First Proteome Analysis of Poplar-Type Propolis.

Propolis is a natural mixture of honeybee-released and plant-derived compounds produced by honeybees. Poplar propolis is rich in bioactive polyphenolic compounds, and due to its many health benefits, it is commonly used as a food supplement or functional food ingredient. However, it is the only honeybee product whose proteome hasn't been analyzed. Here, we report a first proteome analysis of poplar-type propolis, a challenging glue-type resinous sample for protein characterization. Raw propolis mixture was precipitated with cold acetone to obtain the protein fraction. Proteins were digested with trypsin, and generated peptides were analyzed on nano-ESI-qTOF SYNAPT G2-Si mass spectrometer (MS) by data-independent acquisition (DIA) and data-dependent acquisition (DDA). Identified peptides and inferred proteins suggest the presence of new bioactive molecules as components of propolis. The poplar-type propolis proteome is composed of a mixture of proteins from the Apis and Populus genera. This is the first-ever report of the proteome of any type of propolis.

Propolis Extract and Its Bioactive Compounds-From Traditional to Modern Extraction Technologies.

Propolis is a honeybee product known for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. It is rich in bioactive molecules whose content varies depending on the botanical and geographical origin of propolis. These bioactive molecules have been studied individually and as a part of propolis extracts, as they can be used as representative markers for propolis standardization. Here, we compare the pharmacological effects of representative polyphenols and whole propolis extracts. Based on the literature data, polyphenols and extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway. In addition, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway, and they all have antimicrobial activity. These similarities do not imply that we should attribute the action of propolis solely to the most representative compounds. Moreover, its pharmacological effects will depend on the efficacy of these compounds' extraction. Thus, we also give an overview of different propolis extraction technologies, from traditional to modern ones, which are environmentally friendlier. These technologies belong to an open research area that needs further effective solutions in terms of well-standardized liquid and solid extracts, which would be reliable in their pharmacological effects, environmentally friendly, and sustainable for production.

Perforating corneal injury in rat and pentadecapeptide BPC 157.

Based on its healing effects in various tissues, we hypothesized that the stable gastric pentadecapeptide BPC 157 heals corneal ulcerations in rats and effects corneal transparency. We made a penetrant linear 2-mm incision in the paralimbal region of the left cornea at the 5 o'clock position with a 20-gauge MVR incision knife at 45° under an operating microscope. Medication was BPC 157 (2 pg/mL, 2 ng/mL, and 2 µg/mL distilled water, two eye drops/left rat eye) immediately after injury induction and then every 8 h up to 120 h; controls received an equal volume of distilled water. In contrast to the poor healing response in controls, BPC 157 significantly accelerated the healing process in 2 µg and 2 ng BPC 157-treated eyes, starting 24 h after the injury, and the fluorescein and Seidel tests became negative. The epithelial defects were completely healed at 72 h (2 µg BPC 157-treated group) and at 96 h (2 ng BPC 157-treated group) after injury. Aqueous cells were absent at 96 h and 120 h after injury in the 2 µg and 2 ng BPC 157-treated groups, respectively. In conclusion, BPC 157 effects the rapid regaining of corneal transparency. Whereas controls developed new vessels that grew from the limbus to the penetrated area, BPC 157-treated rats generally had no new vessels, and those that did form in the limbus did not make contact with the penetrated area. Thus, BPC 157 eye drops successfully close perforating corneal incisions in rats.

BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by L-NAME/thiopental combination.

AIM: We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157. MAIN METHODS: (1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 µg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 µg/kg), L-NAME (10 mg/kg) and L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L-arginine, alone and/or combined, were applied at 20 min before thiopental. KEY FINDINGS: (1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 µg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose-response curve to the right. (2) L-NAME-L-arginine-BPC 157 interrelations: L-NAME: Thiopental-induced anaesthesia duration was tripled. L-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with L-NAME or BPC 157: potentiating effects of L-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L-NAME: Potentiating effects of L-NAME were abolished. BPC 157 and L-NAME and L-arginine: BPC 157 +L-NAME +L-arginine rats exhibited values close to those in BPC 157 rats. SIGNIFICANCE: Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction) and L-arginine (interference with L-NAME and BPC 157).

Anti-wrinkle efficacy of standardized phenolic acids polymer extract (PAPE) from propolis: Implications for antiaging and skin health.

BACKGROUND: The increasing quest for effective and safe antiaging skincare solutions has led to a surge in the exploration of natural compounds such as phenolic acids. Despite the proven efficacy of traditional antiaging ingredients like retinol, their associated side effects have necessitated the search for alternatives. AIMS: This study aimed to assess the anti-wrinkle efficacy of a standardized phenolic acids polymer extract (PAPE) from propolis, employing both in vitro and clinical methodologies to explore its suitability as a novel antiaging skincare ingredient for sensitive and nonsensitive skin types. PATIENTS/METHODS: The study comprised of evaluating PAPE effects on key skin health biomarkers in dermal fibroblasts and keratinocytes. A double-blind, randomized clinical trial involving female participants aged 30-70 years assessed the wrinkle-reducing effectiveness of face creams formulated with two concentrations of PAPE (1.5% and 3%) over a 28-day period. RESULTS: In vitro studies indicated that PAPE could modulate inflammation and tissue remodeling biomarkers. The clinical trial demonstrated that applying PAPE-enriched cream resulted in significant wrinkle reduction, with 25% and 34% improvements for the 1.5% and 3% PAPE formulations, respectively. Subjective feedback from participants further validated the antiaging efficacy and overall satisfaction with the product. CONCLUSION: Incorporating PAPE offers a compelling antiaging solution, significantly reducing wrinkle depth with a favorable safety profile. The study substantiates PAPE's potential as an effective and safe alternative to conventional antiaging ingredients, aligning with the cosmetic industry's shift toward natural, evidence-based formulations.

Hearing in children with otitis media with effusion--clinical retrospective study.

Hearing loss accompanied with middle ear effusion was analyzed according to audiometric frequencies for different age group. Results for left and right ears were compared in/and between study and control group. Pure tone audiometry for bone and air conduction and tympanometry was performed in study group of ninety-eight children with conductive hearing loss and otitis media with effusion. Control group included fifty-seven children with hearing loss, enlarged adenoids, dysfunction of Eustachian tube and no present middle ear effusion served. Means of hearing loss thresholds for 250 Hz-4 kHz were established and compared between groups of right vs. left ears of tested vs. control ears according to age subgroups: 1-3 yr, 4-6 yr, 7-9 yr, 10-12 yr, 13-15 yr. At age 1-3 yr otitis media with effusion children showed no ear side difference in hearing loss. Age groups of 4-6 and 7-9 yr otitis media with effusion children showed left ears with higher threshold of hearing loss across all of the tested frequencies than right ears in study and control ears. Right ears showed smaller hearing loss in study and control group and no age group predicted for hearing impairment. Higher hearing loss threshold for 4 kHz in adolescence in otitis media with effusion ears is early sign of sequels after repetitive episodes of middle ear effusion. Control groups showed no ear side or age group dependent difference of hearing loss threshold. Age group of 4-6 and 7-9 y have faster craniofacial structural change in soft tissue than bone base so ear side differences suggest being developmentally determined.

Characteristics of the hearing loss in unilateral cleft lip and palate-influence on communication.

Etiology of otitis media with effusion (OME) is still unclear and often described as multi-factorial. It is very usual finding in cleft palate population. We tested relationship between the hearing level, audiometric frequencies, aging and ear side in unilateral cleft lip and palate 101 children (UCLP) and subgroups of left (UCLP)(L) and right cleft side (UCLP)(R). Group of left ears is prone to higher frequency and more severe hearing disturbances than groups of right ears, with less chance of normalizing hearing level with aging. Characteristics of hearing loss level and its improvement, in UCLP children depend of cleft type, ear side and age group.

Nonaqueous Polyethylene Glycol as a Safer Alternative to Ethanolic Propolis Extracts with Comparable Antioxidant and Antimicrobial Activity.

We compared the chemical composition, antioxidant and antimicrobial activity of two propolis extracts: one obtained with nonaqueous polyethylene glycol, PEG 400 (PgEP), and the other obtained with ethanol (EEP). We analyzed the total phenolic content (TPC) and the concentrations of ten markers of propolis antioxidant activity with HPLC-UV: caffeic acid, p-coumaric acid, trans-ferulic acid, trans-cinnamic acid, kaempferol, apigenin, pinocembrin, chrysin, CAPE, and galangin. Antioxidant activity was tested using DPPH and FRAP assay, and antimicrobial activity was assessed through minimum inhibitory concentrations (MICs) and minimum biofilm eradication concentration (MBEC) determination. Maceration gave the yield of propolis of 25.2 ± 0.08% in EEP, and 21.5 ± 0.24% in PgEP. All ten markers of antioxidant activity were found in both extracts, with all marker concentrations, except kaempferol, higher in EEP. There was no significant difference between the TPC and antioxidant activity of the PgEP and the EEP extract; TPC of PgEP was 16.78 ± 0.23 mg/mL, while EEP had TPC of 15.92 ± 0.78 mg/mL. Both extracts had antimicrobial activity against most investigated pathogens and Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli biofilms. EEP was more effective against all tested susceptible pathogens, except E. coli, possibly due to higher content of kaempferol in PgEP relative to other polyphenols. Nonaqueous PEG 400 could be used for propolis extraction. It gives extracts with comparable concentrations of antioxidants and has a good antioxidant and antimicrobial activity. It is a safe excipient, convenient for pediatric and veterinary formulations.

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats.

Providing NO-system importance, we suggest that one single application of the NOS-blocker L-NAME may induce retinal ischemia in rats, and that the stable pentadecapeptide BPC 157 may be the therapy, since it may interact with the NO-system and may counteract various adverse effects of L-NAME application. A rat retinal ischemia study was conducted throughout 4 weeks, including fundoscopy, behavior presentation, tonometry, and histology assessment. Retrobulbar L-NAME application (5 mg/kg; 0.5 mg/0.1 ml saline/each eye) in rats immediately produced moderate generalized irregularity in the diameter of blood vessels with moderate atrophy of the optic disc and faint presentation of the choroidal blood vessels, and these lesions rapidly progressed to the severe stage. The specific L-NAME-induced vascular failure points to normal intraocular pressure (except to very transitory increase upon drug retrobulbar administration). When BPC 157 (10 µg; 10 ng/kg, as retrobulbar application, 1 µg; 1 ng/0.1 ml saline/each eye) is given at either 20 min after L-NAME or, lately, at 48 h after L-NAME, the regular retrobulbar L-NAME injection findings disappear. Instead, fundoscopy demonstrated only discrete generalized vessel caliber irregularity with mild atrophy of the optic disc, and then, quite rapidly, normal eye background and choroidal blood vessels, which remain in all of the subsequent periods. Also, histology assessment at 1, 2, and 4 weeks shows that BPC 157 counteracted the damaged inner plexiform layer and inner nuclear layer, and revealed normal retinal thickness. The poor behavioral presentation was also rescued. Thus, while further studies will be done, BPC 157 counteracted L-NAME-induced rat retinal ischemia.

Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application.

BACKGROUND: The effect of systemic and local peptide treatment effective in muscle contusion and then on counteraction of corticosteroid-induced impairment was tested. The pentadecapeptide BPC 157, given without a carrier, improved the healing of transected quadriceps muscle. It also improved muscle healing in rats with muscle crush injury when applied systemically or locally. Importantly, it counteracted corticosteroid-impairment in tendon to bone healing. Thus BPC 157 is proposed as an effective treatment that can improve muscle healing in spite of corticosteroid treatment. MATERIAL/METHODS: After the gastrocnemius muscle complex had been injured, rats received BPC 157 (intraperitoneally or locally as a cream) and/or 6alpha-methylprednisolone (intraperitoneally) only once (immediately after injury, sacrifice at 2 h) or once daily (final dose 24 hours before sacrifice and/or assessment procedure at days 1, 2, 4, 7, and 14). Muscle healing was evaluated functionally, macroscopically, and histologically. RESULTS: Without therapy, crushed gastrocnemius muscle complex controls showed limited improvement. 6alpha-methylprednisolone markedly aggravated healing. In contrast, BPC 157 induced faster muscle healing and full function restoration and improved muscle healing despite systemic corticosteroid treatment when given intraperitoneally or locally and demonstrated functionally, macroscopically, and histologically at all investigated intervals. CONCLUSIONS: BPC 157 completely reversed systemic corticosteroid-impaired muscle healing.

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 microg/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.

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 microg/kg) (12 ml/rat/day) or intraperitoneally (10 microg/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.

After 40 years gossypiboma caused spleen abscess.

We report a case of spleen abscess cased by foreign body (gossypiboma) after 40 years. After physical examination, laboratory, ultrasonography and CT findings with diagnosis of acute abdomen, 73 years old woman had undergone laparatomy. Operation revealed intraabdominal spleen abscess. Capsulotomy and drainage of the collection was performed before splenectomy. Histological examination showed foreign body material surrounded by chronic inflammation, foreign body-type multinucleated giant cells, extravasated red blood cells and fibroblastic proliferation. From anamnesis we found that woman was operated only once during a life with diagnosis of extrauterine pregnancy, 40 years ago. Spleen abscess caused by gossypiboma after 40 years was never described before. However, diagnosis like this is very well known but rarely published because medical-legal implication. Education, professionalism and cooperation of all persons involved in surgical procedure are very important to prevent accidentally mistakes.

Ultrasound Grade of Liver Steatosis Is Independently Associated with the Risk of Metabolic Syndrome.

The aim of the study was to explore (a) prevalence and grade of nonalcoholic fatty liver (NAFL) among outpatients referred for abdominal ultrasound (US) examination and (b) relationship between the presence and severity of liver steatosis and metabolic syndrome (MS). This was a retrospective analysis of patients without history of liver disease examined by abdominal US in the University hospital setting. US was used to detect and semiquantitatively grade (0-3) liver steatosis. Data on patients' age, gender, body mass index (BMI), impaired glucose metabolism (IGM), atherogenic dyslipidaemia (AD), raised blood pressure (RBP), transaminases, and platelet counts were obtained from medical records. MS was defined as having at least 3 of the following components: obesity, IGM, AD, and RBP. Of the 631 patients (median age 60 years, median BMI 27.4 kg/m2, and 57.4% females) 71.5% were overweight and 48.5% had NAFL. In the subgroup of 159 patients with available data on the components of MS, patients with higher US grade of steatosis had significantly higher BMI and increased prevalence of obesity, IGM, AD, RBP, and accordingly more frequently had MS, whereas they did not differ in terms of age and gender. NAFL was independently associated with the risk of having MS in a multivariate model adjusted for age, gender, BMI, and IGM. The grade of liver steatosis did not correlate with the presence of liver fibrosis. We demonstrated worrisome prevalence of obesity and NAFL in the outpatient population from our geographic region. NAFL is independently associated with the risk of having MS implying worse prognosis.

Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing.

Years ago, we revealed a novel cytoprotective mediator, stable gastric pentadecapeptide BPC 157, particular anti-ulcer peptide that heals different organs lesions when given as a therapy, native in human gastric juice while maintaining GI-tract mucosal integrity, already tested in trials (ulcerative colitis and now multiple sclerosis). The stomach cytoprotection is the most fundamental concept, stomach cell protection and endothelium protection are largely elaborated, but so far cell, protection and endothelium protection outside of the stomach were not implemented in the therapy. However, having managed these two points, stomach cell protection and endothelium protection, either one or together, even much more than standard cytoprotective agents do, BPC 157 employed large scale of its beneficial effects seen in various organs. Providing endothelium protection, BPC 157 was shown to prevent formation and reverse established thrombosis in anastomosed abdominal aorta as well as venous thrombosis after inferior caval vein occlusion, and attenuate bleeding prolongation and thrombocytopenia after amputation, without or with anticoagulants, or venous occlusion, and finally counteract effect of L-NAME and/or L- arginine. Now, with BPC 157 application, we reveal the third most important part of the cytoprotection concept: with the stomach cell and endothelium protection to recover mucosal integrity, BPC 157 as prototype cytoprotective agent should also control blood vessel function, depending upon injury, perforated defect or vessel obstruction. After a perforated injury (i.e., stomach), BPC 157 therapy activates blood vessels "running" towards defect. After obstruction (i.e., inferior caval vein), BPC 157 activates vessels "running" towards bypassing defect, collaterals functioning. Reestablished blood flow, and largely reversed injurious course may practically implement the cytoprotection concept.

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.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

BACKGROUND: BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. METHODS: Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. RESULTS: After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 µg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 µg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 µg+L-NAME; BPC 157 µg+L-arginine, BPC 157 µg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. CONCLUSIONS: L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.

Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone.

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.

Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats.

BACKGROUND: Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). MATERIAL AND METHODS: During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 µg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 µg/kg in drinking water (0.16 µg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. RESULTS: All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (µg-intraperitoneally or per-orally) and BPC 157-VD rats (µg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory's trichrome staining. CONCLUSIONS: Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI.