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1.
Adv Physiol Educ ; 48(3): 639-647, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38932698

RESUMO

Science communication is a core skill for undergraduate science students to acquire in preparation for their future careers, but studies show that this skill is underdeveloped in science graduates. The aim of this study was to discover the resources and approaches undergraduate students use to effectively develop their science communication skills and how the use of these methods relates to academic performance on a communication task. Undergraduate students undertaking a second-year biomedical science course (n = 490) were asked which approaches and resources they used to aid the development of their science communication skills, and the frequency of their responses was correlated against their laboratory report mark, using multiple regression and relative weights analysis. Students' (n = 453) use of Communication Learning in Practice for Scientists (CLIPS; an open-access interactive website on science communication), resources provided by the university, interactions with university teaching staff, and engagement with the scientific literature significantly predicted the laboratory report mark. Students enrolled in a blended format or in remote online learning only, and in different programs, performed comparably in the written report and used similar approaches and resources, other than remote students reporting more use of other online resources and students in blended learning engaging more with university resources. Together, these findings provide insight into which strategies are most helpful for undergraduate students to engage with to improve their scientific communication skills. The findings highlight that the provision of well-designed interactive communication resources, guided assessment resources, and opportunities to engage with teaching staff can assist in the development of science communication skills.NEW & NOTEWORTHY This study identifies the approaches and resources that undergraduate science students use to develop their science communication skills. It reveals which of these approaches and resources predict improved academic performance in a written science communication assessment task. The findings point to the importance of explicit guidance, and engagement with teaching staff, in advancing the development of science communication skills.


Assuntos
Comunicação , Estudantes , Humanos , Feminino , Masculino , Estudantes/psicologia , Universidades , Adulto Jovem , Ciência/educação , Currículo
2.
J Clin Monit Comput ; 36(3): 871-877, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33991270

RESUMO

Patients with acute kidney injury who need continuous renal replacement therapy with locoregional citrate anticoagulation are at risk of citrate accumulation with disruption of the calcium balance. We aimed to evaluate the safety of detecting citrate accumulation and adjusting electrolyte disbalances during continuous venovenous hemodialysis (CVVHD) in critically ill patients with acute kidney injury using a blood sample frequency every 6 h. A prospective single center study in critically ill intensive care unit patients who suffered from acute kidney injury with the need of renal replacement therapy. We evaluated the deviations in pH, bicarbonate and calcium during CVVHD treatment with local regional citrate anticoagulation. Values indicate median and interquartile range. Severe hypocalcemia (below 1.04 mmol/L) or hypercalcemia (above 1.31 mmol/L) occurred in 10.5% and 4.8% respectively. During treatment changes of systemic ionized calcium, post-filter ionized calcium, pH and bicarbonate were corrected with protocolized adjustments. No arrhythmias or citrate accumulation were seen. The values stabilized after 42 h and after that no statistically significant changes were observed. After 42 h of citrate CVVHD, systemic ionized calcium, pH and bicarbonate levels stabilized. A blood sample frequency every 6 h is probably safe to detect citrate accumulation and to adjust the settings of electrolytes to avoid serious electrolyte disturbances in ICU patients without severe metabolic acidosis or severe liver failure.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Anticoagulantes/uso terapêutico , Bicarbonatos , Cálcio , Citratos , Ácido Cítrico , Estado Terminal , Eletrólitos , Humanos , Estudos Prospectivos , Diálise Renal , Terapia de Substituição Renal
3.
Neoplasma ; 64(5): 762-769, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28592129

RESUMO

Presented are updated results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 25 adult patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) after a reduced intensity conditioning (RIC) combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg or recently 4.0 mg/kg) followed by early initiation of reduction and withdrawal of prophylactic posttransplant immunosuppression. The median post-transplant follow-up was 32 (range, 4-87) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute graft versus host disease (GVHD) as well as the chronic one were equally observed in four cases (16%). Five patients (20%) relapsed with ALL in the median of 9 (range, 3-15) months after HSCT. During the above post-transplant follow-up, 4 recipients (16%) died. Disease progression and posttransplant complications were the cause of death in three (12%) and one (4%) of them, respectively. The probabilities of 2-year event-free (EFS) and overall survival (OS) were 70.3% (95% CI 51.9-88.7%) and 86.1% (95% CI 71.6-100%), respectively. Presented study confirmed our previously reported promising results and this approach may be considered as an alternative to traditional HSCTs performed in high-risk patients with ALL.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Melfalan/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Vidarabina/análogos & derivados , Adulto , Humanos , Imunossupressores , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Vidarabina/uso terapêutico
4.
Neoplasma ; 62(1): 146-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25563379

RESUMO

UNLABELLED: Acute promyelocytic leukemia is a unique entity among acute leukemias. Introduction of all-trans retinoic acid and, subsequently, arsenic trioxide in its treatment has markedly improved treatment outcomes for this once frequently fatal disease. Improved outcomes have also been observed in elderly patients, including those in whom standard intensive therapy is contraindicated because of comorbidities.In our center, a total of 60 APL patients were treated in 1993-2013, of whom 9 were aged 60 or more years. Although most of them had significant comorbidities at the time of diagnosis, eight achieved complete remission. At the time of the analysis, six patients were alive and in long-term remission; two patients died of causes other than APL. The median follow-up was 59 months.Included is case report of a patient with a high comorbidity score whose treatment was markedly reduced and individualized.Our experience shows that, in APL patients a curative approach is generally tolerated and should always be attempted regardless of age and comorbidities. KEYWORDS: APL - elderly patients - comorbidity.

5.
Neoplasma ; 62(5): 805-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26278139

RESUMO

Presented are results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 13 patients with high-risk acute lymphoblastic leukemia (ALL) in the first complete remission after a reduced intensity conditioning combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg). The immunosuppressive effect of T-cell depletion reducing the risk of graft-versus-host disease (GVHD) and non-relapse mortality was compensated by early initiation of reduction and withdrawal of prophylactic immunosuppression aimed at maintaining effective immunological antileukemic control. The median post-transplant follow-up was 23 (range, 10-65) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute GVHD was observed in two cases (15.4%); the chronic form was not noted. Two patients (15.4%) relapsed with ALL at 3 and 16 months after transplantation. During the above post-transplant follow-up, all 13 recipients were alive, with a probability of 2-year disease-free survival of 76.9% (95% CI 51-100%). Although the results were obtained with a small pilot study group it may be assumed that, given the prognostic risk of most patients and the nearly 2-year median post-transplant follow-up, the approach may be considered as an alternative to HSCTs after traditional myeloablative or reduced conditioning regimens with standard GVHD prophylaxis.

6.
Unfallchirurg ; 115(12): 1123-5, 2012 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-23052701

RESUMO

The aim of this article was to raise the awareness of the difficulties physicians face in the diagnosis and treatment of esophageal perforation following blunt thoracic trauma. We present a case of esophagus perforation following blunt chest trauma in the course of a motorcycle accident. Within 24 h the patient was admitted to the University hospital, and presented with progressive pain, subfebrile temperature, leukocytosis and pneumomediastinum. Emergency surgery revealed extensive esophageal lesions. A two-stage surgical approach was chosen with initial resection and temporary closure of the esophagus. After 2 months the integrity of the esophagus could be restored without complications.


Assuntos
Esôfago/lesões , Esôfago/cirurgia , Traumatismos Torácicos/complicações , Traumatismos Torácicos/cirurgia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/cirurgia , Adolescente , Esôfago/diagnóstico por imagem , Humanos , Masculino , Radiografia , Traumatismos Torácicos/diagnóstico por imagem , Resultado do Tratamento , Ferimentos não Penetrantes/diagnóstico por imagem
7.
Zentralbl Chir ; 137(5): 430-5, 2012 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-23136103

RESUMO

INTRODUCTION: True aneurysms of the deep femoral artery (APFA) are rare and are usually presented as case reports. Recommendations for diagnostics and therapy of APFAs are based on low-level evidence only. The purpose of this paper was to summarise the existing world experience with APFA. MATERIAL/METHODS: On the occasion of our own case a systematic review of the literature was performed for diagnostics and therapy for true APFA. Publications retrieved from PubMed, EMBASE, and the Cochrane Collaboration as well as by hand search from their references were reviewed. RESULTS: From 2002 onwards 25 papers on true APFAs were published in the English and German literature. Apart from two retrospective studies over a longer period of time these were exclusively case reports. A total of 55 true APFAs were reported in 47 patients with a mean age of 63 years. Therapeutic intervention was due to a rupture in 10 cases (18 %). The mean maximal diameter of APFA at presentation was 5.4 cm (2-18 cm). APFAs that were not ruptured presented frequently as a painful pulsatile mass in the groin and thigh. Therapeutic options for APFA included, apart from surgical resection with or without reconstruction of the deep femoral artery, the endovascular repair. DISCUSSION: Symptoms of swelling and pain in the presence of a mass at the proximal thigh should raise the suspicion of an APFA. Surgical therapy should be performed electively in APFAs with a diameter of more than 2 cm or in cases of rapid progression as well as in all symptomatic or ruptured cases. The endovascular approach should be considered as an alternative option in all cases.


Assuntos
Aneurisma/cirurgia , Artéria Femoral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aneurisma/diagnóstico , Aneurisma Roto/cirurgia , Angioplastia/métodos , Prótese Vascular , Criança , Diagnóstico por Imagem , Embolização Terapêutica/métodos , Humanos , Perna (Membro)/irrigação sanguínea , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Sensibilidade e Especificidade , Stents
8.
Neuron ; 56(4): 621-39, 2007 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-18031681

RESUMO

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.


Assuntos
Córtex Cerebral/anormalidades , Córtex Cerebral/citologia , Dendritos/ultraestrutura , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas do Tecido Nervoso/genética , Células Piramidais/citologia , Animais , Diferenciação Celular/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Células Cultivadas , Córtex Cerebral/metabolismo , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Dendritos/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Proteína 4 Homóloga a Disks-Large , Potenciais Pós-Sinápticos Excitadores/genética , Feminino , Guanilato Quinases , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/fisiopatologia , Vias Neurais/anormalidades , Vias Neurais/citologia , Vias Neurais/metabolismo , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Células Piramidais/metabolismo , Transmissão Sináptica/genética
9.
Neoplasma ; 58(3): 263-70, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21395368

RESUMO

Antibody (rituximab) dependent cellular cytotoxicity is a key mechanism in killing CD20+ lymphoma cells. FcγRIIIA-158 V/F gene polymorphism results in expression of 3 variants of the FcγRIIIA receptor (FcγRIIIA) on cytotoxic lymphocytes with different receptor affinity. We studied 102 patients with newly diagnosed FL to assess whether the FcγRIIIA genotype influences outcome in patients treated with risk-adapted immunochemotherapy. The median age was 52 years (31-84); 90% of the patients had advanced (III/IV) clinical stages. The Follicular Lymphoma International Prognostic Index (FLIPI) scores were as follows: low 18.9%, intermediate 33.7% and high 47.4%. The front-line treatment was stratified according to the commonly used risk factors (FLIPI, beta-2-microglobuline and serum-Tyrosine-Kinase levels, bulky disease) into 3 treatment groups: (1) patients with FLIPI 0-1 treated with (R)-CHOP (51%), (2) patients under 60 (65) years of age with intermediate-risk disease (FLIPI 2) indicated for an intensive protocol (ProMACE-CytaBOM or sequential chemotherapy) (21%), and (3) patients under 60 (65) years with high-risk disease (FLIPI ≥3) treated with intensive chemotherapy plus autologous stem cell transplantation (28%). Rituximab was added to front-line chemotherapy in 59% of the patients. Generally, complete remission (CR) or unconfirmed CR was achieved in 85% of the patients, 11% had partial remission and 4% stable disease. Molecular CR (CRm) was achieved in 67.4% of 86 evaluable patients. Overall survival (OS) at 5 years reached 84% (95% CI 0.74-0.93); event-free survival (EFS) at 5 years was 58% (95% CI 0.45-0.71). The frequencies of FcγRIIIA-158 gene polymorphisms V/V, V/F and F/F were 8%, 50% and 42%, respectively. The FLIPI score distribution was not different in F/F patients as compared to V/F+V/V carriers (chi-square, P=0.7). The treatment modalities (treatment arm or rituximab administration) had the same distribution in V/V+V/F vs F/F patients (chi-square, P=0.16 and P=0.62, respectively). The CRm rates were similar in both subgroups of V/V+V/F vs F/F patients (chi-square, P=0.92). Survival curves for OS and EFS were not significantly different when comparing the subgroups of V/V+V/F vs F/F patients (P=0.28 and P=0.57, respectively). We found no difference in the quality of treatment response or survival after front-line immunochemotherapy between FcγRIIIA subgroups. FcγRIIIA polymorphism have no influence on the outcome of patients treated with risk-adapted chemotherapy with or without rituximab.


Assuntos
Linfoma Folicular/terapia , Receptores de IgG/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma Folicular/genética , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
10.
Neoplasma ; 58(3): 256-62, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21395367

RESUMO

Tyrosine kinase inhibitors (TKI) have completely changed the prognosis of patients with Ph+ chronic myeloid leukemia (CML). The occurrence of a second malignancy (SM) in CML patients successfully treated with TKI may significantly affect their prognosis. In a retrospective study of 1,038 patients with CML treated at 10 centers in the Czech Republic and Slovakia between 2000 and 2009, SM was detected in 35 (3.37%) patients after TKI therapy was initiated. The median intervals from the diagnosis of CML and from the start of TKI therapy to the diagnosis of SM were 58 months (range 2 - 214) and 32 months (range 1 - 102), respectively. The observed age-standardized incidence of SM after the start of TKI therapy was 8.95 / 1,000 person-years. Comparison of the incidence of SM in CML patients with population data was performed only for patients from the Czech Republic. The age-standardized incidence rate of all malignant tumors except non-melanoma skin cancers was 6.76 (95% CI: 6.74; 6.78) / 1,000 person-years in 2000 - 2007 while the incidence rate of SM in 708 CML patients from the Czech Republic treated with TKI was 9.84 (95% CI: 6.20; 13.48) / 1,000 person-years, i.e. 1.5-fold higher, although the difference was statistically insignificant. The distribution of SM types in CML patients treated with TKI was similar to that in the age-standardized general Czech population. The median overall survival (OS) of patients treated with TKI who also developed SM (57 months) was shorter than the OS of patients treated with TKI but not suffering from SM (median OS not reached, log rank test p < 0.001. Prospective long-term population-based studies in CML patients treated with TKI as first-line therapy are needed to determine the relationship of SM to KTI therapy.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Segunda Neoplasia Primária/epidemiologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , República Tcheca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Eslováquia/epidemiologia
11.
Klin Onkol ; 34(2): 153-162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33906365

RESUMO

BACKGROUND: Oral cavity injuries are very significant complications in the treatment of oncological and hemato-oncological patients. Preventive and curative interventions and patient education reduce the risk of complications and their consequences. A working group of authors from professional groups prepared recommendations for care. PURPOSE: A basic summary of recommended interventions to prevent and treat oral cavity injuries in daily practice, defined on the basis of expert societies guidelines, trials, literature data and proven practice and on the consensus opinions of the authors group members. RESULTS: Preventive measures and patient education are essential in the approach to dealing with oral injuries in chemotherapy, radiotherapy, risky targeted treatment and osteonecrosis of the jaw. Local care products are an important element of care, in case of infections, their antimicrobial action is essential, in case of graft-versus-host disease or in connection with targeted oncological therapy, corticoids are used. CONCLUSION: The recommended procedures contribute to the reduction of the development, severity and consequences of oral complications in oncological and hemato-oncological patients.


Assuntos
Doenças da Boca/terapia , Neoplasias/terapia , Humanos , Doenças da Boca/etiologia , Educação de Pacientes como Assunto
12.
J Physiol ; 588(Pt 8): 1281-92, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20194128

RESUMO

Synaptic activity in the medial prefrontal cortex (mPFC) is fundamental for higher cognitive functions such as working memory. The present study shows that small conductance (SK) calcium-activated potassium channels attenuate excitatory synaptic transmission at layer 2/3 and layer 5 inputs to layer 5 pyramidal neurons in the mPFC. SK channels are located postsynaptically at synapses where they are activated during synaptic transmission by calcium influx through NMDA receptors, L-type calcium channels, R-type calcium channels and by calcium release from IP(3)-sensitive stores. Removal of the SK channel-mediated shunt of synaptic transmission reveals significant NMDA receptor-mediated activation during basal synaptic transmission, which is greater at layer 5 inputs (approximately 30%) than at layer 2/3 inputs (approximately 20%). These findings show that interactions between NMDA receptors, SK channels and voltage-gated calcium channels play a critical role in regulating excitatory synaptic transmission in layer 5 pyramidal neurons in the mPFC.


Assuntos
Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Córtex Pré-Frontal/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/fisiologia , Sinapses/fisiologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/fisiologia , Canais de Cálcio Tipo R/fisiologia , Comunicação Celular , Feminino , Masculino , Modelos Animais , Células Piramidais/citologia , Células Piramidais/fisiologia , Ratos , Ratos Wistar , Transmissão Sináptica/fisiologia
13.
Neoplasma ; 57(4): 355-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20429627

RESUMO

Dasatinib is effective second line treatment for patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. We report here the first experiences with dasatinib therapy in 71 CML patients resistant or intolerant to imatinib from the real clinical practice of 6 hematological centers in the Czech Republic. Dose 100 mg daily and 70 mg twice daily was administered to patients with chronic phase (CP) and advanced phases (AP) CML. In chronic phase (n=46), complete hematological reponse (CHR) was achieved in 97%, major cytogenetic reponse (MCgR) in 77% and complete cytogenetic response (CCgR) in 67%. Major molecular reponse (MMR) was achieved in 19/31 patients in median of 10 months. In advanced phase (n=25), CHR was attained in 77%, MCgR in 39%, CCgR in 33% and MMR in 2/18 patients. Eleven different baseline mutations were followed up in 15 patients. Dasatinib eliminated mutations in most of the patients, but 3 patients acquired a new one. Novel mutations were detected under dasatinib therapy in 2 patients. Dasatinib was well tolerated, cytopenias were common and was managed by dose modification. The estimated progression free survival (PFS) at 12 months was 97+/-3% in CP and 62+/-21% in AP. The median time to treatment failure was 605 days in AP while it was not reached in CP patients. Our clinical experiences, described here, confirmed that dasatinib is associated with high response rates especially in imatinib resistant or intolerant CML patients in chronic phase.


Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Terapia de Salvação , Tiazóis/uso terapêutico , Adulto , Idoso , Benzamidas , Dasatinibe , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Proteínas Tirosina Quinases/antagonistas & inibidores , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
J Neurosci ; 28(43): 10803-13, 2008 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-18945888

RESUMO

Emotionally arousing events are particularly well remembered. This effect is known to result from the release of stress hormones and activation of beta adrenoceptors in the amygdala. However, the underlying cellular mechanisms are not understood. Small conductance calcium-activated potassium (SK) channels are present at glutamatergic synapses where they limit synaptic transmission and plasticity. Here, we show that beta adrenoceptor activation regulates synaptic SK channels in lateral amygdala pyramidal neurons, through activation of protein kinase A. We show that SK channels are constitutively recycled from the postsynaptic membrane and that activation of beta adrenoceptors removes SK channels from excitatory synapses. This results in enhanced synaptic transmission and plasticity. Our findings demonstrate a novel mechanism by which beta adrenoceptors control synaptic transmission and plasticity, through regulation of SK channel trafficking, and suggest that modulation of synaptic SK channels may contribute to beta adrenoceptor-mediated potentiation of emotional memories.


Assuntos
Tonsila do Cerebelo/citologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciação de Longa Duração/fisiologia , Células Piramidais/fisiologia , Receptores Adrenérgicos beta/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Adrenérgicos/farmacologia , Animais , Animais Recém-Nascidos , Apamina/farmacologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Estimulação Elétrica/métodos , Endocitose/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/efeitos da radiação , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Técnicas de Cultura de Órgãos/métodos , Técnicas de Patch-Clamp/métodos , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Wistar , Transfecção
15.
Neoplasma ; 56(1): 76-83, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19152250

RESUMO

We processed data of 79 patients (pts) with malignant lymphoma from the National Registry of haematopoietic stem cell transplants conducted between 1997 and 2006. The haematopoietic stem cell donor in 48 pts was an HLA matched relative, and in 30 pts an unrelated volunteer. Sixty (77%) pts were transplanted with reduced intensity conditioning (RIC), eleven (23%) pts with myeloablative conditioning (MC). Acute graft-versus-host disease (aGVHD) was recorded in 26 (33%) pts. Chronic GVHD was diagnosed in 19 (36%) of the 53 assessable pts. Transplant-related mortality (TRM) in the first 100 days, 1 year and 3 years for the whole group was 26%, 33% and 33%. Twenty (26%) of the pts relapsed. During the median follow-up of 26 months the overall survival (OS) was 44%, the progression free survival (PFS) was 54% and cumulative incidence of relapse was 45%. Pts with chemoresistant disease had significantly worse results (OS at 3 years 22% vs. 56%, p=0.002). We did not find any correlation between the incidence of GVHD and the frequency of relapse. Similarly, we did not observe any difference in survival between patients following MC vs. RIC. Survival of pts transplanted from related donors did not differ statistically from unrelated donors. Key words: Lymphoma, allogeneic, transplantation, GVHD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adulto , Tchecoslováquia , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros
16.
Nat Neurosci ; 8(5): 635-41, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15852010

RESUMO

At glutamatergic synapses, calcium influx through NMDA receptors (NMDARs) is required for long-term potentiation (LTP); this is a proposed cellular mechanism underlying memory and learning. Here we show that in lateral amygdala pyramidal neurons, SK channels are also activated by calcium influx through synaptically activated NMDARs, resulting in depression of the synaptic potential. Thus, blockade of SK channels by apamin potentiates fast glutamatergic synaptic potentials. This potentiation is blocked by the NMDAR antagonist AP5 (D(-)-2-amino-5-phosphono-valeric acid) or by buffering cytosolic calcium with BAPTA. Blockade of SK channels greatly enhances LTP of cortical inputs to lateral amygdala pyramidal neurons. These results show that NMDARs and SK channels are colocalized at glutamatergic synapses in the lateral amygdala. Calcium influx through NMDARs activates SK channels and shunts the resultant excitatory postsynaptic potential. These results demonstrate a new role for SK channels as postsynaptic regulators of synaptic efficacy.


Assuntos
Tonsila do Cerebelo/fisiologia , Sinalização do Cálcio/fisiologia , Plasticidade Neuronal/fisiologia , Canais de Potássio Cálcio-Ativados/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/fisiologia , Animais , Cálcio/antagonistas & inibidores , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Quelantes/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Cálcio-Ativados/antagonistas & inibidores , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/metabolismo , Transmissão Sináptica/efeitos dos fármacos
17.
Klin Mikrobiol Infekc Lek ; 15(3): 95-8, 2009 Jun.
Artigo em Sk | MEDLINE | ID: mdl-19637140

RESUMO

Toxoplasmosis is a parasitic disease associated with high mortality in immunocompromised patients. It may lead to life-threatening conditions, usually neuroinfections, pneumonia or disseminated disease. It may be potentially dangerous, especially for patients with prolonged lymphopenia or those treated with immunosuppressive drugs. In our centre, we have observed 3 cases of toxoplasmosis in patients after allogeneic haematopoietic stem cell transplantation (HSCT) (2.6% of 116 allo-HSCT patients since 2000) and one case after autologous HSCT (0.3% of 395 auto-HSCT patients since 1997). Toxoplasmosis is manifested by neurological symptoms including hemiparesis and paraparesis, cerebral salt-wasting syndrome (hyponatraemia and hypoosmolality), psychoorganic syndrome and signs of respiratory infection. The diagnosis was made by combining clinical signs and results of PCR and CT examinations. The patients were treated with high-dose pyrimethamine, clindamycin, co-trimoxazole and folic acid. Three of the four patients have survived with no signs of the disease. One patient died prior to treatment. The increasing use of highly immunosuppressive chemotherapy and conditioning regimens (including rituximab, fludarabine and anti-thymocyte globulin) is associated with a significant risk of toxoplasmosis. Variable manifestations, non-specific results of MRI or CT examinations and possibility of PCR negativity are the main obstacles to successful diagnosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hospedeiro Imunocomprometido , Toxoplasmose/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Toxoplasmose/imunologia
18.
Int J Immunogenet ; 35(4-5): 401-3, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18976446

RESUMO

Interleukin-6 (IL-6) is an important pro-inflammatory mediator implicated in immune-mediated complications of allogeneic haematopoietic stem cell transplantation (aHSCT). In accord with previous reports, this preliminary study on 56 donor-recipient pairs revealed IL-6-174 single nucleotide polymorphisms as a risk factor for the development of acute graft-versus-host disease and decreased survival after aHSCT.


Assuntos
Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Interleucina-6/genética , Polimorfismo Genético/genética , Transplante Homólogo/imunologia , Adolescente , Adulto , Alelos , República Tcheca , Feminino , Frequência do Gene , Genótipo , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/imunologia , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
19.
Neoplasma ; 55(3): 215-21, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18348654

RESUMO

Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/terapia , Adulto , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo
20.
Vnitr Lek ; 54(12): 1174-84, 2008 Dec.
Artigo em Tcheco | MEDLINE | ID: mdl-19140527

RESUMO

National working group representing clinicians (hematologists, oncologists, infection diseases and ICU specialists), microbiologists, and different special medical societies and working groups prepared evidence-based guidelines for the treatment established fungal infection--invasive candidiasis in the adult hematology and ICU patients. These guidelines updated those published in the Czech Republic in 2003-2004. Evidence criteria of the Infectious Diseases Society of America (IDSA) were used for assessing the quality of clinical trials, and EORTC/MSG Consensus Group for definitions of invasive fungal disease.


Assuntos
Candidíase/tratamento farmacológico , Humanos
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