RESUMEN
PER3 gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess: i) the frequency of allelic variants at two PER3 polymorphic sites (rs57875989 length polymorphism: PER3 4, PER3 5; rs228697 SNP: PER3 C, PER3 G) in relation to sleep-wake timing; ii) the effect of morning light on behavioural/circadian variables in PER3 4 /PER3 4 and PER3 5 /PER3 5 homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19 PER3 4 /PER3 4 and 11 PER3 5 /PER3 5 homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between the PER3 G variant and morningness (OR = 2.10), and between the PER3 G-PER3 4 haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms between PER3 5 /PER3 5 and PER3 4 /PER3 4 subjects at baseline. After light administration, PER3 4 /PER3 4 subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed between PER3 polymorphic variants/their combinations and both diurnal preference and the response to light.
Asunto(s)
Afecto , Ritmo Circadiano , Proteínas Circadianas Period/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Femenino , Frecuencia de los Genes , Humanos , Italia , Masculino , Melatonina/análogos & derivados , Melatonina/orina , Persona de Mediana Edad , Fotofobia/genética , Sueño , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of neuronal signaling in the central nervous system. The beneficial effects of the immunomodulatory treatment with minocycline on schizophrenic patients are consistent with this hypothesis. Using the MIA mouse model, we found an altered microglial transcriptome and phagocytic function in the adult offspring accompanied by behavioral abnormalities. The changes in microglial phagocytosis on a functional and transcriptional level were similar to those observed in a mouse model of Alzheimer's disease hinting to a related microglial phenotype in neurodegenerative and psychiatric disorders. Minocycline treatment of adult MIA offspring reverted completely the transcriptional, functional and behavioral deficits, highlighting the potential benefits of therapeutic targeting of microglia in psychiatric disorders.
Asunto(s)
Hijos Adultos/psicología , Antibacterianos/farmacología , Fenómenos del Sistema Inmunológico/efectos de los fármacos , Microglía/efectos de los fármacos , Minociclina/farmacología , Transmisión Sináptica/fisiología , Transcriptoma/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Animales , Antibacterianos/administración & dosificación , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Fenómenos del Sistema Inmunológico/fisiología , Ratones , Ratones Endogámicos C57BL/inmunología , Microglía/metabolismo , Minociclina/administración & dosificación , Fagocitosis/inmunología , Embarazo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genéticaRESUMEN
This study analyzed the carapace distribution of Ca, Cd, Cr, Cu, Mg, Mn, Pb, Sb, U, V and Zn by GF-AAS and ICP-AES in one specimen of Caretta caretta from Mediterranean Sea. Calcium, Mg, Mn, Pb, U, Zn were mainly distributed in the central area while Cd, Cr, Cu, Sb, V in lateral areas. Cadmium, Cr, Mg, Mn, Sb, U and V were different between lateral areas. The different distribution may be related to several exposures during lifetime and/or the shell ossification during growth. Carapace may be a suitable matrix for metal biomonitoring, however, further studies are required to confirm these findings.
Asunto(s)
Exoesqueleto/química , Monitoreo del Ambiente/métodos , Metales/farmacocinética , Tortugas/metabolismo , Contaminantes Químicos del Agua/análisis , Animales , Exposición a Riesgos Ambientales/análisis , Mar Mediterráneo , Metales/análisis , Distribución Tisular , Contaminantes Químicos del Agua/farmacocinéticaAsunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Common bean (Phaseolus vulgaris F.) is one of the most important crops in Paraná State, which is responsible for almost 10% of the Brazilian production (4). Root knot nematodes, Meloidogyne spp., are common parasites of this crop worldwide, but damage caused by Meloidogyne inornata has not been reported. During a survey of nematode species present on common bean fields in Paraná State, Brazil, galled root samples of cultivars Tuiuiú and Eldorado were submitted, in June 2012, in the Nematology Laboratory from IAPAR, collected in the municipalities of Araucária (25°35'34â³S, 49°24'36â³W) and Santana do Itararé (23°45'18â³S, 49°37'44â³W). Plants did not exhibit any above-ground symptoms. The specimens were identified through perineal patterns and esterase phenotypes of 20 adult females extracted from dissected roots (2,3). The population densities observed in the samples were 140 and 700 J2 and eggs per gram of roots, respectively, for both samples. Characteristics were consistent with those described for M. inornata. For example, perineal patterns of M. inornata showed a high dorsal arch, with smooth to wavy striae, similar to those of M. incognita; but no punctate markings between anus and tail terminus were observed. However, from the esterase electrophoresis we obtained the I3 (Rm = 0.83, 1.15, and 1.32) phenotype, typical of M. inornata, a species-specific phenotype used to differentiate this species from M. incognita (1). Moreover, the excretory pore of adult females was located 32.1 (± 5.4) µm from the anterior end, consistent with the M. inornata description (25 to 53 µm) (1). To the best of our knowledge, this is the first report of M. inornata parasitizing common bean roots. This finding has great importance for Brazilian agriculture, since this nematode may damage common bean plants and become an additional problem for this crop. Additional work is necessary in order to elucidate the losses caused by M. inornata on common bean. References: (1) R. M. D. G. Carneiro et al. Nematology 10:123, 2008. (2) P. R. Esbenshade and A. C. Triantaphyllou J. Nematol. 22:10, 1990. (3) K. M. Hartman and J. N. Sasser. Page 115 in: An Advanced Treatise on Meloidogyne, Volume II Methodology. K. R. Barker et al., eds. Raleigh: North Carolina State University Graphics, 1985. (4) MAPA. Feijão, Ministério da Agricultura, Brasil. Retrieved from http://www.agricultura.gov.br/vegetal/culturas/feijao September 05, 2012.
RESUMEN
Chemical elements and persistent organic pollutants (POPs) are globally present in aquatic systems and their potential transfer to loggerhead marine turtles (Caretta caretta) has become a serious threat for their health status. The environmental fate of these xenobiotics may be traced by the analysis of turtles' tissues and blood. Generally, loggerhead turtles exhibited a higher metal load than other turtle species, this could be explained by differences in diet habits being food the main source of exposure. Literature shows that muscle, liver and kidney are most considered for the quantification of chemical elements, while, organic compounds are typically investigated in liver and fat. This paper is an overview of the international studies carried out on the quantification of chemical elements, polychlorinated biphenyls (PCBs), organochlorines (OCs) and perfluorinated compounds (PFCs), in tissues, organs and fluids of C. caretta from the Mediterranean Sea, the Atlantic and the Pacific Oceans.
Asunto(s)
Monitoreo del Ambiente , Compuestos Orgánicos/análisis , Plásticos/análisis , Tortugas/metabolismo , Contaminantes Químicos del Agua/análisis , Animales , Océanos y Mares , Compuestos Orgánicos/farmacocinética , Plásticos/farmacocinética , Distribución Tisular , Contaminantes Químicos del Agua/farmacocinéticaAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos , Aspergilosis , Glomerulonefritis Membranosa/etiología , Enfermedad Injerto contra Huésped , Humanos , Masculino , Persona de Mediana Edad , Rituximab , Trasplante HomólogoAsunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Hipertensión Pulmonar/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/terapia , Pirimidinas/efectos adversos , Tiazoles/efectos adversos , Disfunción Ventricular Derecha/tratamiento farmacológico , Dasatinib , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Leucemia Mieloide de Fase Crónica/diagnóstico , Masculino , Persona de Mediana Edad , Trasplante Homólogo , Disfunción Ventricular Derecha/complicaciones , Disfunción Ventricular Derecha/diagnósticoRESUMEN
BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Micosis/epidemiología , Complicaciones Posoperatorias/microbiología , Adolescente , Adulto , Anciano , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/microbiología , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Candidiasis/microbiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Micosis/tratamiento farmacológico , Micosis/microbiología , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Proliferación Celular , Trasplante de Células Madre de Sangre del Cordón Umbilical , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/patología , Células Precursoras de Linfocitos B/patología , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Antígenos CD/genética , Antígenos CD/inmunología , Cromosomas Humanos X/genética , Cromosomas Humanos X/inmunología , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Diarrea/tratamiento farmacológico , Diarrea/etiología , Diarrea/genética , Diarrea/inmunología , Resultado Fatal , Femenino , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/efectos adversos , Supervivencia de Injerto/inmunología , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Ileus/tratamiento farmacológico , Ileus/etiología , Ileus/genética , Ileus/inmunología , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Infliximab , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/inmunología , Neoplasia Residual , Células Precursoras de Linfocitos B/inmunología , Quimera por Trasplante/genética , Quimera por Trasplante/inmunología , Acondicionamiento PretrasplanteRESUMEN
The cyanobacterium Planktothrix rubescens Anagnostidis & Komarek (previously Oscillatoria rubescens DC ex Gomont) is present in several Italian lakes and it is known to produce cyanotoxins. The dynamics and toxin production of P. rubescens population in Lake Albano, a volcanic crater lake in Central Italy, has been studied for 5 years (January 2001-April 2005). Winter-spring superficial blooms with frequent scums were observed every year. Total microcystin (MC) levels were measured from April 2004 to October 2005 by liquid chromatography-tandem mass spectrometry. MC levels up to 14.2mug/l were measured, with high concentrations found in summer at a 20-25m depth. The intracellular toxin content varied between 1.5 (surface, January 2004) and 0.21pg/cell (surface, May 2004). Six different MCs were detected, the most abundant being two desmethyl-MC-RR isomers. Of the 13 water wells monitored in the Lake Albano area, two of them showed MC contamination during winter, confirming the ability of these toxins to migrate through groundwater towards public water sources. These results highlight the need for further studies on the mobility and fate of these pervasive cyanobacterial toxins.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Cianobacterias/metabolismo , Monitoreo del Ambiente , Agua Dulce/microbiología , Péptidos Cíclicos/biosíntesis , Microbiología del Agua , Cromatografía Líquida de Alta Presión , Cianobacterias/crecimiento & desarrollo , Agua Dulce/química , Italia , Espectrometría de Masas , Microcistinas , Estaciones del Año , Contaminantes del Agua/análisisRESUMEN
The use of natural products as a diet supplement is increasing worldwide but sometimes is not followed by adequate sanitary controls and analyses. Twenty samples of pills and capsules of lyophilised cyanobacteria (blue-green algae), commercialised in Italy as dietary supplements, were found positive at the Vibrio fischeri bioassay. Further analyses with ELISA and LC-MS/MS methods revealed the presence of four microcystin (MC) analogues, MC-LR, -YR, -LA, -RR and two demethylated forms of MC-RR. The highest total microcystin content was 4.5 and 1.4 microg g-1 in pills and capsules, respectively. The ELISA measurements, compared to the LC-MS/MS analyses, showed significantly lower concentrations of microcystins in pills, this confirming a possible ELISA underestimate of mixed microcystins, due to different sensitivities for some toxic analogues.
Asunto(s)
Toxinas Bacterianas/análisis , Cianobacterias/química , Suplementos Dietéticos/análisis , Péptidos Cíclicos/análisis , Aliivibrio fischeri/crecimiento & desarrollo , Animales , Ensayo de Inmunoadsorción Enzimática , Cromatografía de Gases y Espectrometría de Masas , Toxinas Marinas , MicrocistinasRESUMEN
OBJECTIVE: To evaluate the clinical characteristics and outcome of NK/T-cell lymphoma 'nasal type' developed in Italian patients. PATIENTS: Between 1997 and 2004, 26 new cases of NK/T-cell lymphoma 'nasal type' were diagnosed in 10 Italian Hematology institutions. RESULTS: All patients were Caucasian, male/female ratio was 19/7, with a median age of 50 years (range 20-80). In 23 cases presentation at the onset was in the nasal cavity or adjacent structures, in two cases the lymphoma onset with skin lesions was followed successively by rhynopharyngeal dissemination, while the remaining case had bone marrow and lymph node involvement followed by oro-pharyngeal involvement. Regarding the stage of disease: 12 patients were in stage I; six in stage II; eight in stage IV. Diagnosis was based on the finding of a NK/T-cell phenotype at the histological and immunophenotypic examination of oropharyngeal or cutaneous lesions. All patients but one were treated with chemotherapy, alone in nine cases or associated to radiotherapy in 14 cases; two patients had chemotherapy, radiotherapy and surgery, while one patient underwent only surgery. Chemotherapy was anthracycline-based in 17 out of 25 cases. In those patients in whom radiotherapy was performed, radiation dosages ranged between 36 Gy and 47.5 Gy, with a median dosage of 40 Gy. Nine patients (34%) were responsive to the treatments: six patients obtained a complete remission and other three a partial remission. The remaining 17 patients resulted refractory or presented a limited response to therapy. The median disease-free survival was 14 months and the median overall survival time was 9 months. CONCLUSION: The results of this retrospective survey confirmed that NK/T-cell lymphoma 'nasal type' is a very rare lymphoma in the Italian population, and it is characterized by a very bad prognosis. Due to the rarity of this disease, a standardized therapeutic approach is lacking. More data are needed to know the epidemiology of this kind of lymphoma in Europe.
Asunto(s)
Células Asesinas Naturales/patología , Linfoma de Células T/patología , Cavidad Nasal/patología , Estadificación de Neoplasias , Neoplasias Nasales/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasales/terapia , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Resistance to acetolactate synthase (ALS)-inhibiting herbicides in Brazil has been documented for six species. The probability to select biotypes of Euphorbia heterophylla (EPPHL) with multiple resistance increases in the same order of magnitude as the use of other herbicides belonging to only one mechanism of action. The objectives of this work were to evaluate the distribution of resistant populations (R) in the states of the Parana and Santa Catarina; to determine the existence of populations of EPHHL with multiple resistance to ALS and PROTOX inhibitors, and to confirm the occurrence of cross resistance to compounds of these mechanisms of action. Seeds of EPHHL of areas with suspected resistance had been sampled in 97 places during 2003. In the greenhouse experiment samples of each population were sprayed with imazethapyr or fomesafen, at only one rate. To identify the resistant ones they were sprayed with different levels of the herbicides imazethapyr and fomesafen. Later they were sprayed with diverse herbicides of the same mechanisms of action to confirm the multiple/cross resistance. There is widespread distribution in the region of populations with resistance to ALS inhibitors. Some biotypes demonstrated resistance to herbicides from the two mechanisms of action. The resistance factor (FR), or the relation of resistance between R and susceptible biotypes, confirms the existence of two biotypes of EPHHL with cross resistance to several herbicides inhibitors of ALS and PROTOX.
Asunto(s)
Acetolactato Sintasa/antagonistas & inhibidores , Acetolactato Sintasa/farmacología , Resistencia a Múltiples Medicamentos , Euphorbia/enzimología , Euphorbia/crecimiento & desarrollo , Herbicidas/farmacología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/farmacología , Acetolactato Sintasa/efectos de los fármacos , Adaptación Fisiológica , Brasil , Monitoreo del Ambiente , Inhibidores Enzimáticos/farmacología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/efectos de los fármacos , Control de Plagas , Dinámica Poblacional , Protoporfirinógeno-OxidasaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia Mieloide/tratamiento farmacológico , Neoplasias Primarias Secundarias/inducido químicamente , Enfermedad Aguda , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Insuficiencia del TratamientoRESUMEN
We report two cases of Acremonium fungemia with proven involvement of the skin and probably of the lung in patients who were both undergoing chemotherapy, one for mantle cell lymphoma and the other for acute lymphoblastic leukemia. Both patients failed amphotericin B deoxycholate treatment and were successfully treated with voriconazole with very mild toxicity.
Asunto(s)
Acremonium/efectos de los fármacos , Antifúngicos/uso terapéutico , Fungemia/tratamiento farmacológico , Infecciones Oportunistas/tratamiento farmacológico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Antineoplásicos/uso terapéutico , Femenino , Fungemia/microbiología , Humanos , Linfoma de Células del Manto/complicaciones , Linfoma de Células del Manto/tratamiento farmacológico , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pirimidinas/administración & dosificación , Pirimidinas/farmacología , Triazoles/administración & dosificación , Triazoles/farmacología , VoriconazolRESUMEN
The management of invasive aspergillosis in patients with hematological malignancies remains controversial. A major problem is how to manage patients who had invasive aspergillosis during remission induction and consolidation therapy and then undergo SCT. Indeed in these patients the mortality rate related to invasive aspergillosis recurrence remains unacceptably high. We report two cases of patients who underwent remission induction for AML, developed invasive aspergillosis during antifungal prophylaxis with itraconazole, failed amphotericin B deoxycholate and liposomal amphotericin B treatment, were successfully treated with voriconazole and eventually underwent SCT with voriconazole prophylaxis without reactivation of invasive aspergillosis.
Asunto(s)
Aspergilosis/tratamiento farmacológico , Trasplante de Médula Ósea/efectos adversos , Ácido Desoxicólico/análogos & derivados , Leucemia Megacarioblástica Aguda/terapia , Leucemia Mielomonocítica Aguda/terapia , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Adulto , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aspergilosis/etiología , Aspergilosis/prevención & control , Terapia Combinada , Citarabina/administración & dosificación , Citarabina/efectos adversos , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Ácido Desoxicólico/administración & dosificación , Ácido Desoxicólico/uso terapéutico , Combinación de Medicamentos , Farmacorresistencia Fúngica , Etopósido/administración & dosificación , Etopósido/efectos adversos , Resultado Fatal , Humanos , Huésped Inmunocomprometido , Itraconazol/uso terapéutico , Leucemia Megacarioblástica Aguda/complicaciones , Leucemia Megacarioblástica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/complicaciones , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Liposomas , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Terapia Recuperativa , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo/efectos adversos , Trasplante Homólogo/efectos adversos , VoriconazolRESUMEN
The malaria parasite, Plasmodium falciparum, synthesises and exports several proteins inducing morphological and biochemical modifications of erythrocytes during the erythrocytic cycle. The protein trafficking machinery of the parasite is similar to that of other eukaryotic cells in several ways. However, some unusual features are also observed. The secretion of various polypeptides was inhibited when P. falciparum-infected erythrocytes were incubated with Brefeldin A. Immunoelectron microscopy studies revealed substantial morphological changes in the endoplasmic reticulum following exposure of parasitised erythrocytes to the drug. Immunofluorescence studies of Brefeldin A-treated parasites suggest that polypeptide sorting to different intracellular destinations begins at the endoplasmic reticulum. The parasite also secretes polypeptides by a Brefeldin A-insensitive route that bypasses the classical endoplasmic reticulum-Golgi complex pathway.
Asunto(s)
Plasmodium falciparum/metabolismo , Señales de Clasificación de Proteína/fisiología , Proteínas Protozoarias/metabolismo , Animales , Brefeldino A/farmacología , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/fisiología , Eritrocitos/parasitología , Técnica del Anticuerpo Fluorescente , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/fisiología , Humanos , Malaria Falciparum/parasitología , Microscopía Inmunoelectrónica , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/fisiología , Plasmodium falciparum/ultraestructura , Señales de Clasificación de Proteína/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/farmacología , Proteínas Protozoarias/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVES: We report the activity of two combinations of fludarabine (FLU), one with cyclophosphamide (FLU/CY) and the second with CY plus mitoxantrone (FLU/CY/MITO). The aim of the study was to evaluate the activity and toxicity of these two schedules in patients with non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: Twenty-two patients with recurrent low grade non-Hodgkin's lymphoma (LGL) received FLU/CY (FLU 25 mg/m(2) days 1 to 3, CY 300 mg/m(2) days 1 to 3), and 31 patients received FLU/CY/MITO (FLU 25 mg/m(2) days 1 to 3, CY 300 mg/m(2) days 1 to 3, mitoxantrone 10 mg/m(2) day 1). Patients received antibiotic oral prophylaxis during all treatments and growth factors (G-CSF) when grade III granulocytopenia (WHO scale) occurred. RESULTS: Of the 53 patients, 31 achieved complete remission (CR) (58%) and 16 partial remission (PR) (30%). Response was similar in both arms of the study. After 3 courses, 77% of patients who achieved CR showed a complete disappearance of disease. Seventy-nine per cent of patients experienced granulocytopenia. Few patients had fever, all without infection. One patient died with fever of unknown origin three months after completion of six courses of treatment. INTERPRETATION AND CONCLUSIONS: Both treatments were seen to be effective in recurrent low-grade NHL. Antibiotic prophylaxis with G-CSF support seems to reduce treatment-related infection.