RESUMO
OBJECTIVE: The objective of this study was to investigate whether histamine H4 receptor (H4 R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva. METHODS: Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4 R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated. RESULTS: The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters. CONCLUSIONS: H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4 R could be an attractive strategy to improve periodontal health.
Assuntos
Antagonistas dos Receptores Histamínicos/farmacologia , Indóis/farmacologia , Doenças Periodontais/prevenção & controle , Piperazinas/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/patologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Gengiva/química , Gengiva/efeitos dos fármacos , Gengiva/patologia , Masculino , Cloreto de Metacolina/farmacologia , Terapia de Alvo Molecular , Doenças Periodontais/patologia , Periodontite/tratamento farmacológico , Periodontite/patologia , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos , Receptores Histamínicos H4 , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/patologiaRESUMO
OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. CONCLUSION: Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.
Assuntos
Terapia por Captura de Nêutron de Boro/efeitos adversos , Histamina/uso terapêutico , Neoplasias Bucais/radioterapia , Lesões Pré-Cancerosas/radioterapia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Estomatite/prevenção & controle , Animais , Cricetinae , Modelos Animais de Doenças , Indóis/uso terapêutico , Piperazinas/uso terapêutico , Lesões Experimentais por Radiação/etiologia , Estomatite/etiologiaRESUMO
The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239 ± 12 vs 160 ± 10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radioprotective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials.
Assuntos
Histamina/farmacologia , Intestino Delgado/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Útero/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Intestino Delgado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Útero/patologia , Irradiação Corporal TotalRESUMO
OBJECTIVE: The aim of this work was to analyze the effect of estradiol (E(2)), medroxyprogesterone and the two selective estrogen receptor modulators (SERMs) (tamoxifen (Tam) and raloxifene (Ral)) on the estrogen receptor (ER) conformers profile performed by size exclusion HPLC in relation to hormone dependence of mammary tumors. MATERIALS AND METHODS: Two types of mammary tumors were studied: tumors transplanted in BALB/c mice that are medroxyprogesterone acetate (MPA)-dependent for growth, and tumors induced in Sprague-Dawley rats by intraperitoneal injection of N-nitroso-N-methylurea (NMU). Tumors from mice treated with MPA, E(2), Tam or Ral and NMU-treated rats were analyzed and compared to that of control. RESULTS: The tumor conformer profiles were as follows: control and MPA-treated mice showed only one peak (oligomeric form); E(2)-treated mice also showed only one peak (dimer); Tam-treated mice showed one peak corresponding to a possible proteolytic fragment, and Ral-treated mice showed two peaks (oligomeric and a possible proteolytic fragment). On the other hand, NMU-induced mammary tumors from rats showed three peaks (oligomeric, monomeric and proteolytic). CONCLUSION: Our findings may indicate that SERMs affect the aggregation state of ER and thereby its ability to modulate genomic transcription mechanisms related to growth rate.
Assuntos
Neoplasias Mamárias Experimentais/metabolismo , Cloridrato de Raloxifeno/farmacologia , Receptores de Estrogênio/metabolismo , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Metilnitrosoureia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Hormônio-Dependentes/metabolismo , Conformação Proteica , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/químicaRESUMO
Histidine decarboxylase (HDC) is the single enzyme responsible for histamine synthesis. HDC-deficient mice (HDC(-/-)) have no histamine in their tissues when kept on a histamine-free diet. Therefore, the HDC(-/-) mice provide a suitable model to investigate the involvement of histamine in the regulation of histamine receptor expression. Gene expression of H1 and H2 histamine receptors was studied in several organs of HDC(-/-) mice and compared to standard (HDC(+/+)) mice. In many tissues, prolonged absence of histamine induced down-regulation of the H2 receptor subtype. The expression of the H1 receptor was less sensitive to histamine deficiency. Exogenous histamine present in the diet abolished the differences observed in H2 receptor expression. These results suggest that the expression of mouse H2 receptor is under the control of histamine in a tissue-specific manner.
Assuntos
Cimetidina/análogos & derivados , Regulação para Baixo , Histamina/metabolismo , Histidina Descarboxilase/deficiência , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/metabolismo , Animais , Cimetidina/metabolismo , Deleção de Genes , Perfilação da Expressão Gênica , Histidina Descarboxilase/genética , Histidina Descarboxilase/metabolismo , Camundongos , Camundongos Knockout , Especificidade de Órgãos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The involvement of histamine in cancer growth represents an old controversy and direct experimental evidence proving this hypothesis is not still available. In this paper we review the most relevant mechanisms referring to the role of histamine receptors, histidine decarboxylase and histamine release in the onset of an autocrine loop, that enables histamine to act as an autocrine growth factor. We postulate that this autocrine loop, that has been studied in an experimental mammary carcinoma model induced in rats, may be present in different human neoplasias. Therefore, the better understanding of this novel regulatory pathway that is controlled by histamine may contribute to identifying new therapeutic targets.
Assuntos
Comunicação Autócrina/fisiologia , Substâncias de Crescimento/fisiologia , Histamina/fisiologia , Animais , Liberação de Histamina , Histidina Descarboxilase/metabolismo , Camundongos , Neoplasias/metabolismo , Ratos , Receptores Histamínicos/metabolismoRESUMO
Mammary adenocarcinomas induces in female Sprague-Dawley rats by three intraperitoneal injections of N-nitroso-N-methylurea were studied in order to characterize their estrogen (ER), progesterone (PgR), prolactin (PRLR) and epidermal growth factor (EGFR) receptors. All samples evaluated showed the presence of ER and PgR in the cytosol fraction and PRLR amd EGFR in the membrane fraction. Q (fmol/mg) and K(d) (nM) values were as follows: ER, 56 +/- 11 and 0.5 +/- 0.1; PgR, 109 +/- 25 and 2.2 +/- 0.5 and PRLR, 335 +/- 75 and 0.5 +/- 0.2, respectively. In all tumors studied, two specific sites were found for EGFR, one with Q(1) = 22 +/- 9 and K(d1) = 0.6 +/- 0.3, and the other with Q(2) = 125 +/- 33 and K(d2) = 2.1 +/- 0.5. Receptor content was found to be independent of tumor histopathological variety. Displacement index (DI) with estradiol and tamoxifen of [I(3)H]E2-ER binding showed great heterogeneity, with values ranging from 0.01 to1.54. No correlation between ER content and DI values was found. Antiestrogenic binding sites were not found in the microsomal fraction of ten mammary tumors examined. Proliferation of this experimental mammary tumor may be regulated by a complex interaction of steroid and polypeptide hormones, as well as growth factors.
Assuntos
Carcinoma Ductal de Mama/química , Receptores ErbB/análise , Neoplasias Mamárias Experimentais/química , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Receptores da Prolactina/análise , Animais , Carcinógenos , Carcinoma Ductal de Mama/induzido quimicamente , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Metilnitrosoureia , Ratos , Ratos Sprague-DawleyRESUMO
Two specific binding sites for histamine were characterized in the cell membrane of N-nitroso-N-methylurea (NMU)-induced tumors. The first one, with higher affinity (Kd = 4 +/- 2 nM), was further identified as an H2 type, while the lower affinity one (35 +/- 10 nM) corresponded to an H1 receptor. Histamine concentrations up to 50 nM, as well as H2 agonists, significantly enhanced the phosphoinositide turnover by acting through higher affinity H2 receptors. On the other hand, histamine at concentrations over 50 nM and H1 agonists produced a 100% increase in cAMP levels in a response specifically blocked by mepyramine. These H1 and H2 histamine receptors that exhibit different linkages to second messenger systems may prove to be a characteristic of cells with a high proliferating capacity, such as undifferentiated or transformed cells.
Assuntos
Neoplasias Mamárias Experimentais/metabolismo , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/metabolismo , Transdução de Sinais , Animais , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Metilnitrosoureia , Ratos , Ratos Sprague-DawleyRESUMO
In order to determine the role of endogenous histamine in the regulation of cell growth, the in vitro action of fluoromethyl-histidine (MFMH) was studied in experimental mammary carcinomas induced in rats. Tumor cells were cultured in soft agar using the clonogenic agar technique. The MFMH was added in different concentrations (0.01-100 microM). The effect observed was a 60% inhibition on colony formation with a maximal effect at concentrations over 10 microM. This action was completely reverted by the H2 agonists dimaprit and arpromidine with an IC50 value of 1 microM. The action of the H2 agonists when added alone was a significant increase in cell proliferation (135%), while the H1 agonist produced a dose-dependent inhibition on cell growth. In these experimental carcinomas endogenous histamine is critical for cell proliferation and one of its major effects may be the stimulation of cell growth by acting on specific H2 membrane receptors.
Assuntos
Carcinoma/patologia , Substâncias de Crescimento/fisiologia , Histamina/fisiologia , Neoplasias Mamárias Experimentais/patologia , Animais , Carcinoma/metabolismo , Feminino , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Neoplasias Mamárias Experimentais/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
In order to obtain an experimental model we induced mammary tumors in female Sprague-Dawley rats. The carcinogen N-nitroso-N-methylurea (NMU) was injected intraperitoneally (i.p.) at doses of 50 mg/kg body weight when animals were 50, 80 and 110 days old. Tumor sizes were measured with a caliper and their growth parameters and histopathological properties were tested. For 100 rats, 88.4% of developed lesions were ductal carcinomas, histologically classified as 52.8% cribiform variety, 30.6% solid carcinoma. Metastases in liver, spleen and lung were present. Other primary tumors were detected with low incidence. The influence of the rat estrous cycle during the first exposure to intraperitoneal NMU injection was studied. The latency period in estrus, proestrus and diestrus was 82 +/- 15, 77 +/- 18 and 79 +/- 18 days, respectively. Tumor incidence was significantly higher in estrus (95.2%) than proestrus (71.4%) or diestrus (77.4), (P < 0.01). Mean number or tumors per animal was similar among the three groups (4.4 +/- 3.2, 3.8 +/- 3.6, 3.2 +/- 1.8). The procedure described appears to be the simplest method for inducing experimental mammary tumors in rats.
Assuntos
Estro , Neoplasias Mamárias Experimentais/induzido quimicamente , Metilnitrosoureia , Animais , Feminino , Injeções Intraperitoneais , Neoplasias Mamárias Experimentais/patologia , Ratos , Ratos Sprague-DawleyRESUMO
The presence of H1 and H2 histamine receptors and their associated second messenger systems were studied during the development of the rat mammary gland. In the tissue of the young female, histamine presented a double receptor site as previously described for experimental mammary tumors, namely a high affinity H2 site (Kd = 10 +/- 2 nM, Bmax = 1068 +/- 71 fm/mg prot.), which mediated its effect via the products of phosphoinositide hydrolysis and a low affinity H1 receptor (Kd1 = 5 +/- 2 nM, Bmax = 188 +/- 33 fm/mg prot. and Kd2 = 41 +/- 20 nM, Bmax = 1980 +/- 790 fm/mg prot. when characterized with 3H-mepyramine), coupled to adenylyl cyclase activation. On the other hand, the mammary gland of the adult rat presented these receptors coupled to the classical second messenger systems described for mammalian cells, that is, the H2 receptor produced an increase in intracellular cAMP levels and the H1 receptor increased the phosphoinositide turnover. We conclude that histamine plays a critical role during development and differentiation of the normal rat mammary gland.
Assuntos
Histamina/farmacologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , AMP Cíclico/metabolismo , Feminino , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/efeitos dos fármacos , Fosfatidilinositóis/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H1/fisiologia , Receptores Histamínicos H2/metabolismo , Receptores Histamínicos H2/fisiologia , Sistemas do Segundo Mensageiro/efeitos dos fármacosRESUMO
An experimental mammary carcinoma was induced in Sprague-Dawley rats by the ip administration of N-nitroso-N-methylurea (NMU) in three doses of 50 mg/kg. In order to study the expression of histamine receptors in these experimental tumors, the presence of specific binding sites for histamine was studied. Using [3H]-histamine as a radioligand, two specific binding sites were characterized on the cell membrane. The first site, of high affinity, Kd = 4 +/- 2 nM, was further characterized as an H2 type using [3H]-cimetidine and [3H]-tiotidine as radioligands and by displacement experiments with different histamine agonists and antagonists. The second one of low affinity, Kd = 35 +/- 14 nM, needs further characterization. The determination of cAMP levels showed that histamine and the H2 agonist dimaprit, produced a significant decrease in the nucleotide concentration 6 minutes after stimulation, in a response that was specifically abolished by H2 antagonists. Based on these results, we conclude that neoplastic cells from NMU induced tumors express H2 histamine membrane receptors which are coupled to a transductional pathway different from cAMP production, which may be involved in the regulation of tumor growth.
Assuntos
Carcinoma/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Receptores Histamínicos/metabolismo , Animais , Carcinoma/induzido quimicamente , AMP Cíclico/análise , Antagonistas dos Receptores Histamínicos/farmacologia , Neoplasias Mamárias Experimentais/induzido quimicamente , Metilnitrosoureia/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Non-linear regression and two-step linear fit methods were developed to determine the actual specific activity of 125I-ovine prolactin by radioreceptor self-displacement analysis. The experimental results obtained by the different methods are superposable. The non-linear regression method is considered to be the most adequate procedure to calculate the specific activity, but if its software is not available, the other described methods are also suitable.
Assuntos
Ensaio Radioligante/métodos , Animais , Feminino , Radioisótopos do Iodo , Prolactina/análise , Ratos , Ratos Endogâmicos , Análise de Regressão , OvinosAssuntos
Ratos , Animais , Feminino , Neoplasias da Mama , Levamisol/farmacocinética , Adenocarcinoma , Hormônio Foliculoestimulante/sangue , Histamina/biossíntese , Histidina Descarboxilase/imunologia , Levamisol/imunologia , Levamisol/uso terapêutico , Hormônio Luteinizante/sangue , Metilnitrosoureia/efeitos adversos , Progesterona/sangue , Prolactina/sangueAssuntos
Ratos , Animais , Feminino , Estudo Comparativo , Neoplasias da Mama , Levamisol/farmacocinética , Levamisol/imunologia , Levamisol/uso terapêutico , Metilnitrosoureia/efeitos adversos , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Histamina/biossíntese , Prolactina/sangue , Progesterona/sangue , Adenocarcinoma , Histidina Descarboxilase/imunologiaRESUMO
Adenocarcinomas mamarios fueron inducidos en ratas Sprague-Dawley mediante N-nitraso-N-metil-urea (NMV). Una vez que el primer tumor se hacía evidente, los animales fueron tratados diariamente con una dosis oral de 4 mg/kg de animal de Levamisol (Leva). La actividad de histidina decarboxilasa (HDC), expresada dpm/(g,h), se determinó en el tumor y en el intestino con C-histidina por medición de actividad de CO2 con espectrometría de centelleo líquido. La histopatología demostró que todos los tumores inducidos eran adenocarcinomas mamarios más o menos diferenciados. Como fuera observado en otros casos, la actividad de HDC tumoral fue alta comparada con la de tejidos normales. El tratamiento con Leva durante 7 y 14 días no produjo influencias significativas sobre la actividad de HDC, si bien se evidenció una disminución de la actividad enzimática. La administración de Leva durante más de 20 días provocó una disminución significativa de la actividad de HDC. La actividad de dicha enzima dependió, en todos los casos, de la masa total del tumor (MTT). La actividad de HDC en función de MTT es una función lineal con coeficientes de correlación superiores a 0,9. Para las ratas tratadas con Leva durante 20 días o más, la pedndiente fue de 1,93 ñ 0,89. Para animales no tratados, la pendiente fue de 7,37 ñ 1,23. La diferencia es estadisticamente significativa de acuerdo al criterio de la distribución F (P <0,001). Nuestros resultados demuestran que un agente inmunomodulador exhibe un definido tiempo de retraso antes de ejercer su influencia sobre el metbolismo de la histamina, el cual anormal en diferentes tipos de tumores. En trabajos futuros se estudiará si este efecto está relacionado con la acción inmunomoduladora de la droga
Assuntos
Ratos , Animais , Feminino , Adenocarcinoma/tratamento farmacológico , Histidina Descarboxilase/metabolismo , Levamisol/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológicoRESUMO
Adenocarcinomas mamarios fueron inducidos en ratas Sprague-Dawley mediante N-nitraso-N-metil-urea (NMV). Una vez que el primer tumor se hacía evidente, los animales fueron tratados diariamente con una dosis oral de 4 mg/kg de animal de Levamisol (Leva). La actividad de histidina decarboxilasa (HDC), expresada dpm/(g,h), se determinó en el tumor y en el intestino con C-histidina por medición de actividad de CO2 con espectrometría de centelleo líquido. La histopatología demostró que todos los tumores inducidos eran adenocarcinomas mamarios más o menos diferenciados. Como fuera observado en otros casos, la actividad de HDC tumoral fue alta comparada con la de tejidos normales. El tratamiento con Leva durante 7 y 14 días no produjo influencias significativas sobre la actividad de HDC, si bien se evidenció una disminución de la actividad enzimática. La administración de Leva durante más de 20 días provocó una disminución significativa de la actividad de HDC. La actividad de dicha enzima dependió, en todos los casos, de la masa total del tumor (MTT). La actividad de HDC en función de MTT es una función lineal con coeficientes de correlación superiores a 0,9. Para las ratas tratadas con Leva durante 20 días o más, la pedndiente fue de 1,93 ñ 0,89. Para animales no tratados, la pendiente fue de 7,37 ñ 1,23. La diferencia es estadisticamente significativa de acuerdo al criterio de la distribución F (P <0,001). Nuestros resultados demuestran que un agente inmunomodulador exhibe un definido tiempo de retraso antes de ejercer su influencia sobre el metbolismo de la histamina, el cual anormal en diferentes tipos de tumores. En trabajos futuros se estudiará si este efecto está relacionado con la acción inmunomoduladora de la droga (AU)
Assuntos
Ratos , Animais , Feminino , Levamisol/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Histidina Descarboxilase/metabolismo , Neoplasias Mamárias Experimentais/tratamento farmacológicoRESUMO
Se ha estudiado la cinetica de fagocitosis de coloides de 198Au protegidos con gelatina en ratas Wistar previamente tratadas con Corynebacterium parvum (CBP), con el fin de dilucidar su mecanismo de inmunomodulacion. Para ello se utilizo la tecnica de canulacion carotideo-carotidiana y se analizaron las variaciones de la velocidad de fagocitosis, v, posteriores a la administracion de CBP, obtenidas con una dosis de coloides de 198Au menor o mayor que Ks. En el primer caso no se observaron cambios significativos de v, mientras que en el segundo se determinaron incrementos significativos de v, que se hicieron maximos a los 6 dias luego de la inyeccion de CBP. El analisis cinetico de los datos obtenidos permite deducir que la accion del CBP se ejerce en la etapa de entrada de la particula coloidal al interior de la celula reticuloendotelial