Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats.

(1) Aim: The stable gastric pentadecapeptide BPC 157 is known to heal transected muscle, tendon, and ligament. Thereby, in this study, we investigated the effect of BPC 157 on the dissection of the quadriceps tendon from the quadriceps muscle in rats. (2) Materials and Methods: Myotendinous junction defect, which cannot heal spontaneously in rats, as evidenced with consistent macro/microscopic, biomechanical, functional assessments, eNOS, and COX-2 mRNA levels and oxidative stress and NO-levels in the myotendinous junctions. BPC 157 (10 µg/kg, 10 ng/kg) regimen was given (i) intraperitoneally, first application immediately after surgery, last 24 h before sacrifice; (ii) per-orally, in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat/day), till the sacrifice at 7, 14, 28 and 42 postoperative days. (3) Results: These BPC 157 regimens document prominent therapy effects (macro/microscopic, biomechanical, functional much like eNOS and COX-2 mRNA levels and counteracted oxidative stress and NO-levels in the myotendinous junctions), while controls have a poor presentation. Especially, in rats with the disabled myotendinous junction, along with full functional recovery, BPC 157 counteracts muscle atrophy that is regularly progressive and brings muscle presentation close to normal. Accordingly, unlike the perilous course in controls, those rats, when receiving BPC 157 therapy, exhibit a smaller defect, and finally defects completely disappear. Microscopically, there are no more inflammatory infiltrate, well-oriented recovered tissue of musculotendon junction appears in BPC 157 treated rats at the 28 days and 42 days. (4) Conclusions: BPC 157 restores myotendinous junction in accordance with the healing of the transected muscle, tendon, and ligament.

BPC 157 and Standard Angiogenic Growth Factors. Gastrointestinal Tract Healing, Lessons from Tendon, Ligament, Muscle and Bone Healing.

Commonly, the angiogenic growth factors signify healing. However, gastrointestinal ulceration is still poorly understood particularly with respect to a general pharmacological/pathophysiological role of various angiogenic growth factors implemented in growth factors wound healing concept. Thereby, we focused on the stable gastric pentadecapeptide BPC 157, a peptide given always alone vs. standard peptidergic angiogenic growth factors (EGF, FGF, VEGF), and numerous carriers. Further, we reviewed how the gastrointestinal tract healing could be generally perceived (i) in terms of angiogenic growth factors, and/or (ii) through the healing of extragastrointestinal tissues healing, such as tendon, ligament, muscle and bone, and vice versa. Respected were the beneficial effects obtained with free peptides or peptides with different carriers; EGF, FGF, VEGF, and BPC 157, their presentation along with injuries, and a healing commonality, providing their implementation in both gastrointestinal ulcer healing and tendon, ligament, muscle and bone healing. Only BPC 157 was consistently effective in all of the models of acute/chronic injury of esophagus, stomach, duodenum and lower gastrointestinal tract, intraperitoneally, per-orally or locally. Unlike bFGF-, EGF-, VEGF-gastrointestinal tract studies demonstrating improved healing, most of the studies on tendon, muscle and bone injuries provide evidence of their (increased) presentation along with the various procedures used to produce beneficial effects, compared to fewer studies in vitro, while in vivo healing has a limited number of studies, commonly limited to local application, diverse healing evidence with diverse carriers and delivery systems. Contrary to this, BPC 157 - using same regimens like in gastrointestinal healing studies - improves tendon, ligament and bone healing, accurately implementing its own angiogenic effect in the healing. Thus, we claim that just BPC 157 represents in practice a pharmacological and pathophysiological role of various peptidergic growth factors.

Stable gastric pentadecapeptide BPC 157-NO-system relation.

We reviewed stable gastric pentadecapeptide BPC 157-NO-system-relation, its close participation in Moncada's (maintained vascular integrity, platelets control) homeostatic healing response of NO-system to injury. Namely, BPC 157's particular healing effect also affects all events after vascular integrity loss (dependent on circumstances, it reduces either thrombosis (abdominal aorta anastomosis) or bleeding/thrombocytopenia (amputation, heparin, warfarin, aspirin)) and in a series of different injurious models, acute and chronic, BPC 157 consistently advances healing after severe injuries in various tissues spontaneously unable to heal; stimulates egr-1 and naB2 genes; exhibits high safety (LD1 not achieved)). Hypothesis, that BPC 157 (since formed constitutively in the gastric mucosa, stable in human gastric juice, along with significance of NO-synthase and the basal formation of NO in stomach mucosa, greater than that seen in other tissues) exhibits a general, effective competing both with L-arginine analogues (i. e., L-NAME) and L-arginine, and that this has some physiologic importance (NO-generation), later, practically supports its beneficial effects illustrating BPC 157 and NOsystem mutual (with L-NAME/L-arginine; alone and together) relations in (i) gastric mucosa and mucosal protection, following alcohol lesions, in cytoprotection course, NO-generation, and blood pressure regulation; (ii) alcohol acute/chronic intoxication, and withdrawal; (iii) cardiovascular disturbances, chronic heart failure, pulmonary hypertension, and arrhythmias; (iv) disturbances after hypokalemia and hyperkalemia, and potassium-cell membrane dysfunction; and finally, in (v) complex healing failure, proved by the fistulas healing, colocutaneous and esophagocutaneous. However, how this advantage of modulating NO-system (i. e., particular effect on eNOS gene), may be practically translated into an enhanced clinical performance remains to be determined.

Is chronic groin pain a Bermuda triangle of sports medicine?

Chronic groin pain is one the most complex conditions encountered in the field of sports medicine. Conservative treatment is long lasting and the result of treatment is often uncer- tain and symptom recurrences are common, which can be very frustrating for both the patient and the physician. The complex etiology and uncertainties during treatment of chronic groin pain is the reason why some authors call it the Bermuda Triangle of sports medicine. In our prospective, 7-year study, 114 athletes with chronic groin pain resistant to conservative therapy were treated surgically. In 109 athletes with sports hernia, we performed nerve neurolysis along with resection of the genital branch of the genitofemoral nerve and we also reinforced the posterior wall of inguinal canal using a modified Shouldice technique. In 26 athletes that had concomitant adductor tendinosis and in 5 athletes with isolated tendinosis we performed tenotomy. Eighty-one of 83 patients with isolated sports hernia returned to sports within a mean of 4.4 (range, 3-16) weeks. Thirty-one athletes with adductor tenotomy returned to sports activity within a mean of 11.8 (range, 10-15) weeks. If carefully diagnosed using detailed history taking, physical examination and correct imaging techniques, chronic groin pain can be treated very successfully and quickly, so it need not be a Bermuda Triangle of sports medicine.

Isolated inferior peroneal retinculum tear in professional soccer players.

INTRODUCTION: Peroneal tendon dislocations are rare injuries that can easily be misdiagnosed. Up to date literature mostly describes proximal peroneal tendon dislocations due to superior peroneal retinaculum (SPR) tear. In this article, we present the assessment, diagnostic algorithm and a new therapeutic option for the distal dislocation of the long peroneal tendon due to isolated inferior peroneal retinaculum (IPR) tear. PATIENTS AND METHODS: Between 2001 and 2011 three patients with distal peroneal tendon dislocation were operated. All of them were competitive athletes in the national soccer league. They presented with an ankle sprain and prolonged problems on the lateral side of the foot with no improvement after conservative therapy measures. Coleman block test was performed; ultrasound and MRI showed a tendon dislocation under the IPR. The patients underwent surgical repair that consisted of peroneal tubercle excision, a new lateral calcanear groove formation for both peroneal tendons and IPR plasty. RESULTS: At the two year follow up the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score showed a significant increase. The decrease of painful stimuli assessed by a Visual Analogue Scale (VAS) was significant as well. At an average of 12 weeks after the surgery, the patients returned to their level of sport activity before injury and didn't report similar problems later. CONCLUSION: Description of distal peroneal tendon dislocations is limited in the literature. This topic should be considered in differential diagnostics of an acute and chronic ankle sprain which leads to chronic ankle pain and instability. The authors recommend surgical treatment as a method of choice especially in professional athletes.

Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157.

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert's cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (µg, ng/kg) in parenteral or peroral regimens.

The role of external fixation in displaced pilon fractures of distal tibia.

Results of treatment in patients with high-energy displaced pilon fractures are presented. During five years, 15 patients with displaced pilon fractures (AO type C2 and C3) were treated. All other types of fracture were excluded from the study. Fractures were identified using standard radiographs and computed topography scanning. The method and timing of the operation were dictated by the status of soft tissues. In all fractures, external fixation was placed immediately and was left until the initial callus bridged the fracture fragments. In case of moderate contusion of soft tissues, limited incision and minimal internal osteosynthesis was done in the same act. In patients with more severe soft tissue damage, limited open reduction and restoration of articular surface was undertaken in second procedure after 7 days on average. All fractures united and the average time of healing was 4 months. Two patients had superficial infections that resulted in prolonged wound healing, and another four patients had pin site infection. There were no cases of deep infection, nonunion or malunion, but we had five cases of secondary osteoarthritis. Results were evaluated by Teeny and Wiss rating system. The results were as follows: 5 excellent results, 10 good and fair results, and no poor results. This study showed that external fixation with open reduction and limited internal osteosynthesis, with or without bone grafting, could be an option in the management of displaced multifragmentary pilon fractures with soft tissue injury. It was followed by significantly less complications with better functional results compared to open reduction and internal plate fixation.

Aggressive granulomatosis after cementless total hip arthroplasty as a result of inflammatory reaction to metal debris: case report.

Massive osteolysis and granulomatous pseudotumor tissue reactions are long-term complications of total hip replacement. It is a condition of localized bone resorption in contact with prosthetic material. It is speculated to be a consequence of metal hypersensitivity or inflammatory reaction to excessive wear. Ten years after total cementless hip replacement (metal on polyethylene surface), a 70-year-old patient presented with hip pain and pseudotumor with massive osteolysis of proximal femur on x-ray. Intraoperatively, extensive metallosis with significantly worn metal head (316L stainless steel) and only slightly worn polyethylene insert was found. Upon extraction, parts of the affected tissue and bone that were in direct contact with the prosthesis were sent for histopathologic analysis. Microscopic examination showed necrotic soft and bone tissue, mainly bone marrow with numerous histiocytes and multinucleated giant cells containing lots of pigmented particles (presumed to be metal particles as a result of implant surface wear). In this case, the primary cause of osteolysis and granulomatosis was inflammatory reaction to metal debris. Aggressive granulomatosis has been first described in cemented prostheses and afterwards also in cementless ones. Conditions such as primary or metastatic neoplastic processes and infection should be excluded. The presence of foreign molecular particles due to wear of the prosthesis by different mediators has been presumed to cause an inflammatory reaction that leads to bone resorption and loosening of the prosthesis.

Surgical treatment of chronic groin pain in athletes.

PURPOSE: Conservative treatment of chronic groin pain is prolonged and recurrence is quite common. Coexistence of sports hernia and adductor tendinitis/tendinosis in a single patient is noted in the literature. In our study we evaluated our operative treatment that should enable pain elimination and fast return to sports activities. METHODS: We performed a prospective study over a six-year period. Ninety-nine (99) patients, all male, with chronic groin pain, resistant to conservative treatment, underwent a surgical procedure. RESULTS: Seventy athletes with sports hernia returned to sports in an average 4.23 weeks (range three-16). Adductor tendinosis symptoms were present in 24 patients (2 %) with sports hernia. Twenty-four patients that had an additional adductor tenotomy performed returned to sports in an average 11.6 weeks (range ten-15). Five patients with isolated adductor tendinosis (7 %) returned to sports in an average 13.4 weeks (range 12-16). All athletes except two (2.8 %) treated for sports hernia were satisfied with the results of treatment and could continue their previous level of activity. CONCLUSION: Any surgical procedure used for treating chronic groin pain should address the common causes of pain in this region. Adductor tendinosis can be present in up to 24.2 % of cases with sports hernia or may be isolated in 7 % of cases with chronic groin pain and must be treated by tenotomy. Resection of the genital branch of genitofemoral nerve and ilioinguinal nerve neurolysis should also be performed in patients with sports hernia.

Minimally invasive hip arthroplasty: advantages and disadvantages.

BACKGROUND: To present the method and advantages of anterior minimally invasive surgery (AMIS) in coxarthrosis and hip fractures treatment. METHODS: During 2008 and 2009, 35 patients were treated with AMIS method. They were compared with 35 patients treated with lateral, transgluteal approach (control group) in the same period. All operations were performed by the same surgical team. The main reason for surgery was hip arthrosis, only two patients in AMIS group underwent surgery because of femoral neck fracture. Early postoperative complications and functional status are followed by Haris Hip Score (HHS). RESULTS: Operation time was shorter and postoperative blood loss was lesser in AMIS group (78 min, 490 ml) than in the control group (85 min, 570 ml). In the AMIS group one patient had each post-operative knee pain, fractured tip of a large trochanter, acetabular overreaming, perforation of shaft with rasp, and two patients had parestesis n.cutaneus femoris lat. They had no infections or hip luxation. In the control group early hip luxation and superficial wound infections have occurred in one and two cases, respectively. Patients in the AMIS group were more satisfied, demanded less analgesics and their rehabilitation was faster. Haris Hip Score in the AMIS group after 2 months was 80 compared with 69 in the controls, and after 4 months 92 compared to 88 in controls. CONCLUSIONS: AMIS is a safe, reproducible and rewarding technique which provides low morbidity and fast postoperative recovery for the patient.

Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, safe in inflammatory bowel disease clinical trials (GEPPPGKPADDAGLV, M.W. 1419, PL 14736) and wound healing, stable in human gastric juice and has no reported toxicity. We focused on BPC 157 as a therapy in peridontitis, esophagus, stomach, duodenum, intestine, liver and pancreas lesions. Particularly, it has a prominent effect on alcohol-lesions (i.e., acute, chronic) and NSAIDs-lesions (interestingly, BPC 157 both prevents and reverses adjuvant arthritis). In rat esophagitis and failed function of both lower esophageal sphincter (LES) and pyloric sphincters (PS), BPC 157 increased pressure in both sphincters till normal and reduced esophagitis. However, in healthy rats, it may decrease (PS) or increase (LES) the pressure in sphincters. It has strong angiogenic potential, it acts protectively on endothelium, prevents and reverses thrombus formation after abdominal aorta anastomosis, affects many central disturbances (i.e., dopamine and 5-HT system), the NO-system (either L-arginine and L-NAME effects), endothelin, acts as a free radical scavenger (counteracting CCl4-, paracetamol-, diclofenac-injuries) and exhibits neuroprotective properties. BPC 157 successfully heals the intestinal anastomosis, gastrocutaneous, duodenocutaneous and colocutaneous fistulas in rats, as well as interacting with the NO-system. Interestingly, the fistula closure was achieved even when the BPC 157 therapy was postponed for one month. In short-bowel syndrome escalating throughout 4 weeks, the constant weight gain above preoperative values started immediately with peroral and parental BPC 157 therapy and the villus height, crypth depth and muscle thickness (inner (circular) muscular layer) additionally increased. Thus, BPC 157 may improve gastrointestinal tract therapy.

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157.

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.

Spontaneously ruptured gastrointestinal stromal tumor (GIST) of the jejunum mimicking acute appendicitis.

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.