RESUMO
The effects of temperature on the binding kinetics of phenytoin (PHT) to serum proteins were determined in patients with epilepsy. Serum samples examined in the study were obtained from 59 patients (31 male, 28 female) with epilepsy on PHT monotherapy. Their age ranged from 3 to 64 years (mean (SD), 23.3 (16.3) years). Protein binding of PHT was evaluated by ultrafiltration under current routine laboratory conditions (25 +/- 3 degrees C) or at a temperature of 37 degrees C. The in vivo binding parameters of PHT to serum proteins were determined using a binding equation derived from the Scatchard equation for a one-site binding model. Significant differences were observed in serum concentrations of unbound PHT between paired data (P < 0.05). The mean association constant (K) of PHT to serum proteins is 0.011 microM-1 at 25 +/- 3 degrees C and 0.006 microM-1 at 37 degrees C, while mean total concentration of binding sites (n(Pt)) is 1002 microM for 25 +/- 3 degrees C and 1112 microM for 37 degrees C. Significant differences were observed in the binding kinetics of PHT to serum proteins for the different temperature conditions of ultrafiltration (P < 0.05). Our study confirms that binding affinity for PHT-serum protein interaction is approximately 45% lower at 37 degrees C than at 25 +/- 3 degrees C and consequently, binding potential (K.n(Pt)) is approximately 39% lower at 37 degrees C than at 25 +/- 3 degrees C.
Assuntos
Anticonvulsivantes/sangue , Proteínas Sanguíneas/metabolismo , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Fenitoína/sangue , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Químicos , Fenitoína/uso terapêutico , Ligação Proteica , Termodinâmica , UltrafiltraçãoRESUMO
AIM: The aim of the present study was to determine the binding characteristics of phenytoin (PHT) to serum proteins in the pediatric population. Binding parameters of PHT to serum proteins in our study were conducted to compare with in vivo or in vitro binding parameters of PHT to serum proteins in adult subjects reported by other investigators. SUBJECTS AND MATERIALS: Serum samples in the study were obtained from 40 pediatric patients (16 male, 24 female) receiving PHT monotherapy. Their age ranged from 1 to 15 years (9.2 +/- 3.6 years, mean +/- SD). The in vivo population binding parameters of PHT to serum proteins and theoretical minimal unbound serum PHT fraction (fu) were determined using an equation derived from the Scatchard equation. RESULTS: The association constant (Ka) was 0.014 l/micromol, while the total concentration of binding sites (n(Pt)) was 747 micromol/l. The number of binding sites per albumin molecule (n) was 1.13, while binding ability (n x Ka) was 0.0161/micromol. The fu was 0.087. The n x Ka is approximately 1.2 times higher in PHT monotherapy adult patients of Pospisil et al. [1992] (i.e. 0.0191 l/micromol) than in all our patients. The association constant is approximately 1.3 times higher in the in vitro study of Monks et al. [1978] (i.e. 0.0186 l/micromol) than in our study, while n is similar between the two studies. The fu in our pediatric patients is similar to the unbound serum PHT fraction in adult patients receiving PHT therapy reported by Richens [1979] (i.e. 0.1). CONCLUSION: Our results suggest that there may be small differences in the binding characteristics of PHT to serum proteins between Japanese pediatric and non-Japanese adult subjects. The unbound serum fraction of PHT in pediatric patients with epilepsy can be assumed to be relatively constant in the therapeutic concentration range of PHT.
Assuntos
Anticonvulsivantes/sangue , Proteínas Sanguíneas/metabolismo , Epilepsia/sangue , Fenitoína/sangue , Adolescente , Adulto , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Fenitoína/farmacocinética , Fenitoína/uso terapêutico , Ligação ProteicaRESUMO
An anti-membrane antibody was present in the sera of systemic lupus erythematosus patients in immunoelectrosyneresis with sodium dodecyl sulfate (SDS) solubilized erythrocyte membrane as antigen. The SDS bound to protein was detected by chromatography at 10(-3)M concentration under U.V. light, at 10(-5)M concentration by the distilled water spray method and at 10(-6)M concentration by using rosaniline hydrochloride colorimetry. SDS was removed from the membrane protein at a concentration of 10(-3)M by the first gel filtration of Sephadex G-25 column and at a concentration of 10(-6)M by rechromatography of the same column. More than 99% of SDS in the solubilized erythrocyte membrane was removed by gel filtration. The antigenicity was still positive in the refiltrated fractions of systemic lupus erythematosus patients. Therefore, all precipitates in the gels were antigen-antibody aggregates.
Assuntos
Reações Antígeno-Anticorpo/efeitos dos fármacos , Eritrócitos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Dodecilsulfato de Sódio/farmacologia , Anticorpos , Antígenos , Membrana Celular/imunologia , Cromatografia em Gel , HumanosRESUMO
The effects of coenzyme Q10 (Co Q10) on potassium ion release, membrane potential and fluidity of rabbit red blood cells were studied. Co Q10 inhibited the increased potassium ion release induced by cetylamine or lysolecithin from the cells. Co Q10 slightly decreased the membrane potential monitored by changes in fluorescence intensity of cyanine dye, 3,3'-dipropyl-2,2'-thiodicarbocyanine iodide [diS-C3-(5)], and also slightly decreased the membrane fluidity measured by using 1,6-diphenyl-1,3,5-hexatriene (DPH). These effects of Co Q10 on the membrane are considered to be due to its membrane stabilizing activity by interaction with lipid bilayers of the membrane.
Assuntos
Eritrócitos/efeitos dos fármacos , Fluidez de Membrana/efeitos dos fármacos , Potássio/sangue , Ubiquinona/farmacologia , Aminas/antagonistas & inibidores , Animais , Depressão Química , Eritrócitos/metabolismo , Hidrocarbonetos , Técnicas In Vitro , Íons , Lisofosfatidilcolinas/antagonistas & inibidores , Lipídeos de Membrana/fisiologia , Potenciais da Membrana/efeitos dos fármacos , CoelhosRESUMO
The effect of alpha-tocopherol acetate (VE) on the toxicity and tissue distribution of adriamycin (ADM) in mice was studied. After the administration of ADM in 2 doses of 15 mg/kg, mice pretreated with olive oil survived 7.1 +/- 1.0 days, while mice pretreated with VE in ten doses of 500 mg/kg/day (subcutaneously) survived 5.5 +/- 1.7 days (p less than 0.01). The total concentration of ADM and its major metabolite, aglycone I in the liver (1, 3, 5 h), kidneys (1, 3 h), and heart (3 h), as determined by high performance liquid chromatography was significantly higher in the VE-pretreated group (four doses of 500 mg/kg/day) than in the olive oil-pretreated group. The aglycone levels of the VE-pretreated group were significantly higher than those of the olive oil-pretreated group in the liver, kidney and heart, but there was no significant difference between the groups in the levels of the unmetabolized form. Considering these results, the administration of VE concomitant with anti-tumor drugs, including ADM, requires great caution.
Assuntos
Doxorrubicina/toxicidade , Rim/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , Vitamina E/análogos & derivados , alfa-Tocoferol/análogos & derivados , Animais , Relação Dose-Resposta a Droga , Doxorrubicina/farmacocinética , Coração/efeitos dos fármacos , Injeções Subcutâneas , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Distribuição Tecidual , Tocoferóis , Vitamina E/administração & dosagem , Vitamina E/farmacologiaRESUMO
Protective effects of clinically used drugs against adriamycin (ADM)-induced toxicity were studied in ICR mice. The control mice, which were administered 15 mg/kg of ADM twice, survived 7.48 +/- 1.99 days (mean +/- S.D.). The survival times of mice treated with the following drugs, expressed as a percent of that of the control group, were 293.6% for coenzyme Q10 (Co Q10, 2 mg/kg), 402.2% for dextran sulfate (MDS, 300 mg/kg), 121.6% for flavin adenine dinucleotide (20 mg/kg), 236.3% for adenosine triphosphate disodium (50 mg/kg), 213.7% for reduced glutathione (100 mg/kg), 121.6% for phytonadione (50 mg/kg), 155.2% for inositol nicotinate (Ino-N, 500 mg/kg), 335.5% for nicomol (1000 mg/kg), 157.5% for nicardipine (10 mg/kg) and 123.3% for dipyridamol (50 mg/kg). Anti-hyperlipemic agents such as MDS, nicomol, Ino-N and Co Q10 strongly protected against the ADM-induced toxicity, and the mice administered these drugs lived significantly longer than the control mice. The mechanism of the protective effect was discussed.
Assuntos
Doxorrubicina/toxicidade , Animais , Coenzimas , Sulfato de Dextrana , Dextranos/farmacologia , Hipolipemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ubiquinona/análogos & derivados , Ubiquinona/farmacologiaRESUMO
The tissue concentration of doxorubicin (adriamycin; ADM) and its major metabolite (aglycone I) was examined in mice pretreated with alpha-tocopherol (VE) or coenzyme Q10 (CoQ). In VE-pretreated group, the concentrations of aglycone I of the liver (1, 3 and 5 h after the administration), kidney (1 and 3h) and heart (3h) were significantly higher than those in the saline group. The clinical application of VE or CoQ concomitant with anti-tumor drugs especially ADM, requires caution.
Assuntos
Doxorrubicina/farmacocinética , Ubiquinona/farmacologia , Vitamina E/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Coenzimas , Fluorescência , Masculino , Camundongos , Camundongos Endogâmicos ICR , Concentração Osmolar , EspectrofotometriaRESUMO
The usefulness of liposomes (in neutral, positively and negatively charged forms) as a carrier for adriamycin (ADM) was studied by examining the distribution of ADM and related fluorescent compounds in Ehrlich solid tumor-bearing mice. The mice were given free or liposome-entrapped ADM intraperitoneally. The distribution of ADM and related fluorescent compounds between the administration of the free form and liposome-entrapped form was measured by high performance liquid chromatography : The distribution was dependent on the form of the liposomes. The amounts of ADM and its metabolites in the mouse serum 20 min after administration of neutral-liposome-entrapped ADM were 10 times those after the administration of free ADM, 6 times those after the administration of a negatively charged form, and 3.5 times those in the administration of positively charged form. There was no marked difference in the concentrations of these compounds 5 h after administration. The concentration of these compounds in the liver 60 min after administration of each liposome-entrapped form of ADM were in inverse correlation with the concentrations in the serum obtained at 20 min after administration. Total concentrations of ADM and its metabolites in the tumors 20 min after administration of each entrapped form of ADM were 4-5 times that in administration of free ADM after 20 min. There were no marked differences in the concentration of ADM for administration of the various liposome forms. Statistically significant decreases in mean tumor weight were seen in the groups given neutral, positively and negatively charged liposome-entrapped forms compared to corresponding control groups given with free ADM.
Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Doxorrubicina/uso terapêutico , Lipossomos/administração & dosagem , Animais , Carcinoma de Ehrlich/metabolismo , Cromatografia Líquida de Alta Pressão , Doxorrubicina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fatores de Tempo , Distribuição TecidualRESUMO
Pharmacokinetic analysis of the distribution and concentration of adriamycin (ADM) in mouse plasma and tissues was carried out by differentiating the unmetabolized form from metabolized ones using high-performance liquid chromatography after a single intravenous injection. Marked differences between ADM and total ADM equivalent values (total ADM values) or its metabolized forms were observed in the pharmacokinetic behavior in plasma and tissue distributions. The ratios of tissue per plasma for total ADM and for ADM values in the liver, kidney and heart showed a two-digit magnitude each time they were examined. Twenty four h later, the ratios for ADM values in the liver, kidney, heart and lung were at high levels; 43.1, 48.1, 57.9 and 45.5 times, respectively. Twenty min after injection the ratios for total ADM values in the spleen, lung and tumors were comparatively small, but 24 h later, the ratio had increased 36.5, 45.5 and 6.8 times respectively.
Assuntos
Carcinoma de Ehrlich/metabolismo , Doxorrubicina/metabolismo , Animais , Carcinoma de Ehrlich/sangue , Doxorrubicina/sangue , Cinética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Espectrometria de Fluorescência , Distribuição TecidualRESUMO
The effect of coenzyme Q10 (Co Q10) was examined on the survival time and lipid peroxidation of adriamycin (ADM)-treated ICR mice. Co Q10 showed a protective effect against a subacute toxicity in mice induced by two intraperitoneal administrations of ADM (15 mg/kg). The group treated orally with 10 mg/kg of Co Q10 showed the longest survival time of all the groups studied (16.81 +/- 10.29 days, mean +/- S.D.) and a significantly longer survival time (p less than 0.001) than the ADM-alone group (7.48 +/- 1.99 days). The inhibitory effect of Co Q10 on the plasma and tissue lipid peroxidation levels did not correlate with the effect of prolonging the survival time of mice. Co Q10 tended to inhibit rises in plasma and liver lipid peroxidation levels induced by ADM administration, but there was no statistically significant difference between treatments. There was a statistically significant different inhibitory effect in the kidney lipid peroxidation levels, but was not in those of the heart.
Assuntos
Doxorrubicina/toxicidade , Peróxidos Lipídicos/metabolismo , Ubiquinona/análogos & derivados , Animais , Coenzimas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ubiquinona/farmacologiaRESUMO
When two doses (15 mg/kg) of adriamycin (ADM) were administered to ICR mice pretreated with 500 mg/kg/day of alpha-tocopherol (VE) and alpha-tocopherol acetate (VE-AC) respectively, both the VE and the VE-AC pretreatment groups showed a significant shortening of survival time compared to control group. The concentration of ADM and of total aglycone (AD-NE) was determined in the tissue of mice given a single dose of 15 mg/kg of ADM after pretreatment with 500 mg/kg of VE and VE-AC, respectively, high values were found in liver, kidney and heart tissue compared to the control group. And, particularly the heart tissue of the group pretreated with VE showed significantly higher values of ADM and AD-NE. High AD-NE levels were noted in mouse liver mitochondria (Mt), after pretreatment with both VE and VE-AC, with a significantly higher concentration in the VE-pretreated group. A comparison of the uptake of ADM and AD-NE into mouse Mt pretreated with VE or VE-AC in vitro, showed no difference in the ADM value from that of the control group, but both the VE- and the VE-AC-pretreated groups had significantly higher in AD-NE concentrations compared to the control group.
Assuntos
Doxorrubicina/toxicidade , Vitamina E/análogos & derivados , Vitamina E/farmacologia , alfa-Tocoferol/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Doxorrubicina/farmacocinética , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Miocárdio/metabolismo , Distribuição Tecidual , TocoferóisRESUMO
The effects of Aclarubicin (aclacinomycin A; ACM) and Doxorubicin (adriamycin; ADM) on oxidative phosphorylation in rat liver mitochondria were studied in vitro. The state 3 oxygen uptake of mitochondria was reduced by only 2% by 20 microM of ADM, while the same concentration of ACM caused a 67% reduction. When 20 microM of ADM acted on state 4a oxygen uptake of mitochondria, only a slight decrease in state 3, state 4b, dinitrophenol-stimulated respiration and the respiratory control index was observed. In contrast 20 microM of ACM caused significant inhibition of all the above factors when compared with the controls. It was concluded that ACM has strong inhibitory action on the mitochondrial electron transfer system in vitro, and that one can expect functional failure of mitochondria to occur clinically during adverse response to the administration of this drug.
Assuntos
Aclarubicina/farmacologia , Doxorrubicina/farmacologia , Mitocôndrias Hepáticas/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Animais , Transporte de Elétrons/efeitos dos fármacos , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
This report is a case of intracranial neurinoma of the jugular foramen. A 21-year-old woman was admitted to our hospital with complaints of headache, nausea, tinnitus on the left and deafness on the left. The neurological examination revelaed bilateral choked disc, Bruns Cushing nystagmus, hearing disturbance on the left, slight disturbance of vestibular function on the left, diminished gag reflex on the left, curtain sign on the left, loss of taste on the posterior third of the left side of the tongue, and deviation of the tongue to the left on protrusion, accompanied with atrophy and fasciculation on the left. Skull-XP showed the enlargement of the jugular foramen. Pneumoencephalogram showed the enlargement of the fourth ventricle combined with the superior, posterior displacement of it's floor. We confirmed the diagnosis of the jugular foramen neurinoma on the left. By suboccipital craniectomy a walnutsized tumor was disclosed at the jugular foramen. The tumor was encapsuled with smooth, thick capsule and was colored in dark rouge. This tumor was removed totally and the postoperative course was uneventful. The pathological diagnosis was neurinoma. We consider that this tumor originated in the ninth or tenth cranial nerve.
Assuntos
Neurilemoma/cirurgia , Adulto , Feminino , Humanos , Veias Jugulares , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , RadiografiaRESUMO
Effects of anthracycline type antitumor agents (aclarubicin, ACL; daunorubicin, DAU; doxorubicin, DOX; epirubicin, EPI; pirarubicin, PIR) on the acute toxicity to mouse, rat liver microsomal lipid peroxidation and mitochondrial functions in vitro were studied. ACL showed the least production of liver microsomal lipid peroxidation in all tested anthracyclines in the increasing order of PIR, DOX, DAU and EPI. The increase of production of lipid peroxidation induced by these drugs correlated well with the decrease in body weight of mice administered i.p. at 20 mg/kg and 50% lethal dose of these drugs. On the effect of mitochondrial function, all drugs tested decreased the oxygen uptake of state 3 and the level of respiratory control index. ACL showed the most severe inhibition of these functions in all drugs. These observations suggest that the degree of microsomal lipid peroxidation induced with the anthracycline drugs was related to the development of the drug acute toxicity.
Assuntos
Antibióticos Antineoplásicos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Aclarubicina/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Daunorrubicina/toxicidade , Doxorrubicina/análogos & derivados , Doxorrubicina/toxicidade , Epirubicina/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microssomos Hepáticos/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Ratos , Ratos EndogâmicosRESUMO
The protective effects of the biological membrane stabilizing drugs, coenzyme Q10 (CoQ), dextran sulfate (DS) and reduced glutathione (GSH), on doxorubicin (adriamycin, ADM)-induced toxicity and microsomal lipid peroxidation were studied in mice. The mice administered ADM with combined treatment of CoQ, DS or GSH showed a significantly longer survival time than the ADM control group (which were injected with 15 mg/kg of ADM twice). The optimum protective doses of these drugs against ADM-induced toxicity were 10 mg/kg/day (p.o.) for CoQ, 100 mg/kg/day (s.c.) for DS and 100 mg/kg/day (i.p.) for GSH. The survival times of the mice (expressed as a percent of the treated group per control group) were 224.1% for CoQ, 220.7% for DS and 213.7% for GSH. The groups treated with these drugs showed a significant decrease in mouse liver and heart microsomal lipid peroxidation in comparison to that of the ADM control group. These results suggest that the heart microsomal lipid peroxidation levels may be one of the indications of ADM-induced cardiac toxicity. These drugs tested in the present study may stabilize the heart microsomal membrane lipid or may improve the myocardiac mitochondrial functions over those in ADM-treated mouse.
Assuntos
Antídotos/farmacologia , Sulfato de Dextrana/farmacologia , Doxorrubicina/toxicidade , Glutationa/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Microssomos/efeitos dos fármacos , Ubiquinona/análogos & derivados , Animais , Coenzimas , Relação Dose-Resposta a Droga , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microssomos/metabolismo , Miocárdio/metabolismo , Ubiquinona/farmacologiaRESUMO
Antitumor effect of water-in-oil-in-water type adriamycin emulsion (emulsion ADM) was examined in comparison with free ADM on the survival time of ICR male mice bearing Ehrlich solid tumor after a subcutaneous inoculation and on the tumor growth by the subcutaneous (SC-SC) or intraperitoneal administration (SC-IP). In the SC-SC system at the dose of 0.2 mg/kg or 1.0 mg/kg, the mice administered with the emulsion ADM (emulsion ADM group) showed prolonged survival time and stronger inhibitory effect of the tumor growth than free ADM group, and at 1.0 mg/kg, showed statistically significant different inhibition of the tumor growth from free ADM group. Moreover, at 5.0 mg/kg which dose come to manifest the subacute toxicity, emulsion ADM group showed a statistically significant different prolongation of the mean survival time from free ADM group. In the SC-IP system at the dose of 0.2 mg/kg or 1.0 mg/kg, emulsion ADM group showed a prolonged mean survival time than free ADM group. From these results, it is considered that entrapment of ADM into emulsion reduces the subacute toxicity of the mouse and increases the antitumor effect of the drug against Ehrlich solid tumor.
Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Doxorrubicina/administração & dosagem , Animais , Doxorrubicina/efeitos adversos , Emulsões , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óleos , ÁguaRESUMO
Comparative studies were done on the actions of hydrophobic drugs (cepharanthine, papaverine and cholesterol) regarding chemical modifications of Ehrlich ascites tumor cell membranes. Changes in membrane potential monitored by using cyanine dye (diS-C3-(5)) were induced by cepharanthine and papaverine, but not by cholesterol. Increase in membrane permeability of K+ ions induced with lysolecithin was strongly inhibited in the order of papaverine, cholesterol and cepharanthine. Oxygen uptake by the cells was also strongly inhibited by papaverine, but the inhibitory effect by cepharanthine was little and cholesterol had no effect. Membrane fluidity was decreased in the order of cholesterol, cepharanthine and papaverine. From these results, it was suggested that papaverine maintained the compartmentation of K+ ion and membrane fluidity by regulating the intracellular mitochondrial metabolism or by inhibiting the membrane bound ATPase nucleotidase activity. The membrane stabilizing effect of cepharanthine and cholesterol probably was due to decrease in the membrane fluidity because of the hydrophobic association to the lipid bilayer of the cell membranes.
Assuntos
Alcaloides/farmacologia , Carcinoma de Ehrlich/patologia , Colesterol/farmacologia , Papaverina/farmacologia , Animais , Benzilisoquinolinas , Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Íons , Masculino , Fluidez de Membrana/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Consumo de Oxigênio/efeitos dos fármacos , Potássio/metabolismoRESUMO
The concentrations of adriamycin (ADM) and related fluorescent compounds in lymph and gall were determined by high-performance liquid chromatography (HPLC) after a single intravenous injection into AH 109A tumour-bearing rats. HPLC was carried out by using Zorbax Sil as the stationary phase and chloroform--isopropanol--acetic acid--water--sodium acetate buffer (pH 4.5) (100:100:14:14:1) as the mobile phase, with a fluorescence spectrophotometric detector at an excitation wavelength of 470 nm and an emission wavelength of 585 nm. The detection limit for ADM was down to 1.0 ng/ml. In the thoracic duct lymph, the concentration of total ADM equivalent values (total ADM values) was maximal 30 min after injection and, after a subsequent decrease, increased gradually from 60 to 180 min. The ratio of total ADM in lymph to that in plasma at 180 min was 1.5 times that at 30 min. In gall, the total ADM showed a maximal level of 20.0 microgram/ml at 30 min.
Assuntos
Bile/análise , Doxorrubicina/análise , Linfa/análise , Animais , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Doxorrubicina/sangue , Masculino , Neoplasias Experimentais/metabolismo , Ratos , Espectrometria de FluorescênciaRESUMO
Membrane stabilizing effects of cholesterol on the permeability of K+ and change in membrane potential induced with lysolecithin were investigated. Cholesterol inhibited K+ release from rabbit red blood cells treated with lysolecithin. 3.3 X 10(-6)M of cholesterol was the optimum concentration required to inhibit K+ release from rabbit red blood cells treated with lysolecithin (1.25 microgram/ml) at the level of 100 percent. Change in membrane potential was evident with lysolecithin by the method of fluorescent dye and, cholesterol inhibited the change which was dose dependent. These inhibitory effects of cholesterol on the K+ release and changes in membrane potential served as the membrane stabilizing action on red blood cell membrane. It is assumed that cholesterol acts as an inhibitor to increase membrane fluidity and permeability of malignant transformed cells such as tumor and lymphoid cells.