RESUMO
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.
Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Músculos/efeitos dos fármacos , Músculos/patologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Desmina/metabolismo , Inflamação/patologia , Injeções Intraperitoneais , Masculino , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Ratos , Ratos WistarRESUMO
PURPOSE: Stable gastric pentadecapeptide BPC 157 accelerates the healing of a transected Achilles tendon and a transected quadriceps muscle. It may also be of clinical relevance as a systemic and local peptide treatment for crush injury of a major muscle, such as gastrocnemius muscle complex. BPC 157 is effective without a carrier, and it is presently undergoing trials for inflammatory bowel disease, and no toxicity has so far been reported. METHODS: In crushed rats (force delivered 0.727 Ns/cm2), BPC 157 was applied either intraperitoneally or locally, as a thin cream layer, immediately after injury (sacrifice at 2 h), and once a day for 14 days. RESULTS: BPC 157 improved muscle healing, macroscopically (less hematoma and edema, no post-injury leg contracture), microscopically, functionally, and also based on enzyme activity (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase). CONCLUSION: BPC 157, at all investigated intervals, given locally or intraperitoneally, accelerated post-injury muscle healing and also helped to restore the full function.
Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Traumatismos dos Tendões/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Tendão do Calcâneo/lesões , Tendão do Calcâneo/fisiopatologia , Animais , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Estatísticas não Paramétricas , Estresse Mecânico , Traumatismos dos Tendões/fisiopatologia , Cicatrização/fisiologiaRESUMO
Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 microg/kg, 10 ng/kg, last application 24 h before assessment), or continuously in drinking water at 0.16 microg/ml, 0.16 ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.
Assuntos
Esofagite/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Piloro/efeitos dos fármacos , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Modelos Animais de Doenças , Esfíncter Esofágico Inferior/efeitos dos fármacos , Esfíncter Esofágico Inferior/lesões , Esfíncter Esofágico Inferior/fisiopatologia , Esofagite/etiologia , Esofagite/fisiopatologia , Feminino , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Injeções Intraperitoneais , Intubação Gastrointestinal , Tono Muscular/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Piloro/lesões , Piloro/fisiopatologia , Ranitidina/administração & dosagem , Ranitidina/uso terapêutico , Ratos , Ratos Wistar , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Adaptive cytoprotection could be demonstrated in lesion attenuation within the whole gastrointestinal tract, in particular sequences, with onset and duration longer than the initial short-lasting period (i.e. one hour) defined by Robert in the stomach only. MATERIAL/METHODS: Adaptive cytoprotection possibly appeared and lesions were attenuated when the stomach, duodenum or colon, in various combinations and sequences, were challenged with initial (mild) and/or final (strong) irritants over a two-week period. Rats were challenged with the mild or strong irritants 25% or 96% ethanol intragastrically 1 ml/rat (stomach) and cysteamine 40 mg or 400 mg/kg subcutaneously (duodenum), or intrarectally (colon). To postulate the prostaglandin relationship known in Robert's cytoprotection and adaptive cytoprotection, indomethacin (1 mg/kg subcutaneously) was given simultaneously with the second challenge. RESULTS: Administering the mild and strong irritant protocols within the same part of the gastrointestinal tract, adaptive cytoprotection presents in the stomach (1 h to 14 days), duodenum (2 h to 14 days), but not in the colon. With these protocols applied to different parts of the gastrointestinal tract, adaptive cytoprotection cross-reaction was evident in the stomach-duodenum, duodenum-stomach (1 h-14 days and 2 h-14 days), stomach-colon, and duodenum-colon (both 2-24 hours), but not in the colon-stomach or colon-duodenum. This protection was fully antagonized with indomethacin. CONCLUSIONS: As observed for a day and even weeks, stomach-duodenum-colon adaptive cytoprotection is an important new defensive phenomenon.
Assuntos
Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Irritantes/toxicidade , Adaptação Fisiológica , Animais , Colo/efeitos dos fármacos , Colo/lesões , Colo/patologia , Colo/fisiopatologia , Cisteamina/toxicidade , Duodeno/efeitos dos fármacos , Duodeno/lesões , Duodeno/patologia , Duodeno/fisiopatologia , Etanol/toxicidade , Feminino , Mucosa Gástrica/lesões , Mucosa Gástrica/fisiopatologia , Mucosa Intestinal/lesões , Mucosa Intestinal/fisiopatologia , Necrose , Ratos , Ratos WistarRESUMO
Serious complications after carbamazepine poisoning, such as coma, seizures, respiratory failure, cardiac conduction abnormalities, and death are more likely with serum levels greater than 170 micromol L(-1). We report a case of a single massive carbamazepine overdose in a 19-year-old male, following attempted suicide, without prior history of seizure disorder. On admission, three hours after ingestion, serum carbamazepine concentration was 179 micromol L(-1) and Glasgow Coma Scale scored 6. The patient was intubated and treated with multiple doses of activated charcoal for 48 hours. Twelve hours after ingestion, two repeated generalised myoclonic seizures were noted when serum carbamazepine levels peaked at 181 micromol L(-1), and were successfully treated with diazepam. Carbamazepine serum level fell within the therapeutic range 63 hours after ingestion and the patient was discharged without any long-term sequelae. As there is no antidote for carbamazepine poisoning, supportive treatment remains the only, but usually potent option.