RESUMEN
BACKGROUND: The association between seborrhoeic dermatitis and dandruff and the yeast Malassezia furfur is well recognized. Symptoms include scalp itchiness and scaling. Due to its antimycotic activity, ciclopirox olamine is established as an effective treatment for these scalp conditions. Salicylic acid has keratolytic properties and aids in the removal of scales. OBJECTIVE: To compare the therapeutic efficacy of a shampoo containing 1.5% ciclopirox olamine and 3% salicylic acid (CPO/SA) with Nizoral (2.0% ketoconazole shampoo) in a study involving 154 subjects with dandruff - 70 of whom also had seborrhoeic dermatitis of the scalp. Nizoral is currently a registered treatment for dandruff and seborrhoeic dermatitis. METHODS: The shampoos were used three times week for 4 weeks, with 2-week washout and follow-up periods. Clinical and self-assessments were made throughout treatment and after follow-up (day 43). Within and between-treatment assessments of signs and symptoms were analysed. RESULTS: In the two groups, seborrhoeic dermatitis and dandruff improved significantly throughout treatment, with lower clinical and self-assessment scores at both the end of treatment (day 29) and follow-up (day 43). Only the subjects treated with CPO/SA shampoo showed a significant reduction in the itching of seborrhoeic dermatitis at these times. CONCLUSION: The study demonstrated that both CPO/SA and Nizoral were safe and effective in the treatment of dandruff and seborrhoeic dermatitis.
Asunto(s)
Antifúngicos/administración & dosificación , Dermatitis Seborreica/tratamiento farmacológico , Cetoconazol/administración & dosificación , Piridonas/administración & dosificación , Ácido Salicílico/administración & dosificación , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Administración Cutánea , Adolescente , Adulto , Anciano , Antifúngicos/efectos adversos , Niño , Ciclopirox , Femenino , Humanos , Cetoconazol/efectos adversos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Piridonas/efectos adversos , Seguridad , Ácido Salicílico/efectos adversos , Método Simple Ciego , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Bifenthrin, a synthetic pyrethroid insecticide/miticide, has been fed to male and female Swiss Webster mice at levels of 0, 50, 200, 500, and 600 ppm in the diet for between 604 and 644 days. Tumors of the urinary bladder were observed and initially reported as leiomyosarcomas. Subsequently, the bladders were reviewed and the tumors showed a pattern of both epithelioid cells and spindle cells forming irregular vascular channels. The tumors appeared to arise from the trigone of the bladder and, in some cases, invaded the bladder wall. No metastases were recorded. The tumor is usually considered rare; however, in this study, it was commonly observed in all groups but predominantly in males. The histogenesis of the tumor is uncertain, but from its pleomorphic histological features, including smooth muscle and vascularity, it is probably derived from vascular mesenchyme.
Asunto(s)
Neoplasias de Tejido Muscular/inducido químicamente , Neoplasias de Tejido Muscular/patología , Sarcoma Experimental/inducido químicamente , Sarcoma Experimental/patología , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Vasculares/inducido químicamente , Neoplasias Vasculares/patología , Animales , Carcinógenos/toxicidad , Diferenciación Celular , Femenino , Insecticidas/toxicidad , Masculino , Ratones , Neoplasias de Tejido Muscular/epidemiología , Piretrinas/toxicidad , Sarcoma Experimental/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias Vasculares/epidemiologíaRESUMEN
PURPOSE: The goals of this study were to learn whether the DOTA chelator was useful for targeting lead radionuclides (203,212 Pb) to cells and tissues invaded by the Rauscher leukemia virus (RVB3) and to investigate the therapeutic efficacy of targeted 212Pb in treating the murine leukemia. METHODS AND MATERIALS: Five to 6-week-old BALB/c mice were inoculated i.v. with RVB3. This virus causes marked splenomegaly and death by day 13 and day 70 postinfection, respectively. Biodistribution, tumor targeting, and toxicity studies were performed using varying doses of 212Pb-DOTA-103A. A heavy metal chelator, DMPS, was administered orally and parenterally in two phases of the toxicity study. RESULTS: Biodistribution studies showed marked tumor targeting (58% ID/g spleen) in mice treated with 203Pb-103A as compared with mice treated with control antibody B3 (4.6% ID/g spleen). Histologic cure was achieved in all leukemic mice treated with 20 muCi212Pb-103A; however, all of the mice died with leukopenia and secondary++ bacterial infections due to severe bone marrow toxicity. Nonleukemic mice and mice treated with 20 muCi212Pb-B3 experienced less marrow toxicity and longer survival. Coadministration of the heavy metal chelator did not diminish the bone marrow toxicity. CONCLUSION: An effective, nonlethal dose could not be established to treat this tumor. The severe bone marrow toxicity associated with this radionuclide may limit its usefulness in systemic radioimmunotherapy.
Asunto(s)
Inmunotoxinas/uso terapéutico , Radioisótopos de Plomo/uso terapéutico , Leucemia Eritroblástica Aguda/radioterapia , Radioinmunoterapia , Animales , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/toxicidad , Especificidad de Anticuerpos , Quelantes/química , Quelantes/farmacología , Quelantes/toxicidad , Estabilidad de Medicamentos , Femenino , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/toxicidad , Inmunotoxinas/farmacocinética , Inmunotoxinas/toxicidad , Isotiocianatos/química , Isotiocianatos/farmacología , Isotiocianatos/toxicidad , Leucemia Eritroblástica Aguda/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Distribución Tisular , Unitiol/farmacologíaRESUMEN
To determine its carcinogenic potential, sodium fluoride (NaF) was fed to CD-1 mice for up to 97 weeks. Mice given NaF at a dose of 4, 10, or 25 mg/kg of body weight per day added to a low-fluoride diet were compared to controls given either an unsupplemented low-fluoride diet or laboratory chow. Nonneoplastic changes consistent with those previously recognized from fluoride toxicity were observed in teeth, bones, and joints. Unexpectedly, osteomas occurred in all groups. The incidence of osteomas was similar in groups given the low-fluoride control diet, laboratory chow, or NaF doses of 4 or 10 mg/kg per day. The incidence of osteomas in these groups was increased over that historically experienced at the laboratory and reported in the literature for CD-1 mice. The incidence of osteomas in the mice given 25 mg NaF/kg per day added to a low-fluoride diet was increased over that in the other groups. Osteomas were first observed at Week 55. No malignant bone tumors were observed during the course of the study. The locations, multiplicity, and morphologic features of the osteomas in all groups were similar to those associated with virus-induced bone tumors. Electron microscopic examination revealed abundant retrovirus particles in all osteomas examined from control and test mice. It was concluded that the study was confounded by a retrovirus which contributed to the induction of the osteomas. Because the study was confounded, it cannot be considered a valid bioassay to be used for risk assessment.
Asunto(s)
Carcinógenos/toxicidad , Fluoruro de Sodio/toxicidad , Animales , Neoplasias Óseas/inducido químicamente , Neoplasias Óseas/complicaciones , Neoplasias Óseas/microbiología , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Osteoma/inducido químicamente , Osteoma/complicaciones , Osteoma/microbiología , Virus de la Parainfluenza 1 Humana , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/patología , Factores de Riesgo , Fluoruro de Sodio/metabolismoRESUMEN
The specificity, toxicity, and efficacy of alpha-particle-mediated radioimmunotherapy of murine erythroleukemia was assessed by use of tumor-specific monoclonal antibody 103A labeled with 212Bi. Forty % of the injected dose/g tissue targeted to neoplastic spleens within 1 h after i.v. injection. When 212Bi-103A was injected on day 13 of disease, a dose-dependent response was achieved, as measured by a reduction in splenomegaly and absence of liver metastasis. Mice treated with 212Bi-103A on day 8 of disease showed no histological evidence of erythroleukemia on day 22 and survived significantly longer (median, 118 days) than mice treated with 212Bi-control IgG (78 days) or untreated mice (63 days), indicating successful specific radioimmunotherapy.
Asunto(s)
Partículas alfa/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Bismuto/uso terapéutico , Radioinmunoterapia , Radioisótopos/uso terapéutico , Animales , Bismuto/farmacocinética , Bovinos , Inmunoglobulina G/uso terapéutico , Ratones , Radioisótopos/farmacocinética , Virus RauscherRESUMEN
Male rats treated with either budesonide, prednisolone, or triamcinolone acetonide in drinking water for up to 104 weeks developed slightly increased incidences of basophilic foci, and significantly increased incidences of combined hepatocellular adenomas/carcinomas as compared to controls. Based upon reduced body weight gains and survivals, the doses administered were considered to be toxic. It was concluded that the positive findings represented a class effect, and probably involved glucocorticoid receptors.
Asunto(s)
Adenoma/inducido químicamente , Glucocorticoides/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Adenoma/patología , Administración Tópica , Animales , Antiinflamatorios/toxicidad , Peso Corporal/efectos de los fármacos , Budesonida , Ingestión de Líquidos/efectos de los fármacos , Neoplasias Hepáticas Experimentales/patología , Masculino , Prednisolona/toxicidad , Pregnenodionas/toxicidad , Ratas , Ratas Sprague-Dawley , Triamcinolona Acetonida/toxicidadRESUMEN
A rodent bladder cancer model that is induced by intravesical instillation of N-methyl-N-nitrosourea (MNU) was characterized. Cohorts of four to five week old female Fisher 344 rats received four biweekly 1.5 mg. doses of intravesical MNU and were sacrificed at various intervals. By week 13 all animals had flat atypia and/or papillary transitional cell tumors, and 67% of the lesions were moderately (grade II) or poorly differentiated (grade III). By week 20, 83% had gross muscle invasive tumors that eventually killed the host. A cohort of 40 MNU treated animals was subsequently treated commencing at week 17 after initiation of MNU with one of three intravesical six week regimens: 1) saline; 2) BCG (Tice strain); or 3) recombinant human tumor necrosis factor (RTNF) plus adriamycin. There was no difference in animal survival or tumor growth in any group of animals commencing therapy at week 17. A second cohort of 107 animals commenced therapy at 13 weeks after initiation of MNU with one of five intravesical six week regimens: 1) intravesical BCG (Tice strain); 2) adriamycin; 3) recombinant human tumor necrosis factor (RTNF); 4) RTNF plus adriamycin; or 5) BCG plus adriamycin. BCG, RTNF or adriamycin alone had no effect on tumor growth; however, BCG plus adriamycin and RTNF plus adriamycin commencing at week 13 significantly inhibited tumor growth and progression. In conclusion, this autochthonous intravesical rodent transitional cell carcinoma model appears useful for the following reasons: 1) it closely resembles human transitional cell carcinoma histologically and biologically in that all animals develop neoplastic changes in-situ that progress to muscle invasion and kill the host; 2) as with human bladder cancer these tumors do not respond to intravesical therapy if treated when tumor burden is large; however, tumor growth is inhibited when treated early; and 3) this model appears appropriate for screening and developing new intravesical treatments for superficial bladder cancer.
Asunto(s)
Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/terapia , Doxorrubicina/uso terapéutico , Factor de Necrosis Tumoral alfa/uso terapéutico , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Animales , Carcinoma de Células Transicionales/inducido químicamente , Femenino , Metilnitrosourea , Ratas , Ratas Endogámicas F344 , Proteínas Recombinantes/uso terapéutico , Neoplasias de la Vejiga Urinaria/inducido químicamenteRESUMEN
Cohorts of 4- to 5-wk-old female Fischer 344 rats received four biweekly 1.5-mg doses of N-methyl-N-nitrosourea (MNU) intravesically and were sacrificed at various intervals. By 13 wk after initiation of the carcinogen, all animals have flat epithelial atypia and/or papillary transitional cell bladder carcinomas, and 67% of the lesions are histological Grade II or III. By 20 wk, 83% have gross bladder wall muscle-invasive tumors that eventually kill the host. There was no gross evidence of visceral metastases in any animal. This rat model of transitional cell carcinoma of the bladder is useful because: (a) all animals develop progressive neoplastic changes in situ within 4 mo after initiation of MNU treatment; (b) these lesions progress to grossly detectable bladder tumors which invade the bladder wall and kill the host; (c) this full progression of bladder epithelial cells from atypical hyperplasia through flat carcinoma in situ to transitional cell carcinoma occurs at discrete time points; (d) the histology of the grossly detectable tumors is that of invasive transitional cell carcinomas; and (e) no leukemias, breast cancers, lymphomas, or other non-bladder tumors are induced. Six MNU-induced bladder wall-invasive tumors were karyotyped, and all tumors were diploid with 42 chromosomes. Three of the tumors had apparently normal karyotypes, while three tumors had karyotypes containing one or more cytogenetic structural markers. One of these markers (i.e., 8p+) was observed in two of the three tumors. The level of expression of total ras p21 (N-, Ki-, and Ha-ras p21) and codon 12-mutated c-Ha-ras p21 (i.e., glycine to glutamic acid mutation in codon 12) in a series of these MNU-induced bladder tumors was determined by Western blot analysis. No increase in the total ras p21 nor any expression of codon 12-mutated c-Ha-ras p21 was detected in any of these tumors.
Asunto(s)
Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Animales , Carcinoma de Células Transicionales/inducido químicamente , Carcinoma de Células Transicionales/genética , Transformación Celular Neoplásica , Aberraciones Cromosómicas , Modelos Animales de Enfermedad , FANFT , Femenino , Metilnitrosourea , Proteínas Proto-Oncogénicas p21(ras)/análisis , Ratas , Ratas Endogámicas F344 , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
This report represents the findings of an Expert Panel on the safety of Sanguinaria extract used in Viadent oral rinse and toothpaste products and represents an independent review of the Sanguinaria extract toxicologic data base. It is based on reviews and discussions of the data base by all members of the Expert Panel on Sanguinaria extract. The Panel concluded that the data base on Sanguinaria extract is substantial and indicates that Sanguinaria extract is safe in its present use in Viadent products based on a large margin of safety between levels of human exposure and levels found to produce minimum effect or to be without adverse effect in animals. The panel further concluded that published literature suggesting an association between human exposure to Sanguinaria extract and potential reproductive, cardiovascular, or ocular toxicity, or carcinogenicity is largely anecdotal, unfounded, and not corroborated by or consistent with the substantial data base that was subjected to peer review.
Asunto(s)
Alcaloides/toxicidad , Antiinfecciosos/toxicidad , Alcaloides/administración & dosificación , Animales , Antiinfecciosos/administración & dosificación , Benzofenantridinas , Ensayos Clínicos como Asunto , Método Doble Ciego , Humanos , Isoquinolinas , Antisépticos Bucales/uso terapéutico , Vigilancia de Productos Comercializados , Pastas de Dientes/uso terapéuticoRESUMEN
The interpretation of animal carcinogenicity tests traditionally rely almost exclusively upon a comparison of specific tumor rates in treated vs. matched and, perhaps, historical control animals. Yet, carcinogenicity tests yield much more biological and pathological data than simply final tumor rates. This additional data should also be considered as part of the total weight of evidence, particularly when analyzing a marginal or equivocal test result. If there are no positive findings among the data discussed here and listed in Table 1, it is unlikely that a marginal or equivocal increase in tumor incidence is actually treatment-related, irrespective of statistical analysis.
Asunto(s)
Pruebas de Carcinogenicidad/estadística & datos numéricos , Animales , Carcinógenos/toxicidad , División Celular/efectos de los fármacos , ADN/biosíntesis , Daño del ADN , Interpretación Estadística de Datos , Modelos Animales de Enfermedad , Hiperplasia/inducido químicamente , Ratones , Neoplasias/inducido químicamente , Neoplasias/patología , Oncogenes/fisiología , RatasRESUMEN
The significance of rat liver foci in carcinogenesis testing received major attention following their description in the National Cancer Institute workshop of 1974. However, the biological nature of foci remains uncertain despite numerous studies during the past 15 years. That is, in part, because criteria to define foci have been inconsistent, and studies of spontaneous foci in rats have been very few. This symposium has demonstrated that the induction or enhancement of rat liver foci, per se, may not provide sufficient evidence to classify a test compound as a carcinogen. Evidence presented suggests that some types of rat liver foci may not be related to carcinogenesis, and there is, consequently, a basis to further subclassify these lesions. In cases where foci are considered to be a part of the neoplastic process, semi-quantitative grading of these lesions, as well as of tumors, according to the extent of their development or progression, may assist in the interpretation of equivocal carcinogenicity test findings.
Asunto(s)
Pruebas de Carcinogenicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Hígado/patología , Animales , Hígado/ultraestructura , Neoplasias Hepáticas Experimentales/patología , RatasRESUMEN
Radioimmunotherapy using 90Y-labeled diethylenetriamine pentaacetic acid-antibody conjugates was studied in Rauscher erythroleukemia virus-infected mice. Preliminary experiments showed that biodistribution profiles for nonrelevant mouse monoclonal antibody and polyclonal bovine immunoglobulin were identical in both normal and leukemic mice. Therefore, bovine immunoglobulin G was selected as the control immunoglobulin in order to permit comparison to current clinical trials of radioimmunotherapy regimens. Specific monoclonal antibody was two- to three-fold more potent than bovine immunoglobulin G in therapy, as assessed by reduction of splenomegaly (dose required for half-maximal effect, 9 microCi versus 16 to 27 microCi). Mice treated with 50 microCi 90Y-labeled control immunoglobulin had spleens which were twice the normal size and showed extensive areas of erythropoiesis indicative of the presence of tumor foci; in contrast, doses as low as 27 microCi 90Y-labeled specific antibody resulted in complete remission with no microscopic evidence of tumor foci in either spleen or liver. Although reversible marrow toxicity was observed it was not dose limiting. These results demonstrate that tumor-specific therapy is possible using 90Y-labeled antibody.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Leucemia Experimental/terapia , Radioisótopos de Itrio/uso terapéutico , Acetatos/metabolismo , Ácido Acético , Animales , Inmunoterapia , Leucemia Eritroblástica Aguda/radioterapia , Leucemia Eritroblástica Aguda/terapia , Leucemia Experimental/radioterapia , Ratones , Distribución Tisular , Itrio/metabolismoRESUMEN
Disperse Blue 1 (containing 50% lignosulphonate dispersants) was fed to Fischer 344 rats at dietary levels of 0.01 and 0.1% for 19 months and at 1.0% for 6 months. Fischer 344 rats were also given the dye by gavage at 1 g/kg for 1-3 days or in the diet at 0.5 or 1% for 4 days, and corresponding dietary levels of the colouring without dispersant were also fed for 4 days. Bladders and kidneys were examined after the 1-4 day treatments, in animals dying or killed from month 6 to termination (19 months) in the chronic study and in those killed at wk 5, 9 and 17. At the latter three times, autoradiography following injection of tritiated thymidine showed increased DNA synthesis in the urothelium of high-dose rats, but no other increased labelling in any group. Bladder lesions were seen only at the 1.0% level, epithelial erosion with adhering dye particles being seen by day 4, calculi and hyperplasia by wk 5 and squamous metaplasia by wk 9. The calculi contained more dye in males than in females and more calcium in females. By month 6, dye particles were embedded in the bladder wall, with some evidence of histiocyte accumulation in their vicinity. Two papillomas and one carcinoma, but no leiomyosarcomas, were diagnosed. The earliest tumours, two papillomas, were detected at wk 17. Tumour incidence following surgical removal of calculus was about double that in rats not subjected to surgery and the incidence of normal bladders at month 19 was higher in the latter group. Compound-related effects in the kidneys--inflammation, pelvic epithelial hyperplasia and tubular degeneration and regeneration with interstitial fibrosis--were seen only in the high-dose group. Dye present in the tubules and renal pelvis persisted in many rats for a year after cessation of treatment.
Asunto(s)
Antraquinonas/toxicidad , Sistema Urinario/efectos de los fármacos , Neoplasias Urológicas/inducido químicamente , Administración Oral , Animales , Femenino , Hiperplasia/inducido químicamente , Neoplasias Renales/inducido químicamente , Masculino , Ratas , Ratas Endogámicas F344 , Cálculos de la Vejiga Urinaria/inducido químicamente , Sistema Urinario/patologíaRESUMEN
The effects of HER upon early and late stages of BBN-induced bladder cancer in rats were examined. Female Fischer 344 rats were administered HER in the diet either before and during or continuously after BBN administration and were monitored periodically for up to 2 years. The total dose of BBN was 600 mg administered over a 6-week period. In a separate experiment, the effects of HER administration to syngeneic recipients of a transplanted primary bladder cancer were examined. No effects on neoplastic development were observed as the result of HER treatment before and during carcinogen administration. However, at the 1-year sacrifice, there was a significant increase in bladder tumor incidence in the animals receiving BBN followed by continuous retinoid treatment versus animals receiving BBN only. At the 2-year sacrifice, there was a significant increase in tumor progression in the continuous retinoid group versus the animals receiving BBN alone, based upon grading and staging of tumors, although tumor incidences were not significantly different. In the transplantation experiment, more recipients (9/20 versus 2/20) receiving continuous HER had large, anaplastic tumors following 9 months of observation than did control animals. This study supports the view that retinoids should not be considered as only inhibitors of carcinogenesis, but rather as modifiers which vary in their effects depending upon factors yet to be understood.
Asunto(s)
Tretinoina/análogos & derivados , Neoplasias de la Vejiga Urinaria/prevención & control , Animales , Butilhidroxibutilnitrosamina , Femenino , Trasplante de Neoplasias , Ratas , Ratas Endogámicas F344 , Factores de Tiempo , Tretinoina/farmacología , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Bladder tissues from rats treated with sodium saccharin in a two-generation dose-response study, in which 1.0% in the diet had been identified as the no-effect level for primary bladder cancer, were re-examined without knowledge of the test groups or the previous histopathological findings. Compound-related increases in the incidences of hyperplasia were found at the 6.25 and 7.5% saccharin levels (the highest dietary levels tested). There were also compound-related increased in the incidence of transitional-cell papillomas and/or carcinomas at the 4.0, 5.0, 6.25 and 7.5% levels. There was a slight increase in the incidence of transitional-cell carcinomas at the 3.0% level, but this was not statistically significant (P = 0.25). No compound-related effects were evident at the 1.0% level. All tumours were well to moderately differentiated and there was no increase in mean grades of severity or anaplasia for any proliferative lesion.
Asunto(s)
Sacarina/toxicidad , Vejiga Urinaria/efectos de los fármacos , Animales , Bioensayo , Hiperplasia , Masculino , Ratas , Ratas Endogámicas , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Formaldehyde was recently shown to be carcinogenic in the nasal cavities of rats and mice following chronic inhalation at vapor concentrations which were cytotoxic. The epidemiological, physiological, and toxicological data on formaldehyde are evaluated as they pertain to the analysis of carcinogenic risk. It is concluded that humans are likely to be less susceptible than test rodents to potential carcinogenic effects and that the risk at low-level exposure would not be linearly related to that observed at the higher levels which were found to be carcinogenic in animals. Risk assessment procedures and risk management decisions should incorporate all of the relevant biological information, such as that discussed, rather than rely solely on a mathematical approach which is likely to yield inaccurate and misleading conclusions.