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1.
Curr Pharm Des ; 20(7): 1126-35, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23755725

RESUMO

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.


Assuntos
Óxido Nítrico/metabolismo , Fragmentos de Peptídeos/fisiologia , Proteínas/fisiologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/fisiologia , Mucosa Gástrica/fisiopatologia , Humanos , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Proteínas/farmacologia , Proteínas/uso terapêutico , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
2.
Curr Pharm Des ; 19(1): 76-83, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22950504

RESUMO

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


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antídotos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Animais , Antiulcerosos/efeitos adversos , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antídotos/efeitos adversos , Antídotos/farmacologia , Aspirina/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/fisiopatologia , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/farmacologia , Proteínas/efeitos adversos , Proteínas/farmacologia
3.
Eur J Pharmacol ; 667(1-3): 322-9, 2011 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-21645505

RESUMO

Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 µg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 µg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen.


Assuntos
Antiulcerosos/farmacologia , Encefalopatia Hepática/prevenção & controle , Hepatomegalia/prevenção & controle , Ibuprofeno/efeitos adversos , Peptídeos/farmacologia , Gastropatias/prevenção & controle , Estômago/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antiulcerosos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Lesões Encefálicas/induzido quimicamente , Mucosa Gástrica/metabolismo , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/patologia , Hepatomegalia/induzido quimicamente , Hepatomegalia/patologia , Ibuprofeno/antagonistas & inibidores , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Dados de Sequência Molecular , Tamanho do Órgão/efeitos dos fármacos , Peptídeos/efeitos adversos , Peptídeos/química , Ratos , Ratos Wistar , Estômago/lesões , Estômago/patologia , Gastropatias/induzido quimicamente , Gastropatias/patologia
4.
Life Sci ; 88(11-12): 535-42, 2011 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-21295044

RESUMO

AIMS: We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). MAIN METHODS: Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats. KEY FINDINGS: Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 µg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 µg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons). SIGNIFICANCE: The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (µg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity.


Assuntos
Anti-Inflamatórios não Esteroides , Antiulcerosos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Diclofenaco , Gastroenteropatias/prevenção & controle , Encefalopatia Hepática/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/patologia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/patologia , Injeções Intraperitoneais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Testes de Função Hepática , Masculino , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Ratos , Ratos Wistar
5.
J Med Microbiol ; 58(Pt 9): 1231-1235, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19528156

RESUMO

The impact of bacterial colonization on the severity and pattern of chronic inflammation in rhinosinusitis is not clear. In this study, it was hypothesized that bacterial colonization of the sinus mucosa would have a greater impact on inflammatory response modulation in asthmatic patients than in non-asthmatic patients with chronic rhinosinusitis. In order to test this hypothesis, granulocyte activation was measured and related to bacteria identified in the sinus lavage. Lavages from the maxillary sinuses of 21 asthmatic and 19 non-asthmatic patients with chronic rhinosinusitis (CRS) were microbiologically examined for aerobic and anaerobic growth. Eosinophil cationic protein (ECP), an eosinophil activation marker, and myeloperoxidase (MPO), a neutrophil activation marker, were measured in the sinus lavages. Bacteria were recovered in 20/32 samples from the asthmatics and in 21/33 samples from the non-asthmatics. Gram-positive aerobes and anaerobes were slightly more common than Gram-negative bacteria. A different bacterial profile was found when comparing Gram-negatives between the groups. Concentrations of MPO were significantly higher in samples with bacterial recovery from asthmatic patients, compared to sterile samples of both groups. Concentrations of ECP in the samples from asthmatic patients were significantly higher than in the controls, with no significant difference related to bacterial colonization. Bacterial colonization in chronically inflamed sinuses may have an impact on neutrophil granulocyte activation in patients with bronchial asthma, which was not confirmed for patients with CRS without asthma.


Assuntos
Asma/complicações , Bactérias/isolamento & purificação , Granulócitos/fisiologia , Sinusite Maxilar/microbiologia , Sinusite Maxilar/patologia , Líquido da Lavagem Nasal/microbiologia , Adolescente , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Sinusite Maxilar/complicações , Pessoa de Meia-Idade , Adulto Jovem
6.
Eur Arch Otorhinolaryngol ; 265(10): 1205-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18299868

RESUMO

The aim of the study was to show the difference in the pattern of inflammation, and Th1/Th2 polarization between asthmatic and non-asthmatic patients with CRS, specifically eosinophil activation, local IgE levels in the sinus fluid and tissue, and the severity of inflammation were measured. The maxillary sinus lavages, mucosal biopsies and bacteriological swabs were taken in 17 asthmatic and 36 non-asthmatic adult patients with CRS. The concentrations of IgE, eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase were analyzed and IgE+ cells, eosinophils, lymphocytes and plasma cells were counted. The granulocyte activation markers and IgE in sinus lavages, and the inflammatory and IgE+ cells counts were significantly higher in the asthmatics with the greatest difference in ECP and IgE concentrations. The tryptase concentrations did not differ, but only in the asthmatics they correlated significantly with the IgE concentrations and IgE+ cells count. Asthmatic patients present a distinct subgroup among the patients with chronic rhinosinusitis (CRS). The levels of the cellular markers and IgE in the sinus fluid differ from those of non-asthmatic patients with CRS. The activation of granulocytes (especially eosinophils), local IgE concentrations and the inflammatory cells infiltration are significantly higher in the asthmatics.


Assuntos
Asma/complicações , Imunoglobulina E/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Idoso , Asma/metabolismo , Asma/patologia , Biomarcadores/metabolismo , Doença Crônica , Proteína Catiônica de Eosinófilo/metabolismo , Feminino , Imunoensaio de Fluorescência por Polarização , Seguimentos , Granulócitos/metabolismo , Granulócitos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Peroxidase/metabolismo , Prognóstico , Radioimunoensaio , Rinite/complicações , Rinite/patologia , Índice de Gravidade de Doença , Sinusite/complicações , Sinusite/patologia , Adulto Jovem
7.
Acta Pharmacol Sin ; 24(6): 519-26, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12791177

RESUMO

The frequency and spectrum of antibiotic resistant infections have increased worldwide during the past few decades. This increase has been attributed to a combination of microbial characteristics, the selective pressure of antimicrobial use, and social and technical changes that enhance the transmission of resistant organisms. The resistance is acquired by mutational change or by the acquisition of resistance-encoding genetic material which is transferred from another bacteria. The spread of antibiotic resistance genes may be causally related to the overuse of antibiotics in human health care and in animal feeds, increased use of invasive devices and procedures, a greater number of susceptible hosts, and lapses in infection control practices leading to increased transmission of resistant organisms. The resistance gene sequences are integrated by recombination into several classes of naturally occurring gene expression cassettes and disseminated within the microbial population by horizontal gene transfer mechanisms: transformation, conjugation or transduction. In the hospital, widespread use of antimicrobials in the intensive care units (ICU) and for immunocompromised patients has resulted in the selection of multidrug-resistant organisms. Methicillin-resistant Staphylococci, vancomycin resistant Enterococci and extended-spectrum beta-lactamase (ESBL) producing Gram negative bacilli are identified as major problem in nosocomial infections. Recent surveillance studies have demonstrated trend towards more seriously ill patients suffering from multidrug-resistant nosocomial infections. Emergence of multiresistant bacteria and spread of resistance genes should enforce the application of strict prevention strategies, including changes in antibiotic treatment regimens, hygiene measures, infection prevention and control of horizontal nosocomial transmission of organisms.


Assuntos
Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Transferência Genética Horizontal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecção Hospitalar/prevenção & controle , Enterococcus/efeitos dos fármacos , Enterococcus/genética , Enterococcus/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação
8.
Mutat Res ; 522(1-2): 27-32, 2003 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-12517409

RESUMO

Antimutators are genetic mutants that produce mutations at reduced rates compared to the wild type strain. They are interesting because they may provide insights into the mechanisms by which spontaneous mutations occur. We have investigated a reported antimutator strain of Escherichia coli termed mud for its possible mechanism. The mud strain exhibits a decrease in both spontaneous mutagenesis and mutability with alkylated agents and base analogs. These types of DNA lesions are known to be the substrates for the E. coli methyl-directed mismatch repair encoded by the mutHLSU system. We investigated whether the putative antimutator effect results from the increased expression or activity of the mutHLSU system. To directly measure the mismatch repair capacity of mud cells, we have transfected them with phage lambda heteroduplexes and scored the fraction of mixed (unrepaired) infective centers. This transfection system has been used routinely to assay mismatch repair capacity in E. coli and other organisms. No difference between mud and wild type cells is observed. From the results of the experiments we conclude that the reported antimutator effect of mud does not result from enhanced mismatch repair capacity. This conclusion is consistent with recently published evidence that the mud effect does not represent a real antimutator effect, but is an artifact due to impaired growth of mud cells under certain selective conditions.


Assuntos
Pareamento Incorreto de Bases , Reparo do DNA/genética , Escherichia coli/genética , Mutação , Bacteriófago lambda/genética , Vetores Genéticos , Transformação Genética
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