RESUMEN
INTRODUCTION: The presence of preformed HLA-reactive antibodies in recipient serum before transplantation has long been recognized as a prominent risk factor for a generally worse graft outcome. Screening and identification of HLA antibodies can be used to stratify patients into high- and low-risk categories. MATERIALS AND METHODS: We determined patients' anti-HLA antibodies using flow cytometry panel-reactive antibody (flowPRA) screening, specifying more than 5% after positive screening. According to the results of the screening test, patients were allocated to the induction immunosuppressive protocol according to the actual immunologic risk. RESULTS: In the group of 78 patients, screening with flowPRA of anti-HLA antibodies was done twice a year. Patients were divided into 2 groups of immunologic risk (low or medium), and we chose the induction immunosuppressive protocol according to the risk. Stratification of the risk was correct, because the only predictor for development of acute rejection in the monitored period of 12 months was delayed graft function (odds ratio 33.2501; 95% confidence interval 10.0095-110.4508; P < .0001). The occurrence of acute rejection upon implementing the screening was reduced in our transplant center from 44% to 19% (P < .0001). No difference was recorded in the 12-month survival of grafts and patients according to the applied induction immunosuppressive protocol. CONCLUSION: We confirmed significantly reduced occurrence of acute rejection in the follow-up period of 12 months by using individualized induction according to flowPRA screening of anti-HLA antibodies. FlowPRA screening represents a suitable alternative for screening and specification of anti-HLA antibodies in case the Luminex methodology is unavailable.
Asunto(s)
Citometría de Flujo/métodos , Rechazo de Injerto/prevención & control , Antígenos HLA/inmunología , Prueba de Histocompatibilidad/métodos , Inmunosupresores/uso terapéutico , Isoanticuerpos/sangre , Trasplante de Riñón , Adulto , Funcionamiento Retardado del Injerto/inmunología , Funcionamiento Retardado del Injerto/prevención & control , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Listas de EsperaRESUMEN
We describe two cases of hyperacute humoral rejection of living related kidney grafts despite negative pretransplantation T- and B-lymphocyte flow cytometric crossmatches and blood group identity. Retrospectively, antiendothelial IgG antibodies were detected on a panel of umbilical cord cells in the first case, and IgM antibodies against donor endothelial precursor cells were detected using a new endothelial cell crossmatch kit in the second case. Standard crossmatch methods using donor lymphocytes failed to detect these pathogenic antibodies and did not predict the danger of hyperacute rejection.
Asunto(s)
Rechazo de Injerto/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Isoanticuerpos/sangre , Trasplante de Riñón/inmunología , Enfermedad Aguda , Adulto , Linfocitos B/inmunología , Endotelio Vascular/inmunología , Familia , Femenino , Prueba de Histocompatibilidad , Humanos , Trasplante de Riñón/patología , Donadores Vivos , Masculino , Linfocitos T/inmunologíaRESUMEN
The effects of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE/MLV, radioprotective immunomodulator; 10 mg/kg) and indomethacin (INDO, inhibitor of prostaglandin production; 2 mg/kg) on post-irradiation recovery of hematopoietic functions in mice were investigated. Two agents with distinct radioprotective mechanisms were administered alone or in combination 24 h and 3 h before exposure to 7 Gy (60)Co radiation. In the post-irradiation period (3-14 days) combined pre-treatment of mice accelerated recovery of bone marrow cellularity, weight of spleen and myelopoietic and erythropoietic activity in both hematopoietic organs, compared to treatment with MTP-PE/MLV or indomethacin alone. In the peripheral blood, improved radioprotective effects of combined drug administration were found in the recovery of reticulocytes and platelet count. No further significant differences in the recovery of leukocyte count were observed in the examined groups until post-irradiation day 14. Within the first 3-6 post-irradiation days, the bone marrow and peripheral blood smears of mice pre-treated with indomethacin alone or its combination with MTP-PE/MLV more frequently featured blast cells and large cells with abundant cytoplasm which could be considered the hematopoietic stem cells.
Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/farmacología , Antiinflamatorios no Esteroideos/farmacología , Hematopoyesis/efectos de los fármacos , Factores Inmunológicos/farmacología , Indometacina/farmacología , Fosfatidiletanolaminas/farmacología , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de la radiación , Femenino , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de la radiación , Recuento de Leucocitos , Liposomas , Ratones , Tamaño de los Órganos , Protectores contra Radiación/farmacología , Bazo/citología , Bazo/efectos de los fármacos , Bazo/efectos de la radiación , Irradiación Corporal TotalRESUMEN
Positive effects of repeated administration of diclofenac, an inhibitor of prostaglandin synthesis, in terms of prevention of tumor development and stimulation of hematopoiesis have been observed in C3H mice transplanted subcutaneously with G:5:113 fibrosarcoma cells. Fourteen-day treatment with diclofenac (3.75 microg/kg/day) started from day 5 after tumor cell transplantation. Measurements of tumors and hematological examinations were performed on day 30. The results strongly suggest the possibility that inhibitors of prostaglandin synthesis (non-steroidal anti-inflammatory drugs) may be used in oncological practice where the observed effects are highly desirable.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Diclofenaco/farmacología , Fibrosarcoma/tratamiento farmacológico , Hematopoyesis/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Diclofenaco/uso terapéutico , Evaluación Preclínica de Medicamentos , Masculino , Ratones , Ratones Endogámicos C3H , Trasplante de Neoplasias , Sarcoma Experimental/tratamiento farmacológico , Células Tumorales CultivadasRESUMEN
Data in this report describes the effect of a single injection of bacterial lysate IRS-19 prior to irradiation of C57Bl/6 mice on recovery of colony-forming cells (CFC) after sublethal and lethal doses of radiation. The injection of IRS-19 promoted an earlier recovery of colony-forming cells in the bone marrow and spleen. For example, 5 and 9 days after 7.5 Gy irradiation, the number of CFU-S per femur was approximately 1.7-2.3-fold higher in IRS-19-injected mice than in saline-injected mice. Also, pretreatment of mice with IRS-19 induced an increase in the number of endogenous haemopoietic stem cells (endoCFU-S). In the postradiation period (5-21 days) significantly increased bone marrow and spleen cellularity and accelerated myelopoietic regeneration (committed progenitor granulocyte-macrophage-colony-forming cells, GM-CFC) in the bone marrow and spleen compared with saline-treated controls. At the time of presumed irradiation, (i.e. 24 h after administration of the drug to the non-irradiated mice), there was no significant difference between the control mice and mice treated with IRS-19 in numbers of femoral and spleen GM-CFC. In contrast, the number of nucleated femoral cells decreased significantly in the group treated with IRS-19. Moreover, treatment with IRS-19 caused a sustained increase in serum colony-stimulating activity which was followed by an enhanced repopulation of GM-CFC in the femoral marrow and spleen. Administration of the agent 24 h prior to irradiation rather than postirradiation appeared most effective with respect to radioprotection. Intravenous rather than i.p. and p.o. was the most effective route of administration in the mouse. Furthermore, single, high-dose injection appeared to be more effective than repeated, lower dose injections. Results suggest that the radioprotective properties associated with the administration of IRS-19 are largely a consequence of the induction of haemopoietic colony-stimulating activities and potentially the activation and/or enhancement of cytokine cascades in the recipient animals. These changes may ultimately impact the cell cycle profile of the haemopoietic cells and therefore their ability to withstand and/or recover from radiation insult.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Células Madre Hematopoyéticas/efectos de la radiación , Protectores contra Radiación/farmacología , Animales , Bacterias , Femenino , Células Madre Hematopoyéticas/fisiología , Ratones , Ratones Endogámicos C57BLRESUMEN
We have studied the effect of age as well as the effect of short-term and long-term intake of K and Mg salts of aspartic acid (Cardilan) on haemopoiesis in ICR mice strain. The cellularity of the bone marrow does not change with aging, but the number of granulocyte-macrophage colony-forming cells (GM-CFC) and also the number of spleen colony-forming units (CFU-S) and erythroid burst-forming units (BFU-E) in two-year-old mice increased in the bone marrow. In two-year-old mice the number of leukocytes decreased in the peripheral blood with aging, mainly as a result of a decrease in mononuclear cells. Short-term drinking (STD) of Cardilan caused increased numbers of CFU-S and BFU-E in bone marrow and increased numbers of reticulocytes in the peripheral blood of one-year old animals (STD/12 months old). In the oldest mice (STD/24) increased weight and cellularity of the spleen and rapid increase of leukocytes and reticulocytes in the peripheral blood was recorded. After long-term drinking (LTD) of Cardilan the number of spleen GM-CFC rose markedly in one-year-old mice (LTD/12) and in two-year-old mice (LTD/24) the number of reticulocytes in the peripheral blood rose. Our results indicate that K and Mg salts of aspartic acid influence erythropoietic activity most widely.
Asunto(s)
Envejecimiento/fisiología , Ácido Aspártico/metabolismo , Hematopoyesis , Niacina/análogos & derivados , Niacina/metabolismo , Animales , Ácido Aspártico/farmacología , Células Cultivadas , Femenino , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Magnesio , Ratones , Ratones Endogámicos ICR , Niacina/farmacología , PotasioRESUMEN
The effect of antigenic bacterial lysate IRS-19 on the recovery of blood cells was studied in mice injured by a single dose of 7 Gy irradiation. The preirradiation administration of IRS-19 accelerated the recovery of leukocytes, reticulocytes and platelets in peripheral blood. The recovery of leukocytes 9-14 days after irradiation in protected animals was accompanied by a higher level of band forms of granulocytes as well as activated lymphoid and monocytoid cells.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Recuento de Células Sanguíneas , Células Madre Hematopoyéticas/efectos de la radiación , Irradiación Corporal Total , Adyuvantes Inmunológicos/administración & dosificación , Animales , Bacterias , Femenino , Granulocitos , Recuento de Leucocitos , Leucocitos Mononucleares , Ratones , Ratones Endogámicos C57BL , Recuento de Plaquetas , Recuento de ReticulocitosRESUMEN
AIM OF STUDY: To assess the prevalence of markers of autoimmune destruction of pancreatic beta-cells in patients with non-insulin dependent diabetes mellitus (NIDDM). SUBJECTS: 127 hospitalized NIDDM patients subdivided to the following subgroups: non-obese with C-peptide < 0.3 nmol/l (NIDDM-(-)), non-obese with C-peptide > 0.3 nmol/l (NIDDM-(+)), obese with C-peptide < 0.3 nmol/l (NIDDM+(-)) and obese with C-peptide > 0.3 nmol/l (NIDDM2+). METHODS AND MEASURED PARAMETERS: Age, BMI, C-peptide, autoantibodies to glutamic acid decarboxylase (antiGAD-Ab), autoantibodies to islet cells (ICA), markers of specific cellular immunity CD4, CD8, CD19, CD4/CD8, CD4/CD45/RA+, CD4/CD45/RA-, NK (CD16+56), CD3/HLADR, organ specific/non-specific autoantibodies. RESULTS: AntiGAD-Ab were positive in 5/15 (33.3%) NIDDM-(-), 1/32 (3.1%) NIDDM-(+), 2/9 (22.2%) NIDDM+(-) and in 3/71 (4.2%) NIDDM2+. The positivity of antiGAD-Ab in NIDDM-(-) and NIDDM+(-) was significantly higher (p < 0.05) than in NIDDM-(+) and NIDDM2+. CONCLUSION: Some patients with manifestation of diabetes in older age initially classified and treated as having NIDDM may have in fact slowly evolving autoimmune insulin-dependent diabetes mellitus (LADA). These patients can be identified by measurement of antiGAD-Ab or other markers (ICA, IA-2) of autoimmune destruction of pancreatic beta-cells (AID). Moreover, in some patients both AID and insulin resistance may coexist in parallel.
Asunto(s)
Autoanticuerpos/análisis , Diabetes Mellitus Tipo 2/inmunología , Glutamato Descarboxilasa/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Péptido C/sangre , Diabetes Mellitus/sangre , Diabetes Mellitus/inmunología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Islotes Pancreáticos/patología , Masculino , Persona de Mediana Edad , ObesidadRESUMEN
A whole-body gamma irradiation of rats with a dose of 8.5 Gy caused a significant decrease in the RNA concentration in the blood. The original level of concentration was restored within 3 weeks after irradiation and exceeded by the 21st day after irradiation. The changes were studied in terms of the haematological indices of a radiation-induced damage.
Asunto(s)
Células Sanguíneas/efectos de la radiación , ARN/efectos de la radiación , Traumatismos Experimentales por Radiación/sangre , Animales , Recuento de Células Sanguíneas/efectos de la radiación , Células Sanguíneas/metabolismo , Masculino , ARN/sangre , Ratas , Ratas Wistar , Factores de Tiempo , Irradiación Corporal TotalRESUMEN
The effect of immunomodulatory agents on reparation processes in the thymus was studied in mice injured by a single sublethal or lethal dose of ionizing radiation ranging between 6.5-9.5 Gy. Reparation of thymus weight was not influenced by pretreatment with immunomodulators. Furthermore, the morphological picture did not exhibit appreciable differences between non-protected and protected groups, except for greater proliferation of fibroblasts and macrophages in protected animals.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Bacterias , Extractos Celulares , Enfermedades Linfáticas/terapia , Traumatismos por Radiación/terapia , Timo , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/uso terapéutico , Amifostina/uso terapéutico , Animales , Atrofia , División Celular , Radioisótopos de Cobalto , Femenino , Fibroblastos/patología , Enfermedades Linfáticas/etiología , Enfermedades Linfáticas/patología , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos , Fosfatidiletanolaminas/uso terapéutico , Protectores contra Radiación/uso terapéutico , Timo/patología , Timo/efectos de la radiaciónRESUMEN
We have reported previously [Fedorocko, P., Int. J. Radiat., Biol. 65:465, 1994] that liposomal muramyl tripeptidephosphatidyl ethanolamine (MTP-PE/MLV) given prior to irradiation results in augmented hemopoietic recovery and enhanced animal survival as evidenced by increased pluripotent stem cells (CFU-S) and progenitor cells committed to granulocyte and/or macrophage development (GM-CFC) or white blood cells, neutrophil counts, as well as by survival rates of lethally irradiated mice. In this report the effects of liposomal MTP-PE (radioprotective immunomodulator; 10 mg/kg i.p., 24 h before irradiation) and indomethacin (inhibitor of prostaglandin production; 2 mg/kg i.m., 24 h and 3 h before irradiation) were studied. Both of the agents were administered either alone or in combination. The results included the assessment of preirradiation hemopoietic effects of drugs and postirradiation hemopoietic recovery in terms of bone marrow cellularity, number of bone marrow GM-CFC, endogenous spleen colony formation (endoCFU-S), and the determination of the survival of lethally irradiated mice. Experimental evidence elevated by the increased preirradiation numbers of GM-CFC and hydroxyurea kill of GM-CFC as well as a simultaneous significant diminution in bone marrow cellularity indicated that the beneficial action of the combined treatment could be a consequence of increased cell proliferation in the hemopoietic tissue and mobilization with redistribution of stem cells from bone marrow into the circulation. In the postirradiation period (3-14 days), combined pretreatment of mice accelerated myelopoietic regeneration in the bone marrow compared to treatment with MTP-PE/MLV alone or indomethacin alone. Combined administration of MTP-PE/MLV (10 mg/kg, -24 h, i.p.) and indomethacin (2 mg/kg, -24 h and -3 h, i.m.) to mice, prior to lethal irradiation, exerted an additional radioprotective effect and protected 100% of the C57B1/6 mice.
Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adyuvantes Inmunológicos/uso terapéutico , Hematopoyesis/efectos de los fármacos , Hematopoyesis/efectos de la radiación , Indometacina/uso terapéutico , Fosfatidiletanolaminas/uso terapéutico , Protectores contra Radiación/uso terapéutico , Acetilmuramil-Alanil-Isoglutamina/uso terapéutico , Animales , Ensayo de Unidades Formadoras de Colonias , Quimioterapia Combinada , Femenino , Rayos gamma , Liposomas , Ratones , Ratones Endogámicos C57BL , Quimera por RadiaciónRESUMEN
The effects of single subcutaneous injection of cadmium chloride on haemopoiesis in normal (non-irradiated) or irradiated mice were investigated. Cadmium doses used ranged from 1-8 mg/kg body weight Twenty-four hours after treatment with cadmium (doses from 3 to 8 mg/kg) there were no significant changes in bone marrow cellularity and the granulocyte-macrophage progenitor cell (GM-CFC) number per femur in non-irradiated female ICR mice. Similarly, during the 30-day postinjection period bone marrow cellularity and marrow GM-CFC number in mice treated with a cadmium dose of 5 mg/kg were not significantly different from the control values. Cadmium significantly reduced the lethal effects of gamma rays. In addition, increasing the doses of cadmium administered 24 h prior to sublethal irradiation increased the number of endogenous haemopoietic stem cells (endoCFU-S) in a concentration-dependent manner. Pretreatment with cadmium also decreased the radiation damage to endoCFU-S and haemopoietic progenitor cells committed to granulocyte/macrophage development (GM-CFC). The survival of stem cells was higher and the regeneration of cellularity and GM-CFC of irradiated bone marrow was accelerated in mice pretreated with 5 mg Cd/kg body weight in comparison with saline-injected mice.
Asunto(s)
Cadmio/farmacología , Hematopoyesis/efectos de los fármacos , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de la radiación , Células Madre/efectos de los fármacos , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/efectos de la radiación , Femenino , Rayos gamma , Granulocitos/efectos de los fármacos , Granulocitos/efectos de la radiación , Macrófagos/efectos de los fármacos , Macrófagos/efectos de la radiación , Ratones , Ratones Endogámicos ICR , Bazo/citología , Bazo/efectos de los fármacos , Bazo/efectos de la radiación , Análisis de SupervivenciaRESUMEN
The effect of administration of cadmium alone in non-irradiated mice as well as the effect of pre-irradiation administration of cadmium on the reparation processes of haemopoiesis were investigated in mice irradiated by a dose of 7.5 Gy. The pre-irradiation administration of cadmium accelerated the reparation processes in the bone marrow and spleen as well as the number of leukocytes and thrombocytes in the peripheral blood. The administration of cadmium alone caused a temporary weight decrease of the thymus and reduced number of erythrocytes, reticulocytes and haemoglobin values in the peripheral blood. The temporary rapid increase in the number of leukocytes on the 21st day after cadmium administration was investigated.
Asunto(s)
Recuento de Células Sanguíneas/efectos de los fármacos , Recuento de Células Sanguíneas/efectos de la radiación , Células Sanguíneas/efectos de los fármacos , Células Sanguíneas/efectos de la radiación , Cadmio/farmacología , Hematopoyesis/efectos de los fármacos , Hematopoyesis/efectos de la radiación , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/efectos de la radiación , Femenino , Rayos gamma , Ratones , Ratones Endogámicos ICR , Bazo/citología , Bazo/efectos de los fármacos , Bazo/efectos de la radiación , Timo/citología , Timo/efectos de los fármacos , Timo/efectos de la radiaciónRESUMEN
Possibilities of combined radioprotection, using preirradiation WR-2721 administration and post- or preirradiation Broncho-Vaxom administration in lethally whole-body gamma-irradiated mice were investigated. Combined modality treatments were more effective than individual treatments alone. The ameliorative influence of the combined radioprotection could be explained by the hemopoietic stem cell protection with WR-2721 and the stimulation by Broncho-Vaxom.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Amifostina/farmacología , Bacterias , Células Sanguíneas/efectos de los fármacos , Extractos Celulares , Hematopoyesis/efectos de los fármacos , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/farmacología , Animales , Quimioterapia Combinada , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Irradiación Corporal Total/efectos adversosRESUMEN
In the present study, we show that the bacterial extract Broncho-Vaxom (BV, 500 micrograms/mouse; free of endotoxin) has radiation recovery activity when administered i.p. 24 h before sublethal irradiation. In the postirradiation period (5-12 days), pretreatment of mice with BV induced significantly increased bone marrow cellularity and accelerated myelopoietic regeneration (committed progenitor granulocyte-macrophage colony-forming cells; GM-CFC) in the bone marrow compared with saline-treated controls. The earlier hemopoietic recovery in BV-injected mice was not associated with an increase in the number of bone marrow GM-CFC and CFU-S (colony-forming units-spleen) within 24 h after injection. Simultaneously, a significant diminution in bone marrow cellularity occurred. In addition, the percentage of both GM-CFC and CFU-S in the S-phase of the cell cycle was significantly increased 24 h after a single treatment. In our experiments colony stimulating activity (CSA) in the serum of treated mice was not observed within 24 h after injection. Administration of BV 24 h prior to lethal irradiation, resulted in an increase in the number of surviving mice. Combined administration of BV (24 h) and indomethacin (24 h and 3 h) to mice, prior to irradiation, caused an additional radioprotective effect. These results demonstrate that BV stimulates myelopoietic regeneration and suggest a mechanism by which this treatment protects mice from otherwise lethal irradiation.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Bacterias , Extractos Celulares , Hematopoyesis/efectos de los fármacos , Protectores contra Radiación/farmacología , Animales , Ensayo de Unidades Formadoras de Colonias , Femenino , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de la radiación , Indometacina/farmacología , Ratones , Ratones Endogámicos C57BL , Traumatismos Experimentales por Radiación/mortalidad , Traumatismos Experimentales por Radiación/prevención & controlRESUMEN
The possibilities of combined radioprotection, using preirradiation WR-2721 administration and post- or preirradiation Broncho-Vaxom administration in lethally whole-body gamma-irradiated mice were investigated. LD50/30 dose reduction factors (DRFs) for mice treated with WR-2721 (200 mg/kg i.p. 30 min before irradiation), Broncho-Vaxom (25 mg/kg i.p. 24 h before irradiation), or both agents were 1.92, 1.17 and 2.07, respectively. These results demonstrated at least additive radioprotective effects of both agents, manifested in increased survival of irradiated mice. Radioprotection from 17 Gy was optimal when WR-2721 in combination with Broncho-Vaxom was given 30 min before irradiation and Broncho-Vaxom 24 h before or 4-8 h after irradiation. Combined modality treatments were also more effective than individual treatments alone in accelerating the bone marrow GM-CFC restoration. During the first days after irradiation enhanced colony-stimulating activity (CSA) of the lungs was observed in mice with postirradiation injection of Broncho-Vaxom alone or in mice injected with WR-2721 and Broncho-Vaxom (8 h after irradiation), as well as in mice only irradiated.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Amifostina/farmacología , Bacterias , Extractos Celulares , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Protectores contra Radiación/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Amifostina/administración & dosificación , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de la radiación , Quimioterapia Combinada , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
Effects of the bacterial extract Broncho-Vaxom (BV), free of endotoxin, on haematopoietic parameters of peripheral blood, bone marrow, spleen and thymus were investigated in normal and irradiation-myelosuppressed C57BL/6 mice. BV in normal (nonirradiated) mice induced transient lymphocytopenia and increased granulocytes, particularly neutrophils, six to nine hours after administration. Elevated numbers of peripheral blood macroreticulocytes were observed during the third hour. In the splenic red pulp, enhancing haemopoietic activity, foci of fibroblasts began to appear more frequently from the first hour to 24 h. In lymphatic follicles of the spleen and thymus, the incidence of macrophages or monocytes began to increase three hours after BV application. Twenty-four hours later thymus weight decreased by 27%. In the bone marrow, enhanced proliferation of eosinophils was observed from hour nine, with maximum proliferation at hour 24. BV treatment 24 h before irradiation had a notable radio-protective effect, manifested by accelerated haemopoietic recovery during the postirradiation period. Accelerated myelopoiesis, erythropoiesis and megakaryocytopoiesis resulted in accelerated peripheral blood recovery. However, BV had no effect on thymus reparation as suggested by similar effects in BV protected and BV nonprotected animals during the entire period which followed a 6.5 Gy dose.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Bacterias , Extractos Celulares , Sistema Hematopoyético/efectos de los fármacos , Sistema Hematopoyético/efectos de la radiación , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/farmacología , Animales , Sangre/efectos de los fármacos , Sangre/efectos de la radiación , Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/efectos de la radiación , Timo/efectos de los fármacos , Timo/efectos de la radiaciónRESUMEN
The effect of muramyl tripeptide (MTP-PE) encapsulated in liposomes (multilamellar vesicles, MLV) on hemopoiesis and hemopoietic recovery after sublethal single irradiation with a dose of 6 Gy was investigated. MTP-PE/MLV during 24 h after administration stimulated the monocyte/macrophage system and accelerated recovery from radiation-induced damage of hemopoiesis. The above reparative processes were accompanied by hyperplasia of granulocytes in the bone marrow on days 6-8 after irradiation, acceleration of erythropoiesis in the spleen and recovery of granulocyte count in the peripheral blood. The repair of thymic and splenic lymphoid tissues as well as recovery of the number of mononuclear cells in peripheral blood was not influenced by MTP-PE/MLV application.
Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Antineoplásicos/farmacología , Hematopoyesis/efectos de los fármacos , Fosfatidiletanolaminas/farmacología , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/farmacología , Acetilmuramil-Alanil-Isoglutamina/administración & dosificación , Acetilmuramil-Alanil-Isoglutamina/farmacología , Acetilmuramil-Alanil-Isoglutamina/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Médula Ósea/efectos de los fármacos , Células de la Médula Ósea , División Celular/efectos de los fármacos , Terapia Combinada , Esquema de Medicación , Portadores de Fármacos , Femenino , Hematopoyesis/efectos de la radiación , Inyecciones Intraperitoneales , Recuento de Leucocitos/efectos de los fármacos , Liposomas , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Fosfatidiletanolaminas/administración & dosificación , Fosfatidiletanolaminas/uso terapéutico , Protectores contra Radiación/administración & dosificación , Protectores contra Radiación/uso terapéutico , Bazo/citología , Bazo/efectos de los fármacos , Timo/citología , Timo/efectos de los fármacos , Factores de TiempoRESUMEN
Pretreatment of mice with 50-1000 micrograms of the bacterial extract Broncho-Vaxom (BV, free of endotoxin) before sublethal irradiation induced an increase in the number of endogenous haemopoietic stem cells (E-CFU). The degree of radioprotection was dependent on both the time of administration and the dose of BV. An optimal E-CFU survival was observed when 500 micrograms of BV was administered i.p. 24 h before irradiation. BV did not affect the day 9 CFU-S survival in the bone marrow directly after irradiation. However, 5, 9 and 12 days after irradiation, the number of day 9 CFU-S was almost 2-fold higher in the bone marrow of BV injected mice. Pretreatment with BV protected C57B1/6 mice in a dose-dependent manner from the lethal effect of ionizing radiation. A single dose (50, 100, 250, or 500 micrograms) of bacterial lysate injected i.p. 24 h before 9.5 Gy gamma-rays (LD100/21) protected 16%, 25%, 80%, and 94% of C57B1/6 mice, respectively. The dose reduction factor in the case when the BV (500 micrograms per mouse) was administered at that time was 1.18 (95% CL 1.12, 1.25).
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Bacterias , Extractos Celulares , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Animales , Supervivencia Celular/efectos de la radiación , Femenino , Células Madre Hematopoyéticas/efectos de la radiación , Ratones , Ratones Endogámicos C57BLRESUMEN
The effect of thymus cell-conditioned medium (TCCM) on haemopoiesis recovery in spleen, bone marrow and thymus was studied in mice injured by a single dose of 5.8 Gy of ionizing radiation. TCCM given 18 h before irradiation accelerated haemopoiesis recovery in splenic red pulp, and in part in bone marrow. Reparation of splenic white pulp and thymus was not influenced by TCCM application.