RESUMO
Aim of the study was to assess the concordance of the thromboprophylactic treatment in patients with nonvalvular atrial fibrillation (nAF) at the time of admission due to ischemic stroke with clinical guidelines of the European Society of Cardiology. METHODS: In the cross-sectional study were included 327 patients [143 (44%) males] treated because of ischemic stroke associated with nAF. The index of the thromboembolic risk (TE) has been established by the CHA2DS2-VASc score, whereas the bleeding risk has been assessed by the HAS-BLED score. RESULTS: Before the ischemic stroke, 98.2% of patients belonged to the group of high TE risk. Among these patients only 179 (55%) were received thromboprophylaxis: 67.5% patients acetylsalicylic acid, 30.5% warfarin, and 4% clopidogrel. Previous ischemic stroke was independently correlated with warfarin administration (OR 2.5; 95% Cl 1.4-4.5; p=0.003), while poorly controlled arterial hypertension was independently correlated with warfarin non-administration (OR 0.47; 95% Cl 0.25-0.88; p=0.019). The 83.7% of 55 patients, who experienced ischemic stroke during anticoagulant treatment, had an INR values lower than therapeutic. CONCLUSION: Thromboprophylaxis among the patients with nAF admitted because of ischemic stroke did not correlate with their TE risk and contemporary guidelines of the European Society of Cardiology.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Hemorragia/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Croácia , Estudos Transversais , Feminino , Hemorragia/induzido quimicamente , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Varfarina/efeitos adversosRESUMO
Gait apraxia is most commonly a part of the Hakimov triad (gait apraxia, urinary incontinence, dementia) in normotensive hydrocephalus (NPH), although it may be a symptom of some other conditions. In our case the patient was a long term Parkinson's disease sufferer who developed normotensive hydrocephalus and consequently gait apraxia. Only after a third successive evacuation of the CSF his gait apraxia improved (Fig. 1, Ref. 15). Full Text (Free, PDF) www.bmj.sk.
Assuntos
Apraxia da Marcha/etiologia , Hidrocefalia de Pressão Normal/complicações , Doença de Parkinson/complicações , Idoso , Encéfalo/patologia , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Doença de Parkinson/patologiaRESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas , Anti-Hipertensivos/uso terapêutico , Hipertensão Portal/prevenção & controle , Hepatopatias Alcoólicas/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Propranolol/uso terapêutico , Proteínas/uso terapêutico , Ranitidina/uso terapêutico , Animais , Hipertensão Portal/tratamento farmacológico , Hepatopatias Alcoólicas/tratamento farmacológico , Masculino , Ratos , Ratos WistarRESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas , Antiulcerosos/farmacologia , Citoproteção , Fragmentos de Peptídeos/farmacologia , Propranolol/farmacologia , Proteínas/farmacologia , Ranitidina/farmacologia , Gastropatias/tratamento farmacológico , Gastropatias/prevenção & controle , Animais , Masculino , Ratos , Ratos Wistar , Gastropatias/etiologia , Fatores de TempoRESUMO
Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.
Assuntos
Antiulcerosos/farmacologia , Antidepressivos/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Estresse Psicológico/tratamento farmacológico , Sequência de Aminoácidos , Animais , Doença Crônica , Avaliação Pré-Clínica de Medicamentos , Feminino , Imobilização , Dados de Sequência Molecular , Ratos , Ratos Endogâmicos F344 , Estresse Psicológico/psicologiaRESUMO
Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either haloperidol or reserpine alone. The failure of dopaminomimetics could be most likely due to more extensive inhibition of endogenous dopamine system activity, and need for remained endogenous dopamine for their salutary effect, whereas the beneficial activities of ranitidine, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems parallel those of dopamine system, and they may function despite extensive inhibition of endogenous dopamine system activity.
Assuntos
Antiulcerosos/uso terapêutico , Atropina/uso terapêutico , Dopamina/fisiologia , Mucosa Gástrica/patologia , Omeprazol/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Ranitidina/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Dopaminérgicos/farmacologia , Antagonistas de Dopamina , Haloperidol , Masculino , Ratos , Ratos Wistar , Reserpina , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologiaRESUMO
A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs, was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cataleptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the present report. Prominent catalepsy, otherwise consistently seen in the mice treated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) and fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1.5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated when pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w., i.p.) was coadministered with the neuroleptic. The number of cataleptic mice was markedly lower throughout most of the experimental period. Moreover, on challenge with lower doses of neuroleptics, catalepsy appearance was postponed and the mice, otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if protected with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the above mentioned doses, reduced not only catalepsy but somatosensory disorientation (for 7.5 h after administration of a neuroleptic, assessed at intervals of 1.5 h, by a simple scoring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it did in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy was absent. In other experiments, considering the gastric origin of this pentadecapeptide, the focus was shifted to the evidence that a dose of haloperidol, cataleptogenic due to dopamine receptors blockade, induces gastric ulcers in rats. Coadministration of pentadecapeptide BPC 157 (10 microg, 10 ng, 1.0 ng, 100 pg/kg b.w., i.p.) to rats completely inhibited the lesions otherwise regularly evident 24 h after haloperidol (5.0 mg/kg b.w., i.p.) in control rats (18 of 20 rats had gastric lesions). This activity accompanied the antagonism of the haloperidol catalepsy in rats (assessed at 60-min intervals from I to 5 h after haloperidol), when 10-microg- or 10-ng regimens were given (lower doses could not influence catalepsy). Together, these findings indicate that pentadecapeptide BPC 157 fully interacts with the dopamine system, both centrally and peripherally, or at least, that BPC 157 interferes with some steps involved in catalepsy and/or ulcer formation.
Assuntos
Catalepsia/prevenção & controle , Flufenazina/toxicidade , Haloperidol/toxicidade , Úlcera Péptica/prevenção & controle , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Animais , Antiulcerosos/síntese química , Antiulcerosos/farmacologia , Antipsicóticos/farmacologia , Catalepsia/induzido quimicamente , Clozapina/farmacologia , Antagonistas de Dopamina/toxicidade , Relação Dose-Resposta a Droga , Interações Medicamentosas , Masculino , Camundongos , Orientação/efeitos dos fármacos , Úlcera Péptica/induzido quimicamente , Fragmentos de Peptídeos/síntese química , Proteínas/síntese química , Ratos , Ratos Wistar , Sulpirida/farmacologia , Fatores de TempoRESUMO
Adaptive cytoprotection in the stomach was originally defined by applying the exogenous irritants only. The contribution of endogenous irritants as inductors of initial lesions was not specially evaluated. No attempt was made to either focus antiulcer agent activity on adaptive cytoprotection, or split their 'cytoprotection' into complex adaptive cytoprotective activity and simple cytoprotective effects. Agents had so far not been applied simultaneously with the second challenge with ethanol (or irritant), when differences between cytoprotection and adaptive cytoprotection appear. Gastrojejunal anastomosis for 24 h in rats was introduced as new model for analyzing cytoprotection/adaptive cytoprotection. The contribution of the up-normal level of endogenous irritants and the endogenous small irritant-induced minor lesions during the adaptive cytoprotection were studied. The effect of late challenge with 96% ethanol in the presence of an up-normal level of endogenous irritants and endogenous small irritant-induced minor lesions was compared with results of classic studies of ethanol-induced gastric lesions in normal rats (1 ml/rat i.g.). Antiulcer agents or a prostaglandins-synthesis inhibitor, indomethacin, given once only in classic studies, were given at several points during injury induction: (i) surgery, (ii) mild ethanol, (iii) strong ethanol, (iv) strong ethanol applied after a suitable period following either mild ethanol or surgery). Their effects were compared in rats treated as follows: exogenous irritant studies (96% or 20% ethanol), exogenous/exogenous irritant studies (20% ethanol 1 h before 96% ethanol), endogenous irritant studies (gastrojejunal anastomosis for 24 h), and endogenous/exogenous irritant studies (gastrojejunal anastomosis for 24 h before 96% ethanol). Characteristic of the various irritants differed: the (preceding) small irritants (exogenous (i.e., mild ethanol in healthy intact rats) (exogenous irritant studies) vs. endogenous (e.g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple 'cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 microg or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events preceding the late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essential link between the various reactions in cytoprotection/adaptive cytoprotection.
Assuntos
Antiulcerosos/farmacologia , Inibidores de Ciclo-Oxigenase/toxicidade , Citoproteção/efeitos dos fármacos , Indometacina/toxicidade , Irritantes/metabolismo , Úlcera Péptica/patologia , Sequência de Aminoácidos , Anastomose Cirúrgica , Animais , Atropina/farmacologia , Relação Dose-Resposta a Droga , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Irritantes/toxicidade , Jejuno , Masculino , Dados de Sequência Molecular , Omeprazol/farmacologia , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Ranitidina/farmacologia , Ratos , Ratos Wistar , EstômagoRESUMO
A novel gastric pentadecapeptide BPC 157 with different beneficial activities and anticonvulsant effect interacting with GABAergic system could improve diazepam efficacy coadministered (10 microg/kg, 10 ng/kg i.p.) with diazepam (5.0 mg/kg i.p.) twice daily for 10 days, since diazepam chronic medication would otherwise predispose for diazepam- tolerance/withdrawal development (shorter latency to convulsion after convulsant). In diazepam chronically treated mice, it attenuated diazepam tolerance (provoked by later acute administration of diazepam together with convulsant) and postponed physical dependence/withdrawal effects (provoked by later administration of isoniazid). In tolerance assay, at 42 h after the end of conditioning regimen, shorter preconvulsive latencies than in healthy (non-diazepam conditioned) mice following isoniazid (800 mg/kg i.p.) (as hallmark of tolerance) were observed if diazepam (5.0 mg/kg i.p.) was again given acutely to mice previously conditioned with diazepam alone (use of picrotoxin 3.0 mg/kg i.p., as convulsant, with acute application of diazepam in previously diazepam conditioned mice did not lead to tolerance hallmark). This was completely avoided in diazepam+BPC 157 10 microg or diazepam+BPC 157 10 ng chronically treated animals. In physical dependence assay (isoniazid challenge assessed at 6, 14, 42 and 72 h after conditioning medication), when compared to diazepam non-conditioned healthy mice, in diazepam conditioned mice residual anticonvulsive activity was not present already at the earliest post-conditioning interval (i.e., not different latency to isoniazid-convulsions), whereas shorter preconvulsive latencies (as physical dependence/withdrawal hallmark) were noted in diazepam conditioned mice following isoniazid challenge at 42 h and at 72 h after end of conditioning treatment. In diazepam+BPC 157 10 microg- conditioned mice, a residual anticonvulsive activity (i.e., longer latency to isoniazid convulsion) was noted at 6 h post-conditioning, whereas shorter preconvulsive latencies appeared only at 72 h-post-conditioning period. In conclusion, taken together these data (lack of tolerance development (tolerance studies), prolonged residual anticonvulsive activity, and postponed physical dependence/withdrawal hallmark in diazepam+BPC 157 chronically treated mice) with common benzodiazepines tolerance/withdrawal knowledge, it could be speculated that BPC 157 acts favoring the natural homeostasis of the GABA receptor complex as well as enhancing the GABAergic transmission, and having a mechanism at least partly different from those involved in diazepam tolerance/withdrawal, it may be likely used in further therapy of diazepam tolerance and withdrawal.
Assuntos
Antiulcerosos/farmacologia , Anticonvulsivantes/farmacologia , Diazepam/farmacologia , Tolerância a Medicamentos , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Sequência de Aminoácidos , Animais , Antiulcerosos/química , Antituberculosos/farmacologia , Química Encefálica/efeitos dos fármacos , Interações Medicamentosas , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Isoniazida/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Picrotoxina/farmacologia , Proteínas/química , Receptores de GABA-A/fisiologia , Síndrome de Abstinência a Substâncias/tratamento farmacológicoRESUMO
A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1 x 1 x 0.25 cm; V = 0.25 mL) with the same quantities of BPC 157 (10 ng x mL(-1), 10 microg x mL(-1), 50 microg x kg(-1)) or reference agents (cimetidine: 10, 100, 500 mg x mL(-1); ranitidine: 2.5, 25, 250 mg x mL(-1); famotidine: 10, 50, 100 mg x mL(-1); omeprazole: 10, 50, 100 mg x mL(-1); sucralfate: 1, 5, 10 mg x mL(-1) were implanted subcutaneously in the lumbar region. The sponges were removed after 3 or 7 d, fixed in formalin, and processed for histologic and histochemical evaluation and morphometry assessment. Compared with the control values, the number of newly formed endothelial spaces inside newly formed granulation tissue was markedly increased in all animals treated with BPC 157, cimetidine, ranitidine, famotidine, sucralfate and omeprazole, a consistent finding noted after either 3 or 7 d. Compared with control values, markedly more granulation tissue was noted in the rats in the groups of animals treated with BPC 157 (50 microg) and in the rats treated with sucralfate in all dosages used, euthanized after 3 d. In all groups treated with H2-blockers however, similar values to those of controls were noted. Thus, it could be concluded that an evident angiogenic property was consistently noted for the novel pentadecapeptide BPC 157, H2-blockers (cimetidine, famotidine and ranitidine) and omeprazole, besides the well known angiogenic effect of sucralfate. Furthermore, unlike H2-blockers and omeprazole, BPC 157 stimulates the formation of granulation tissue, suggesting a particular activity, similar to that previously noted for sucralfate.
Assuntos
Antiulcerosos/farmacologia , Fármacos Gastrointestinais/farmacologia , Tecido de Granulação/efeitos dos fármacos , Antagonistas dos Receptores H2 da Histamina/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Omeprazol/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Sucralfato/farmacologia , Animais , Procedimentos Cirúrgicos Dermatológicos , Tecido de Granulação/patologia , Masculino , Poríferos , Próteses e Implantes , Ratos , Ratos WistarRESUMO
The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP.
Assuntos
Antiulcerosos/farmacologia , Comportamento Animal/efeitos dos fármacos , Doença de Parkinson/patologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Gastropatias/induzido quimicamente , Gastropatias/prevenção & controle , Animais , Temperatura Corporal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Catalepsia/prevenção & controle , Hipotermia/induzido quimicamente , Hipotermia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/mortalidade , Doença de Parkinson/fisiopatologia , Reserpina/farmacologia , Gastropatias/patologiaRESUMO
BACKGROUND AND AIMS: The aim of this study was to provide information on the diagnosis and treatment of kinking -- bends in the extracranial internal carotid artery (KICA), a rate but major and treatable cause of cerebral ischemia. PROJECT: A retrospective review of the seven-year experience in Split Hospital. ESSENTIAL DATA: The role of the surgical correction of carotid artery kinking has not yet been precisely defined. MATERIALS AND METHODS: Of the 86 carotid revascularization operations performed in 76 patients from 1988 to 1994, 21 (29%) patients underwent surgery owing to symptomatic kinking of the internal carotid artery. This group included 8 females and 13 males with a mean age of 57.3+/-5.5 years (range 44-70). Symptoms included cerebrovascular insults in 43%, hemispheric transient ischemic attacks in 33%, reversible ischemic neurological deficit in 24% of patients. The diagnosis was made using two-dimensional ultrasound scan and Doppler, computerised tomography and angiographic evaluation. Two methods were used: the elimination of kinking and graft of the internal artery onto the common carotid artery with excision of the kinked section of the artery and end-to-end anastomosis. Dense fibrous tissues around the kinked artery were removed and the artery was freed along its entire course. The anomalous relationship between the internal carotid artery, occipital artery and hypoglossal nerve was corrected. RESULTS: After surgery seventeen patients fully recovered without neurological complications. One patient died, one patient suffered permanent neurological deficit, two suffered from transient ischemic attacks. CONCLUSIONS: Anatomic reconstruction together with the correction and elimination of the affected segments of the carotid artery may prevent progressive cerebrovascular symptoms and is associated with a low morbidity and mortality rate.
Assuntos
Artéria Carótida Interna/anormalidades , Estenose das Carótidas/cirurgia , Adulto , Idoso , Anastomose Cirúrgica , Angiografia , Velocidade do Fluxo Sanguíneo , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Seguimentos , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia DopplerRESUMO
BACKGROUND: A novel gastric pentadecapeptide, BPC 157, has been shown to attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas, somatosensory neurons). This suggests an interaction with the dopamine system. When used alone, BPC 157 does not affect gross behavior or induce stereotypy. METHODS: We first investigated the effect of pentadecapeptide BPC 157 on stereotypy and acoustic startle response in rats, given as either a prophylactic (10 micrograms/kg i.p.) or therapeutic (10 ng/kg i.p.) regimen, with the dopamine indirect agonist amphetamine (10 mg/kg i.p.). RESULTS: There was a marked attenuation of stereotypic behavior and acoustic startle response. When the medication was given at the time of maximum amphetamine-induced excitability, there was a reversal of this behavior. A further focus was on the effect of this pentadecapeptide on increased climbing behavior in mice pretreated with the dopamine antagonist haloperidol (5.0 mg/kg i.p.), and subsequently treated with amphetamine (20 mg/kg i.p. challenge 1, 2, 4, and 10 days after haloperidol pretreatment). This protocol is usually used for the study of behavioral supersensitivity to the amphetamine stimulating effect. CONCLUSIONS: An almost complete reversal was noted when pentadecapeptide was coadministered with haloperidol. Together, these data provide compelling evidence for the interaction of pentadecapeptide BPC 157 with the dopamine system.
Assuntos
Anfetamina/antagonistas & inibidores , Antiulcerosos/farmacologia , Antagonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/antagonistas & inibidores , Haloperidol/antagonistas & inibidores , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Comportamento Estereotipado/efeitos dos fármacos , Sequência de Aminoácidos , Anfetamina/farmacologia , Animais , Inibidores da Captação de Dopamina/farmacologia , Interações Medicamentosas , Haloperidol/farmacologia , Masculino , Dados de Sequência Molecular , Ratos , Ratos Wistar , Reflexo de Sobressalto/efeitos dos fármacosRESUMO
The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N(G)-nitro-L-arginine methylester (L-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-NAME completely abolished the effect of L-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired L-NAME-blood pressure increase, when applied prophylactically and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME)) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and L-arginine were combined. In summary, BPC 157 could interfere with the effects of NO on both gastric mucosal integrity and blood pressure maintenance in a specific way, especially with L-arginine, having a more prominent and/or particularly different effect from that of NO.
Assuntos
Antiulcerosos/farmacologia , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Animais , Etanol/farmacologia , Mucosa Gástrica/química , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
A superior effectiveness in various lesion assays was noted for the novel pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and claimed to be a cytoprotective agent. From this viewpoint, as a previously untreated experimental improvement to create an acid-free environmental for cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic procedure. In the absence of stomach and gastric acid, the damaging effects of cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10 microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was compared with reference agents [cimetidine (50), ranitidine (10), omeprazole (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before cysteamine] known to be also cytoprotective. In naive rats, with intact stomach, all of them showed a strong beneficial effect. Interestingly, in gastrectomized animals, the application of BPC 157 or the reference agents before cysteamine significantly prevented the otherwise severe duodenal lesion development noted in the control gastrectomized cysteamine rats. In groups without cysteamine, no lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical period), nor was lesion potentiation seen in cysteamine-treated laparotomized animals. In summary, these findings--equal damaging effect of cysteamine and equal protection of pentadecapeptide BPC 157 and reference agents in gastrectomized and rats with intact stomach--seem to be particularly relevant for a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was convincingly defined as an essential gastric acid-independent injury (analogous to ethanol gastric lesions). Likewise, a high "cytoprotective capacity," apparently acid independent, common for all tested agents (novel pentadecapeptide BPC 157, cimetidine, ranitidine, omeprazole and atropine) could be clearly stressed.
Assuntos
Antiulcerosos/farmacologia , Cisteamina/toxicidade , Úlcera Duodenal/prevenção & controle , Gastrectomia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Animais , Atropina/farmacologia , Bromocriptina/farmacologia , Cimetidina/farmacologia , Úlcera Duodenal/induzido quimicamente , Feminino , Omeprazol/farmacologia , Ranitidina/farmacologia , Ratos , Ratos WistarRESUMO
Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10 micrograms/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500 micrograms/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.
Assuntos
Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Úlcera Gástrica/patologia , Fatores Etários , Animais , Animais Recém-Nascidos , Capsaicina/toxicidade , Etanol/toxicidade , Mucosa Gástrica/patologia , Indometacina/toxicidade , Masculino , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Ratos , Ratos Wistar , Restrição Física , Estômago/inervação , Úlcera Gástrica/etiologia , Úlcera Gástrica/fisiopatologia , Úlcera Gástrica/prevenção & controle , Estresse Fisiológico/complicaçõesRESUMO
Nootropics are psychoactive substances that activate, protect and restore functions of the neuronal cells. Piracetam is the first representative of these compounds, often cited to act as an activator and protector of neuronal cells function, especially in hypoxic conditions. Therefore, we examined the effect of piracetam on the cortical neuronal activity in conditions when both carotid arteries have been ligated. We assumed that oligaemia occurred as the result of arterial obstruction and consequent hypoxic state developed. Evoked somatosensory potentials were used as an objective indicator of neuronal cells functional state. Our results demonstrate that the occlusion of both carotid arteries induces the extension of latency and reduction of the amplitude in the somatosensory evoked potentials of the adult cat. Piracetam (100 mg/kg i.v.) improves the evoked potentials returning both, latencies and amplitude to the control values, i.e. as measured before the ligature of arteries has been settled. Regarding a number of papers claiming that piracetam facilitates cholinergic neurotransmitter system, and that the amplitude of the somatosensory evoked potentials is increasing depending on the amount of the acetylcholine released, we think that the effect of piracetam on the evoked potentials during the occlusion of both carotid arteries, registered in our experiments, is mediated through the action of piracetam on the cholinergic system.
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Doenças das Artérias Carótidas/fisiopatologia , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Piracetam/farmacologia , Animais , Gatos , Feminino , MasculinoRESUMO
A single dose of the dopamine agonists L-dopa, bromocriptine or apomorphine produced a protective effect by significantly shortening of the length of stomach ulcerations. A single dose of the dopamine antagonists haloperidol, sulpiride or domperidone potentiated the ulcerogenic effect by extending the length of stomach ulcerations. These results point to the fact that dopamine is involved in the rise and development of experimental stomach ulcers.