Alpha-lipoic acid versus nimodipine protective effect against vinblastine induced neurological and haematological toxicities in adult albino rats

Vinblastine [VBL] is an antimicrotubule vinca alkaloid that is used for the treatment of resistant metastatic breast cancer. In this work, it had been studied in adult albino rats to define its neurological and haematological toxicities. Alpha lipoic acid and nimodipine were used to evaluate their protective role against VBL induced toxicities. 63 adult albino rats of both sexes were divided into 9 equal groups: negative control group [Gr I], olive oil group [Gr II], 5% dextrose solution group [Gr III], Alpha-lipoic acid group [Gr IV], nimodipine group [Gr V], VBL group [Gr VI], Alpha-lipoic acid + VBL group [Gr VII], nimodipine + VBL group [Gr VIII] and Alpha-slipoic acid + nimodipine + VBL group [Gr IX]. The materials and drugs were given intraperitoneally for 2 consecutive days every 3 weeks [1 cycle] and the course was repeated for six cycles. Neurological investigations were carried out by the flowcytometer and the spectrophotometer for detection of the percentage of both the apoptotic cells in the pre G1 phase and the DNA fragmentation. Haematological investigations included CBC s and bone marrow film examination. The chain breaking antioxidants were also measured. The results revealed that VBL had neurological and haematological toxicities while Alpha-lipoic acid and nimodipine showed protective effects against such toxicities. The protective effect of Alpha-lipoic acid was better than nimodipine as regards the haematological toxicity. The best protection was offered by combined administration of [Alpha-lipoic acid + nimodipine with VBL

Detection of metastatic potential capacity in colorectal carcinoma using flow cytometry and imunocytochemistry

Improved staging in all forms of gastro intestinal cancers is a desirable task because many of these cancers are understaged even after curative surgical resection. Indeed, early dissemination of isolated tumour cells is a frequent characteristic of epithelial tumours. The present work at detection of these micrometastatic cells in BM of colorectal cancer [CRC] patients using flow cytometry and immunocytochemistry on mononuclear cells [MNC] and on bone marrow [BM] smears, and comparing the results of the 3 techniques. Presence of micrometastasis was assessed using monoclonal antibody [MoAb] against intracellular cytokeratin 18. the material of the study consisted of 40 cases of CRC constituting the subjects of the study, 28 of them with no overt metastasis while the remaining 12 patients expressed overt metastasis. The results of the cases revealed the following: 1. Using flow cytometry the mean number of micrometastatic cells detected was much higher than those detectd by immunocytochemistry on BM and MNC. 2. The presence of positive micrometastasis was 70% with flow cytometry and 69.2% with immunocytochemistry on BM smear and 50% on MNC. 3. All cases having macrometastasis were positive for micrometastasis using the 3 techniques. In cases showing no overt metastasis, more than half of the patients [57%] were positive for micrometastasis using flow cytometry and a nearly similar% age [55%] with immunocytocemistry on BM smear, while only 37% of these cases had micrometastasis with immunocytochemistry on MNC. As regards the comparison between the 3 techniques, we found that nearly all positive cases by flow cytometry were positive by immunocytochemistry on BM smear except for 2 cases, while only 17 cases were positive by immunocytochemistry on MNC out of 22 cases positive by flow cytometry. Thus flow cytometry can be considered a more sensitive technique, followed by immunocytochemistry on BM smear. Immunocytochemistry on MNC revealed no positive cells at all when applied on negative control cases, while 30% of the cases showd moderately staining cells when using immunocytochemistry on BM smear. Also 20% of negative control cases showed low positivity with flow cytometry. Thus immunocytochemistry on MNC can be considered less sensitive but more specific than the 2 other methods

Estudio cromosómico: experiencia del laboratorio de genética del Hospital San Juan de Dios / Chromosomal study: experience at the genetics laboratory at the San Juan de Dios Hospital

Se revisan los estudios cromosómicos realizados en el Hospital San Juan de Dios entre abril y diciembre de 1995. De total de 58 exámenes, el mayor porcentaje de alteraciones (57 por ciento) correspondió a trisomía 21 libre (síndrome de Down); en menor proporción se encontraron aneuploidia de cromosomas sexuales (síndrome de Klinefelter) 9,5 por ciento y síndrome de Turner (4,8 por ciento). Otras alteraciones correspondieron a trisomía 18, trisomía 13, trisomía 22 parcial, deleción 5p, deleción 13q en un paciente con retinobalstoma y translocación 9,22 (cromosoma Philadelfia)

Bone marrow aspirates examination for iron deficiency amonog Iraq in patients: pre-versus post blockade periods

Bone marrow aspirates revealed iron deficiency in 174 [23.1%] out of 753 inpatients for the period 1991-1994 as compared to iron deficiency in 82 [14.6] out of 562 inpatients diagnosed in the pre blockade period [1986-1989]. This statistically significant increase in proportion [P < 0.001] of patients affected after the blockade could be explained on the basis of nutritional deficiency or poor health status as a result of the blockade imposed on Iraq. Females are more significantly affected by higher rates of iron deficiency in the post blockade period [29.8%] as compared to female patients with iron deficiency examined in the pre blockade period [18.0%] [P < 0.001]

Clastogenic effect of cisplatin on Wistar rat bone marrow cells

The clastogenic effect of the drug cis-diamminedichloroplatinum II (cisplatin, CDDP) was investigated in Wistar rat bone marrow cells. Male rats, 3 per treatment time, aged months and weighing 250-350 g were injected intraperitoneally with 6.0 mg/Kg CDDP solution, and the control group received isotonic saline. The animals were sacrificed 6, 12, 18, 24 and 48h after the injection. the chromosome preparation was obtained from bone marrow cells. Chromatid and chromosome aberrations were investigated in 300 metaphases per animal. A significant increase in number of chromosome aberration was observed from 6 to 24h, the majority being of the break and gap type. After 48 h a progressive reduction was observed, without differences from the negative control. These date confirm the mutagenic effect of CDDP in rats demonstrated for mice bone marrow by micronuclei assay, for murine ovary cells and mice spermatocytes

Enhancement of erythroid colony growth by triiodothyronine in cell cultures from bone marrow of normal and anemic rats with chronic renal failure

Para contribuir a clarificar el rol de las hormonas tiroideas en la modulación de la eritropoyesis y profundizar en el conocimiento de los efectos de estas hormonas en la anemia de la insuficiencia renal crónica (CRF), estudiamos "in vitro" la acción de la l-triiodotironina (LT) y DT3, un isómero dextrorotatorio no-calorigénico de la T3 sobre precursores eritroides comprometidos maduros (CFU-E) y primitivos (BFU-E) de la médula ósea de ratas normales anémicas. Los cultivos fueron preparados usando la técnica de la metilcelulosa conteniendo una dosis standard de eritropoyetina (Ep) (182 mU/ml), LT3 y DT3 en dosis de o.5, y 1.5 ug/ml. Las hormonas tiroideas fueron agregadas a los cultivos en ausensia de Ep. Nuestros resultados demuestram que LT3 y DT3 producen una estimulación significativa y directa sobre la formación de CFU-E y un moderado incremento de BFU-E. Hubo una aparente relación dosis-dependiente en los cultivos que contienen las hormonas tiroideas. La DT3 fue menos activa que la LT3. Como se esperaba, la Ep produjo un significativo incremento en la formación de colonias eritroides, principalmente CFU-E. Los efectos de LT3, DT3 y Ep sobre el desarrollo de las colonias eritroides fue significativamente mayor en cultivos celulares de médula ósea de ratas anémicas con CRF, indicando la existencia de una cinética celular proliferativa más elevada en los progenitores eritroides comprometidos en respuesta a estas drogas.

Absence of genotoxic effects of crude and refined red palm oil on mouse bone marrow cells

Red Palm Oil (RPO), extracted from fruits of Elaeis guineensis, is a complex mixture consisting of over 99 per cent glycerides and about 1 per cent non-glyceride compounds. Its orange-red colour is due to its high content of carotenoid pigments, mainly alpha- and beta-carotene. Based on the fact that palm oil is a rich source of provitamin A, and because it is largely consumed in North and Northeastern Brazil, we evaluated possible clastogenic and cytotoxic activities of this oil on mouse bone marrow cells in vivo, as well as the alpha- and beta-carotene content. The experiments were performed using samples of refined and crude palm oil, of which two different phases, supernatant, sediment, and the mixture of both, were tested. The animals were treated by gavage, at daily doses of 4.5 g/Kg, for five consecutive days, and killed 24 hours after the last treatment, for chromosome preparations. The negative control group was treated with corn oil. There was no statistically significant difference in the frequency of chromosomal aberrations and in mitotic index when the animals which received palm oil were compared with the negative control. The beta-carotene content was higher than that of alpha-carotene, and the supematant phase was the richest source of carotenoids. These findings suggest that RPO has no genotoxic effect.

Trasplante autólogo de médula ósea y tratamiento in vitro en leucemia aguda no linfoblástica / Autologous bone marrow transplant in the treatment in vitro in acute nonlymphoblastic leukemia

Se reporta un paciente de 4 años y 9 meses de edad con el diagnóstico de leucemia aguda no linfoblástica (LANoL) M4 el cual presentó el antecedente de una recaída medular. Al momento de ser referido a nuestro departamento se encontró en remisión completa, clínica y hematológica. Previa evaluación por aparatos y sistemas se sometió el paciente al programa de trasplante autólogo de médula ósea (TAMO) y dado el diagnóstico, se trata la médula ósea in vitro con quimioterapia además de administrar megalodosis (terapia ablativa) de quimioterapia sistémica. Se describe el tratamiento in vitro de la médula ósea y el procedimiento tanto de evaluación para viabilidad celular antes y después del procesamineto de congelación. Por otro lado se señala la evolución del paciente, observando que la recuperación medular aconteció dentro del periodo descrito en la literatura. Este es el primer paciente pediátrico en México con LANoL sometido a TAMO con tratamiento in vitro de la médula ósea y con éxito terapéutico. Se discuten en términos generales tanto el tratamiento del paciente como el manejo de la médula ósea en el laboratorio. Actualmente el paciente se encuentra a más de 9 meses del trasplante en remisión completa y en excelente estado general. Se concluye que este procedimiento puede constituir en instituciones hospitalarias de tercer nivel otra opción de tratamiento, siempre y cuando la selección del paciente sea la correcta

Efectos de la osteosíntesis medular sobre la eritropoyesis / Effects of medular osteosynthesis on erithropoiesis

Una preocupación general de los ortopedistas al colocar un clavo intramedular consiste en la lesión de la médula ósea, lo que pudiera afectar la eritropoyesis. Con el propósito de revisar lo anterior, los autores efectuaron osteosíntesis con clavo Colchero intramedular con pernos en 39 pacientes con 23 fracturas (8 de fémur y 15 de tibia), 15 no uniones (3 de fémur y 12 de tibia) y una dismetría congénita de tibia. Para saber si la lesión de la médula ósea afectaba o no la eritropoyesis, se analizó en cada uno de los pacientes el comportamiento de los reticulocitos, precursores de los eritrocitos, encontrando que no sólo no hubo alteración en estas células, sino un aumento en los 15 primeros días, volviendo después a la normalidad. El estudio se dividió en tres etapas: prequirúrgica, quirúrgica y posquirúrgica, ésta última con un seguimiento de 15, 30, 60 y 90 días. Se añadió un grupo control de 60 personas no fracturadas.

Effects of deltamethrin on the growth and differentiation of bone marrow hematopoietic stem cells

1. The effects of deltamethrin on mouse bone marrow and spleen progenitor cell responsiveness to granulocyte and macrophage colony-stimulating factors (CSFs) were evaluated. 2. Deltamethrin (1-5 mg/kg) was administered four times subcutaneously on alternate days for one week to male BALB/c mice, 5-8 weeks old (N = 6 mice/group), raised under pathogen-free conditions and maintained in conventional animal rooms for four weeks before use. Soft agar colony formation (CFU-C), marrow and spleen cell counts as well as body, spleen and thymus weights were determined. 3. Although treatment with the lowest dose (1 mg kg-1 48 h-1) produced no significant effect on CFU-C, the administration of 3 and 5 mg kg-1 48 h-1 caused a more than two-fold increase in the formation of granulocyte and macrophage colonies in the marrow, but not in the spleen (control value = 100.5 +/- 12 for N = 6). Colony numbers returned to normal values within five days after the end of deltamethrin administration. 4. No changes were observed in the total (range: 1-3 x 10(8) per spleen) and differential marrow and spleen cell counts, nor was there any alteration in spleen weight. However, treatment with the three doses resulted in a dramatic reduction in thymus weight. 5. These effects were not due to the liberation of endotoxin, because if endotoxin had been present it would have been < 0.060 ng/ml, a concentration that would not have a biological effect. 6. In vitro addition of 0.10 to 10 microM deltamethrin to marrow cell cultures obtained from untreated mice did not induce any response. 7. These data indicate that the CSF-driven granulocyte and macrophage development provides a useful model for the study of the effects of toxicants on myelopoiesis

Trasplante de médula ósea

Gracias a una cuidadosa selección de donantes y mediante la administración de un tratamiento inmunosupresor apropiado antes del trasplante, muchos receptores de trasplante de médula ósea puedan obtener una mejor calidad de vida e incluso la curación de su enfermedad. El autor revisa las indicaciones para este procedimiento, las complicaciones más frecuentes y el manejo de éstas, y comentan algunas técnicas, actualmente en investigación, que podrían mejorar el procedimiento y sus resultados en el futuro.

Estudio citogenético en 22 adultos y tres niños con leucemia linfoblástica aguda / Cytogenetic study in 22 adults and therr children with acute lymphoblastic leukemia

Se presentan los resultados del estudio citogenético realizado en sangre periférica y/o médula ósea de 25 pacientes (22 adultos y 3 niños) con LLA estudiados entre 1987 a 1990. Todos los casos presentaron alteraciones cromosómicas (25/25), aunque en 23 pacientes (23/25) estaba presente una línea celular normal. Entre las aberriguaciones estructurales encontradas están t(17;19) (q11;p13), t(2;9;22)(q34;q34;q11), t(1;7)(p13;q33), t(6;11)(q26;p16), t(3;4)(q24-25;q26), t(1;12)(q23;q34), t(2;18)(q15;p12), t(2;4;)(q23;35) y t(4;11)(q21ñq23). Estos rearreglos fueron indicadores de riesgo y se correlacionaron con la respuesta al tratamiento y la supervivencia de los pacientes. Algunas de estas anomalías no habían sido previamente descritas en LLA; sin embargo, los puntos de ruptura coinciden con los observados en otras neoplasias hematológicas, lo cual suguiere que esas regiones son críticas en la patogénesis de estos desórdenes.

Effect of IL-3 and E. coli LPS on the proliferation of mouse bone marrow cells in vitro

Bone marrow cells from adult BALB/c mice were cultured at 37-C, with 5% CO2 in air, in RPMI 1640 medium complemented with fetal serum. The addition of IL-3 (5% of WEHI-3-conditioned medium) or E. coli lipopolysaccharides (LPS, 50 µg/ml) to the cultures stimulated cell proliferation (1.29 and 1.22-fold, respectively, relative to control culture), whereas the simultaneous addition of the two factors reduced the number of cells recovered by 38% relative those from control cultures (which were around 2.83 x 10***5 cells for each 10***6 plated cells). The frequency of blasts and cells with surface Ig presented the same pattern of variation (o.07 and 0.02%, respectively, in control cultures). The inhibitory effect of IL-3+LPS on cell proliferation was evident from the first day of culture, but more apparent on day 3. Macrophage-colony stimulating factor (M-CSF, L929-conditioned medium) and LPS each given alone stimulated proliferation but reduced it when given together. In contrast, fetal liver cells were not affected by the simultaneous addition of IL-3 and LPS or by M-CSF and LPS. The mechanism of action of the cumulative effect of these two factors in unknown. Since crude cell-conditioned medium was used as the source of IL-3, it is possible that another factor present in this medium interacts with LPS to cause the inhibitory effect on cell proliferation

Analise citogenetica relacionada a idade e ao tratamento com drogas em macrofagos peritoneais e celulas da medula ossea de camundongos femeas Swiss hiperimunes intactos ou ooforectomizados / Citogenetic studies relationships to age and to tretment with drugs in peritoneal macrophages and bone marrow cells in the intact and ovarectomized female mouse Swiss hiperimunes

Estudos citogeneticos relacionados com a idade em camundongos Swiss femeas hiperimunes intactos mostraram aumento da frequencia de macrofgos peritoneais com alteracoes cromossomicas estruturais aos 6 meses e aumento progressivo da frequencia de macrofagos hiperdiploides dos 6 aos 15 meses de idade. Nos animais ooferectomizados, os macrofagos apresentaram estes aumentos aos 2 meses, 30 dias apos a ooferectomia, e dos 6 aos 18 meses, respectivamente. Os resultados evidenciam uma relacao entre alteracoes hormonais e aberracoes cromossomicas nos macrofagos peritoneais. Estas aberracoes cromossomicas nao foram observadas em celulas da medula ossea dos animais intactos e dos ooferectomizados, sugerindo respostas diferentes nos macrofagos peritoneais e seus precurssores na medula ossea.Os antioxidantes acido ascorbico e alfa-tocoferol protegeram os macrofagos peritoneais de camundongos ooforectomizados das aberracoes cromossomicas estruturais, evidenciando papel dos radicais livres no aparecimento das mesmas. Considerando que os estrogenos têm acao antioxidante na peroxidacao lipidica, que o tocoferol é um captador de radicais lipofilicos e que o ácido ascórbico pode ser um regenarador do tocoferol, é provável que as quebras verificadas nos cromossomos dos macrófagos peritoneais de camundongos ooforectomizados resultam de peridoxidacao lipidica. O metotrexato mostrou efeito sinergico com a ooforectomia em relacäo ás alteracöes cromossômicas, e teve este efeito parcialmente suprimido pelo ácido ascórbico, tanto nos animais intactos, como nos ooferectomizados, sugerindo que, além da inibicäo de reparo de DNA, a droga tenha possível acäo através dos radicais livres. O benzonidazol provocou um grande número de delecöes, sobretudo nos macrófagos peritoneais de animais ooferectomizados. Seu efeito foi antagonizado, em grande proporcäo, pelo tocoferol, o que corrobora os dados da literatura em relacäo á atuacäo do benzonidazol através da formacäo de radicais livres. Por serem mais suscetíveis ás alteracöes hormonais e aos tratamentos com drogas que as celulas da medula óssea, conclui-se que os macrófagos säo adequados para estudos dos fenômenos ligados ao envelhecimento, dos mecanismos de inducäo de aberracöes cromossomicas, dos efeitos de drogas e seu modo de acäo, constituindo, assim, importante modelo para investigacöes em citogenetica

Evaluation of the effect of ionizing radiation of mouse hemocytopoietic tissue by reticulocyte count

The effects of exposure to a single, whole body X-ray dose of 154.8 mC/Kg (600 R) on mouse (Mus musculus) hemocytopoietic tissue were analyzed by means of reticulocyte counts in peripheral blood, evaluating indirectly variations of the erythrocyte sector of bone marrow. The efficiency of the method for the evaluation of this tissue was demonstrated, constituting one more radiobiologic parameter to corroborate those existing already

Mutagenic bioassay of certain pharmacological drugs: II. Mebendazole (MBZ)

El Mebendazole (MBZ), o 5-benzoyl- 1H-benzimidazole-2- il ácido metil éster carbámico fue estudiado con tres ensayos de corto plazo. Se probó su capacidad para inducir micronúcleos "in vivo" en eritrocitos policromáticos de médula ósea de ratones CFW. Se analizaron 3 dosis, 25, 50 y 100 mg/kg de peso corporal inyectados intraperitonealmente. Las 3 dieron incremento significativo (p < 0.01). Las pruebas "in vitro" se realizaron en células CHO. Se analizó la capacidad para inducir aberraciones cromosómicas y figuras anormales por prueba de anafase-telofase. Se detectó una frecuencia aumentada en la formación de dicéntricos, gaps, C-mitosis, puentes y cromosomas rezagados. La acción genotóxica observada puede asociarse con la estructura química de un æester carbámico derivado que sugeriría un papel de mutágeno directo

Avaliaçäo dos efeitos da radiaçäo ionizante e da ciclofosfamida na medula óssea de camundongos, pela contagem das células näo nucleadas e nucleadas / Evaluation of the effects of ionizing radiation and cyclophosphamide on the bone marrou of mice, by the count of unnucleated and nucleated cells

Os efeitos da exposiçäo aos raios X, na dose única de 103,2mC/kg corpo inteiro, e da ciclofosfamida injetada intraperitonealmente, na dose de 7mg (350mg/kg), na medula óssea de camundongos (Mus musculus) foram estudados, empregando-se métodos histológicos usuais, para naálise morfológica e obtençäo da relaçäo numérica entre as células näo nucleadas e nucleadas (NN/N), para análise morfométrica. Ficou evidenciada a eficiência da metodologia proposta na avaliaçäo, tanto dos efeitos da radiaçäo ionizante, quanto das drogas quimioterápicas, sobre a medula óssea