RESUMO
The pharmacological activity of granulocyte CSF (G-CSF) immobilized using electron-beam synthesis nanotechnology (imG-CSF) was evaluated in an experimental model of ovarian reserve depletion. The effectiveness of the drug was compared with that of its unmodified form. Depletion of the ovarian follicular pool in female Sprague-Dawley rats was caused by a single intravenous injection of the antitumor drug etoposide in the maximum tolerated dose. The effectiveness of the studied drugs was assessed by serum concentration of anti-Mullerian hormone (AMH) measured by ELISA and by the number of primordial, two-layer, multilayer, and atretic follicles counted on serial sections of the ovaries (5-µm thick; through the entire organ) stained with hematoxylin and eosin. It was found that imG-CSF prevents depletion of the ovarian reserve in the model used, which was confirmed by high AMH concentration and higher numbers of primordial, two- and multilayer follicles in comparison with the corresponding parameters in the control (etoposide), and by a decrease in the severity of atretic processes. Unmodified form of the drug demonstrated lower efficiency.
Assuntos
Reserva Ovariana , Ratos , Animais , Feminino , Etoposídeo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Elétrons , Ratos Sprague-Dawley , Hormônio Antimülleriano , Modelos TeóricosRESUMO
We studied ante- and postnatal development of the offspring of intact female rats crossed with males injected with low doses of methotrexate 3 and 6 months before mating. The time of crossing corresponded to the manifestation of the cytostatic effect on spermatogonial stem cells. The offspring of methotrexate-treated males was characterized by increased preimplantation losses and fetal growth restriction in the antenatal period and inhibition of physical development, delayed formation of sensory-motor reflexes, and impaired learning abilities in the postnatal period.
Assuntos
Metotrexato , Efeitos Tardios da Exposição Pré-Natal , Humanos , Ratos , Animais , Gravidez , Feminino , Masculino , Metotrexato/farmacologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução , Aprendizagem , ReflexoRESUMO
Delayed gonadotoxic effects were revealed in outbred male sexually mature rats (SD) after exposure to paclitaxel in the prepubertal period, and the possibility of their correction with p-tyrosol was shown. It was found, that administration of paclitaxel does not inhibit the ability of animals to conceive, but impairs the reserve capacity of the testicular tissue. In intact female rats crossed with male rats receiving paclitaxel, increased post-implantation fetal death was observed. Combined administration of paclitaxel and p-tyrosol alleviated the delayed effects of the cytostatic treatment on the prepubertal testis.
Assuntos
Álcool Feniletílico , Testículo , Animais , Feminino , Masculino , Paclitaxel/toxicidade , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , RatosRESUMO
The regenerative properties of p-tyrosol were investigated in a model of testicular insufficiency caused by a toxic effect on spermatogonial stem cells (single administration of paclitaxel in the maximum tolerable dose). Against the background of p-tyrosol administration, we observed an increase in the number of normal spermatogonia and Sertoli cells, stimulation of spermatogenesis, and renewal of the spermatogenic tissue. The treatment with p-tyrosol also led to a decrease in DNA damage in cells of the testicular tissue. These changes were accompanied by a decrease in the level of free radicals, an increase in antioxidant protection, and normalization of the redox potential.
Assuntos
Espermatogônias , Testículo , Humanos , Masculino , Álcool Feniletílico/análogos & derivados , Espermatogênese , Células-TroncoRESUMO
The morphological and functional state of the reproductive system was studied in male outbred rats (SD stock) and male F1(CBA×C57BL/6) mice after long-term (3 months) methotrexate administration. The drug was administered subcutaneously once a week for 4 weeks, the dose for male rats was 1 mg/kg, for male mice 2.2 mg/kg. It was found that male rats retained the ability to conceive, their reproductive potential was not limited by increased risk of embryo death. At the same time, signs of astheno- and pathospermia were revealed. The testicular tissue was characterized by reduced content of the sources of the proliferative pool of spermatogenesis. In mice treated with methotrexate, increased content of DNA breaks was detected in the testicular cells.
Assuntos
Metotrexato , Espermatogênese , Animais , Masculino , Metotrexato/toxicidade , Camundongos , Ratos , Reprodução , TestículoRESUMO
The effect of p-tyrosol on the spontaneous level of DNA damage in the cells of the bone marrow, liver, kidney, and rectum of mice (series I) and on the genotoxic effects of cytostatic drugs with different mechanisms of action in rat testicular cells (series II) was studied by DNA comet assay on C57BL/6 mice. p-Tyrosol was administered in a dose of 40 mg/kg once (series I) or for 5 days before and 5 days after cytostatic exposure (busulfan, paclitaxel, methotrexate; series II). It was found that p-tyrosol reduced spontaneous level of DNA damage in all studied organs. p-Tyrosol exhibited an antigenotoxic effect with respect to the DNA-damaging action of methotrexate and produced no genoprotective effect in case of busulfan and paclitaxel.
Assuntos
Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Mutagênicos/toxicidade , Álcool Feniletílico/análogos & derivados , Animais , Bussulfano/farmacologia , Dano ao DNA/genética , Masculino , Metotrexato/farmacologia , Metanossulfonato de Metila/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/farmacologia , Álcool Feniletílico/farmacologiaRESUMO
We studied the effects of combined chemotherapy with doxorubicin/docetaxel on erythroid and granulocytic hematopoietic lineages with particular attention focused on their recovery in patients with stages III-IV breast cancer. Intensification of differentiation of erythroid and granulocytic CFU (even under conditions of their suppressed proliferation) provided the increase in the content of mature and morphologically differentiated elements in the bone marrow and peripheral blood. High proliferative activity of erythroid and granulomonocytic precursors resulted from enhanced production of hematopoiesis-stimulating activities by microenvironment elements.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Doxorrubicina/uso terapêutico , Eritropoese/efeitos dos fármacos , Leucopoese/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/metabolismo , Linhagem da Célula/efeitos dos fármacos , Eritrócitos/citologia , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Granulócitos/citologia , HumanosRESUMO
Experimental model of sulpiride-provoked benign prostatic hyperplasia was employed to comparatively assess the effect of phenolic antioxidants (dihydroquercetin, p-thyrozol, dibornol, and prostagenin) on prostate morphology. All examined agents decreased the degree of hyperplasia in acinar epithelium; the greatest efficacy was demonstrated by prostagenin. Moreover, dihydroquercetin and p-thyrozol increased the cross-section area of acinar lumina and prostate volume, which is inadmissible in this pathology. These results suggest that the use of phenolic antioxidants in the therapy of benign prostatic hyperplasia should be strictly controlled.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Metimazol/farmacologia , Fenóis/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Quercetina/análogos & derivados , Células Acinares/efeitos dos fármacos , Células Acinares/patologia , Animais , Animais não Endogâmicos , Modelos Animais de Doenças , Humanos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Quercetina/farmacologia , Ratos , Sulpirida/administração & dosagemRESUMO
The effect of phenolic antioxidants (dihydroquercetin, p-tyrosol, dibornol) on the morphology, functions, and redox processes in the reproductive cells of male rats was studied on the model of experimental pathospermia. All antioxidants reduced the percentage of degenerative forms of spermatozoa. Dibornol was most effective. Dihydroquercetin and p-tyrosol did not increase the total number of spermatozoa and the percentage of their mobile forms. These indicators were improved only by dibornol. After administration of all test drugs, the antioxidant potential of spermatozoa increased and did not significantly differ from the baseline values.
Assuntos
Antioxidantes/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , Oligospermia/complicações , Oligospermia/tratamento farmacológico , Fenóis/uso terapêutico , Animais , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/uso terapêutico , Quercetina/análogos & derivados , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacosRESUMO
We studied myelotoxicity of modern schemes of chemotherapy for breast cancer (docetaxel/doxorubicin and cyclophosphamide/doxorubicin/5-fluorouracil) towards granulocytopoiesis, the mechanisms determining the differences of hematological effects of these schemes, and the efficiency of correction of the observed changes with granulocyte CSF (filgrastim). Granulocytopoiesis stimulation with filgrastim during the treatment with docetaxel/doxorubicin combination was more pronounced than during cyclophosphamide/doxorubicin/5-fluorouracil therapy. The observed differences were found at all levels of granulocyte lineage organization (central and peripheral), which is related to different effects of the cytostatic substances used in the proposed protocols on the structures controlling hemopoiesis.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Filgrastim/uso terapêutico , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/metabolismo , HumanosRESUMO
We studied the effects of elastase, cigarette smoke extract, D-galactosamine hydrochloride, and tyrosine kinase inhibitor SU5416 on endothelial progenitor cells and angiogenesis precursors, as well as on Notch-1 expression by immature endothelial cells. Simultaneously with pulmonary emphysema, different damaging factors with diverse mechanisms of action caused pathological changes in the microvascular network of the lungs and destroyed the alveolar endothelium in female C57Bl/6 mice. D-galactosamine hydrochloride disturbed mobilization of endothelial progenitor cells expressing VEGFR (CD45-CD309+) and angiogenesis progenitors (CD45-CD309+CD117+) and their migration into emphysema expanded lungs. Elastase inhibited VEGFR-expressing endothelial progenitor cells, while cigarette smoke extract inhibited cells with CD45-CD31+CD34+ phenotype. In pulmonary emphysema provoked by elastase or D-galactosamine hydrochloride, angiogenesis was provided by endothelial cells with CD45-CD31+CD34+ phenotype, whereas in emphysema modeled with SU5416 or cigarette smoke extract, it was provided by the endothelial VEGFR-expressing cells and mature CD31+ endothelial cells, respectively. Replenishment of immature endothelial cells damaged by elastase and SU5416 involved Notch-1+ angiogenesis precursors and Notch-1+ endothelial progenitor cells with VEGFR.
Assuntos
Células Progenitoras Endoteliais/citologia , Neovascularização Fisiológica , Enfisema Pulmonar/metabolismo , Receptor Notch1/genética , Regeneração/fisiologia , Transdução de Sinais , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Misturas Complexas/isolamento & purificação , Misturas Complexas/toxicidade , Células Progenitoras Endoteliais/metabolismo , Endotélio/citologia , Endotélio/metabolismo , Feminino , Galactosamina/toxicidade , Regulação da Expressão Gênica , Indóis/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Elastase Pancreática/toxicidade , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Pirróis/toxicidade , Receptor Notch1/metabolismo , Nicotiana/química , Nicotiana/toxicidade , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
We studied the efficiency of dihydroquercetin on the model of chronic nonbacterial inflammation of the prostatic gland in rats. It was found that administration of dihydroquercetin was followed by a significant decrease in the area of the connective tissue in the prostatic gland to initial levels, which attested to antifibrotic properties of this oxidant. Additionally, the substance prevented the development of atrophy of acinus epithelium. After administration of reference drug Prostamol Uno, only moderate antifibrotic effects were observed.
Assuntos
Inflamação/patologia , Próstata/imunologia , Próstata/patologia , Prostatite/tratamento farmacológico , Prostatite/imunologia , Quercetina/análogos & derivados , Animais , Doença Crônica , Inflamação/imunologia , Masculino , Próstata/efeitos dos fármacos , Quercetina/uso terapêutico , Ratos , Ratos WistarRESUMO
Course administration streptozotocin to male C57Bl/6 mice induces a complex of symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin deficiency, focal inflammatory infiltration of the pancreas, destructive changes in the Langerhans islets, damage to the insular apparatus (reduced number of PDX1+ cells and insulin expression by the secreting cells). Male reproductive disorder are serious complications of type 1 diabetes mellitus. In "diabetic" mice, interstitial edema with inflammatory infiltration and microvascular disorders in the testicular tissue are observed, the number of endothelial precursors (CD45-/CD31+) and the total number and percentage of motile spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of into the lumen of the tubules. Disturbances in the proliferation and differentiation of various spermatogonial stem cell populations (c-kit-/CD90+, c-kit+/CD90+, and CD51-/CD24+/CD52+) in diabetes can be explained by the inhibitory influence of inflammatory factors on testosterone-producing Leydig cells.
Assuntos
Diabetes Mellitus Experimental/patologia , Disfunção Erétil/patologia , Células Intersticiais do Testículo/efeitos dos fármacos , Oligospermia/patologia , Células de Sertoli/efeitos dos fármacos , Estreptozocina/toxicidade , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/genética , Disfunção Erétil/metabolismo , Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Insulina/genética , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligospermia/induzido quimicamente , Oligospermia/genética , Oligospermia/metabolismo , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Espermatogônias/efeitos dos fármacos , Espermatogônias/metabolismo , Espermatogônias/patologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Transativadores/genética , Transativadores/metabolismoRESUMO
The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Granulócitos/metabolismo , Neoplasias Pulmonares/metabolismo , Antraciclinas/farmacologia , Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Cisplatino/farmacologia , Dissacarídeos/farmacologia , Docetaxel , Doxorrubicina/farmacologia , Eritropoese/efeitos dos fármacos , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Macrolídeos/farmacologia , Compostos de Nitrosoureia/farmacologia , Compostos Organoplatínicos/farmacologia , Taxoides/farmacologiaRESUMO
The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90+ and epithelial progenitors CD45-CD31-Sca-1+CD49f+ derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24+CD52+ had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90+ and CD117+CD90+ as well as endothelial progenitors CD45-CD31+ derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan.
Assuntos
Células Progenitoras Endoteliais/citologia , Células-Tronco/citologia , Animais , Bussulfano/farmacologia , Antígeno CD24/metabolismo , Antígeno CD52/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Inflamação/metabolismo , Integrina alfaV/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-kit/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogônias/citologia , Espermatogônias/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Antígenos Thy-1/metabolismoRESUMO
The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117-CD90+ and CD51-CD24+CD52+ from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45-CD31-Sca-1+CD49f+) and endothelial (CD45-CD31+) precursors exhibited lower self-renewal capacity. On day 30 after injection of stem and progenitor cells from ischemic testes to the rete testis zone of the testes of busulfantreated animals, an increase in the count of CD117-CD90+ spermatogonial stem cells, total count, and mobile sperm count in the testes of recipient mice was observed. In addition, we observed an increase in Sca-1+ cell count, recovery of the spermatogenic epithelium in the seminiferous tubules, and appearance of immature Leydig cells in "busulfan" testes; the level of tissue testosterone and fertility index also increased.
Assuntos
Bussulfano/toxicidade , Isquemia/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogônias/metabolismo , Animais , Antígenos CD/genética , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica , Isquemia/patologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Ligadura , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/patologia , Cordão Espermático/irrigação sanguínea , Cordão Espermático/cirurgia , Espermatogônias/efeitos dos fármacos , Espermatogônias/patologia , Transplante de Células-Tronco , Testosterona/biossínteseRESUMO
Effectiveness of the granulocyte colony-stimulating factor immobilized by using electronbeam synthesis nanotechnology was investigated on the model of experimental testicular failure caused by the toxic effect on stem spermatogonia. Administration of the drug to experimental paclitaxel-treated animals increased the number of sources of the proliferative pool of spermatogenesis and its productivity. The effectiveness of immobilized granulocyte colony-stimulating factor was based on its ability to stimulate reparative regeneration of the spermatogenic tissue, which manifested in a decrease in spermatogenic layer maturity and increase in the number of microenvironment cells. Effectiveness of the immobilized form of the drug was superior to that of non-immobilized form.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Proteínas Imobilizadas/farmacologia , Infertilidade Masculina/tratamento farmacológico , Espermatogônias/fisiologia , Animais , Antineoplásicos/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Proteínas Imobilizadas/uso terapêutico , Infertilidade Masculina/induzido quimicamente , Masculino , Nanotecnologia , Paclitaxel/efeitos adversos , Ratos Wistar , Regeneração , Espermatogênese , Espermatogônias/efeitos dos fármacosRESUMO
The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing ß-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1ß and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor ß-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor ß-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing ß-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Diabetes Mellitus Experimental/terapia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Hiperglicemia/terapia , Células Secretoras de Insulina/citologia , Leucopenia/terapia , Animais , Células da Medula Óssea , Diferenciação Celular , Diabetes Mellitus Experimental/patologia , Fluoruracila , Granulócitos/citologia , Ácido Hialurônico/sangue , Hiperglicemia/induzido quimicamente , Inflamação/terapia , Células Secretoras de Insulina/patologia , Interleucina-1beta/sangue , Leucopenia/induzido quimicamente , Leucopenia/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , EstreptozocinaRESUMO
PURPOSE: To compare diagnostic efficacy of multigated acquisition (MUGA) scan and Tc-99m MIBI gated SPECT for evaluation and forecast of anthracycline-induced cardiotoxicity. MATERIAL AND METHODS: We included into this study 80 patients (72 women and 8 men, mean age 43 ± 4.2 years) with malignant tumors without overt pathology of the cardiovascular system. These patients received doxorubicin (50 mg/m2 per course) based cytostatic therapy. All patients were studied either by MUGA (n = 40) or 99MTc MIBI gated SPECT (n = 40) before initiation of chemotherapy 1 hour after first administration of doxorubicin and after the 4th course. RESULTS: After administration of 50 mg/m2 of doxorubicin 14 patients according to MUGA scan and 16 patients according to 99mTc MIBI gated SPECT had significant (≥ 10%) reduction of left ventricular ejection fraction (LVEF). Significant inhibition of systolic function in these patients remained after the 4th course of treatment. Individual analysis of the MUGA and 99mTc MIBI gated SPECT data registered after the fourth course (achievement of total doxorubicin dose of 200 mg/m2) showed that ≥ 10% LVEF reduction in response to the first dose of doxorubicin could predict the development of cumulative cardiotoxicity. CONCLUSION: MUGA scan and 99mTc MIBI gated SPECT can be applied with equal effectiveness for assessment of acute and chronic anthracycline-induced cardiotoxicity in patients with malignant tumors. LVEF reduction ≥ 10% in response to the first dose of doxorubicin appeared to be a predictor of development of chronic cardiotoxicity.
Assuntos
Antraciclinas/efeitos adversos , Imagem do Acúmulo Cardíaco de Comporta/métodos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Antraciclinas/uso terapêutico , Cardiotoxicidade , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Haemonchus contortus is a blood-sucking parasite causing the presence of faecal occult blood (FOB). The objective was to study three different FOB tests in order to have a new indicator of H. contortus infection in sheep that could be included in the genetic evaluation system as an alternative selection criterion to faecal worm egg count (FEC). A total of 29 Corriedale lambs were experimentally infected with 10.000 larvae of H. contortus. Stool samples were recorded for FEC and FOB tests (Hexagon, Hematest(®) and Multistix(®)), blood for packed cell volume (PCV), haemoglobin, white and red blood cell count (RBC), and FAMACHA(©) for scoring anaemia. At the end of the experiment lambs were slaughtered to worm burden count. Field infection was achieved in 309 Merino lambs under natural parasite challenge. FEC data were normalized through logarithmic transformation (LnFEC). Pearson correlation was estimated to examine the relationship between all traits. The three tests were able to detect the presence of FOB at day 11. FEC, PCV and RBC decreased to sub-normal values from day 18. FAMACHA(©) score 3 was considered to be indicative of anaemia. Most of the correlations were of high magnitude, with the exception of Multistix(®) test that was moderately correlated with haematological parameters, LnFEC and FEC. In field infection, most samples were negative to FOB tests and the correlations were lower than those calculated under experimental infection. In conclusion, FOB tests were able to detect haemonchosis earlier than FEC under high experimental parasite challenge. However, they were not able to detect FOB under natural mixed parasite challenge. FAMACHA(©) and PCV demonstrated to be good indicators of Haemonchosis, having moderate to high correlations with FEC.