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Acetabular fractures are prognostic relevant fractures in terms of function and daily activities. Open reduction and internal fixation (ORIF) is still the gold-standard in treating these injuries. Over recent years, several reports are dealing with outcome evaluations but have the main disadvantage of combining several fracture types., Thus, it remains unclear to discuss a fracture-based prognosis. This analysis evaluated fracture-type specific results in terms of clinical and radiological outcome. Analyzing elementary fracture types, pure transverse and isolated posterior column fractures are associated with relevant functional impairments. Except for posterior column fractures all other elementary fracture types were associated with degenerative changes in nearly 20%. Anterior column fractures seems to be "forgiving fractures" as they are associated with the longest median time until hip joint failure occurs. In associated fracture-types T-shaped fractures are still demanding fractures with < 60% anatomic reductions and a high rate of functional impairments. All associated fracture types are associated with a relevant rate of secondary degeneration of the hip joint between 20 and 40% of patients. Early hip joint failure (THR, Femoral head necrosis, severe heterotopic ossification) within the 1st year is frequently seen in associated posterior column and posterior wall fractures, but with a relative good prognosis, if the joint survived the first year after ORIF. The highest survival rates of the hip joint is observed with ABC-fractures. Also, these fractures seem to be "forgiving fractures".
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PURPOSE: Application of supraacetabular Schanz screws is usually performed under image intensifier guidance. The aim of this study was to perform it without imaging, with the hypothesis that, respecting anatomical landmarks, pre- and intraoperative fluoroscopy can be avoided. MATERIAL & METHODS: Insertion of the supra-acetabular Schanz screws was performed by two trauma surgery residents in a study sample of 14 human adult cadavers which had been embalmed by use of Thiel`s method. With cadavers placed in supine position, the anterior superior iliac spine (ASIS) was palpated. Starting from this landmark, 2 cm were measured in a distal and 2 cm in the medial direction. At this point, a 2 cm long oblique skin incision was performed. Through this approach, 150 mm Schanz screws were drilled bilaterally into the supra-acetabular corridor with an angulation of 20° to distal as well as 20° to medial. Following screw application, combined obturator oblique-outlet views (COOO) were taken bilaterally in each specimen by use of an Arcadis© Orbic 3D C-arm to prove the screw position. Six of the specimens underwent a 3D-CT-scan. Images were evaluated concerning correct screw positioning by a further traumatologist. Skin and subcutaneous tissues were removed in the ilioinguinal region and possible lesions to the lateral femoral cutaneous nerve (LFCN) or to the joint capsule were evaluated. RESULTS: The sample consisted of eight pelves from female and six pelves from male cadavers. During radiographic evaluation of the COOO-scans (14 specimens) and the 3D-scans (6 specimens), the Schanz screws were placed inside the supra-acetabular corridor in all specimens (14/14). During dissections, no intracapsular screw placements or LFCN lesions were found. CONCLUSION: According to the described anatomical data, we defined a 2-2-2-20-20 concept, starting with a 2 cm skin incision 2 cm distal and 2 cm medial to the ASIS with a drill angulation of 20° inferior and 20° lateral orientation. Using this technique, all Schanz screws could be sufficiently inserted without intraprocedural x-ray imaging.
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Tornillos Óseos , Ilion , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Adulto , Femenino , Fluoroscopía , Humanos , Masculino , RadiografíaRESUMEN
INTRODUCTION: Acromioclavicular (AC) joint dislocations usually occur in a young active population as a result of a fall on the shoulder. Rockwood divided these dislocations into six types. Optimal treatment is still a matter of discussion. Many operative techniques have been developed, but the main choice is between open and minimally-invasive arthroscopic procedures. The aim of this study was to compare two different surgical methods on two groups of patients to find out which method is superior in terms of benefit to the patient. The methods were evaluated through objective and subjective scores, with a focus on complications and material costs. MATERIAL AND METHODS: A retrospective two-centre study was conducted in patients with acute AC joint dislocation Rockwood types III and V. The two methods conducted were an open procedure using K-wires combined with FiberTape(®) (Arthrex, Naples, USA) (Group 1) and an arthroscopic procedure using the TightRope System(®) (Arthrex, Naples, USA) (Group 2). Groups underwent procedures during a two-year period. Diagnosis was based on the clinical and radiographic examination of both AC joints. Surgical treatment and rehabilitation were performed. RESULTS: Sixteen patients were included in this study: Group 1 comprised 10 patients, all male, average age 41.6 years (range 17-64 years), Rockwood type III (eight patients) and Rockwood type V (two patients); Group 2 had six patients, one female and five male, average age 37.8 years (range 18-58 years), Rockwood type III (two patients) and Rockwood type V (four patients). Time from injury to surgery was shorter and patients needed less time to return to daily activities in Group 1. Duration of the surgical procedure was shorter in Group 2 compared with Group 1. Complications of each method were noted. According to the measured scores and operative outcome between dislocation Rockwood type III and V, no significant difference was found. Implant material used in Group 2 was 4.7 times more expensive than that used in Group 1. CONCLUSION: Both methods offer many advantages with satisfying evaluated scores. K-wires with FiberTape(®) offer a shorter period for complete recovery and a significantly more cost-effective outcome, whereas the TightRope System(®) offers shorter operative procedure, better cosmetic result and avoidance of intraoperative fluoroscopy.
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Articulación Acromioclavicular/cirugía , Artroscopía , Hilos Ortopédicos , Inestabilidad de la Articulación/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Luxación del Hombro/cirugía , Cinta Quirúrgica , Articulación Acromioclavicular/lesiones , Articulación Acromioclavicular/fisiopatología , Adolescente , Adulto , Croacia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Luxación del Hombro/diagnóstico por imagen , Luxación del Hombro/fisiopatología , Anclas para Sutura , Resultado del TratamientoRESUMEN
Proximal fifth metatarsal (V MT) bone fractures are common injuries that are a major diagnostic and therapeutic challenge. Lawrence and Botte considered different treatment options and the possibility of recovery and divided these fractures into three different regions: tuberosity avulsion fractures (zone I), acute fractures of the metaphysis at the level of the intermetatarsal junction (zone II) and proximal diaphysis stress fracture (zone III). A total of 42 athletes with fracture of the V MT bone in zone II and III were treated in our institution during a 6-year period. All patients were offered surgical treatment, but nine patients refused surgery. Thus, the patients were divided into two groups: group 1 comprised 33 patients who underwent an intramedullary screw fixation operation under regional anaesthesia immediately after the fracture was diagnosed; group 2 contained the remaining nine patients who had refused surgery and received conservative therapy with non-weight-bearing short-leg casts or orthosis. Follow-up ranged from 6 to 24 months. All fractures healed in group 1: healing occurred within 8 weeks in 26 patients and was prolonged to 16 to 18 weeks in four patients. In group 2, fractures healed in four patients but did not heal in five patients even after 6 months. Four of the five patients in whom the fracture did not heal required subsequent osteosynthesis because they had constant problems that caused absence from sport. After the operation, their fractures healed in an average of 10 weeks. One patient decided not to undergo the operation due to the absence of subjective symptoms. Three patients in group 1 who started intensive training sustained a refracture and underwent re-operation in which osteosynthesis was performed with a stronger screw. The fractures then healed again. Treatment results were evaluated radiologically and clinically using the Modified Foot Score. Results in group 1 were significantly better than those in group 2 and there was an earlier return to full athletic activity. The authors concluded that intramedullary fixation of V MT zone II and III fractures with cannulated compression screws was associated with excellent functional results and early and complete recovery.
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Atletas , Traumatismos en Atletas , Fijación Intramedular de Fracturas , Fracturas Óseas/cirugía , Fracturas por Estrés/cirugía , Huesos Metatarsianos/lesiones , Adolescente , Adulto , Tornillos Óseos , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Huesos Metatarsianos/cirugía , Volver al Deporte , Resultado del Tratamiento , Soporte de PesoRESUMEN
Croatian Trauma Society (CTS) has a 51 year of history and tradition. This article represents a brief overview from the times when it was founded, June 30, 1961, until the present time. It tells us about the idea how, where and when the "Section for Traumatology" was founded, its activities and influence not only to promote patient trauma care but initiation of other societies dealing with traumatized patients as well, including the evolution of the CTS itself. The authors thank to all the contributors that made this article possible.
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Sociedades Médicas/historia , Traumatología , Croacia , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Angiogenesis is a natural and complex process controlled by angiogenic and angiostatic molecules, with a central role in healing process. One of the most important modulating factors in angiogenesis is the vascular endothelial growth factor (VEGF). Pentadecapeptide BPC 157 promotes healing demonstrating particular angiogenic/angiomodulatory potential. We correlated the angiogenic effect of BPC 157 with VEGF expression using in vitro (cell culture) and in vivo (crushed muscle and transected muscle and tendon) models. Results revealed that there is no direct angiogenic effect of BPC 157 on cell cultures. On the other hand, immunohistochemical analysis of muscle and tendon healing using VEGF, CD34 and FVIII antibodies showed adequately modulated angiogenesis in BPC 157 treated animals, resulting in a more adequate healing. Therefore the angiogenic potential of BPC 157 seems to be closely related to the healing process in vivo with BPC 157 stimulating angiogenesis by up-regulating VEGF expression.
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Tendón Calcáneo/efectos de los fármacos , Moduladores de la Angiogénesis/uso terapéutico , Neovascularización Fisiológica/efectos de los fármacos , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Músculo Cuádriceps/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Tendón Calcáneo/lesiones , Moduladores de la Angiogénesis/farmacología , Animales , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Línea Celular , Factor VIII/metabolismo , Miembro Posterior , Inmunohistoquímica , Masculino , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Músculo Cuádriceps/lesiones , Ratas , Ratas Wistar , Factores de Tiempo , Regulación hacia Arriba/efectos de los fármacos , Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Three higher hydrocarbon phase change materials (PCMs) with melting points of 25, 40 and 50 degrees C were microencapsulated by in situ polymerization of amino-aldehyde resins. Trimethylolmelamine (TMM) and hexamethoxymethylolmelamine (HMMM) were studied as amino-aldehyde pre-polymers for microcapsule wall formation, in combination with emulsifying/modifying agents based on styrene-malein anhydride copolymers (SMA) of different molecular weights and different styrene-maleic acid anhydride ratios. Microcapsule sizes, size distribution and wall permeability were analysed. A mathematical model was developed for comparing the mechanical resistance of different batches of microcapsules, produced at different TMM-SMA ratios. Larger microcapsules with thicker walls and larger pores (M(LAR)) expressed lower resistance to breakage than slightly smaller microcapsules with thinner walls and finer pore structure (M(SMA)). Mathematical data were confirmed by a smudging colouration test. Laboratory microencapsulation process parameters were optimized to obtain impermeable microcapsules with improved mechanical stability. The process was transferred into a 10l pilot reactor for two PCMs with melting points of 25 and 40 degrees C. Dry powder of microencapsulated PCMs was obtained by spray drying of aqueous microcapsule suspensions.
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Composición de Medicamentos/métodos , Calor , Hidrocarburos , Transición de Fase , Humanos , Industrias , Ensayo de Materiales , Microscopía Electrónica de Rastreo , PolímerosRESUMEN
In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-beta, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157+HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE+BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.
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Tendón Calcáneo/efectos de los fármacos , Antiulcerosos/farmacología , Elasticidad/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Traumatismos de los Tendones , Cicatrización de Heridas/efectos de los fármacos , Tendón Calcáneo/patología , Tendón Calcáneo/fisiopatología , Aldehídos/farmacología , Animales , Antiulcerosos/administración & dosificación , División Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Inyecciones Intraperitoneales , Masculino , Fragmentos de Péptidos/administración & dosificación , Proteínas/administración & dosificación , Ratas , Ratas Wistar , Estrés Mecánico , Traumatismos de los Tendones/tratamiento farmacológico , Traumatismos de los Tendones/patología , Traumatismos de los Tendones/fisiopatología , Resistencia a la Tracción/efectos de los fármacos , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta1 , Cicatrización de Heridas/fisiologíaRESUMEN
The amelioration of corticosteroid-impairment of healing by a stable gastric pentadecapeptide BPC-157 (GEPPPGKPADDAGLV, M(w) 1419, currently in early clinical trials for inflammatory bowel disease) was studied in thermally injured mice. Its effects on corticosteroid impaired healing of deep partial skin thickness burns, and burn-gastric lesions were investigated. Male NMRI-Hannover mice (sacrificed at 1-3,7,14 and 21 days following burning 20% of total burn area at the back (open flame for 7s) received intraperitoneally (per kg bw) 6alpha-methylprednisolone (Depo-medrol, 1.0 or 10.0mg), or an equal volume of saline (5.0 ml), once daily, first application 30 min after injury, last 24h before sacrifice. The injury was subsequently treated by topical application of a thin layer of pentadecapeptide BPC-157 cream at three different levels a neutral cream of no treatment. Pentadecapeptide BPC-157 consistently improved given burn healing (both microscopical and tensionmetry assessment), and counteracted corticosteroid-impairment of burn healing. In burn-gastric lesions investigation of the effects of BPC showed an anti-ulcer effect of its own in burned non-corticosteroid-treated mice and potentiated the anti-ulcer effect observed in 6alpha-methylprednisolone-treated mice. Pentadecapeptide BPC-157 inhibited corticosteroid immunosuppression. In vitro, in spleenic cells assessment, animals (sacrificed at day 21) treated with 6alpha-methylprednisolone 1mg showed decreased reactivity to nitrogen in comparison with control, healthy animals, while the addition of BPC-157 (1 microg/g cream) returned cell reactivity to values noted in control healthy animals.
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Antiinflamatorios/uso terapéutico , Antiulcerosos/uso terapéutico , Quemaduras/tratamiento farmacológico , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Análisis de Varianza , Animales , Masculino , Ratones , Modelos Animales , Pomadas , Resultado del TratamientoRESUMEN
AIM: To study anxiolytic effect of a gastric pentadecapeptide, BPC-157. METHODS: In shock probe/burying test, pentadecapeptide BPC-157 (10 microg/kg, 10 ng/kg, ip), diazepam (0.075, 0.0375 mg/kg, ip), and an equivolume of saline (5 mL/kg, ip) were given at 30 min prior test. In light/dark test, the same dosage of diazepam, BPC-157, and saline were given at 45 min prior procedure. RESULTS: Shock probe/burying test: rats treated with either diazepam or pentadecapeptide BPC-157 were much less afraid after the shock: almost not burying and the total time spent in burying was clearly less than in controls. However, while in the diazepam treated rats the number of shocks received increased over control values, in pentadecapeptide BPC-157 treated groups the number of shocks remained not modified compared with the control values. Light/dark test: after exposure to the intense light, diazepam treated mice had longer latencies of crossing to the dark compartment, a greater number of crossing and a greater number of exploratory rearing, and spent longer time in the light compartment, as compared to the control mice, while BPC-157 mice had a similar behavior to that of the control mice. In contrast with the effect in light area, in dark zone diazepam produced no change with respect to controls, while BPC-157 (10 microg/kg) mice had a greater number of crossing and a greater number of exploratory rearing. CONCLUSION: Both diazepam and BPC-157 displayed a bidirectional effect, but the activity of pentadecapeptide BPC-157 was particular, and different from diazepam.
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Ansiolíticos/farmacología , Ansiedad , Conducta Animal/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Animales , Oscuridad , Diazepam/farmacología , Luz , Masculino , Ratones , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Hemorrhagic mucosal lesions in the stomach in the rat induced by an intragastrical application of 1 ml of 50 or 75% ethanol were aggravated by preceding lung damage provoked by an intratracheal instillation of pyrogen-free saline or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particular preceding aggravating circumstances, these lesions were taken to be of a special kind, rather than ordinary. So far, it is not known whether and how antiulcer agents may influence these lesions. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung-lesion), and an intragastric instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), and were sacrificed 1 h after ethanol. Basically, in lung injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for a 1-h observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (PL-10, PLD-116; 10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (1) once, only prophylactically [as a pre-treatment (at -1 h), or as a co-treatment (at 0)], or only therapeutically (at +18 h or +24 h); (2) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h) or (0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. In general, the antiulcer agents did protect against ethanol gastric lesions regardless of the presence of the severe lung injury, in all of the used regimens. Of note, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) may increase the antiulcer potential, and the effect that had been not seen already with single application, became prominent after repeated treatment.
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Antiulcerosos/uso terapéutico , Etanol , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/complicaciones , Enfermedades Pulmonares/complicaciones , Animales , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Ácido Clorhídrico , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratas , Ratas WistarRESUMEN
Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were also attenuated by these agents application (given in the same doses, i.p., 1 h before cysteamine), with only exception to sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect, cysteamine colon/duodenum lesion-link and an extenuation of agents protection from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole) and vice versa (remedies for inflammatory bowel disease) evidenced in the present study may be potentially important for both further experimental and clinical research.
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Antiulcerosos/farmacología , Colon/efectos de los fármacos , Cisteamina/farmacología , Duodeno/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Glucocorticoides/farmacología , Metilprednisolona/farmacología , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Sulfasalazina/farmacología , Animales , Colon/patología , Cisteamina/antagonistas & inhibidores , Duodeno/patología , Femenino , Necrosis , Ratas , Ratas WistarRESUMEN
Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.
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Antiulcerosos/uso terapéutico , Atropina/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/prevención & control , Omeprazol/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Proteínas/uso terapéutico , Ranitidina/uso terapéutico , Animales , Ácido Clorhídrico , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratas , Ratas WistarRESUMEN
Liver lesions and portal hypertension in rats, following chronic alcohol administration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg b.w. of alcohol given in drinking water for 3 months, were counteracted by a stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in a variety of models of gastrointestinal or liver lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughout either the whole 3 months period (1) or the last month only (2) (last application 24 h before sacrifice). In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all control saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats that received gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats. Besides, a raised surface area (microm(2)) and increased circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver), an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were markedly attenuated (values less than in drinking controls, still higher than in healthy rats, i.e. circumference and area of hepatocytes nucleus). On the other hand, ranitidine application attenuated only steatosis development. In summary, despite continuous chronic alcohol drinking, pentadecapeptide BPC 157, and propranolol may prevent portal hypertension as well as reverse already established portal hypertension along with related liver disturbances.
Asunto(s)
Consumo de Bebidas Alcohólicas , Antihipertensivos/uso terapéutico , Hipertensión Portal/prevención & control , Hepatopatías Alcohólicas/prevención & control , Fragmentos de Péptidos/uso terapéutico , Propranolol/uso terapéutico , Proteínas/uso terapéutico , Ranitidina/uso terapéutico , Animales , Hipertensión Portal/tratamiento farmacológico , Hepatopatías Alcohólicas/tratamiento farmacológico , Masculino , Ratas , Ratas WistarRESUMEN
After demonstration that cysteamine induced duodenal lesions in gastrectomized rats, while a number of antiulcer drugs mitigated these lesions, it was shown that one single intrarectal (i.r.) cysteamine application produced severe colon lesions in acute studies in rats. Thus, the further focus was on the protracted effect of cysteamine challenge (400 mg/kg b.w. i.r.) and therapy influence in chronic experiments in female rats. Regularly, cysteamine colon lesions were markedly mitigated by ranitidine (10), omeprazole (10), atropine (10), methylprednisolone (1), sulphasalazine (50; mg/kg), pentadecapeptide BPC 157 (PL-10, PLD-116; 10 microg or 10 ng/kg). Specifically, after 1 or 3 months following initial challenge (cysteamine 400 mg/kg i.r.) in female rat, the therapy [BPC 157 (PL-10, PLD-116 (10.0 microg or 10.0 ng/kg; i.g., i.p., i.r.), ranitidine, omeprazole, atropine, methylprednisolone, sulphasalazine (i.p.)] reversed the protracted cysteamine colon injury: the 1 week-regimen (once daily application) started after 1 month post-cysteamine, as well as the 2 weeks-regimen (once daily application), which started after 3 months. The effect on recidive lesion was also tested. These cysteamine lesions may reappear after stopping therapy (after stopping therapy for 3 weeks at the end of 2-weeks regimen started in 3 months-cysteamine female rats) in sulphasalazine group, while this reappearance is markedly antagonized in pentadecapeptide BPC 157 (PL-10, PLD-116)-rats (cysteamine-colon lesion still substantially low).
Asunto(s)
Antiulcerosos/farmacología , Colon/efectos de los fármacos , Colon/patología , Cisteamina/farmacología , Animales , Femenino , Ratas , Ratas Wistar , RecurrenciaRESUMEN
Unlike severe gastric damage acutely induced by ethanol administration in rat, the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28 g/kg b.w.) given in drinking water, producing liver lesions and portal hypertension, is far less investigated. Therefore, focus was on the antiulcer effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in variety of gastrointestinal lesions models (10 microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They were given once daily (1) throughout 10 days preceding alcohol consumption, (2) since beginning of alcohol drinking till the end of the study, (3) throughout the last month of alcohol consumption, 2 months after alcohol drinking had been initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1), (2)] or with respect to therapeutic effect of medication before medication or at the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may prevent gastric lesion development if given prophylactically, before alcohol drinking. Likewise, they attenuate the lesion appearance given once daily throughout the drinking period. Importantly, when given therapeutically, they may antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine and propranol may prevent, attenuate or reverse the gastric lesions appearance in chronically alcohol drinking rats, and may be used for further therapy, while the other studies showed that their effect (except to ranitidine) is parallel with their beneficial effect on liver lesion and portal hypertension.