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2.
Expert Opin Pharmacother ; 14(16): 2263-80, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24053161

RESUMO

INTRODUCTION: Bendamustine is a unique bifunctional alkylating agent with promising activity in multiple myeloma (MM). It is currently licensed in Europe for use as frontline treatment with prednisolone for patients with MM who are unsuitable for transplantation and who are contraindicated for thalidomide and bortezomib therapy. AREAS COVERED: Studies evaluating the safety and efficacy of bendamustine administered alone or in combination in both the upfront and relapse settings of MM patients, including those with renal insufficiency, were reviewed. The use of bendamustine as conditioning for autologous stem-cell transplantation and the possibility of stem-cell mobilization after bendamustine therapy are discussed. EXPERT OPINION: Bendamustine seems to be efficacious either in monotherapy or in combination with other drugs in previously treated or untreated patients. This is due to its unique mechanism of action including its ability to activate apoptosis and inhibit mitotic checkpoints, making it potentially more effective than other alkylating agents. Moreover, it has an acceptable toxicity profile and is suitable for patients with renal impairment. Finally, this drug does not seem to compromise the possibility of achieving a stem-cell mobilization. Nonetheless, data from Phase III studies demonstrating its effectiveness in terms of overall survival are not yet available.


Assuntos
Alquilantes/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Compostos de Mostarda Nitrogenada/uso terapêutico , Cloridrato de Bendamustina , Humanos , Resultado do Tratamento
3.
Case Rep Genet ; 2013: 573841, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23509644

RESUMO

Objective. To assess aetiology of a POF in a 33-year-old woman and, if possible, plan a cure. Design. Case report. Setting. medical genetics diagnostic unit in a university hospital. Patient. A 33-year-old woman with premature ovarian failure (POF). Intervention(s). Genetic counseling, karyotyping, FISH study. Result(s). Turner-like diagnosis. Conclusion(s). Most cases of POF remain idiopathic. Turner syndrome can occur in very different phenotypes; cytogenetic and molecular profiling can provide a definitive diagnosis in cases with nonclassical phenotype.

4.
Behav Neurosci ; 120(6): 1235-41, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17201467

RESUMO

The hibernating golden hamster (Mesocricetus auratus) is becoming a useful rodent model to study the neurophysiological role of some neuromediators on vital behaviors such as sleep and thermoregulation. Recent works have shown that the histamine neuroreceptor subtypes (H-sub(1-3)R) are able to modulate such behaviors. Here, specific subtype(s) and cerebral nuclei that were actively operating on feeding behaviors in pubertal and adult hamsters were identified. Of the subtypes assessed, H-sub-3R antagonist (thioperamide) provoked significant (p < .001) changes in behavior (very low total food and water intake) in adults, whereas it did not significantly modify these behaviors in pubertals. The H-sub-3R antagonist's role seemed to be related to elevated amounts of stress-induced damaged neurons displaying, mainly, shrunken crenated cell membranes and altered synaptic processes in limbic areas such as amygdala, cortex, and hippocampus. At the transcription level, an evident expression pattern of H-sub-3R messenger RNA appeared in pubertals, especially in neurons of the cortex and hippocampus, whereas the same trend was featured in amygdalar areas of hibernating adult hamsters, suggesting early H-sub-3R regulatory activities, at least in limbic sites of this rodent model.


Assuntos
Envelhecimento/fisiologia , Encéfalo/metabolismo , Comportamento Alimentar/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Receptores Histamínicos H3/metabolismo , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Encéfalo/ultraestrutura , Cricetinae , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Histamina/farmacocinética , Antagonistas dos Receptores Histamínicos H1/farmacologia , Hibridização In Situ/métodos , Masculino , Mesocricetus , Microscopia Eletrônica de Transmissão/métodos , Ligação Proteica/efeitos dos fármacos , Receptores Histamínicos H3/genética , Trítio/farmacocinética
5.
J Pharmacol Exp Ther ; 315(1): 188-95, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15976014

RESUMO

The neurotoxic 3-nitropropionic acid (3-NP), a freckled milk vetch-derived inhibitor of mitochondrial enzymatic processes that is capable of mimicking the typical pathological features of neurodegenerative disorders, behaved in a differentiated manner in a hibernating rodent (hamster) with respect to a nonhibernating rodent (rat). Treatment of the two rodents with both an acute and chronic 3-NP dose supplied deleterious neuronal effects due to distinct histamine receptor (H(n)R) transcriptional activities, especially in the case of the rat. In hamsters, these treatment modalities accounted for overall reduced global activity in a freely moving environment and overt motor symptoms such as hindlimb dystonia and clasping with respect to the greater abnormal motor behaviors in rats. This behavioral difference appeared to be strongly related to qualitative fewer neuronal alterations and, namely, lesser crenated cell membranes, swollen mitochondria, and darkened nuclei in hamster brain areas. Moreover, a mixed H(1,3)R mRNA expression pattern was reported for both rodents treated with a chronic 3-NP dose as demonstrated by predominantly low H1R mRNA levels (>50%) in rat striatum and cortex, whereas extremely high H3R levels (>80%) characterized the lateral and central amygdala nuclei plus the striatum of hamsters. Interestingly, the H3R antagonist (thioperamide) blocked 3-NP-dependent behaviors plus induced an up-regulation of H1R levels in mainly the above-reported hamster amygdalar nuclei. Overall, these results show, for the first time, that a major protective role against neurodegenerative events appears to be strongly related to the expression activity of H(1,3)R subtypes of amygdalar neurons in this hibernating model.


Assuntos
Doenças Neurodegenerativas/prevenção & controle , Nitrocompostos/toxicidade , Propionatos/toxicidade , Receptores Histamínicos H1/fisiologia , Receptores Histamínicos H3/fisiologia , Transdução de Sinais/fisiologia , Animais , Cricetinae , Mesocricetus , RNA Mensageiro/análise , Ratos , Ratos Wistar , Receptores Histamínicos H1/genética , Receptores Histamínicos H3/genética
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