal and ileal overdilation, and disturbed jejunum/ileum relation. In contrast, constant weight gain above preoperative values was observed immediately with BPC 157 therapy, both perorally and parenterally, and villus height, crypt depth, and muscle thickness [inner (circular) muscular layer] also increased, at 7, 14, 21, and 28 days. Moreover, rats treated with pentadecapeptide BPC 157 showed not different jejunal and ileal diameters, constant jejunum-to-ileum ratio, and increased anastomosis breaking strength. In conclusion, pentadecapeptide BPC 157 could be helpful to cure short bowel syndrome.     

Psychometric Characteristics of the Croatian and the Serbian Versions of the Oral Health Impact Profile for Edentulous Subjects,with a Pilot Study on the Dimensionality

IntroductionThe aim was to adapt the Croatian and the Serbian versions of the Oral Health Impact Profile for the edentulous population (OHIP-EDENT-CRO and OHIP-EDENT-SRB).MethodsThe translation and cross-cultural adaptation were carried out in accordance with accepted international standards. A total of 95 and 177 removable denture wearers were recruited in Croatia and Serbia respectively. The reliability was evaluated by calculating Cronbach’s alpha coefficient and by test-retest (30 participants in each country). The concurrent validity was determined by calculating the Spearman’s rank coefficient between the OHIP-EDENT summary scores and one question related to removable denture satisfaction. Construct validity was determined by exploratory factor analysis (EFA). Responsiveness was determined by comparison of the OHIP-EDENT summary scores before and after dental implant placement to support mandibular overdentures (23 patients in Croatia, 21 in Serbia).ResultsCronbach’s alpha coefficient was 0.92 in Croatia and 0.87 in Serbia. The intraclass correlation coefficient was 0.98 in Croatia and 0.94 in Serbia. In Croatia the Spearman’s correlation coefficient was -0.71 (p<0.001) and in Serbia -0.74 (p<0.001). Both confirmed concurrent validity. Construct validity was tested by EFA, which extracted four factors in each country, accounting for 66.59% of the variance in Croatia and 59.33% in Serbia. Responsiveness was confirmed in both countries by a significant OHIP-EDENT summary score reduction and a high standardised effect size (3.9 in Croatia, 1.53 in Serbia).ConclusionThe results prove that both instruments, the OHIP-EDENT-CRO and the OHIP-EDENT-SRB, have very good psychometric properties for assessing OHRQoL in the edentulous population.     

Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases

Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40?±?14.09 vs. 95.24?±?14.28 pg/ml, p?=?0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40?±?14.09 vs. 81.74?±?23.14 pg/ml, p?=?0.583, and 88.40?±?14.09 vs. 56.83?±?17.77 pg/ml, p?=?0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function.     

Laparoscopic Treatment of Cystadenocarcinoma of the Appendix Penetrating in the Sigmoid Colon

Adenocarcinoma of the vermiform appendix is a rare neoplasm of the gastrointestinal tract that most commonly presents as right lower abdominal pain, mimicking acute appendicitis. Presentation caused by loco-regional spread with involvement of adjacent structures is rare. An accurate and complete preoperative diagnosis has been rare in the past; however, modern imaging techniques allow recognition of most complications and associated conditions. The diagnosis is confirmed postoperatively. Aggressive surgical management is the treatment of choice in appendicular adenocarcinoma. We report the case of appendicular mucinous cystadenocarcinoma in a 55-year-old lady with penetration of the sigmoid colon treated with laparoscopic-assisted sigmoid and en block right hemicolectomy.It was possible to manage this complex case by using a laparoscopic procedure with all the known benefits of minimally invasive surgery.     

Placenta accreta: diagnosis,management and the molecular biology of the morbidly adherent placenta

Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and insulin-like 4, an insulin-like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta.     

Increased levels of osteoprotegerin in hemodialysis patients.

Recently identified soluble circulating osteoprotegerin (OPG), a member of tumor necrosis factor receptor family, is the osteoclastogenesis inhibitory factor (OCIF). It acts as a "decoy" receptor for receptor activator of NF-kappaB ligand (RANKL) and antagonises RANKL/RANK activity. This way OPG exerts the protective effect on bone, which is also important in hyperparathyroidism. The studies measuring OPG levels in secondary hyperparathyroidism have shown contradictory results and inconsistent conclusions. The aim of our work was to evaluate OPG levels in hemodialysis patients and their correlation with the intensity of bone turnover, bone formation and bone resorption. Serum OPG levels, bone alkaline phosphatase activity (bALP) and beta-CrossLaps (CTx) were measured in a control group (n = 20, age 30+/-6.7 years) and in two groups of dialysis patients: the first group with serum intact parathyroid hormone (iPTH) concentration below 200 pg/ml (n = 28, age 62.6+/-14.8 years) and the second group with iPTH concentration above 200 pg/ml (n = 16, age 63.7+/-14.8 years). Compared to controls, serum OPG levels were 6.4-fold higher in dialysis patients. OPG levels in patients with high PTH were approximately 1.2-fold higher than in the low-PTH group. OPG correlated weakly with bALP (r = 0.277, p = 0.153), as well as with CTx (r = 0.018, p = 0.929) in the low-PTH group, and there was an insignificant negative correlation in the high-PTH group (r = -0.145, p = 0.593 and r = -0.219, p = 0.416, respectively). In conclusion, 6.4-fold increase in OPG might protect bone against intensive bone loss in hemodialysis patients, but this increase is probably not mediated by the increased bone formation; rather, it seems to be the consequence of the imbalance of bone kinetics in renal disease. The precise role of OPG in the pathogenesis of renal osteodystrophy remains unknown and establishing it requires further studies.