Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutations.

The efficacy of tyrosine kinase (TK) inhibitors on non-cycling acute myeloid leukaemia (AML) cells, previously shown to have potent tumourigenic potential, is unknown. This pilot study describes the first attempt to characterize non-cycling cells from a small series of human FMS-like tyrosine kinase 3 (FLT3) mutation positive samples. CD34+ AML cells from patients with FLT3 mutation positive AML were cultured on murine stroma. In expansion cultures, non-cycling cells were found to retain CD34+ expression in contrast to dividing cells. Leukaemic gene rearrangements could be detected in non-cycling cells, indicating their leukaemic origin. Significantly, the FLT3-internal tandem duplication (ITD) mutation was found in the non-cycling fraction of four out of five cases. Exposure to the FLT3-directed inhibitor TKI258 clearly inhibited the growth of AML CD34+ cells in short-term cultures and colony-forming unit assays. Crucially, non-cycling cells were not eradicated, with the exception of one case, which exhibited exquisite sensitivity to the compound. Moreover, in longer-term cultures, TKI258-treated non-cycling cells showed no growth impairment compared to treatment-naive non-cycling cells. These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted.

Low frequency of the TEL/AML1 fusion gene in acute lymphoblastic leukaemia in Spain.

We report on a series of Spanish patients with acute lymphoblastic leukaemia in whom the t(12;21) [TEL/AML1] translocation could not be identified with two sensitive techniques: reverse transcript-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH). 101 cases were analysed: 38 children (29 B-cell precursor; nine T-cell precursor) and 63 adults (48 B-cell precursor; 15 T-cell precursor). Specific RT-PCR to amplify the TEL/AML1 fusion transcript was negative in all 101 cases. Moreover, all 38 paediatric samples were also negative by interphase FISH analysis for the presence of the TEL/AML1 fusion. These results suggest the existence of geographic/race variations in the genotype of acute lymphoblastic leukaemia (ALL).

Usefulness of clinical observations and blood chemistry values for predicting clinical outcomes in dairy goats with pregnancy toxaemia

Background Pregnancy toxaemia (PT) is a disease that affects pregnant goats during their last month of gestation and is characterized by a high case fatality rate. This study involved 32 does maintained on a commercial dairy goat farm that were diagnosed with PT. A physical examination was performed on and haematology parameters obtained from each doe, at the time of diagnosis. The data from the 24 PT goats that died was compared with the corresponding data from the 8 PT goats that survived. Results Polypnea, swollen limbs, anorexia with absence of ruminal motility, recumbency, nervous signs and drooping ears were the most frequently observed clinical manifestations. Nineteen out of 21 recumbent goats died. Sixteen out of 17 goats with anorexia and absence of ruminal motility died. Mean beta-hydroxybutyric acid (BHBA) values in the goats that died were not significantly different from those in goats that survived. The blood values for pH and pCO2 (p < 0.005) as well as for HCO3 −, BE and K+ (p < 0.001) were significantly lower in the goats that died than in those that survived. Conclusions The clinical signs most indicative of a poor prognosis are anorexia with absence of ruminal motility and recumbency. Among the blood parameters to be considered, hypokalaemia and metabolic acidosis are the most relevant. Goats with PT have a high mortality and their condition can deteriorate very fast. Based on the authors’s experience, a good strategy to minimize the economic losses caused by PT is to focus on the offspring survival rate since an early decision (induction of kidding or caesarian surgery) can increase the number of alive kids.

Haematological characteristics of Brazilian Teleosts: III. Parameters of the hybrid tambacu (Piaractus mesopotamicus Holmberg x Colossoma macropomum Cuvier) (Osteichthyes, Characidae)

Fifty six specimens of the hybrid tambacu (Piaractus mesopotamicus Holmberg, 1887 male x Colossoma macropomum Cuvier, 1818 female) were collected from fishfarm of Guariba, São Paulo, to evaluate their haematology. Fishes presented 400.0 to 3,100.0 g total weight and 20.0 to 52.0 cm total length. Haemoglobin, haematocrit, mean corpuscular haemoglobin content (MCHC) and percentage of defense blood cells including leucocytes and thrombocytes, were studied. Statistical analysis showed positive correlation (P<0.01) between haematocrit, MCHC and haemoglobin rate. Nevertheless, thrombocytes and lymphocytes showed negative correlation (P<0.01).

Revisión del uso de los medicamentos biosimilares vs. biológicos: implicaciones para la salud en Colombia.

Este documento tiene como objetivo describir las implicaciones para la salud con el uso de medicamentos biosimilares en comparación con los medicamentos biológicos en Colombia. Así mismo, describir el contexto normativo acerca del uso de medicamentos biosimilares, las recomendaciones y lineamientos sobre seguridad y efectividad del uso de medicamentos Biosimilares y Biológicos, partiendo de sus diferencias biomoleculares. Para esto, se desarrolló una revisión documental electrónica y manual de la literatura en bases de datos, revistas y libros limitada a términos MeSH. La selección de los artículos incluyo documentos completos publicados en revistas indexadas de los últimos 10 años, en español e inglés; la información recolectada se organizó para la construcción del presente documento. Concluyendo, se encontró que las patentes de muchos medicamentos biológicos han vencido o están próximas a caducar y varios biosimilares están desarrollándose y comercializándose incluso en países sin regulaciones estrictas. Los biosimilares nunca podrán ser iguales al original por su complejidad molecular, por ello debemos integrarlos a los sistemas de farmacovigilancia mejorando trazabilidad e identificando su origen mientras se establecen denominaciones comunes distinguibles. La evidencia actual sugiere que la regulación de medicamentos biosimilares debe ser evaluada y armonizada en todo el mundo.