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1.
Scand J Med Sci Sports ; 24(1): 80-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22540893

RESUMO

Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p-CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p-CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 µM) and underwent a submaximal exercise test until fatigue. Icv TRP-treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p-CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p-CPA administration accelerated cutaneous heat dissipation when compared with saline-pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p-CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.


Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Fadiga , Fenclonina/farmacologia , Condicionamento Físico Animal/fisiologia , Triptofano Hidroxilase/antagonistas & inibidores , Triptofano/farmacologia , Animais , Cloro/farmacologia , Teste de Esforço , Injeções Intraventriculares , Masculino , Fenilalanina/farmacologia , Ratos , Ratos Wistar , Serotonina , Triptofano/metabolismo , Triptofano Hidroxilase/fisiologia
2.
Acta Trop ; 257: 107275, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38851624

RESUMO

Mosquito-borne diseases constitute a significant global impact on public and animal health. Climatic variables are recognized as major drivers in the mosquitoes' life history, principally rainfall and temperature, which directly influence mosquito abundance. Likewise, urbanization changes environmental conditions, and understanding how environmental variables and urbanization influence mosquito dynamics is crucial for the integrated management of mosquito-borne diseases, especially in the context of climate change. In this study, our aim was to observe the effect of temperature, rainfall, and the percentage of impervious surface on the abundance of mosquito species over a temporal scale of one complete year of fortnightly samplings, spanning from June 2021 to June 2022 in Yucatan, Mexico. We selected nine localities along an urbanization gradient (three natural, three rural, and three urban) from Mérida City to Reserva de la Biosfera Ría Celestún. Using BG-traps, mosquitoes were collected biweekly at each locality. Additionally, we estimated the percentage of impervious surface. Daily data of the maximum, mean and minimum temperatures, diurnal temperature range and rainfall were accumulated weekly. We calculated the accumulated quantities of temperatures and rainfall and lagged from one to four weeks before sampling for each locality. Generalized linear mixed models were then performed to study the influence of environmental variables and percentage of impervious surfaces on each of the 15 most abundant species. A total of 131,525 mosquitoes belonging to 11 genera and 49 species were sampled with BG-Sentinel traps baited with BG-lure and dry ice. The most frequently significative variable is the accumulated precipitation four weeks before the sampling. We observed a positive relationship between Cx. quinquefasciatus and Cx. thriambus with the diurnal temperature range. For Ae. aegypti, we observed a positive relationship with minimum temperature. Conversely, the percentage of impervious surface serves as a proxy of anthropogenic influence and helped us to distinguishing species exhibiting habitat preference for urban and rural environments, versus those preferring natural habitats. Our results characterize the species-specific effects of environmental variables (temperature, rainfall and impervious surface) on mosquito abundance.


Assuntos
Culicidae , Estações do Ano , Temperatura , Animais , México , Culicidae/fisiologia , Culicidae/classificação , Culicidae/crescimento & desenvolvimento , Urbanização , Mosquitos Vetores/fisiologia , Mosquitos Vetores/crescimento & desenvolvimento , Dinâmica Populacional , Chuva , Mudança Climática
3.
Scand J Med Sci Sports ; 23(1): 46-56, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21672029

RESUMO

We investigated brain mechanisms modulating fatigue during prolonged physical exercise in cold environments. In a first set of studies, each rat was subjected to three running trials in different ambient temperatures (T(a)). At 8 °C and 15 °C, core body temperature (T(core)) decreased and increased, respectively, whereas at 12 °C, the T(core) did not change throughout the exercise. In another set of experiments, rats were randomly assigned to receive bilateral 0.2 µL injections of 2.5 × 10(-2) M methylatropine or 0.15 M NaCl solution into the ventromedial hypothalamic nuclei (VMH). Immediately after the injections, treadmill exercise was started. Each animal was subjected to two experimental trials at one of the following T(a) : 5 °C, 12 °C or 15 °C. Muscarinic blockade of the VMH reduced the time to fatigue (TF) in cold environments by 35-37%. In all T(a) studied, methylatropine-treated rats did not present alterations in T(core) and tail skin temperature compared with controls. These results indicate that, below the zone of thermoneutrality, muscarinic blockade of the VMH decreases the TF, independent of changes in T(core). In conclusion, our data suggest that VMH muscarinic transmission modulates physical performance, even when the effects of thermoregulatory adjustments on fatigue are minimal.


Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Temperatura Baixa , Hipotálamo Médio/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Receptores Muscarínicos/fisiologia , Animais , Regulação da Temperatura Corporal/fisiologia , Hipotálamo Médio/fisiologia , Masculino , Fadiga Muscular/efeitos dos fármacos , Esforço Físico/fisiologia , Ratos , Ratos Wistar , Receptores Muscarínicos/administração & dosagem , Corrida/fisiologia
4.
Physiol Res ; 59(2): 165-175, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19537936

RESUMO

The effects of blocking ventromedial hypothalamic nucleus (VMH) muscarinic cholinoceptors on cardiovascular responses were investigated in running rats. Animals were anesthetized with pentobarbital sodium and fitted with bilateral cannulae into the VMH. After recovering from surgery, the rats were familiarized to running on a treadmill. The animals then had a polyethylene catheter implanted into the left carotid artery to measure blood pressure. Tail skin temperature (T(tail)), heart rate, and systolic, diastolic and mean arterial pressure were measured after bilateral injections of 0.2 microl of 5 x 10(-9) mol methylatropine or 0.15 M NaCl solution into the hypothalamus. Cholinergic blockade of the VMH reduced time to fatigue by 31 % and modified the temporal profile of cardiovascular and T(tail) adjustments without altering their maximal responses. Mean arterial pressure peak was achieved earlier in methylatropine-treated rats, which also showed a 2-min delay in induction of tail skin vasodilation, suggesting a higher sympathetic tonus to peripheral vessels. In conclusion, muscarinic cholinoceptors within the VMH are involved in a neuronal pathway that controls exercise-induced cardiovascular adjustments. Furthermore, blocking of cholinergic transmission increases sympathetic outflow during the initial minutes of exercise, and this higher sympathetic activity may be responsible for the decreased performance.


Assuntos
Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Condicionamento Físico Animal/fisiologia , Receptores Muscarínicos/fisiologia , Núcleo Hipotalâmico Ventromedial/fisiologia , Animais , Derivados da Atropina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Parassimpatolíticos/farmacologia , Ratos , Ratos Wistar , Temperatura Cutânea/efeitos dos fármacos , Temperatura Cutânea/fisiologia , Sistema Nervoso Simpático/fisiologia , Cauda , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Núcleo Hipotalâmico Ventromedial/efeitos dos fármacos
5.
J Hematol Oncol ; 11(1): 96, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041662

RESUMO

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteína Supressora de Tumor p14ARF/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico
6.
J Physiol Pharmacol ; 58(1): 3-17, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17440222

RESUMO

The aim of this study was to evaluate the effects of the stimulation of central cholinergic synapses in the regulation of heat loss in untrained rats during exercise. The animals were separated into two groups (exercise or rest) and tail skin temperature (T(tail)), core temperature and blood pressure were measured after injection of 2 microL of 5x10(-3) M physostigmine (Phy; n = 8) or 0.15 M NaCl solution (Sal; n = 8) into the lateral cerebral ventricle. Blood pressure was recorded by a catheter implanted into the abdominal aorta, T(tail) was measured using a thermistor taped to the tail and intraperitoneal temperature (T(b)) was recorded by telemetry. During exercise, Phy-treated rats had a higher increase in mean blood pressure (147 +/- 4 mmHg Phy vs. 121 +/- 3 mmHg Sal; P < 0.001) and higher T(tail) (26.4 +/- 1.0 degrees C Phy vs. 23.8 +/- 0.5 degrees C Sal; P < 0.05) that was closely related to the increase in systolic arterial pressure (r = 0.83; P < 0.001). In addition, Phy injection attenuated the exercise-induced increase in T(b) compared with controls without affecting running time. We conclude that the activation of central cholinergic synapses during exercise increases heat dissipation due to the higher increase in blood pressure.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Esforço Físico/fisiologia , Fisostigmina/farmacologia , Corrida , Acetilcolina/metabolismo , Animais , Área Sob a Curva , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Inibidores da Colinesterase/administração & dosagem , Injeções Intraventriculares , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Condicionamento Físico Animal , Fisostigmina/administração & dosagem , Ratos , Ratos Wistar , Temperatura Cutânea/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Telemetria , Fatores de Tempo
7.
Curr Mol Med ; 2016 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-26585986

RESUMO

Central nervous system (CNS) malignances include tumors of the brain and spinal cord. Taking into account the cell type where they originate from, there are almost 120 different types of CNS tumors. Benign tumors are not aggressive and normally do not invade other organs; however, they require surgical removal before they alter the surrounding brain functions. Primary malignant brain tumors commonly include astrocytomas, oligodendrogliomas, and ependimomas, where astrocytomas represent around 76%. The World Health Organization (WHO) has defined four histological grades of astrocytomas that range from the less aggressive tumors (grade I) to highly malignant tumors (grade IV). These grade IV tumors, also called glioblastoma (GBM), are the most aggressive of the primary malignant brain tumors. Patients with GBM have a median survival of 12 to 15 months. Current treatment for GBM includes surgery, radiotherapy and chemotherapy. Although there have been some advances in diagnosis and treatment, there is still no optimal treatment available for GBMs. In this review, we will discuss the approaches for GBM diagnosis and treatment, with a special emphasis to post-treatment imaging, and whether novel targeted therapies have impacted the survival of GBM patients. In addition, we will discuss clinical trials and the future of GBM diagnosis and treatment.

8.
J Clin Oncol ; 14(4): 1353-63, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8648394

RESUMO

PURPOSE: To evaluate prospectively the feasibility and results of bone marrow transplantation (BMT) after induction and intensification chemotherapy (CT) in patients with de novo acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 159 patients less than 51 years of age were treated. Induction CT consisted of daunorubicin 60 mg/m2 for 3 days, cytarabine (ARA-C) 100mg/m2 for 7 days, and etoposide 100 mg/m2 for 3 days. The first intensification therapy included mitoxantrone 10 mg/m2 for 3 days and ARA-C 1.2 g/m2 every 12 hours for 4 days. Amsacrine (100 or 150 mg/m2 for 3 days) and ARA-C (1.2 g/m2 every 12 hours for 2 or 4 days) were given as the second intensification therapy. Depending on the availability of a human leukocyte antigen (HLA)-identical sibling, the intention of treatment after CT was allogeneic BMT (allo-BMT) or autologous BMT (ABMT). RESULTS: Complete remission (CR) was obtained in 120 patients (75%) and partial remission (PR) in 11 (7%), while 15 patients (10%) were refractory and 13 (8%) died during induction. There was a trend for better leukemia-free survival (LFS) at 4 years for patients assigned to the ABMT group (50% +/- 6%) compared with the allo-BMT group (31% +/- 7%) (P = .08). This difference in LFS reached statistical significance when considering only transplanted patients (63% +/- 3% at 4 years after ABMT and 38% +/- 11% after allo-BMT, P = .02). The favorable results in patients who received ABMT (no toxic deaths and 37% +/- 7% probability of relapse at 4 years) contrast with the poor outcome of allografted patients (11 patients with transplant-related mortality). CONCLUSION: Our study reflects the difficulties in the completion of a therapeutic strategy that include BMT and suggests that intensification before BMT may be useful in the setting of ABMT, but this approach was associated with a high mortality rate in allo-BMT patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Adulto , Quimioterapia Adjuvante , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Lactente , Leucemia Mieloide/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Análise de Sobrevida , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
9.
Leukemia ; 17(1): 76-82, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12529663

RESUMO

The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.


Assuntos
Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Leucemia Mieloide/genética , Neoplasia Residual/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Doença Aguda , Adolescente , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/imunologia , Antígenos CD/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Southern Blotting , Cromossomos Humanos Par 11/genética , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Citometria de Fluxo , Duplicação Gênica , Histona-Lisina N-Metiltransferase , Humanos , Imunofenotipagem , Cariotipagem , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/patologia , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Reação em Cadeia da Polimerase , Prognóstico , Indução de Remissão
10.
J Parasitol ; 91(2): 284-92, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15986602

RESUMO

We describe here a fatty acid-binding protein (FABP) isolated and purified from the parasitic protozoon Giardia lamblia. The protein has a molecular mass of 8 kDa and an isoelectric point of 4.96. A Scatchard analysis of the data at equilibrium revealed a dissociation constant of 3.12 x 10(-8) M when the labeled oleic acid was displaced by a 10-fold greater concentration of unlabeled oleic acid. Testosterone, sodium desoxycholate, taurocholate, metronidazol, and alpha-tocopherol, together with butyric, arachidonic, palmitic, retinoic, and glycocholic acids, were also bound to the protein. Assays with polyclonal antibodies revealed that the protein is located in the ventral disk and also appears in the dorsal membrane, the cytoplasm, and in the vicinity of the lipid vacuoles.


Assuntos
Proteínas de Transporte/análise , Giardia lamblia/química , Proteínas de Protozoários/análise , Animais , Proteínas de Transporte/química , Proteínas de Transporte/isolamento & purificação , Proteínas de Transporte/metabolismo , Cromatografia de Afinidade , Eletroforese em Gel de Poliacrilamida , Proteínas de Ligação a Ácido Graxo , Técnica Indireta de Fluorescência para Anticorpo , Giardia lamblia/metabolismo , Giardia lamblia/ultraestrutura , Imuno-Histoquímica , Imunoprecipitação , Focalização Isoelétrica , Ponto Isoelétrico , Microscopia Imunoeletrônica , Peso Molecular , Proteínas de Protozoários/química , Proteínas de Protozoários/isolamento & purificação , Proteínas de Protozoários/metabolismo , Espectrometria de Fluorescência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
11.
Cytogenet Genome Res ; 101(3-4): 266-73, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14684993

RESUMO

The Arvicolidae is a widely distributed rodent group with several interesting characteristics in their sex chromosomes. Here, we summarize the actual knowledge of some of these characteristics. This mammalian group has species with abnormal sex determination systems. In fact, some species present the same karyotype in both males and females, with total absence of a Y chromosome, and hence of SRY and ZFY genes. Other species present fertile, sex-reversed XY females, generally due to mutations affecting X chromosomes. Furthermore, in Microtus oregoni males and females are gonosomic mosaic (the females are XO in the soma and XX in the germ cells, while the males are XY in the soma and OY in the germ cells). Regarding sex chromosomes, some species present enlarged (giant) sex chromosomes because of the presence of large blocks of constitutive heterochromatin, which have been demonstrated to be highly heterogeneous. Furthermore, we also consider the alterations affecting composition and localization of sex-linked genes or repeated sequences. Finally, this rodent group includes species with synaptic and asynaptic sex chromosomes. In fact, several species with asynaptic sex chromosomes have been described. It is interesting to note that within the genus Microtus both types of sex chromosomes are present.


Assuntos
Arvicolinae/genética , Cromossomos Sexuais , Processos de Determinação Sexual , Animais , Sequência de Bases , Mapeamento Cromossômico , Pareamento Cromossômico , Elementos de DNA Transponíveis , Proteínas de Ligação a DNA/genética , Feminino , Masculino , Sequências Repetitivas de Ácido Nucleico , Cromossomos Sexuais/química , Cromossomos Sexuais/ultraestrutura , Cromossomo X , Cromossomo Y
12.
Cytogenet Genome Res ; 106(2-4): 344-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15292614

RESUMO

Traditionally, B chromosomes have been classified as parasitic or heterotic, depending of whether or not they show selfish behaviour. Nevertheless, experimental evidence has been found supporting the idea that supernumerary chromosomes may evolve from parasitism to neutrality. In this work, B chromosome transmission in Rattus rattus has been analysed by performing several crosses between individuals carrying different numbers of supernumerary chromosomes. Our results demonstrated a Mendelian transmission rate through males, but slight accumulation of the Bs through females. This parasitic behaviour is shared in populations as distant as Asia and Africa, and even in a related species in Australia, suggesting the possibility of an ancient origin of these supernumerary chromosomes.


Assuntos
Cromossomos de Mamíferos/genética , Meiose/genética , Muridae/genética , África do Norte , Animais , Feminino , Masculino , Ratos
13.
Bone Marrow Transplant ; 21(10): 1023-7, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9632276

RESUMO

Over a 9-year period 37 consecutive adults with primary refractory (n = 13) or first relapse of ALL (n = 24) received an intensive salvage chemotherapy regimen with the final intention of undergoing stem cell transplantation (SCT). Twenty-nine patients who achieved complete remission (CR) were assigned to receive autologous SCT (autoSCT) or allogeneic SCT (alloSCT) based on age and availability of a histocompatible sibling. Of the 19 patients assigned to autoSCT, 10 did not reach the transplant due to early relapse (n = 9) or fungal infection (n = 1), and nine were transplanted a median of 2.5 months (1-8) from CR, eight with an immunologically purged graft. One patient died early from ARDS and eight relapsed 2-30 months post-SCT. Three of the 10 patients assigned to alloSCT relapsed early, but all 10 received the assigned transplant a median of 2.5 months (1-7) from CR. Four died from transplant-related complications 0.7-12 months post-SCT, and six are alive and disease-free 9.7-92.6 months after the procedure. In an intention-to-treat analysis, the mean overall survival from CR for those assigned to autoSCT and alloSCT are 11.3 months (0.5-34.3) and 60.1 (2.3-98.3), respectively (log-rank, P < 0.01). Only 65% of patients who reached CR and 51% of the initial 37 cases underwent the intended SCT. We conclude that few adults with refractory or relapsed ALL actually reach SCT in CR even when the protocol used is designed for this purpose. AutoSCT appears to offer little benefit in this setting, and an alloSCT from a related or unrelated donor should be rapidly pursued after achieving CR.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Terapia de Salvação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Transplante Autólogo , Transplante Homólogo
14.
Leuk Lymphoma ; 20(3-4): 321-6, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8624474

RESUMO

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 micrograms/kg) or granulocyte-macrophage colony-stimulating factor (10 micrograms/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 X 10(9)/l for three consecutive days. Eleven patients (58%, 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 X 10(9)/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leucemia/tratamento farmacológico , Terapia de Salvação/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
15.
Leuk Lymphoma ; 21(5-6): 467-72, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-9172812

RESUMO

Fludarabine produces high response rates in patients with B-cell chronic lymphocytic leukemia (CLL). Nevertheless, response to fludarabine of patients with previously treated CLL varies from 17% to 74% (0% to 38% CR). In 68 patients with heavily pretreated and advanced CLL, an overall response rate to fludarabine of 28% (4% CR) was observed. Response correlated with sensitivity of the disease to previous treatments (relapsing vs. refractory disease) (62% vs. 20%; p = 0.005) and, albeit not significantly, with the number of cycles of fludarabine (>3 vs. < or = 3) that patients could receive (36% vs. 15%; p = NS). Responding patients had a longer survival (median, not reached) than those not responding (median, 11 months) (p = 0.03). Severe toxicity was observed in some cases. It is concluded that fludarabine is a highly useful agent in CLL. However, in order to improve its effectiveness and decrease its toxicity, fludarabine should be given as soon as a lack of response to front-line therapy is observed and before the disease becomes completely resistant to therapy.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Vidarabina/análogos & derivados , Anemia Hemolítica Autoimune/induzido quimicamente , Anemia Hemolítica Autoimune/terapia , Antimetabólitos Antineoplásicos/efeitos adversos , Causas de Morte , Avaliação de Medicamentos , Febre/etiologia , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/induzido quimicamente , Humanos , Infecções/etiologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Tábuas de Vida , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação , Espanha/epidemiologia , Análise de Sobrevida , Reação Transfusional , Resultado do Tratamento , Vidarabina/efeitos adversos , Vidarabina/uso terapêutico
16.
Anat Embryol (Berl) ; 189(6): 531-7, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7978357

RESUMO

Male and female gonads from 7- to 9-day-old chick embryos were cultured for 6 days in Sertoli cell-conditioned medium or in serum-free medium to investigate the possible effect of substances secreted by rat Sertoli cells on chick gonad development. Histological analysis showed that whereas all female gonads proceed through normal ovarian development in both culture media, most of male gonads showed clear feminization only when cultured in Sertoli cell-conditioned medium; male gonads cultured in serum-free medium developed as normal testes. Because the only substance detected in our conditioned medium with the potential to cause these effects was sex-specific antigen (Sxs), our results provide further evidence that Sxs antigen may play a role in sexual differentiation in birds, and probably in mammals.


Assuntos
Síndrome de Resistência a Andrógenos/etiologia , Células de Sertoli/metabolismo , Testículo/citologia , Testículo/embriologia , Síndrome de Resistência a Andrógenos/patologia , Síndrome de Resistência a Andrógenos/fisiopatologia , Animais , Diferenciação Celular/efeitos dos fármacos , Embrião de Galinha , Meios de Cultivo Condicionados/farmacologia , Meios de Cultura Livres de Soro/farmacologia , Feminino , Antígeno H-Y/farmacologia , Masculino , Ovário/citologia , Ovário/efeitos dos fármacos , Ratos , Células de Sertoli/citologia , Diferenciação Sexual/efeitos dos fármacos , Diferenciação Sexual/fisiologia , Testículo/efeitos dos fármacos
17.
Theriogenology ; 43(3): 551-6, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16727646

RESUMO

This study was conducted over a 12-mo period to determine the rate of bovine embryo death between 30 and 60 d of gestation. In addition, palpation per rectum as a means of pregnancy detection was evaluated as a possible cause of embryo death. Estrus was synchronized in Holstein heifers (n = 1358), weighing > or = 385 kg, with a single intramuscular injection of 25 mg prostaglandin F(2alpha). Estrus was primarily detected by the absence of paint marks on the tailhead. The heifers were artificially inseminated with semen from 5 Holstein sires. Blood was collected between 30 and 45 d after breeding, and sera were evaluated for the presence of bovine pregnancy-specific protein B (bPSPB) by RIA to determine pregnancy. Palpation for fetal membrane slip was conducted by an experienced technician in approximately one-half of the inseminated heifers. To determine embryonic survival, a second blood sample was collected at approximately 60 d from 862 heifers that were determined to be pregnant at the first blood sampling. Embryonic loss averaged 5.3% during the interval between the initial detection of pregnancy at 30 to 45 d and the subsequent detection of pregnancy at 60 d of gestation. Embryo loss in heifers that were palpated was 6.5% compared with that of 4.3% in the control heifers (X(2): P = 0.145). These findings establish that there was substantial loss of embryos between 30 and 60 d post breeding but that embryo loss was not affected by palpation per rectum.

18.
J Anim Sci ; 75(12): 3089-93, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9419980

RESUMO

The efficacy of erodible norgestomet implants for preventing pregnancy in postpubertal heifers was evaluated in two experiments at five locations each. Heifers (n = 896) within each study location were stratified by weight and allotted randomly to receive an ear implant containing either 0, 24, 36, or 48 mg of norgestomet (d 0). Heifers were exposed to fertile bulls immediately after implantation for 75 d (d 0 to 74) in Exp. 1 (n = 476) or for 80 d (d 75 to 154) in Exp. 2 (n = 420). Weights were recorded on d 0 and 74 (Exp. 1 and 2) and d 154 (Exp. 2). Each heifer was palpated rectally for pregnancy at the end of each experiment. Pregnancy rates were higher (P < .01) for control heifers (0 mg implant) than for heifers that received 24, 36, or 48 mg of norgestomet. In Exp. 1, pregnancy rates were 96, 29, 6, and 4% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. In Exp. 2, pregnancy rates were 85, 36, 19, and 9% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. Estrous activity during the first 3 wk of bull exposure was reduced (P < .05) among heifers that received norgestomet implants compared to control heifers but was not completely abolished at any dosage in Exp. 1. During the first 75 d of Exp. 1 and 2, heifers treated with 36 or 48 mg norgestomet implants gained weight faster (P < .05) than control heifers. Combined across both experiments, ADG during the first 74 d were .53, .56, .59, and .60 kg/d for heifers treated with 0, 24, 36, and 48 mg implants of norgestomet, respectively. These data indicate that norgestomet implants increased rate of weight gain, reduced estrous activity, and reduced the occurrence of pregnancy in heifers on pasture.


Assuntos
Ração Animal , Bovinos/fisiologia , Prenhez/efeitos dos fármacos , Pregnenodionas/farmacologia , Congêneres da Progesterona/farmacologia , Animais , Relação Dose-Resposta a Droga , Implantes de Medicamento , Estro/efeitos dos fármacos , Estro/fisiologia , Feminino , Fertilidade/efeitos dos fármacos , Fertilidade/fisiologia , Masculino , Gravidez , Taxa de Gravidez , Prenhez/fisiologia , Pregnenodionas/administração & dosagem , Congêneres da Progesterona/administração & dosagem , Distribuição Aleatória , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/fisiologia
19.
Rev Neurol ; 35(11): 1027-9, 2002.
Artigo em Espanhol | MEDLINE | ID: mdl-12497308

RESUMO

INTRODUCTION: Systemic lymphoma with meningeal involvement is frequent and diagnosis is based on the clinical features, the study of the cerebrospinal fluid and evaluation by magnetic resonance imaging (MRI). Lymphoma with involvement of the orbitary region is more frequent in the optic nerve (ON) than of the eye itself. CLINICAL CASE: We report the case of a patient with diffuse non Hodgkin gastric lymphoma of the large B cell type, which coursed with amaurosis, exophthalmus and signs of tumorous meningeal involvement. The ophthalmologic study revealed a thrombosis in the central retinal vein. The MRI exploration only showed an infiltration of the ON with no pathological meningeal enhancement. ON involvement consisted in a peripheral enhancement of the sheath with obliteration of the subarachnoid space. This pattern accounts for the existence of an ischemic neuropathy by direct compression over the central retinal vein and artery. There are different anatomopathologic or ophthalmologic studies of neuropathy of the ON by lymphoma in the literature, but there is only one case of diagnosis by MRI. CONCLUSIONS: ON involvement can be the only radiological sign in cases of neoplastic tumours with meningeal involvement. The radiological pattern consists in a peripheral infiltration of the sheath of the ON.


Assuntos
Linfoma/diagnóstico , Linfoma/patologia , Neoplasias do Nervo Óptico/diagnóstico , Neoplasias do Nervo Óptico/patologia , Humanos , Linfoma de Células B/patologia , Linfoma não Hodgkin/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias do Nervo Óptico/secundário
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