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1.
Scand J Gastroenterol ; 55(12): 1454-1466, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33142068

RESUMO

OBJECTIVES: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota. METHODS: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors. RESULTS: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p = .038) and eight weeks (p = .038), indigestion at eight (p = .045) and 12 weeks (p = .006), disease-related worries at four (p = .027) and eight weeks (p = .027), and quality of life at six months (p = .009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed. CONCLUSIONS: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.


Assuntos
Colite Colagenosa , Colite Ulcerativa , Microbiota , Colite Colagenosa/terapia , Fezes , Humanos , Projetos Piloto , Qualidade de Vida
2.
Orv Hetil ; 158(27): 1051-1057, 2017 Jul.
Artigo em Húngaro | MEDLINE | ID: mdl-28670984

RESUMO

INTRODUCTION AND AIM: The aim was to study the patients' adherence to some evidence-based medication (statins, beta blockers, platelet and RAS inhibitors) after suffering a myocardial infarction, and its impact on the outcome. METHOD: Retrospective observational cohort study was carried out from the data of the Hungarian Myocardial Infarction Registry between January 1, 2013, and December 31, 2014. 14,843 patients were alive at the end of hospital treatment, from them, those who had no myocardial infarction or death until 180 days were followed for one year. The adherence was defined as the proportion of time from the index event to the endpoint (or censoring) covered with prescription fillings. The endpoint was defined as death or reinfarction. Information on filling prescriptions for statins, platelet aggregation inhibitors, beta blockers and ARB/ACEI-inhibitors were obtained. Multivariate regression was used to model adherence and survival time. RESULTS: Good adherence (\>80%) to clopidogrel, statins, beta blockers, aspirin and ARB/ACEI was found in 64.9%, 54.4%, 36.5%, 31.7% and 64.0%, respectively. Patients treated with PCI during the index hospitalization had higher adherence to all medication (all p<0.01), except for beta-blocker (p = 0.484). Multivariate analysis confirmed that adherence to statins, to clopidogrel and ARB/ACEI-inhibitors was associated with 10.1% (p<0.0001), 10.4% (p = 0.0002) and 15.8% (p<0.0001) lower hazard of endpoint respectively for 25% points increase in adherence, controlling for age, sex, performing of PCI, 5 anamnestic data and date of index event. Adherence to aspirin and beta blockers was not significantly associated with the hazard. CONCLUSION: Higher adherence to some evidence-based medications was found to be associated with improved long term prognosis of the patients. Orv Hetil. 2017; 158(27): 1051-1057.


Assuntos
Adesão à Medicação/estatística & dados numéricos , Infarto do Miocárdio/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Sistema de Registros , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Coortes , Hungria/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/epidemiologia , Prognóstico , Análise de Regressão , Estudos Retrospectivos
3.
Orv Hetil ; 158(3): 90-93, 2017 Jan.
Artigo em Húngaro | MEDLINE | ID: mdl-28110568

RESUMO

The authors summarize the most relevant data of myocardial infarction patients according to the National Myocardial Infarction Registry data base. In 2015 12,681 patients had 12,941 acute myocardial infarctions. Less than half of patients (44.4%) were treated with ST elevation myocardial infarction. National Ambulance Service was the first medical contact of more than half (51.4%) of patients with ST elevation infarction. Prehospital thrombolysis was occasionally done (0.23%), but 91.6% of the patients were treated in hospital with invasive facilities. The median of the ischaemic time (time between onset of symptoms and arrival at the invasive laboratory) was 223 minutes. Most of the patients (94%) with positive coronary arteriography were treated with percutaneous coronary intervention. The 30 day mortality of the whole group was 12.8% vs. 8.6% of patients treated with an invasive procedure. CONCLUSION: comparing the national and international registry data we conclude that we should analyse and decrease the prehospital delay time to improve the patient care in Hungary. Orv. Hetil., 2017, 158(3), 90-93.


Assuntos
Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Sistema de Registros/normas , Terapia Trombolítica/estatística & dados numéricos , Adulto , Idoso , Angioplastia Coronária com Balão/estatística & dados numéricos , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hungria/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
4.
J Thromb Thrombolysis ; 41(3): 522-4, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26305043

RESUMO

A 71-year old female patient with inferior ST-elevation myocardial infarction underwent primary percutaneous coronary intervention (PCI) within 3 h of symptom onset. She was preloaded with 300 mg aspirin and 600 mg clopidogrel before PCI. Coronary angiogram showed occlusion of the right coronary artery. During PCI, eptifibatide was initiated due to the large thrombus burden. Few hours after the procedure, on eptifibatide infusion, a severe drop in platelet count was observed (from 210,000/µl to 35,000/µl) and the infusion was discontinued. One hour later, still under eptifibatide effect and with severe thrombocytopenia, acute stent thrombosis developed. Lack of prior heparin exposure, quick onset of thrombocytopenia made heparin induced thrombocytopenia improbable that was later excluded by specific immunoassay. However, platelet function testing suggested that eptifibatide induced thrombocytopenia was mediated by activating autoantibodies since platelet reactivity was paradoxically very high at the time of stent thrombosis but decreased radically with eptifibatide washout. The patient was successfully managed without further complications on the basis of platelet function data obtained in the subsequent days. This rare subtype of thrombocytopenia highlights that not only platelet count but also platelet function should be closely monitored in case of severe thrombocytopenia to better balance bleeding and thrombosis.


Assuntos
Peptídeos/efeitos adversos , Stents/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Doença Aguda , Idoso , Eptifibatida , Humanos , Peptídeos/administração & dosagem
5.
J Cardiovasc Med (Hagerstown) ; 22(6): 459-468, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941327

RESUMO

AIMS: After enhancing the survivorship of cancers, the impact of cardiovascular diseases on mortality is increasing among cancer patients. However, anticancer therapies pose a higher cardiovascular risk to patients. As prevention against cancer therapy-induced cardiomyopathy has yet to be explored, the preventive ability of concomitant cardiovascular medications against incident heart failure was assessed. METHODS: A retrospective, population-based study was run using anonymized integration of healthcare databases. All the Hungarian patients diagnosed with breast or colorectal carcinoma and undergoing chemotherapy or biological therapy were analysed. Participants were not treated with any anticancer therapy nor suffered from heart failure/dilated cardiomyopathy during the preceding observational period (≥6.5 years). The heart failure endpoint was established by I50 International Classification of Diseases codes upon discharge from hospital or issuance of an autopsy report. RESULTS: Among the 9575 patients who were enrolled, the cumulative incidence of heart failure over 4 years was 6.9%. The time until the first heart failure event in the propensity score-matched treated and untreated groups was compared using Cox proportional-hazards models. A significant association between lower heart failure risk and concomitant statin therapy was observed (hazard ratio: 0.748, P = 0.038); the preventive ability was more pronounced in the anthracycline/capecitabine/platinum-treated subgroup (hazard ratio: 0.660, P = 0.032). For angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy, a significantly lower heart failure risk was also observed (hazard ratio: 0.809, P = 0.032). Among beta blockers, nebivolol administered to anthracycline/capecitabine-treated patients was associated with a nonsignificant trend to lower heart failure risk (hazard ratio: 0.584, P = 0.069). CONCLUSION: Only concomitant statin and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapies were associated with significantly lower risk of anticancer therapy-related heart failure.


Assuntos
Antineoplásicos , Cardiomiopatias , Fármacos Cardiovasculares , Insuficiência Cardíaca , Neoplasias , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico , Cardiomiopatias/prevenção & controle , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Fármacos Cardiovasculares/classificação , Fármacos Cardiovasculares/uso terapêutico , Bases de Dados Factuais , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Hungria/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Proteção , Estudos Retrospectivos , Risco Ajustado/métodos
6.
Magn Reson Chem ; 48(5): 386-91, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20205207

RESUMO

Three new natural ecdysteroids viz. 22-dehydro-20-deoxy-ajugasterone C (1), 1-hydroxy-22-deoxy-20,21-didehydro-ecdysone (2) and 22-deoxy-20,21-didehydro-ecdysone (3) were isolated from the methanol extract of the roots of Serratula wolffii. The structures of compounds 1-3 were established by various spectroscopic techniques, including one- and two-dimensional NMR, circular dichroism and mass spectroscopic methods.


Assuntos
Asteraceae/química , Ecdisteroides/química , Raízes de Plantas/química , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta
7.
Orv Hetil ; 161(26): 1094-1102, 2020 06.
Artigo em Húngaro | MEDLINE | ID: mdl-32541088

RESUMO

INTRODUCTION: The incidence of dilated cardiomyopathy after anthracycline chemotherapy is mainly influenced by anthracycline cumulative dose. Previous researches showed doxorubicin treatment under cumulative dose of 450 mg/m2 associated with a low incidence of heart failure. Nowadays, doxorubicin is administered with a lower dose, the development of heart failure is largely determined by other factors. AIM: Our purpose was to identify the risk factors for heart failure due to doxorubicin therapy. METHOD: With the use of the Hungarian financial healthcare databases merged with the National Cancer Registry, we performed a retrospective study. All the patients having confirmation for breast carcinoma between 2004 and 2015 were enrolled. The subjects with a preceding period characterized by any chemotherapy or diagnoses suggesting heart failure were excluded. Heart failure outcome event was defined by the assignment of I50 diagnosis code at hospital discharge or in autopsy reports. STATISTICAL ANALYSIS: We used multivariate binary logistic regression to calculate odds ratios for heart failure. Besides the baseline characteristics, oncological state and cumulative doses of the chemotherapies were also taken into account. RESULTS: Among the analysed 3288, doxorubicin-treated patients, heart failure cumulative incidence was 6.2%. Doxorubicin cumulative dose over 400 mg/m2 increased the risk. The heart failure incidence was essentially influenced by age, even over 50 years the risk rose. Diabetes mellitus and the treatments with pyrimidine-analogues, carboplatin or bevacizumab were also associated with higher risk. CONCLUSION: By the integration of national financial and clinical databases, we could identify the risk factors for doxorubicin-associated heart failure. Orv Hetil. 2020; 161(26): 1094-1102.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Hungria , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
8.
Int J Oncol ; 34(4): 995-1003, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19287956

RESUMO

The immunosuppressant cyclosporine A (CsA) is a specific pharmacological inhibitor of calcineurin, the Ca2+-calmodulin activated phospho-Ser/Thr-specific protein phosphatase. Although calcineurin-inhibiting compounds are applied for local treatment of psoriasis or atopic dermatitis in dermatological practice, little is known about the functions of calcineurin in epidermis-derived malignancies. We investigated the effects of CsA on two human melanoma cell lines, the metastasis forming HT168 and WM35 established from an RGP primary lesion. CsA of 2 microM lowered the enzyme activity by 50% and caused elevation in both mRNA and protein expression of calcineurin. Cell proliferation was diminished, as well as the cellular morphology and the actin organization were altered in both cell lines. CsA increased cell death moderately in both cell lines and reduced the metabolic activity of HT168 cells, but not that of WM35 cells. CsA also elevated the expressions of both Bcl-2 and ERK1/2. Fibronectin guided migration of HT168 cells was stimulated under the effect of CsA, while that of WM35 cells was reduced, moreover, HT168 cells switched from the expression of beta3 to beta1 integrin, but WM35 cells continued to express beta3. Based on our results we propose a multiple, partly malignancy-dependent role of calcineurin in these melanoma cell lines.


Assuntos
Inibidores de Calcineurina , Ciclosporina/farmacologia , Regulação Neoplásica da Expressão Gênica , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Apoptose , Cálcio/química , Cálcio/metabolismo , Calmodulina/química , Linhagem Celular Tumoral , Proliferação de Células , Citosol/metabolismo , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Psoríase/metabolismo , RNA Mensageiro/metabolismo
9.
Anal Bioanal Chem ; 394(8): 2105-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19578835

RESUMO

A three-step gradient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the separation of dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), its three C7-oxidized metabolites (7alphaOH-DHEA, 7betaOH-DHEA, 7-keto-DHEA), and its biosynthetic congeners (androstenedione, testosterone, estradiol, pregnenolone). This new method allows the quantitative characterization of DHEA metabolism and biosynthetic transformation under given physiological, pathological, or therapeutically influenced circumstances. Tetrahydrofuran probably acts as a proton acceptor coadsorbent, while isopropanol behaves as a proton donor during the separation of testosterone, estradiol, and the stereoisomers of 7-OH-DHEA.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Desidroepiandrosterona/análise , Desidroepiandrosterona/metabolismo , Desidroepiandrosterona/isolamento & purificação , Furanos , Sensibilidade e Especificidade
10.
Brain Res Bull ; 75(2-4): 371-4, 2008 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-18331900

RESUMO

The aim of this study was to investigate whether primary vestibular afferent fibers establish direct connections with the motor and sensory trigeminal system in the brainstem of the frog. The experiments were carried out on Rana esculenta. In anaesthetized animals the trigeminal and vestibular nerves were prepared, and their proximal stumps were labeled either with fluorescein binding dextran amine (trigeminal nerve) or tetramethylrhodamine dextran amine (vestibulocochlear nerve). With a confocal laser scanning microscope we could detect close connections between the vestibular fibers and branches of the dorsal dendritic array of the jaw-closing motoneurons, suggestive of monosynaptic contacts. In the other parts of the brainstem, vestibular terminals were detected in the termination areas of the mesencephalic trigeminal nucleus and of the Gasserian (Vth) ganglion and they were probably involved in polysynaptic connections. In agreement with the results obtained in mammalian species, the present findings suggest that the vestibulotrigeminal relationship is quite complex and uses multiple pathways to connect the vestibular apparatus with the motor and sensory nuclei of the trigeminal nerve in the anurans as well.


Assuntos
Rana esculenta/anatomia & histologia , Núcleos do Trigêmeo/anatomia & histologia , Vestíbulo do Labirinto/anatomia & histologia , Animais , Dextranos/metabolismo , Fluoresceínas/metabolismo , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Núcleos do Trigêmeo/metabolismo , Vestíbulo do Labirinto/metabolismo
11.
Brain Res Bull ; 75(2-4): 414-8, 2008 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-18331908

RESUMO

One major component of the extracellular matrix is hyaluronan (HA) which is thought to play a crucial role in the development of different organs including the central nervous system (CNS). HA is bound by specific receptors, CD44 and RHAMM, depending on cell types of CNS. However, data are lacking on the relation of HA to different cell populations in developing CNS. To provide new data about the co-localization of HA with the various cellular structures of the developing spinal cord, we studied the distribution pattern of hyaluronan in chicken embryos at Hamburger-Hamilton (HH) stages 8-39. A biotinylated HA-binding complex was used in combination with immunohistochemistry for proliferating and differentiating neurons. The intensity of the HA signal was determined by digital densitometry from histological sections. We found three mediolaterally oriented layers in the HA distribution pattern in stage HH23: (1) a moderate HA signal was detected in the ventricular zone; (2) strong HA accumulation was measured around Lim1,2-expressing cells (differentiating neurons) and early MNR2-expressing neurons (early motoneurons), corresponding to the intermediate zone; (3) a strong pericellular HA reaction was found around the neurons of the marginal zone. Interestingly, the peripheral nerves did not show HA signals. These findings suggest a crucial role of HA during neuronal development. We propose that HA may be involved in cell migration and axonal growth in the developing spinal cord.


Assuntos
Diferenciação Celular/fisiologia , Embrião de Galinha/anatomia & histologia , Ácido Hialurônico/metabolismo , Neurônios/metabolismo , Medula Espinal/citologia , Fatores Etários , Animais , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Proteínas de Membrana/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Medula Espinal/embriologia
12.
Brain Res Bull ; 75(2-4): 419-23, 2008 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-18331909

RESUMO

Gaze fixation requires very fast movements of the eye during body displacement. The morphological and physiological background of the very fine and continuous tuning of gaze fixation is not yet fully understood. In a previous study we have shown that the dendrites of oculomotor neurons form bundles which invade the trochlear nucleus, and vice versa, trochlear dendritic bundles invade the oculomotor nucleus. Earlier physiological observations demonstrating electrotonic coupling between dendrites of spinal motoneurons in the frog suggest a similar mechanism between the oculomotor and trochlear motoneurons. We studied a possible morphological basis of gaze fixation. The experiments were carried out on common water frogs, Rana esculenta. The trochlear and oculomotor nerves were cut, and their proximal stumps were labeled simultaneously with different retrograde fluorescent tracers. Using confocal laser scanning microscope we detected a large number of close contacts in both nuclei, the majority of them were dendrodendritic apposition. The distance between the adjacent profiles suggested close membrane appositions without intercalating glial or neuronal elements. At the ultrastructural level, the dendrodendritic and dendrosomatic contacts did not show any morphological specialization; the long membrane appositions may provide ephaptic interactions between the neighboring profiles. This electrotonic coupling between the oculomotor and trochlear nerve motoneurons may promote the co-activation of the muscles responsible for vertical eye movements.


Assuntos
Anuros/anatomia & histologia , Axônios/fisiologia , Tronco Encefálico/citologia , Dendritos/fisiologia , Junções Comunicantes/fisiologia , Neurônios Motores/citologia , Animais , Axônios/ultraestrutura , Dendritos/ultraestrutura , Dextranos/metabolismo , Fluoresceínas/metabolismo , Junções Comunicantes/metabolismo , Junções Comunicantes/ultraestrutura , Nervo Oculomotor/fisiologia , Nervo Troclear/fisiologia
13.
Orv Hetil ; 149(8): 353-9, 2008 Feb 24.
Artigo em Húngaro | MEDLINE | ID: mdl-18281231

RESUMO

INTRODUCTION: This paper assesses the first controlled multicentric investigation of outpatient cardiac rehabilitation in Hungary. Framing and starting of the program was carried out beside the Hungarian experts by the United States Department of Health and Human Services. AIMS: To prove the extreme importance of cardiac rehabilitation, both inpatient and outpatient, after the hospital treatment of cardiac emergencies. METHODS: 531 patients were collected at the beginning of the study from three Hungarian cardiological centers having cardiac surgery and cardiac rehabilitation ward. 167 patients were ranked into the outpatients group (Group A), 311 were rehabilitated in hospital (Group B) and 53 served as control (group C). After physical, ergometric and echocardiographic examinations and psychometric evaluation (Beck and WHOBREF questionnaires) the patients of Group A and B performed a conducted training three times weekly for 3 months. All the patients were examined 3 and 12 months later. RESULTS: Significant improvement of ergometric data was observed in both groups of patients who underwent rehabilitation training, but this was not the case with control patients. This improvement could not be observed after one year. The number of anginal attacks and the need of hospital treatment also showed a significant reduction in Groups A and B. CONCLUSIONS: The data have proved that cardiac rehabilitation has an extremely important role in the stabilisation of heart functions and general health of patients after acute myocardial infarction or heart surgery. It was also proved, that 12-week rehabilitation training is not sufficient to achieve long-term stabilization. Sufficient data have accumulated during the study about the effectiveness and safety of outpatient cardiac rehabilitation as an alternative to inpatient service.


Assuntos
Assistência Ambulatorial , Procedimentos Cirúrgicos Cardíacos/reabilitação , Terapia por Exercício , Infarto do Miocárdio/reabilitação , Adulto , Idoso , Angina Pectoris/epidemiologia , Angina Pectoris/prevenção & controle , Ecocardiografia , Ergometria , Feminino , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Pacientes Ambulatoriais , Testes Psicológicos , Psicometria , Fatores de Tempo , Resultado do Tratamento
14.
Curr Vasc Pharmacol ; 16(5): 446-450, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29345592

RESUMO

Platelet activation plays a central role in triggering and complicating acute coronary syndromes, especially in case of stent thrombosis and myocardial infarction. On top of aspirin, P2Y12- inhibitors are successfully used to treat and prevent these events for a duration of one year after an acute coronary episode or 6 months after drug-eluting stent implantation. However, patients with acute coronary syndromes remain at heightened risk for recurrent ischemic events after the recommended durations of P2Y12-inhibitors and therefore, prolonging treatment is often considered in clinical practice. However, the higher risk for bleeding limits the utility of such approach to a restricted group who is still poorly defined by available measures. This review aims to discuss potential benefits and highlight important pitfalls of prolonged treatment with P2Y12-inhibitors, with a focus on ticagrelor, an attractive reversible P2Y12-inhibitor in patients after myocardial infarction.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Tomada de Decisão Clínica , Esquema de Medicação , Quimioterapia Combinada , Stents Farmacológicos , Hemorragia/induzido quimicamente , Humanos , Seleção de Pacientes , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Recidiva , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
J Cardiovasc Pharmacol Ther ; 23(2): 149-154, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28914074

RESUMO

BACKGROUND: Platelet function testing was suggested to help tailor P2Y12-inhibitor therapy; however, the lack of proper standardization is still a limitation. METHODS: In a prospective study, we enrolled clopidogrel-treated and P2Y12-inhibitor naive patients to investigate the influence of (1) time from blood collection, (2) stability of the stored Adenosine diphosphate (ADP) reagent, and (3) the use of enoxaparin on results of the Multiplate assay. Measurements were performed from samples kept for 0, 30, 60, 120, and 240 minutes at room temperature before processing. To determine the impact of the reagent stability, freshly thawed ADP was compared with ADP kept for 3 to 5 or 8 to 13 days at 2°C to 8°C. Finally, samples containing enoxaparin at therapeutic or prophylactic doses were compared with enoxaparin-free blood. RESULTS: A total of 180 measurements were performed. ADP-stimulated platelet reactivity values decreased significantly over time (67 ± 40 U to 68 ± 37 U to 58 ± 37 U to 45 ± 33 U to 35 ± 33 U; P < .0001). Consequently, a dramatic reduction was observed in the proportion of patients with high platelet reactivity ( P < .0001). A significant drop in platelet reactivity was observed with ADP stored for 8 to 13 days as compared to freshly thawed ADP ( P = .011). Enoxaparin triggered a slight, concentration-dependent increase in platelet reactivity ( P < .05). CONCLUSION: Test conditions may have profound impacts on the obtained results with the Multiplate assay. Our findings highlight the large influence of the time from sample collection until testing, suggesting that measurements should be performed within an hour of blood collection.


Assuntos
Difosfato de Adenosina/normas , Plaquetas/efeitos dos fármacos , Clopidogrel/uso terapêutico , Monitoramento de Medicamentos/normas , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária/normas , Agonistas do Receptor Purinérgico P2Y/normas , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Difosfato de Adenosina/química , Idoso , Anticoagulantes/farmacologia , Plaquetas/metabolismo , Estabilidade de Medicamentos , Enoxaparina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Agonistas do Receptor Purinérgico P2Y/química , Reprodutibilidade dos Testes , Manejo de Espécimes/normas , Fatores de Tempo
16.
Brain Res ; 1178: 65-72, 2007 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-17920568

RESUMO

The circuits that generate rhythmic locomotor activities are located in the ventromedial area of the lumbar spinal cord and comprise commissural interneurons necessary for left-right alternation during walking movements. In this study we injected biotinylated dextran amine (BDA) into the ventromedial gray matter of the lumbar spinal cord of neonatal rats to label commissural interneurons. Anterogradely labeled axons arose from the site of injection, crossed the midline in the anterior commissure and arborized extensively in the contralateral ventral horn of the spinal cord. The presence of neurotransmitter systems in labeled axon terminals of commissural interneurons was investigated by using antibodies raised against specific transmitter-related proteins. Boutons potentially containing inhibitory amino acids were identified by applying glutamic acid decarboxylase (GAD65/67) and glycine transporter 2 antibodies. Out of 1146 BDA-labeled axon terminals, 663 boutons were assumed on this basis to be inhibitory; 76% of these terminals were immunoreactive for glycine transporter, 53% were immunoreactive for GAD and about 30% of inhibitory boutons might contain both inhibitory amino acids. Boutons potentially containing putative excitatory neurotransmitter were revealed with antibodies raised against vesicular glutamate transporters 1 and 2. Out of 590 BDA-labeled boutons about one fourth (158) were immunoreactive for glutamate transporters. These mammalian commissural interneurons are compared to the glycinergic commissural interneurons in the swimming CPGs of lamprey and the Xenopus tadpole. Our results show that commissural interneurons in the mammalian spinal cord form a heterogeneous group including glutamatergic excitatory and GABAergic and glycinergic inhibitory neurons.


Assuntos
Animais Recém-Nascidos/fisiologia , Interneurônios/fisiologia , Neurotransmissores/fisiologia , Medula Espinal/fisiologia , Animais , Biotina/análogos & derivados , Contagem de Células , Dextranos , Corantes Fluorescentes , Glutamato Descarboxilase/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/fisiologia , Glicina/metabolismo , Glicina/fisiologia , Proteínas da Membrana Plasmática de Transporte de Glicina/metabolismo , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Locomoção/fisiologia , Região Lombossacral , Microscopia Confocal , Proteínas de Transporte de Neurotransmissores/metabolismo , Terminações Pré-Sinápticas/fisiologia , Ratos , Ratos Wistar , Medula Espinal/citologia , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/fisiologia
17.
Eur J Pharm Sci ; 30(1): 56-63, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17125978

RESUMO

AIM: To establish the effects of Na(+)/Ca(2+) exchanger (NCX) blockers on 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) and (11)C-choline accumulation in different cancer cells. METHODS: The tumor cells were incubated with NCX inhibitors, and the uptakes of (18)FDG and (11)C-choline were measured. Flow cytometric measurements of intracellular Ca(2+) and Na(+) concentrations were carried out. The presence of the NCX antigen in the cancer cells was proved by Western blotting, flow cytometry and confocal laser scanning microscopy. RESULTS: The NCX is expressed at a noteworthy level in the cytosol and on the cytoplasmic membrane of the examined cells. Incubation of the cells with three chemically unrelated NCX blockers (bepridil, KB-R7943 or 3',4'-dichlorobenzamil hydrochloride) resulted in an increase in the intracellular Ca(2+) concentration, with a simultaneous decrease in the intracellular Na(+) concentration. The treatment with the NCX inhibitors increased the energy consumption of the tumor cells by 50-100%. Thapsigargin abolished the NCX-induced (18)FDG accumulation in the cells. The NCX blockers applied decreased the (11)C-choline accumulation of all the investigated cancer cells by 60-80% relative to the control. CONCLUSION: A possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans.


Assuntos
Colina/farmacocinética , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons , Trocador de Sódio e Cálcio/antagonistas & inibidores , Bepridil/farmacologia , Cálcio/metabolismo , Radioisótopos de Carbono , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Neoplasias/diagnóstico , Neoplasias/metabolismo , Traçadores Radioativos , Sódio/metabolismo , Trocador de Sódio e Cálcio/biossíntese , Tapsigargina/farmacologia
18.
Pharmacol Rep ; 59(4): 428-36, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17901572

RESUMO

Up to one-third of serious vascular events in high-risk patients is attributable to a failure of aspirin (ASA) to suppress platelet aggregation. We hypothesized that inhibition of NAD(P)H oxidase may inhibit aggregation of platelets from ASA-resistant (ASA-R) patients. Thus, platelet-rich plasma was isolated from ASA-sensitive (ASA-S) and ASA-R patients (aspirin resistance was defined as higher than expected aggregation to collagen and epinephrine [> or = 40%] after chronic oral treatment with 100 mg/day ASA). Aggregation to adenosine diphosphate (ADP) (5 and 10 micromol/l), collagen (2 microg/ml) and epinephrine (10 micromol/l) in the absence and presence of the NAD(P)H oxidase inhibitors: diphenylene iodonium (DPI) (1 micromol/l) and apocynin (3 x 10(-4) mol/l) was measured by optical aggregometry. Maximal aggregation of ASA-R platelets to collagen and epinephrine was significantly decreased by DPI and apocynin, whereas they had no effect in ASA-S platelets. Maximal aggregation to ADP was unaffected by NAD(P)H oxidase inhibition in either group. In ASA-R platelets both NADPH-driven O2(.-) production (lucigenin chemiluminescence assay) and expression of gp91phox and p67phox subunits of the NADPH oxidase (Western blotting) tended to increase. Collectively, inhibition of NAD(P)H oxidase effectively suppressed collagen and epinephrine-induced aggregation of platelets from ASA-R patients, which may represent a novel pharmacological target for cardioprotection in high-risk cardiac patients.


Assuntos
Aspirina/uso terapêutico , Resistência a Medicamentos , Inibidores Enzimáticos/farmacologia , Cardiopatias/sangue , NADPH Oxidases/antagonistas & inibidores , Agregação Plaquetária/efeitos dos fármacos , Acetofenonas/farmacologia , Difosfato de Adenosina/farmacologia , Administração Oral , Idoso , Aspirina/administração & dosagem , Aspirina/farmacologia , Western Blotting , Colágeno/farmacologia , Relação Dose-Resposta a Droga , Feminino , Cardiopatias/enzimologia , Humanos , Medições Luminescentes , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , Fosfoproteínas/metabolismo , Testes de Função Plaquetária/métodos , Plasma Rico em Plaquetas/efeitos dos fármacos , Plasma Rico em Plaquetas/metabolismo
19.
J Chromatogr Sci ; 45(2): 76-86, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17425136

RESUMO

Numerous ecdysteroids are isolated from the herb of Serratula wolffii Andrae, a cultivated plant. The isolation procedure includes a variety of low-pressure liquid chromatography, thin-layer chromatography (TLC), gel chromatography, and high-performance liquid chromatography (HPLC) methods. The progress of separation is monitored by TLC, and the final proof of purity is carried out by HPLC. The isolation process involves the removal of proteins, flavonoids, chlorophylls, other sterines, etc. The purification also includes the separation of the target ecdysteroids from each other. Isolation of the pure compounds requires 2-8 chromatographic steps. The consecutive steps are based on the different physicochemical properties of the ecdysteroids. In some cases, a special peak-cut method employing a flush of dichloromethane into the dichloromethane-isopropanol-water mobile phase is used. This flush of dichloromethane leads to an almost perfect separation of otherwise unresolved peaks. Two ecdysteroids, 25-hydroxydacryhainansterone and 14-epi-20-hydroxyecdysone, are identified as natural products for the first time. The structure-chiroptical relationships for some ecdysteroids are also discussed.


Assuntos
Asteraceae/química , Cromatografia Líquida de Alta Pressão/métodos , Ecdisteroides/isolamento & purificação , Cromatografia em Camada Fina , Dicroísmo Circular , Ecdisteroides/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrofotometria Ultravioleta
20.
Orv Hetil ; 148(44): 2087-94, 2007 Nov 04.
Artigo em Húngaro | MEDLINE | ID: mdl-17959552

RESUMO

UNLABELLED: The 6-min walk test (6MWT) is a simple, low-cost method for estimating physical exercise capacity of cardiac patients, when exercise test cannot be performed, as in patients early after coronary artery bypass surgery. As the test requests active cooperation of patients, possibly not only somatic, but psychological factors can influence the results. 358 patients who arrived to Phase II residential cardiac rehabilitation after their first coronary artery bypass surgery were included in the prospective study. 6-MWT was performed at the beginning and at the end of 3 weeks program. Hospital Anxiety and Depression Scale (HADS), Type-D personality test were filled in 3 weeks after surgery. RESULTS: Patients characterized as Type-D personality (8.5%) covered considerably shorter distance than non-Type-D patients both at the beginning (255 +/- 91 m vs. 319 +/- 106 m, p < 0.01) and at the end of 6MWT (361 +/- 91 m vs. 411 +/- 106 m, p < 0.05) without any substantial differences in heart rate or rating of perceived exertion. Patients with high level of anxiety (16.5%) had lower walking distance compared to non anxious patients both at the beginning and the ending test (274 +/- 97 m vs. 320 +/- 106 m, p < 0.01 and 374 +/- 110 m vs. 413 +/- 104 m, p < 0.05), and evaluated higher rate of perceived exertion (12.5 +/- 1.1 vs. 11.9 +/- 1.4, p < 0.05 and 11.7 +/- 0.8 vs. 11.3 +/- 1.3, p < 0.05). Patients who were depressed according to HADS (14%) walked shorter distance than non depressed patients both at the beginning (267 +/- 88 m vs. 320 +/- 107 m, p < 0.01), and end of 6MWT (347 +/- 99 m vs. 416 +/- 104 m, p < 0.001). There were no differences in somatic function of patients with and without psychological alternations. CONCLUSION: Psychological factors (Type D personality, anxiety and depression) considerably influence 6MWT walking distance after coronary artery bypass surgery.


Assuntos
Ansiedade , Ponte de Artéria Coronária , Depressão , Teste de Esforço , Pacientes/psicologia , Personalidade , Caminhada , Idoso , Ansiedade/fisiopatologia , Ponte de Artéria Coronária/psicologia , Doença da Artéria Coronariana/psicologia , Depressão/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Esforço Físico , Estudos Prospectivos , Desempenho Psicomotor , Fatores de Risco
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