The efficacy of a novel SWEEPS laser-activated irrigation compared to ultrasonic activation in the removal of pulp tissue from an isthmus area in the apical third of the root canal.

This study aimed to evaluate the efficacy of Shock Wave Enhanced Emission Photoacoustic Streaming (SWEEPS) in the removal of remaining pulp tissue from the root canal isthmus area in lower molars and compare it with ultrasonically activated irrigation (UAI) and conventional needle irrigation (NI). Forty-one lower molars with isthmuses between mesial canals were included in the study. The teeth were randomly distributed into experimental groups (n = 12/each) based on the final irrigation protocol (SWEEPS, UAI, or NI) and a control group (C) (n = 5). The traditional access cavity of the mesial part of each tooth was made in all samples. The mesial root canals in the experimental groups were instrumented with a Wave One Gold Primary (25/.07) file using 3% sodium hypochlorite (NaOCl) while the distal canal served as a control for the presence of pulp tissue. No treatment was performed in the C group. Sections from the isthmus region were processed for histopathology to measure the remaining pulp tissue (RPT). The results were analyzed using analysis of variance and the Kruskal-Wallis test (α = 0.05). There were no significant differences in the relative surface area of root canals and isthmus among the groups (p > 0.05). Samples in the SWEEPS group had significantly less RPT than UAI, NI, and C (p = 0.003, 0.014, 0.003, respectively). There were no significant differences between the UAI and NI (p = 0.583). SWEEPS was the most efficient in debridement of the root canal isthmus area. UAI and NI showed similar but lower efficiency.

Stable Gastric Pentadecapeptide BPC 157 and Wound Healing.

Significance: The antiulcer peptide, stable gastric pentadecapeptide BPC 157 (previously employed in ulcerative colitis and multiple sclerosis trials, no reported toxicity (LD1 not achieved)), is reviewed, focusing on the particular skin wound therapy, incisional/excisional wound, deep burns, diabetic ulcers, and alkali burns, which may be generalized to the other tissues healing. Recent Advances: BPC 157 has practical applicability (given alone, with the same dose range, and same equipotent routes of application, regardless the injury tested). Critical Issues: By simultaneously curing cutaneous and other tissue wounds (colocutaneous, gastrocutaneous, esophagocutaneous, duodenocutaneous, vesicovaginal, and rectovaginal) in rats, the potency of BPC 157 is evident. Healing of the wounds is accomplished by resolution of vessel constriction, the primary platelet plug, the fibrin mesh which acts to stabilize the platelet plug, and resolution of the clot. Thereby, BPC 157 is effective in wound healing much like it is effective in counteracting bleeding disorders, produced by amputation, and/or anticoagulants application. Likewise, BPC 157 may prevent and/or attenuate or eliminate, thus, counteract both arterial and venous thrombosis. Then, confronted with obstructed vessels, there is circumvention of the occlusion, which may be the particular action of BPC 157 in ischemia/reperfusion. Future Directions: BPC 157 rapidly increases various genes expression in rat excision skin wound. This would define the healing in the other tissues, that is, gastrointestinal tract, tendon, ligament, muscle, bone, nerve, spinal cord, cornea (maintained transparency), and blood vessels, seen with BPC 157 therapy.

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.

Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine in rats.

BACKGROUND: After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats, there is failed vasculature, and finally, increased adhesion formation. We hypothesized that unlike nitric oxide (NO)-agents, L-NAME and/or L-arginine, the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects ("vascular recruitment") means attenuated bowel adhesion formation and NO- and malondialdehyde (MDA)-tissue values. AIM: To focused on the bowel adhesion and the therapy with the BPC 157, its most and application of NO-agents. METHODS: Along with defect creation, medication was (1) during surgery, once, at 1 min after defect creation as an abdominal bath (1 mL/rat), BPC 157 (10 µg/kg, 10 ng/kg, 1 mL/rat), an equivolume of saline, L-NAME (5 mg/kg), L-arginine (200 mg/kg) alone and/or combined. Alternatively, medication was (2) intraperitoneally once daily, first application at 30 min after surgery, last application 24 h before assessment at d 7 or d 14. As a postponed therapy to pre-existing adhesion (3), BPC 157 (10 µg/kg, 10 ng/kg intraperitoneally, 1 mL/rat) was given once daily since d 7. RESULTS: The recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect, which occurs rapidly. Lastly, also applied as post-treatment, BPC 157 creates attenuated adhesions, minimal or no adhesion. Contrarily, NO-agents have diverse initial and final effects: The initial weakening of blood vessel disappearance and finally, severe worsening of adhesions (L-NAME) vs the initial weakening of blood vessel disappearance and finally, attenuation of adhesions formation (L-arginine), which counteract each other response given together. Importantly, BPC 157 maintains its beneficial effect also when given with NO-agents (L-NAME + BC 157; L-arginine + BPC 157; L-NAME + L-arginine + BPC 157). Finally, with respect to the increased NO- and MDA- values-adhesion tissue formation relation, unlike diverse effect of the NO-agents, the BPC 157 application effect regularly combines decrease on the increased NO- and MDA- values and the beneficial outcome (less adhesion formation). CONCLUSION: BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation.

Differentiating Between Malignant Mesothelioma and Other Pleural Lesions Using Fourier Transform Infrared Spectroscopy.

Histopathology, despite being the gold standard as a diagnostic tool, does not always provide a correct diagnosis for different pleural lesions. Although great progress was made in this field, the problem to differentiate between reactive and malignant pleural lesions still stimulates the search for additional diagnostic tools. Our research using vibrational spectroscopy and principal component analysis (PCA) statistical modeling represents a potentially useful tool to approach the problem. The objective method this paper explores is based on the correlation between different types of pleural lesions and their vibrational spectra. Obtained tissue spectra recorded by infrared spectroscopy allowed us to categorize spectra in different groups using a created PCA statistical model. The PCA model was built using tissues of known pathology as the model group. The validation samples were then used to confirm the functionality of our PCA model. Student's t-test was also used for comparing samples in paired groups. The PCA model was able to clearly differentiate the spectra of mesothelioma, metastasis and reactive changes (inflammation), and place them in discrete groups. Thus, we showed that Fourier transform infrared spectroscopy combined with PCA can differentiate pleural lesions with high sensitivity and specificity. This new approach could contribute in objectively differentiating specific pleural lesions, thus helping pathologists to better diagnose difficult pleural samples but also could shed additional light into the biology of malignant pleural mesothelioma.

Therapy of the rat hemorrhagic cystitis induced by cyclophosphamide. Stable gastric pentadecapeptide BPC 157, L-arginine, L-NAME.

We focused on the cyclophosphamide-induced hemorrhagic cystitis (100 mg/kg/day intraperitoneally throughout three days) as a particular NO-system disturbance, and therapy possibilities. We demonstrated that it may be attenuated by subsequent administration of the NOS substrate L-arginine (100 mg/kg/day intraperitoneally), aggravated by NOS-blocker L-NAME (5 mg/kg/day intraperitoneally), all influenced by the stable gastric pentadecapeptide BPC 157 (10 µg/kg/day, 10 ng/kg/day, intraperitoneally or perorally, in drinking water). Regularly, cyclophosphamide dose- and time-dependently induced severe hemorrhagic cystitis lesions, gross lesions, and corresponding urothelial necrosis, vesical edema, erosion, hemorrhage, inflammation, and ulceration, microscopically. The bladder wet weight dramatically increased. Functionally, already after first cyclophosphamide administration, there is an increased leak point pressure. Until the second cyclophosphamide administration, L-arginine consistently attenuated regular cyclophosphamide-induced severe hemorrhagic cystitis lesions, grossly and microscopically, but not functionally. L-NAME aggravated these lesions and eradicated beneficial effect of L-arginine when combined. BPC 157 administration after cyclophosphamide, given in either dose or in either regimen markedly attenuated all cyclophosphamide lesions, grossly, microscopically. The increase of the bladder wet weight was consistently attenuated. Functionally, increased leak point pressure was reversed to the values noted in normal rats. The similar findings were noted in rats that received BPC 157 together with L-NAME or L-arginine, given alone or combined. Thus, the lesions are NO-related based on the administration of L-NAME as well as administration of L-arginine, and their mutual interaction, and counteraction by BPC 157 application. Likewise, we reveal new therapeutic possibilities, emphasizing stable gastric pentadecapeptide BPC 157 and L-arginine, versus L-NAME in rats underwent cyclophosphamide-induced cystitis.

Stable gastric pentadecapeptide BPC 157 in the therapy of the rats with bile duct ligation.

Recently, stable gastric pentadecapeptide BPC 157 reversed the high MDA- and NO-tissue values to the healthy levels. Thereby, BPC 157 therapy cured rats with bile duct ligation (BDL) (sacrifice at 2, 4, 6, 8 week). BPC 157-medication (10 µg/kg, 10 ng/kg) was continuously in drinking water (0.16 µg/ml, 0.16 ng/ml, 12 ml/rat/day) since awakening from surgery, or since week 4. Intraperitoneal administration was first at 30 min post-ligation, last at 24 h before sacrifice. Local bath BPC 157 (10 µg/kg) with assessed immediate normalization of portal hypertension was given immediately after establishing portal hypertension values at 4, 6, 8 week. BPC 157 therapy markedly abated jaundice, snout, ears, paws, and yellow abdominal tegmentum in controls since 4th week, ascites, nodular, steatotic liver with large dilatation of main bile duct, increased liver and/or cyst weight, decreased body weight. BPC 157 counteracts the piecemeal necrosis, focal lytic necrosis, apoptosis and focal inflammation, disturbed cell proliferation (Ki-67-staining), cytoskeletal structure in the hepatic stellate cell (α-SMA staining), collagen presentation (Mallory staining). Likewise, counteraction includes increased AST, ALT, GGT, ALP, total bilirubin, direct and indirect and decreased albumin serum levels. As the end-result appear normalized MDA- and NO-tissue values, next to Western blot of NOS2 and NOS3 in the liver tissue, and decreased IL-6, TNF-α, IL-1ß levels in liver tissue. Finally, although portal hypertension is sustained in BDL-rats, with BPC 157 therapy, portal hypertension in BDL-rats is either not even developed or rapidly abated, depending on the given BPC 157's regimen. Thus, BPC 157 may counteract liver fibrosis and portal hypertension.

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.

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.

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.

BACKGROUND: Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. METHODS: Review of our research on BPC 157 in terms of brain-gut axis. RESULTS: BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. CONCLUSION: BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.

Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats.

AIM: Rectovaginal fistula is a devastating condition providing more than 99% of patients for surgical treatment. We hypothesized that rectovaginal fistula may be healed by therapy with stable gastric pentadecapeptide BPC 157, in consistence with its initial clinical application and effect on external fistulas. MAIN METHODS: BPC 157 (10µg/kg or 10ng/kg) was given perorally, in drinking water (0.16µg/ml or 0.16ng/ml, 12ml/rat/day) till sacrifice, or alternatively, intraperitoneally, first application at 30min after surgery, last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). The assessment (i.e., rectal and vaginal defect, fistula leakage, defecation through the fistula, adhesions and intestinal obstruction as healing processes) was at day 1, 3, 5, 7, 10, 14 and 21. KEY FINDINGS: Regularly, rectovaginal fistulas exhibited poor healing, with both of the defects persisting, continuous fistula leakage, defecation through the fistula, advanced adhesion formation and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally, in µg- and ng-regimens rapidly improved the whole presentation, with both rectal and vaginal defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised till the values of healthy rats were achieved, there were no signs of defecation through the fistula. A counteraction of advanced adhesion formation and intestinal obstruction was achieved. Microscopic improvement was along with macroscopic findings. SIGNIFICANCE: BPC 157 effects appear to be suited to induce a full healing of rectovaginal fistulas in rats.

BPC 157 and blood vessels.

This review focuses on the described effects of BPC 157 on blood vessels after different types of damage, and elucidate by investigating different aspects of vascular response to injury (endothelium damage, clotting, thrombosis, vasoconstriction, vasodilatation, vasculoneogenesis and edema formation) especially in connection to the healing processes. In this respect, BPC 157 was concluded to be the most potent angiomodulatory agent, acting through different vasoactive pathways and systems (e.g. NO, VEGF, FAK) and leading to optimization of the vascular response followed, as it has to be expected, by optimization of the healing process. Formation of new blood vessels involves two main, partly overlapping mechanisms, angiogenesis and vasculogenesis. The additional mechanism of arteriogenesis is involved in the formation of collaterals. In conjunction with blood vessel function, we at least have to consider leakage of fluid/proteins/plasma, resulting in edema/exudate formation as well as thrombogenesis. Blood vessels are also strongly involved in tumor biology. In this aspect, we have neoangiogenesis resulting in pathological vascularization, vascular invasion resulting in release of metastatic cells and the phenomenon of homing resulting in formation of secondary tumors--metastases.

[Synovial chondromatosis]. / Sinovijalna hondromatoza.

Synovial chondromatosis is an uncommon benign disorder of the synovial membrane ofjoints, tendon sheaths, or bursae characterized by the formation of multiple cartilaginous nodules or osseus loose bodies. It is usually a monoarticular disease, and 33 different localizations have been described until now. The aim of this review article is to present the newest knowledge on the etiology, diagnosis, differential diagnosis, and management of synovial chondromatosis. Malignant transformation to chondrosarcoma is an unusual but possible complication. It is closely connected with recurrence rate and usually occurs many years after surgical treatment. More specific details related to surgical treatment of most often affected joints, i.e. shoulder, elbow, hip, knee, and ankle are reported as well at the end of this review article.

Pleomorphic liposarcoma of the foot: a case report.

BACKGROUND: Liposarcomas are among the most common sarcomas of adult life. Pleomorphic liposarcoma, characterized by pleomorphic lipoblasts, is the rarest subtype. To our knowledge only three cases of pleomorphic liposarcoma of the foot or ankle have been reported so far. CASE PRESENTATION: A 71-year-old female presented with a large growing mass on the dorsum of her right foot. Computed tomography showed invasive tumorous mass. Excision biopsy revealed the mass to be a pleomorphic liposarcoma, and below the knee amputation was performed. CONCLUSION: Although the incidence of pleomorphic liposarcoma in the foot is very low, it is essential to perform thorough histological analysis of all soft tissue masses, regardless of their benign appearance, because only prompt radical surgery can result in a good prognosis for the patient.

Prognostic significance of DNA cytometry in combination with AgNOR investigation.

CONCLUSION: While most results concerning DNA and nucleolar organizer region (AgNOR) parameters fit with previous studies, the percentage of aneuploidy looks like a promising prognostic parameter. The observed intratumoral heterogeneity could represent a possible source of conflicting and inconsistent results. OBJECTIVES: The aims of our study were to determine the prognostic relevance of different DNA and AgNOR parameters in laryngeal squamous cell carcinoma (SCC) and compare these findings with established prognostic factors including tumor stage and grade, as well as the detection of possible intratumoral heterogeneity. MATERIALS AND METHODS: Sections from 62 laryngeal SCCs were analyzed for DNA content, DNA index, S-phase, percentage of aneuploidy, and AgNOR. Of 62 samples, 31 morphologically similar tumor samples were analyzed for the same parameters in three different tumor areas defined as tumor center, invasive tumor margin, and transformation margin between tumor and normal-appearing mucosa. RESULTS: Our study showed that DNA and AgNOR parameters correlated with T stage, lymph node involvement, and histologic grade regardless of tumor areas. Significant correlation was found between mean number of AgNOR per nucleus and percentage of aneuploidy. Clinical stage and percentage of aneuploidy correlated with survival (p<0.02). Heterogeneity DNA study revealed aneuploidy in central portions of 90% of tumors, while in margins aneuploidy was demonstrated in about half of the patients.

Mast-cell sarcoma of the tibia.

The mast-cell sarcoma of a bone is described here for the first time. The tumour presented in a 4-year-old boy, with pain, oedema and deformation of his right lower leg. Radiological findings revealed a destructive tumourous mass. Histopathological examination showed the tumour to be composed of large, atypical cells, with hyperchromatic oval and polygonal nuclei. The cytoplasm around them was eosinophilic with many basophilic and toluidine-blue-positive granules. These atypical mast cells were positive for chloroacetate esterase, c-kit, tryptase and negative for myeloperoxidase. The primary disease quickly progressed to mast-cell leukaemia, and despite intensive chemotherapy the patient died 18 months after first symptoms.