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1.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37513963

RESUMO

Recently, stable gastric pentadecapeptide BPC 157 therapy by activation of collateral pathways counteracted various occlusion/occlusion-like syndromes, vascular, and multiorgan failure, and blood pressure disturbances in rats with permanent major vessel occlusion and similar procedures disabling endothelium function. Thereby, we revealed BPC 157 cytoprotective therapy with strong vascular rescuing capabilities in glaucoma therapy. With these capabilities, BPC 157 therapy can recover glaucomatous rats, normalize intraocular pressure, maintain retinal integrity, recover pupil function, recover retinal ischemia, and corneal injuries (i.e., maintained transparency after complete corneal abrasion, corneal ulceration, and counteracted dry eye after lacrimal gland removal or corneal insensitivity). The most important point is that in glaucomatous rats (three of four episcleral veins cauterized) with high intraocular pressure, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, nor- mal retinal and choroidal blood vessel presentation, and normal optic nerve presentation. The one episcleral vein rapidly upgraded to accomplish all functions in glaucomatous rats may correspond with occlusion/occlusion-like syndromes of the activated rescuing collateral pathway (azygos vein direct blood flow delivery). Normalized intraocular pressure in glaucomatous rats corresponded to the counteracted intra-cranial (superior sagittal sinus), portal, and caval hypertension, and aortal hypotension in occlusion/occlusion-like syndromes, were all attenuated/eliminated by BPC 157 therapy. Furthermore, given in other eye disturbances (i.e., retinal ischemia), BPC 157 instantly breaks a noxious chain of events, both at an early stage and an already advanced stage. Thus, we further advocate BPC 157 as a therapeutic agent in ocular disease.

2.
Biomedicines ; 10(12)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36551886

RESUMO

Recently, it was found that when confronted with major vessel occlusion and vascular failure, stable gastric pentadecapeptide BPC 157 therapy might rapidly functionally improve minor vessels to take over the function of disabled major vessels, reorganize blood flow, and compensate failed vessel function. We focused on the BPC 157 therapy effect obtained by giving 10 ng/kg ip to rats 5 min before sacrifice on the rat thoracic aorta, which we assessed with Fourier transform infrared spectroscopy (FTIR) 90 min thereafter. We applied a principal component analysis (PCA). The PCA model showed, with a clear distinction being mostly due to the PC1 score, differences between the spectra of BPC 157- and saline-treated rats. The comparison of the averaged spectra of these two groups with their differential spectrum and PC loadings allowed us to identify the parts of the FTIR spectra that contributed the most to the spectral separation of the two observed groups. The PC1 loadings and the differential spectrum showed that the main bands affecting the separation were the amid I band around 1650 cm-1, the amid II band around 1540 cm-1, and the vibrational band around 1744 cm-1. Fitting the spectral range between 1450 and 1800 cm-1 showed changes in protein conformation and confirmed the appearance of the vibrational band at 1744 cm-1. Controls had a substantially more intense vibrational band at 1744 cm-1. These spectral results showed the cells from saline-treated (control) rats to be in the early stage of cell death, while the samples from BPC 157-rats were protected. Thus, BPC 157 therapy changed the lipid contents and protein secondary structure conformation, with a rapid effect on vessels, within a short time upon application.

3.
Biomedicines ; 10(7)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35884767

RESUMO

We attempted throughout the NO-system to achieve the particular counteraction of the ketamine-induced resembling "negative-like" schizophrenia symptoms in rats using pentadecapeptide BPC 157, and NO-agents, NG-nitro-L-arginine methylester (L-NAME), and/or L-arginine, triple application. This might be the find out the NO-system organized therapy (i.e., simultaneously implied NO-system blockade (L-NAME) vs. NO-system over-stimulation (L-arginine) vs. NO-system immobilization (L-NAME+L-arginine)). The ketamine regimen (intraperitoneally/kg) included: 3 mg (cognitive dysfunction, novel object recognition test), 30 mg (anxiogenic effect (open field test) and anhedonia (sucrose test)), and 8 mg/3 days (social withdrawal). Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), and BPC 157 (0.01), alone and/or together, given immediately before ketamine (L-NAME, L-arginine, and combination) or given immediately after (BPC 157 and combinations). BPC 157 counteracted ketamine-cognition dysfunction, social withdrawal, and anhedonia, and exerted additional anxiolytic effect. L-NAME (antagonization, social withdrawal) and L-arginine (antagonization, cognitive dysfunction, anhedonia) both included worsening cognitive dysfunction, anhedonia, and anxiogenic effect (L-NAME), social withdrawal, and anxiogenic effect (L-arginine). Thus, ketamine-induced resembling "negative-like" schizophrenia symptoms were "L-NAME non-responsive, L-arginine responsive" (cognition dysfunction), "L-NAME responsive, L-arginine non-responsive" (social withdrawal), "L-NAME responsive, L-arginine responsive, opposite effect" (anhedonia) and "L-NAME responsive, L-arginine responsive, parallel effect" (both anxiogening). In cognition dysfunction, BPC 157 overwhelmed NO-agents effects. The mRNA expression studies in brain tissue evidenced considerable overlapping of gene overexpression in healthy rats treated with ketamine or BPC 157. With the BPC 157 therapy applied immediately after ketamine, the effect on Nos1, Nos2, Plcg1, Prkcg, and Ptgs2 (increased or decreased expression), appeared as a timely specific BPC 157 effect on ketamine-specific targets.

4.
Acta Stomatol Croat ; 56(4): 376-386, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36713271

RESUMO

Objective: The aim of this study was to examine the satisfaction of parents and caregivers of patients who underwent dental treatment in general anesthesia (GA) in a day-care surgery setting. Material and Methods: Anonymous questionnaire was sent to parents/caregivers of patients who underwent full mouth restoration in GA. The survey consisted of 4 parts: general data, data about procedure, satisfaction with various aspects of care and the perception of parents/caregivers about the condition of their child in relation to the time before dental treatment in GA. Results: 66 parents/caregivers (30.5%) responded to the questionnaire. Overall satisfaction with the treatment was high (4.69). Respondents expressed the highest degree of satisfaction with communication with nurses (4.92), and the lowest with the waiting time for the procedure (3.89). Parents/caregivers of patients who reported difficulty eating expressed significantly lower overall satisfaction than the subjects whose children did not report difficulty eating. Also, the more treatments the patients underwent, the lower was the overall satisfaction than of those subjects whose children were never treated in such a manner before. Conclusions: Since patient satisfaction has a beneficial impact on treatment outcome and adherence to preventive recommendations, all health care providers should strive to achieve it.

5.
Acta Stomatol Croat ; 55(2): 168-176, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34248150

RESUMO

OBJECTIVE: To review the frequency and management of post-discharge complications in patients who underwent dental treatment in general anesthesia (GA) in a day-care surgery setting and identify the factors that increase the risk for these complications. MATERIAL AND METHODS: Anonymous questionnaire was sent to parents/caregivers of patients who underwent full mouth restoration in GA at our institution between 1st January 2017 and 31st July 2019. Demographic and clinical data of patients as well as the data about the occurrence and management of complications were collected. RESULTS: Sixty-six parents/caregivers (30.5%) responded to the questionnaire. Most frequent complications were drowsiness and pain in 40(60.6%) patients. Complications were managed by parents or caregivers with conservative measures at home in 57(91.9%) cases. Phone consultation with dentist was required in 5(8.1%) cases. One patient (1.6%) was readmitted. Younger age and diagnosis were associated with increased risk for drowsiness. CONCLUSION: Post discharge complications of dental treatment in GA in a day-care service are common and they can be managed by parent/caregiver with conservative measures at home. The rate of readmission is low. Dental treatment in GA in a day-care service is a safe procedure that can be performed with acceptable risk in carefully selected patients.

6.
Emerg Med Int ; 2020: 6805354, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566305

RESUMO

Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other's response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.

7.
Acta Clin Croat ; 59(3): 394-406, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34177048

RESUMO

We focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 µg/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other's effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics.


Assuntos
Óxido Nítrico , Tetracaína , Anestesia Local , Animais , Humanos , NG-Nitroarginina Metil Éster , Fragmentos de Peptídeos , Procaína/análogos & derivados , Proteínas , Ratos , Ratos Wistar
8.
World Neurosurg ; 129: 242-244, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207372

RESUMO

BACKGROUND: Acute stent thrombosis is a rare adverse event following endovascular treatment of carotid artery. Experience on the topic is scarce, making the therapeutic approach a clinical challenge. In cases of intraprocedural acute carotid stent thrombosis, thromboaspiration, thrombectomy, and thrombolysis have been used as successful modalities for achieving recanalization. CASE DESCRIPTION: We describe a case of carotid artery dissection treated endovascularly and complicated by intraprocedural stent thrombosis, which was ultimately managed by emergent extracranial-intracranial bypass with radial artery graft connecting the external carotid artery to the ipsilateral middle cerebral artery. CONCLUSIONS: Neurosurgical management may represent a rescue option for otherwise unmanageable acute carotid stent thrombosis.


Assuntos
Trombose das Artérias Carótidas/etiologia , Estenose das Carótidas/cirurgia , Revascularização Cerebral/métodos , Procedimentos Endovasculares/efeitos adversos , Complicações Intraoperatórias/cirurgia , Stents/efeitos adversos , Trombose das Artérias Carótidas/cirurgia , Procedimentos Endovasculares/métodos , Humanos , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade
9.
Acta Stomatol Croat ; 53(1): 64-71, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31118534

RESUMO

OBJECTIVE: To analyze data on full-mouth rehabilitation under general anesthesia (GA) performed at the University Clinical Hospital Zagreb with emphasis on patient characteristics, type of procedure and postoperative complications. MATERIALS AND METHODS: Retrospective chart review of 100 patients treated under GA at the Dental clinic's day care surgery. Patient's demographic (sex, age) and clinical data (diagnosis, GA technique, intubation type, procedure duration, number of carious teeth, presence of visible calculus, number of sealed teeth, fillings, extractions and endodontic treatments, discharge time, postoperative complications) were registered. RESULTS: Eighty patients were treated under GA because of noncompliance due to different reasons and twenty patients because of either their poor physical condition or extensive dental procedure. Median DMFT per patient was 9(0-21). Eighty nine patients underwent full-mouth dental restoration and 11 patients underwent other types of procedures. Ninety-six patients were safely discharged the same day. Four patients experienced postoperative complications and three of them were hospitalized for another 24-48 hours for postoperative follow-up. CONCLUSION: Patients with physical and/or intellectual disabilities have higher caries activity and increased dental treatment needs compared to the general population. Dental treatment under GA in day care service is a safe and effective way of providing dental care for noncompliant patients.

10.
Surg Neurol Int ; 9: 200, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386670

RESUMO

BACKGROUND: Etomidate may be given in continuous infusion for maintenance of general anesthesia, although that practice is rarely seen due to beliefs that it has possibility of interfering with cortisol synthesis. However, etomidate is sometimes preferable choice as it has least influence on hemodynamics and rarely causes allergic reactions. CASE DESCRIPTION: We describe a case of 13-year-old boy with aneurysm of left middle cerebral artery, planned for aneurysmal clipping, and previously treated for ruptured aneurysm of right middle cerebral artery. As he was tested and proved allergic to most of the anesthetic drugs, and stable hemodynamic conditions were of most importance during planned neurosurgery, general anesthesia was maintained with etomidate infusion. He was prepared with metilprednisolon, antihistaminic, and ranitidine before the surgery. Cortisol and adrenocorticotropic hormone levels were measured on three consecutive postoperative days. Only cortisol value, in the morning the day after the surgery, was below reference range, with the values back to normal until that evening. He was dismissed from the intensive care unit with Glasgow Coma Score 15. CONCLUSION: Etomidate may be a choice for neuroanesthesia in specific group of people. We have good experience with our algorithm for continuous infusion of etomidate, with serum cortisol values in the reference range, if corticosteroids were not given before the surgery. Administration of metilprednisolon may diminish influence of perioperative stress on cortisol synthesis inhibition.

11.
Asian J Neurosurg ; 13(3): 938-942, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30283588

RESUMO

Despite growing popularity of endovascular techniques, certain subsets of patients with cerebrovascular compromise may benefit from bypass surgery. We present four cases in which pending ischemic lesion was prevented by (1) A3 resection and reanastomosis following falx meningioma removal, (2) rescue superficial temporal artery-middle cerebral artery (STA-MCA) bypass after pituitary adenoma surgery, (3) STA-MCA bypass for chronic internal carotid artery occlusion, and (4) external carotid artery-MCA bypass using radial artery grafting. Following the procedure, there were no further clinical or radiological deteriorations and long-term patency was confirmed in all four cases.

12.
Surg Neurol Int ; 9: 46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29541487

RESUMO

BACKGROUND: Low brain tissue oxygen tension (PbtO2), or brain hypoxia, is an independent predictor of poor outcome. Increasing inspirational fraction of oxygen could have a significant influence on treating lower PbtO2. Combined PbtO2 therapy, compared to the approach that focus only on regulation of cerebral perfusion pressure and intracranial pressure, shows better patient outcomes. Monitoring of PbtO2 could be helpful in individualizing treatment, preventing or limiting secondary brain injury, and maintaining better patient outcome. CASE DESCRIPTION: We present a case of a patient with subarachnoidal hemorrhage to whom PbtO2 monitor was implanted, and normobaric hyperoxia treatment was adjusted according to PbtO2 measurement. The patient progressively recovered and was dismissed with Glasgow Coma Score 4/5/6. CONCLUSION: The use of PbtO2 monitoring may be useful for monitoring the local tissue values that are useful for induction of normobaric hyperoxia and optimizing the therapy toward more target-defined values. It is an important part of multimodal neuromonitoring, and is the gold standard for brain oxygenation monitoring that can lead to better patient outcome.

14.
World Neurosurg ; 103: 952.e5-952.e9, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28435115

RESUMO

BACKGROUND: In some cases when risk of occlusion of a blood vessel is greater than risk of bleeding when patients undergo urgent or unplanned bypass during neurosurgery, the use of eptifibatide may be an option. We describe 2 patients who underwent arterial bypass in whom eptifibatide was used successfully intraoperatively during neurosurgery for prevention of bypass occlusion. CASE DESCRIPTION: The first patient presented with a right middle cerebral artery (MCA) aneurysm with subocclusive stenosis of the M1 branch. After right-sided osteoplastic frontotemporal craniotomy, the MCA bifurcation was exposed with a bifurcational 6-mm aneurysm with a wide neck. Prebifurcation stenosis was found, with yellow calcification of the vessel wall, and postbifurcation calcification was found on the upper M2 branch. Superficial temporal artery-MCA bypass and occlusion of the MCA aneurysm was done. Before the bypass, continuous intravenous infusion of eptifibatide 1 µg/kg/minute was administered. The patient recovered normally without hemorrhage or neurologic deficit. The second patient presented with a left-sided lateral sphenoid wing meningioma. Left-sided frontotemporal craniotomy was performed, and the tumor was completely removed from the arachnoid layer. The temporal M3 branch was invaded by the meningioma. As there was no flow through the invaded segment of the aforementioned artery, termino-terminal M3 arterial anastomosis was done. Continuous intravenous infusion of eptifibatide 1 µg/kg/minute was administered. Indocyanine green angiography showed normal flow through the anastomosis, and the patient recovered normally. CONCLUSIONS: Future studies are needed to test the safety and potential efficacy of eptifibatide in intraoperative settings.


Assuntos
Revascularização Cerebral/métodos , Aneurisma Intracraniano/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Artéria Cerebral Média/cirurgia , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Osso Esfenoide/cirurgia , Artérias Temporais/cirurgia , Idoso , Anastomose Cirúrgica , Angiografia Digital , Angiografia Cerebral , Constrição Patológica , Eptifibatida , Humanos , Infusões Intravenosas , Aneurisma Intracraniano/diagnóstico por imagem , Cuidados Intraoperatórios/métodos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Osso Esfenoide/diagnóstico por imagem
15.
Inflammopharmacology ; 25(4): 439-449, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28210905

RESUMO

AIM: Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects. MAIN METHODS: Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV. KEY FINDINGS: L-NAME + magnesium-rats and L-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, L-NAME + L-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by L-NAME or L-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro. SIGNIFICANCE: BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both L-NAME and L-arginine to affect the same events adversely. These events were also opposed by BPC 157.


Assuntos
Arginina/administração & dosagem , Sulfato de Magnésio/sangue , Sulfato de Magnésio/toxicidade , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/antagonistas & inibidores , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Sequência de Aminoácidos , Animais , Antiulcerosos/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Células HEK293 , Humanos , Masculino , Debilidade Muscular/sangue , Debilidade Muscular/tratamento farmacológico , Ratos , Ratos Wistar
16.
Eur J Pharmacol ; 793: 56-65, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27815173

RESUMO

Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Most importantly, BPC 157 successfully prevents and counteracts bupivacaine cardiotoxicity; BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with bupivacaine (100mg/kg IP) exhibited bradycardia, AV-block, ventricular ectopies, ventricular tachycardia, T-wave elevation and asystole. All of the fatalities had developed T-wave elevation, high-degree AV-block, respiratory arrest and asystole. These were largely counteracted by BPC 157 administration (50µg/kg, 10µg/kg, 10ng/kg, or 10pg/kg IP) given 30min before or 1min after the bupivacaine injection. When BPC 157 was given 6min after bupivacaine administration, and after the development of prolonged QRS intervals (20ms), the fatal outcome was markedly postponed. Additionally, the effect of bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells. Bupivacaine (1mM) alone caused depolarization of the cells, while in combination with BPC 157 (1µm), the bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide BPC 157 should be a potential antidote for bupivacaine cardiotoxicity.


Assuntos
Bupivacaína/toxicidade , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Proteínas/química , Proteínas/farmacologia , Estômago/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Eletrocardiografia/efeitos dos fármacos , Células HEK293 , Coração/efeitos dos fármacos , Coração/fisiologia , Humanos , Canais Iônicos/metabolismo , Masculino , Estabilidade Proteica , Ratos , Ratos Wistar
17.
Eur J Pharmacol ; 781: 83-91, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27060013

RESUMO

After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Succinilcolina/antagonistas & inibidores , Succinilcolina/farmacologia , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Relação Dose-Resposta a Droga , Hiperpotassemia/complicações , Hiperpotassemia/fisiopatologia , Resposta de Imobilidade Tônica/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Paralisia/complicações , Agitação Psicomotora/complicações , Ratos , Ratos Wistar
18.
Inflammopharmacology ; 23(6): 329-36, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26563892

RESUMO

AIM: We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157. MAIN METHODS: (1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 µg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 µg/kg), L-NAME (10 mg/kg) and L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L-arginine, alone and/or combined, were applied at 20 min before thiopental. KEY FINDINGS: (1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 µg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose-response curve to the right. (2) L-NAME-L-arginine-BPC 157 interrelations: L-NAME: Thiopental-induced anaesthesia duration was tripled. L-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with L-NAME or BPC 157: potentiating effects of L-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L-NAME: Potentiating effects of L-NAME were abolished. BPC 157 and L-NAME and L-arginine: BPC 157 +L-NAME +L-arginine rats exhibited values close to those in BPC 157 rats. SIGNIFICANCE: Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction) and L-arginine (interference with L-NAME and BPC 157).


Assuntos
Anestésicos Gerais/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Tiopental/farmacologia , Anestesia/métodos , Animais , Antiulcerosos/farmacologia , Arginina/metabolismo , Sinergismo Farmacológico , Masculino , Ratos , Ratos Wistar
19.
Coll Antropol ; 38(2): 665-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25145004

RESUMO

Intravascular device infections could be serious complications with significant contributable morbidity and mortality. The aim of this prospective clinical study is to demonstrate the infection rate related to peripheral arterial catheters and their clinical significance in neurosurgical intensive care unit (ICU) patients. After removal, all arterial catheter tips were cultivated by semiquantitative method and clinical data were collected. During a period of two years, 186 arterial catheters were placed in 105 neurosurgical ICU patients. In 6 cases (3.2%) infection was presumably related to the arterial catheter. The rate of such probable catheter related infections was found to be 5/1000 catheter days. The isolated microorganisms were: Methicillin resistant Staphylococcus epidermidis (MRSE) in 4 cases, Corynebacterium species and Candida albicans each in one case respectively. Thirteen cases (7.0%) were interpreted as contamination and one as colonization. An association was found between the presence of infection from different sources and significant bacterial growth on the catheter. Patients with positive catheter culture had a significantly longer ICU stay, more cumulative catheter days, and a higher mortality rate than those with sterile catheters. We can conclude that the rate of probable peripheral arterial catheter related infection is low. A higher mortality rate in patients who experienced probable catheter related infection does not seem to be a consequence of the aforementioned infection. A more suitable explanation would be that patients with nosocomial infections and higher mortality risk have prolonged ICU stays. There is an increased chance of developing a catheter related infection in those patients who have more cumulative catheter days.


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Infecção Hospitalar/epidemiologia , Unidades de Terapia Intensiva , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Eur J Pharmacol ; 727: 75-9, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24486708

RESUMO

Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone.


Assuntos
Anafilaxia/prevenção & controle , Antialérgicos/farmacologia , Dextranos , Clara de Ovo , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Administração Intravenosa , Anafilaxia/induzido quimicamente , Animais , Cimetidina/farmacologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/prevenção & controle , Etilenodiaminas/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Masculino , Camundongos , Ratos Wistar , Fatores de Tempo
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