RESUMO
Pigs have recently become very popular for use not only in xenotransplantation field, but in regeneration studies as well, sometimes with pigs being used as the scaffold. We have already presented our findings related to the pig immune system against human cells, including the complement systems, natural antibodies (NAs), and NK cells. In this study, we investigated the pig innate immunological reaction against human cells further. Our investigations included issues such as the production of NAs in newborns, day 0 and day 1, and sow colostrum. The alternative pathway for pig complement reacted with human cells, and pig NK cells and macrophages directly injured human aortic endothelial cells. Pig serum clearly contains the natural antibodies IgG and IgM to human peripheral blood mononuclear cells (PBMCs). Pig plasma from day 1 newborns contained almost the same levels of these natural antibodies to human PBMCs as those of sow plasma. On the other hand, pig plasma from day 0 newborns did not contain IgG and IgM to human PBMCs. In addition, sow colostrum clearly contained both IgG and IgM to human PBMCs. As expected, the pig innate immunity system reacted to human cells, including natural antibodies. However, the NAs of pigs, both IgM and IgG, against human cells do not exist in pig serum at day 0, but at day 1 and in mother's milk, indicating that NAs in newborns did not come from the placenta but from sow colostrum.
Assuntos
Colostro/imunologia , Imunidade Inata/imunologia , Suínos/imunologia , Imunologia de Transplantes/imunologia , Transplante Heterólogo , Animais , Animais Recém-Nascidos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Leucócitos Mononucleares/imunologia , GravidezRESUMO
Regulation of the adhesion of mononuclear cells to endothelial cells is considered to be a critical step for the treatment of inflammatory diseases, including autoimmune diseases. K-13182 was identified as a novel inhibitor for these adhesions. K-13182 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) on human umbilical vein endothelial cells (HUVECs) and on mouse vascular endothelial cell line (MAECs) induced by tumour necrosis factor (TNF)-alpha. K-13182 also inhibited the adhesion of mononuclear cells to these HUVECs and MAECs, indicating that K-13182 suppressed these adhesions mediated by cellular adhesion molecules including VCAM-1. To evaluate the therapeutic effect in autoimmune disease model mice, K-13182 was orally administered to non-obese diabetic (NOD) mice as Sjögren's syndrome (SS) model mice. Severe destructive inflammatory lesions were observed in the lacrimal glands of vehicle-treated control mice; however, 8-week administration of K-13182 inhibited the mononuclear cell infiltration into the inflammatory lesions of the lacrimal glands. In K-13182-treated mice, the decrease in tear secretion was also prevented compared to the control mice. In addition, the apoptosis and the expression of FasL (CD178), perforin, and granzyme A was suppressed in the lacrimal glands of K-13182-treated mice. Therefore, K-13182 demonstrated the possibility of therapeutic efficacy for the inflammatory region of autoimmune disease model mice. These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dacriocistite/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Dacriocistite/metabolismo , Dacriocistite/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
The 1'alpha-phenylselenouridine derivative 13 was successfully synthesized by enolization of the 3',5'-O-TIPDS-2'-ketouridine 8, and was subjected to a radical reaction with a vinylsilyl tether--an efficient procedure for preparing 1'alpha-branched-chain sugar pyrimidine nucleosides. Successive treatment of 8 with LiHMDS and PhSeCl in THF at < -70 degrees C gave the desired 1'-phenylseleno products in 85% yield as an anomeric mixture of the 1'alpha-product 11 and the 1'beta-product 12 (11/12= 2.5:1). Highly stereoselective reduction at the 2'-carbonyl of the 1'alpha-product 11 occurred from the beta-face by using NaBH4/CeCl3 in MeOH, and subsequent introduction of a dimethylvinylsilyl tether at the 2'-hydroxyl gave the radical reaction substrate 14. The photochemical radical atom-transfer reaction of 14 by using a high-pressure mercury lamp proceeded effectively in benzene to give the exo-cyclized PhSe-transferred product 18, in which (PhSe)2 proved to be essential as an additive for radical atom-transfer cyclization reactions. Subsequent phenylseleno-group elimination of 18 gave the sugar-protected 1'alpha-vinyluridine. With this procedure, 1'alpha-vinyluridine (22) and -cytidine (25), designed to be potential antitumor agents, were successfully synthesized. This study is the first example of functionalization at the anomeric 1'-position of a nucleoside by starting from a natural nucleoside to produce a ribo-type 1'-modified nucleoside.
Assuntos
Compostos Organosselênicos/síntese química , Nucleosídeos de Pirimidina/síntese química , Ribonucleosídeos/síntese química , Selênio/química , Uridina/síntese química , Ciclização , Citarabina/análogos & derivados , Citarabina/química , Citidina/análogos & derivados , Citidina/síntese química , Citidina/química , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Glicosilação , Estrutura Molecular , Nucleosídeos de Pirimidina/química , Ribonucleosídeos/química , Silício/química , Estereoisomerismo , Relação Estrutura-Atividade , Uridina/análogos & derivados , Compostos de Vinila/síntese químicaRESUMO
Although several cytokines are known to be somnogenic, no study has been conducted to examine whether colony-stimulating factors (CSF) affect sleep. Therefore, we studied the effects of granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) on sleep in rats and their possible mechanism of action. At the dose of 10 pmol, GM-CSF or M-CSF significantly increased both non-rapid eye movement and rapid eye movement (REM) sleep or REM sleep only when infused intracerebroventricularly during the dark period. When injected locally in the hypothalamus, GM-CSF and M-CSF increased nitric oxide (NO) production. Thus, NOergic neural signals in the hypothalamus may take part in the somnogenic action of CSF.
Assuntos
Ritmo Circadiano/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Fator Estimulador de Colônias de Macrófagos/fisiologia , Fases do Sono/fisiologia , Sono REM/fisiologia , Animais , Hipotálamo/fisiologia , Masculino , Óxido Nítrico/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo. In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use.
Assuntos
Antioxidantes/farmacologia , Arteriosclerose/prevenção & controle , Benzofuranos/farmacologia , Animais , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Técnicas In Vitro , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Oxirredução , Coelhos , Receptores de LDL/genética , Receptores de LDL/metabolismoRESUMO
A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment. We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids. We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows: a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS. b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995). c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment. d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc). e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS. f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS. In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.
Assuntos
Ácido Ascórbico/uso terapêutico , Desidroepiandrosterona/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , 17-Hidroxicorticosteroides/urina , 17-Cetosteroides/urina , Idoso , Androsterona/urina , Antibacterianos/uso terapêutico , Ácido Ascórbico/farmacologia , Broncopneumonia/diagnóstico , Broncopneumonia/tratamento farmacológico , Cloranfenicol/uso terapêutico , Desidroepiandrosterona/farmacologia , Eritromicina/uso terapêutico , Etiocolanolona/urina , Humanos , Imunidade/efeitos dos fármacos , Imunidade/imunologia , Masculino , RadiografiaRESUMO
This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons: i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment; ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS. We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows: a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes. b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies. c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS. d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment. e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS. f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS. g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.
Assuntos
Ácido Ascórbico/uso terapêutico , Desidroepiandrosterona/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , Instituições de Assistência Ambulatorial , Antibacterianos/uso terapêutico , Cloranfenicol/uso terapêutico , Resfriado Comum/tratamento farmacológico , Resfriado Comum/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Eritromicina/uso terapêutico , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/etiologia , Feminino , Humanos , Imunidade/imunologia , Japão , Leucócitos/metabolismo , Masculino , Pneumonia/tratamento farmacológico , Pneumonia/epidemiologiaRESUMO
Male Brown-Norway rats given purified diets containing safflower oil (SFO, linoleic acid, 18:2 n-6), evening primrose oil (EPO, gamma-linolenic acid, 6,9,12- 18:3 n-6) or Korean pine seed oil (PSO, 5,9,12- 18:3) at the 10% level were immunized twice with intraperitoneal ovalbumin, on days 14 and 35 of the feeding diets, and killed one day after the second booster. The relative population of CD4+ T-lymphocytes in the spleen was significantly lower in rats fed SFO than in those fed EPO or PSO, while that of CD8+ subsets remained unchanged. There was a significant increase in the splenic production of IgG and IgE in the PSO group compared to the SFO group, while EPO significantly increased IgE. The periodical response patterns of the serum levels of IgG and IgE varied depending on the source of dietary fats, and the initial rise of total immunoglobulins tended to be higher in the EPO group. The release by peritoneal exudate cells of histamine was comparable among three groups irrespective of saturation by calcium ionophore A23187, while PSO significantly increased leukotriene B4 production. These observations not only indicate specific roles of gamma-linolenic acid but also diverse influences of different octadecatrienoic acids in various immune measurements.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Sistema Imunitário/efeitos dos fármacos , Ácidos Linoleicos/farmacologia , Ácido gama-Linolênico/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Ácidos Graxos/análise , Liberação de Histamina , Isotipos de Imunoglobulinas/sangue , Isomerismo , Leucotrieno B4/análise , Ácido Linoleico , Fígado/química , Masculino , Ovalbumina/imunologia , Periodicidade , Óleos de Plantas/farmacologia , Ratos , Ratos Endogâmicos BN , Baço/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacosRESUMO
Histologic diagnosis of poorly differentiated gastric adenocarcinomas by conventional hematoxylin-eosin (HE) staining is often limited by the quality of gastroendoscopic biopsy specimens. In this study we attempted to identify gastric cancer cells in biopsy specimens and ascites of gastric cancer patients using the gastric cancer reactive monoclonal antibodies S202 and S74. Twenty-four of 25 specimens shown to contain cancer cells by HE staining were stained positively by monoclonal antibody S202. In contrast, 3 of 16 specimens that were diagnosed as not including cancer cells by HE staining was stained positively by S202. The possibility that cancer cells in the biopsy specimens were not detected by HE staining cannot be ruled out. Cancer cells in ascites of patients diagnosed with carcinomatous peritonitis by Papanicolaou staining were stained positively by monoclonal antibody S74. From these results, we conclude that monoclonal antibodies S202 and S74 may be useful supplemental agents for the diagnosis of gastric cancer.
Assuntos
Adenocarcinoma/patologia , Anticorpos Monoclonais , Neoplasias Gástricas/patologia , Animais , Biópsia , Corantes , Amarelo de Eosina-(YS) , Hematoxilina , Humanos , Imunoglobulina G , Imuno-Histoquímica/métodos , Camundongos/imunologiaRESUMO
In the present study, we investigated how the recent clinical use of antibiotics have altered the antibiotic susceptibility of strains isolated from postoperative infections, especially Gram-negative rods. For Pseudomonas aeruginosa, serogroup E strains accounted for about 20 per cent of postoperative infections, but were unable to be isolated from either the feces of patients on admission or from the appendix contents of patients with appendicitis. It therefore appeared that serogroup E strains were responsible for the nosocomial infections in our department. The strains of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa serogroup E, which we assumed to be nosocomial pathogens, acquired a high level of resistance to antibiotics soon after third-generation cephems became widely used. On the other hand, the antibiotic susceptibility of Enterobacter cloacae, Citrobacter freundii, and the serogroups of Pseudomonas aeruginosa other than E, which were considered to originate from the bacterial flora of patients, did not vary throughout the several years of the study period.
Assuntos
Bactérias/efeitos dos fármacos , Infecção Hospitalar/microbiologia , Resistência Microbiana a Medicamentos , Complicações Pós-Operatórias/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Cefalosporinas/uso terapêutico , Bactérias Aeróbias Gram-Negativas/efeitos dos fármacos , Bactérias Aeróbias Gram-Negativas/isolamento & purificação , Humanos , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Sorotipagem , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificaçãoRESUMO
A case of acute pulmonary complication following intra-arterial infusion of Lipiodol-Adriamycin emulsion for hepatocellular carcinoma was reported. Intra-arterial infusion chemotherapy was performed on a 75-year-old male with Lipiodol-Adriamycin emulsion (Lipiodol 8 ml + Adriamycin 40 mg). Severe dyspnea and cyanosis started about 30 minutes after the infusion, and blood gas analysis revealed hypoxemia and hypocapnia. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. He was on positive end-expiratory pressure breathing for 4 days. Clinical symptoms and chest X-ray improved rapidly in the course of two weeks, he became almost asymptomatic. We concluded that the nature of this pulmonary damage was pulmonary edema due to the large amount of Adriamycin that flowed into pulmonary artery via arterio-venous shunt present in the hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/terapia , Doxorrubicina/administração & dosagem , Embolização Terapêutica , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/terapia , Embolia Pulmonar/etiologia , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/efeitos adversos , Humanos , Infusões Intra-Arteriais , Óleo Iodado/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , MasculinoRESUMO
Spontaneous unit discharges during the natural sleep-wakefulness cycle in two different neuronal groups, the hippocampal pyramidal cells and thalamic ventrobasal neurons, have been analyzed. The results show that both neurons fire with white-noise-like fluctuations during the slow-wave sleep, and with slow fluctuations with power spectral densities inversely proportional to the frequency in the frequency range of 0.02-1.0 Hz, during the paradoxical sleep. This confirms that the characteristics of fluctuations in neuronal activities of the mesencephalic reticular formation observed in our previous study are more general phenomena in the cat's brain. Partly similar behavior of spectral densities is also observed during the alert state. These observations are quantitatively confirmed by the statistical time series analysis of the spike density processes of spontaneous activities.
Assuntos
Hipocampo/fisiologia , Sono/fisiologia , Tálamo/fisiologia , Vigília/fisiologia , Potenciais de Ação , Animais , Gatos , Córtex Cerebral/fisiologia , Potenciais Evocados , Corpos Geniculados/fisiologiaRESUMO
A series of experiments was carried out both in the hippocampal pyramidal and thalamic ventrobasal neurons to investigate the effect of serotonin level in the brain on slow fluctuations of neuronal discharges. Single neuronal activities were recorded in the following two pharmacologically treated states: (1) a 5-hydroxytryptamine depleted state by p-chlorophenylalanine administration (PCPA phase) and (2) a 5-methoxy-N,N-dimethyltryptamine administered state under the PCPA pretreatment (5-MeODMT phase). The slow fluctuations of neuronal activities in the frequency range of 0.02-1.0 Hz in both nuclei were prominent during the PCPA phase and were similar to those during the paradoxical sleep. In contrast, slow fluctuations were suppressed during the 5-MeODMT phase and neuronal activities during this phase were similar to those during slow wave sleep (SWS). The results show that serotonin in the brain definitely plays a role in stabilizing single neuronal activities.
Assuntos
Hipocampo/fisiologia , Serotonina/fisiologia , Tálamo/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Gatos , Fenclonina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Metoxidimetiltriptaminas/farmacologia , Tálamo/efeitos dos fármacos , Tálamo/metabolismoRESUMO
Functioning parathyroid lipoadenoma (hamartoma) composed of abundant adipose or myxomatous stroma and epithelial cell nests is an unusual cause of primary hyperparathyroidism. We report herein four new cases. None of them belongs in the category of multiple endocrine neoplasia or familial hyperparathyroidism. The clinical manifestations and the laboratory findings are indistinguishable from those of the usual forms of primary hyperparathyroidism. Ultrasonography of the neck demonstrated an enlarged parathyroid gland as a hyperechoic mass in the two patients tested. At operation in each case, a single enlarged gland was found and resected, the weight being 3, 0.3, 0.45 and 1 g, respectively. The patients are normocalcemic 1 to 10 years after surgery. Pathological examination disclosed that the lesions were consistent with lipoadenoma or its variants. On reviewing 20 cases of functioning lipoadenoma which were reported in the literature, including the present cases, we found that the size of the tumors varied and a functioning lipoadenoma is hence by no means unusually large as previously reported. Without knowledge of this specific clinicopathologic entity, the lesion may be overlooked at the preoperative localization study and misdiagnosed as a normal or hyperplastic parathyroid.
Assuntos
Hamartoma/patologia , Neoplasias das Paratireoides/patologia , Ultrassonografia , Cálcio/sangue , Feminino , Hamartoma/complicações , Hamartoma/fisiopatologia , Humanos , Hiperparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/fisiopatologia , Fósforo/sangueRESUMO
In an attempt to develop a selective long-acting chemotherapy for hepatocellular carcinoma, lipiodol emulsion (Lp-Em) was prepared using non-ionic surfactant, poloxamer-188. A pharmacokinetic study of Adriamycin (ADM) was carried out according to the paddle method, and concentrations of ADM were measured with spectrophotometer at wave length 475 nm. The half time of ADM levels in Lp-Em were longer than that in lipiodol urografin suspension. Histological findings of chemical hepatocarcinogenic rat after their administration showed Lp-Em, lipiodol and ADM accumulations in hepatocellular carcinoma lesion. Transcatheter arterial embolization with Lp-Em containing 40 mg of ADM was performed in 6 patients with unresectable hepatocellular carcinoma. CT scan after treatments revealed high-density areas in the hepatocellular carcinoma lesion as the deposition of lipiodol. Serum concentrations of ADM were significantly lower in a patient treated with Lp-Em than with lipiodol urografin suspension. In conclusion, Lp-Em is thought to be useful for the treatment of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/metabolismo , Doxorrubicina/farmacocinética , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Hepatocelular/terapia , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Embolização Terapêutica , Emulsões , Artéria Hepática , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/terapia , Poloxaleno , RatosRESUMO
The purpose of this investigation was to clarify the relation between the therapeutic efficacy of cyclophosphamide and the activity of the endogenous and exogenous corticosteroid hormones using ICR female mice with ascitic Ehrlich tumor. A single ip injection of the drug, 3 mg/mouse, was given to each mouse 36 hr after tumor inoculation (1 X 10(6) tumor cells, ip), and the drug effect was assessed in terms of the number of 1-month survivors with and without tumor. The clock time of drug administration which produced minimal therapeutic efficacy chronologically coincided with the dark period (8 PM approximately 8 AM) and/or with a stage of increased plasma corticosterone in mice. In support of this, concomitant administration of corticosterone (hydrocortisone or corticosterone) significantly depressed the anti-tumor effect of the drug. Evidence is presented to indicate that the adverse effect of corticosteroids is related to an accelerated metabolism of cyclophosphamide within the host. The drug effect for a given total dose was improved by the use of hourly partitioned injections in place of a single injection. It was concluded that the therapeutic efficacy of cyclophosphamide is dependent on the time of exposure to drug action on the scale of hours, but not days, and that the anti-tumor effect of the drug can be suppressed by increased activity of endogenous and exogenous corticosteroid hormones through acceleration of the drug metabolism.
Assuntos
Corticosteroides/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Corticosteroides/fisiologia , Animais , Ritmo Circadiano , Ciclofosfamida/administração & dosagem , Ciclofosfamida/metabolismo , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Masculino , CamundongosRESUMO
In combination with chemotherapy [ftorafur (FT)], allogeneic lymphoid cells were transferred to inhibit the growth of a 3-methylcholanthrene-induced transplantable KMT-17 fibrosarcoma in Wistar-King-Aptekman/Hok rats. The transference of allogeneic lymphoid cells 4 days after tumor inoculation did not prove effective in inhibiting the growth of the tumor; administration of FT (300 mg/kg) on Day 3 resulted in a 16.7% survival rate. However, a combination of the transfer of cells and administration of FT resulted in an improved effect of 55.0%. A low dose of FT (100 mg/kg) also increased the therapeutic effect in combination with allogeneic lymphoid cell transfer (28.0%). However, a high dose of FT (500 mg/kg) did not increase the therapeutic effect (30.0%), even if combined with allogeneic lymphoid cell transfer on Day 2, 4, 6, or 9, although a high dose of FT administered alone on Day 4 showed a direct antitumor effect (32.0%). This effect was rather diminished when the transfer was combined on Day 2. (7.1%). The differences in the combination effect of doses of FT seem to depend on the immune status of the host induced by treatment with FT. In order to investigate the mechanism of combination timing of FT and allogeneic lymphoid cell transfer, the specific delayed hypersensitivity reaction to KMT-17 tumor was assayed by the radioisotopic footpad method. The specific delayed hypersensitivity reaction was strengthened by an injection of FT (300 mg/kg).