RESUMO
OBJECTIVE: Ethnic differences in the metabolic syndrome could be explained by perceived ethnic discrimination (PED). It is unclear whether PED is associated with the metabolic syndrome. We assessed this association and quantified the contribution of PED to the metabolic syndrome. METHODS: Baseline data were used from the Healthy Life in an Urban Setting study collected in the Netherlands from 2011 to 2014. The population-based sample included South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan participants (aged 18 to 70 years). PED was measured using the Everyday Discrimination Scale. The metabolic syndrome was determined according to the harmonized definition of the International Diabetes Federation, American Heart Association, and others. Logistic regression was used for analysis. population-attributable fraction was used to calculate the contribution of PED. RESULTS: PED was positively associated with the metabolic syndrome in South-Asian Surinamese, African Surinamese, and Moroccan participants (odds ratio [95% confidence interval] = 1.13 [0.99-1.30], 1.15 [1.00-1.32], and 1.19 [1.03-1.38], respectively) after adjusting for potential confounders and mediators. No significant association was observed among Ghanaian and Turkish participants. For the individual components, the associations were statistically significant for blood pressure, fasting glucose, and waist circumference among Surinamese participants. PED was associated with dyslipidemia in Moroccan participants. The population-attributable fractions were 5% for South-Asian Surinamese and Moroccan participants, and 7% for African Surinamese participants. CONCLUSIONS: We found a positive association of PED with the metabolic syndrome in some ethnic groups, with PED contributing around 5% to 7% to the metabolic syndrome among Surinamese and Moroccans. This suggests that PED might contribute to ethnic differences in the metabolic syndrome.
Assuntos
Síndrome Metabólica/etnologia , Grupos Minoritários/estatística & dados numéricos , Preconceito/etnologia , Sistema de Registros/estatística & dados numéricos , Adulto , Ásia Ocidental/etnologia , População Negra/etnologia , Feminino , Gana/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos/etnologia , Países Baixos/etnologia , Racismo/etnologia , Suriname/etnologia , Turquia/etnologia , População Urbana/estatística & dados numéricosRESUMO
PURPOSE: Perceived ethnic discrimination (PED) is positively associated with depressive symptoms in ethnic minority groups in Western countries. Psychosocial factors may buffer against the health impact of PED, but evidence is lacking from Europe. We assessed whether ethnic identity, religion, and ethnic social network act as buffers in different ethnic minority groups in Amsterdam, the Netherlands. METHODS: Baseline data were used from the HEalthy Living In a Urban Setting study collected from January 2011 to June 2014. The random sample included 2501 South-Asian Surinamese, 2292 African Surinamese, 1877 Ghanaians, 2626 Turks, and 2484 Moroccans aged 18-70 years. Depressive symptoms were assessed using the Patient Health Questionnaire-9. PED was measured with the Everyday Discrimination Scale. Ethnic identity was assessed using the Psychological Acculturation Scale. Practicing religion was determined. Ethnic social network was assessed with the number of same-ethnic friends and amount of leisure time spent with same-ethnic people. RESULTS: PED was positively associated with depressive symptoms in all groups. The association was weaker among (a) those with strong ethnic identity in African Surinamese and Ghanaians, (b) those practicing religion among African Surinamese and Moroccans, (c) those with many same-ethnic friends in South-Asian Surinamese, Ghanaians, and Turks, and (d) those who spend leisure time with same-ethnic people among African Surinamese and Turks. CONCLUSIONS: Ethnic identity, religion, and ethnic social network weakened the association between PED and depressive symptoms, but the effects differed by ethnic minority group. These findings suggest that ethnic minority groups employ different resources to cope with PED.
Assuntos
Transtorno Depressivo/etnologia , Transtorno Depressivo/psicologia , Grupos Minoritários/psicologia , Racismo/psicologia , Religião e Psicologia , Identificação Social , Apoio Social , Adolescente , Adulto , Idoso , Feminino , Gana/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos/etnologia , Países Baixos , Suriname/etnologia , Turquia/etnologia , Adulto JovemRESUMO
BACKGROUND: Current disease burden estimates do not provide evidence across different ethnic groups. This study aims to assess the disease burden as measured by the disability-adjusted life years (DALYs) for six ethnic groups in Amsterdam, the Netherlands, for 2011 and 2030. METHODS: The DALYs were calculated by combining three components: disease-/sex-/age-specific DALYs per person; disease-specific relative risks (RRs) by ethnicity; and sex-/age-specific population sizes by ethnicity in Amsterdam in 2011 and 2030. Disease-specific DALYs were derived from the National Institute of Public Health. The RRs were obtained through a systematic review of studies published in 1997-2008. The population figures were gathered from the Statistics Netherlands and municipality of Amsterdam. RESULTS: The findings suggest that cardiovascular diseases and anxiety and depressive disorders dominate disease burden in all ethnic groups in 2011 and 2030. In most of the non-Western ethnic minorities, diabetes mellitus is the strongest contributor to the disease burden. The total disease burden will increase more strongly in non-Western ethnic minorities than ethnic Dutch. The 2030 disease burden is estimated to be highest among Surinamese and Antilleans. CONCLUSIONS: In ethnic minorities, diabetes plays an important role in the disease burden, and the total disease burden will grow stronger than ethnic Dutch, resulting in a higher total disease burden for some ethnic groups in 2030. We encourage researchers to estimate the disease burden by ethnicity so that health priorities can be set in the fields of policy, health care and research.
Assuntos
Etnicidade/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Marrocos/etnologia , Países Baixos/epidemiologia , Antilhas Holandesas/etnologia , Fatores Sexuais , Suriname/etnologia , Turquia/etnologia , Adulto JovemRESUMO
PURPOSE: It has been suggested that the cancer risk of migrants from low-income to high-income countries will converge toward the levels of their host country. However, comparisons with country of origin are mostly lacking. We compared cancer incidence and mortality rates of Surinamese migrants in the Netherlands to both native Dutch and Surinamese levels. METHODS: Data covering the period 1995-2008 were obtained from Surinamese and Dutch national cancer registries and national cause-of-death registries. Cancer incidence was studied for 21 types of cancer and cancer mortality for nine types. We calculated age-standardized incidence/mortality ratios (SIR/SMR) for the Surinamese migrants and for Suriname, using the native Dutch population as reference. RESULTS: Significantly lower overall cancer incidence (SIR = 0.77, 95% CI = 0.69-0.84) and mortality rates (SMR = 0.63, 95% CI = 0.55-0.72) were found for Surinamese migrants compared to native Dutch. Generally, cancer risk was lower for most cancers (e.g., cancer of the breast, colon and rectum, lung), but higher for other cancers (e.g., cancer of the uterine cervix, liver). For most cancers, cancer risk of the Surinamese migrants was in-between Surinamese and native Dutch levels. Importantly, for many cancers, migrants' incidence and mortality rates had not closely approached native Dutch rates. For skin cancer, incidence levels for Surinamese migrants were lower than both Surinamese and native Dutch levels. CONCLUSIONS: The results suggest that cancer incidence and mortality rates of Surinamese migrants generally converge from Surinamese toward Dutch levels, though not for all cancer types. Overall, Surinamese migrants still had a much more favorable cancer profile than the native Dutch population.
Assuntos
Neoplasias/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etnologia , Países Baixos/epidemiologia , Suriname/etnologia , Taxa de Sobrevida , MigrantesRESUMO
BACKGROUND: Living in a particular region might affect health. We aimed to assess variations between regions in individual health. The role of socio-economic factors in the associations was also investigated. METHODS: World Health Survey data were analysed on 220 487 individuals. Main outcomes included self-reported health, health complaints and disability. The main predictor variable was a modified regional classification of countries. Multilevel logistic regression was used to assess associations between individual health and regions, while accounting for individual and country-level socio-economic factors, notably occupation, education, national income and female literacy. RESULTS: Individual health varied significantly between regions. For instance, compared with Western Europeans, Southern Asians and Western Africans reported poorer health, the odds ratios (ORs) being 2.05 [95% confidence interval (CI) 1.31-3.23] and 1.88 (95% CI 1.26-2.81), respectively. Accounting for socio-economic factors attenuated or, in a few cases, reversed the associations. For example, the OR for Southern Asia and Western Africa respectively became 0.94 (95% CI 0.37-2.37) and 0.77 (95% CI 0.26-2.25). Individuals from Central Europe and the Former Soviet Union were the most likely to report poor health, OR 1.92 (95% CI 1.07-3.44) and OR 4.17 (95% CI 1.91-9.10) respectively. Overall, men were less likely than women to report poor health. CONCLUSION: Substantial regional variations in individual health exist, only partly explained by socio-economic factors. Additional policy and health research are needed to investigate Central Europe and Former Soviet Union rates that consistently lag behind Latin America, Asia and Africa.
Assuntos
Saúde Global/normas , Nível de Saúde , Fatores Socioeconômicos , África , Ásia , Região do Caribe , Estudos Transversais , Europa (Continente) , Feminino , Saúde Global/estatística & dados numéricos , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Análise Multinível , América do Sul , U.R.S.S. , Organização Mundial da SaúdeRESUMO
OBJECTIVE: To compare blood pressure and the prevalence of hypertension in white Dutch and Dutch of Suriname-hindustani and Suriname-creole ethnic derivation with corresponding ethnic minority groups in England and to assess the quality of hypertension treatment in these groups. DESIGN: Retrospective; comparison of cross-sectional studies. METHOD: Secondary analyses were performed on data from 3 population-based studies with 13,999 participants in total of European, African of South-Asian origin from England and the Netherlands. RESULTS: English South-Asian men and women had lower blood pressure and lower prevalence of hypertension than people of South-Asian origin in the Netherlands (Suriname-hindustani), except for systolic blood pressure in men of Indian extraction in England. There was no difference in systolic blood pressure between groups of African origin in the Netherlands and England. Diastolic blood pressure levels, however, were lower in English men and women of African origin than in people of African origin in the Netherlands (Suriname-creole). White Dutch had higher systolic blood pressure levels, but lower diastolic blood pressure levels than white English men and women. There was no difference in the prevalence of hypertension between the white groups. In persons being treated for hypertension, a substantially lower percentage of the Suriname-hindustani and Suriname-creole persons in the Netherlands had well controlled blood pressure (lower than 140/90 mmHg) than their English equivalents, with the exception of English of Indian extraction. CONCLUSION: There were marked differences in blood pressure and prevalence of hypertension between comparable ethnic groups in England and the Netherlands. The relatively poor blood pressure control in Dutch ethnic minority groups partly explained the relatively high blood pressure levels in these groups.
Assuntos
Etnicidade , Hipertensão/prevenção & controle , Grupos Minoritários , Povo Asiático , População Negra , Comparação Transcultural , Estudos Transversais , Inglaterra , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/etnologia , Masculino , Países Baixos , Prevalência , Estudos Retrospectivos , Suriname/etnologiaRESUMO
OBJECTIVE: This paper aimed to examine immigrant mortality according to duration of residence in the Netherlands and to compare duration-specific mortality levels to levels of mortality in the native Dutch population. STUDY DESIGN AND SETTING: For the years 1995-2000, we linked the national cause of death register, that contains information on deaths of legal residents, to the municipal population register, that contains information on all legal residents. We studied mortality in relation to period of immigration by means of directly standardized mortality rates and Poisson regression. RESULTS: All cause mortality was not related to year of immigration among Turkish and Moroccan men and women, and among Surinamese women. Among Surinamese men and among Antilleans/Aruban men and women, mortality was higher in more recent immigrants. Part of their excess mortality was due to their relatively low socioeconomic status. For most specific causes of death, no consistent relation with duration of residence was observed. CONCLUSION: A consistent relation between duration of residence and immigrant mortality was only observed in some immigrant groups. The results suggest that the healthy migrant effect or adaptation of health-related behaviors were no predominant determinants of immigrant mortality in the Netherlands.
Assuntos
Emigração e Imigração , Mortalidade , Aculturação , Adulto , Distribuição por Idade , Idoso , Causas de Morte , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Marrocos/etnologia , Países Baixos/epidemiologia , Distribuição por Sexo , Fatores Socioeconômicos , Suriname/etnologia , Fatores de Tempo , Turquia/etnologia , Urbanização , Índias Ocidentais/etnologiaRESUMO
BACKGROUND: Migrant populations consist of migrants with differences in generational status and length of residence. Several studies suggest that health outcomes differ by generational status and duration of residence. We examined the association of generational status and age at immigration of the mother with infant mortality in migrant populations in The Netherlands. METHODS: Data from Statistics Netherlands were obtained from 1995 through 2000 for infants of mothers with Dutch, Turkish and Surinamese ethnicity. Mothers were categorized by generational status (Dutch-born and foreign-born) and by age at immigration (0-16 and >16 years). The associations of generational status and age at immigration of the mother with total and cause-specific infant mortality were examined. RESULTS: The infant mortality rate in Turkish mothers rose with lower age at immigration (from 5.5 to 6.4 per 1000) and was highest for Dutch-born Turkish mothers (6.8 per 1000). Infant death from perinatal and congenital causes increased with lower age at immigration and was highest in the Dutch-born Turkish women. In contrast, in Surinamese mothers infant mortality declined with lower age at immigration (from 8.0 to 6.3 per 1000) and was lowest for Dutch-born Surinamese mothers (5.5 per 1000). Generational status and lower age at immigration of Surinamese women were associated with declining mortality of congenital causes. CONCLUSIONS: Total and cause-specific infant mortality seem to differ according to generational status and age at immigration of the mother. The direction of these trends however differs between ethnic populations. This may be related to acculturation and selective migration.
Assuntos
Aculturação , Causas de Morte/tendências , Emigração e Imigração/estatística & dados numéricos , Mortalidade Infantil/tendências , Idade Materna , Grupos Minoritários/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Declaração de Nascimento , Criança , Pré-Escolar , Comparação Transcultural , Atestado de Óbito , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Gravidez , Modelos de Riscos Proporcionais , Sistema de Registros , Suriname/etnologia , Fatores de Tempo , Turquia/etnologiaRESUMO
STUDY OBJECTIVE: To analyse socioeconomic inequalities in mortality in Dutch, Turkish, Moroccans, Surinamese, and Antillean/Aruban men and women living in the Netherlands and to assess the contribution of specific causes of death to these inequalities. DESIGN: Open cohort design using data from the Municipal Population Registers and cause of death registry. SETTING: the Netherlands from 1995 through 2000. PARTICIPANTS: All inhabitants of the Netherlands. MAIN OUTCOME MEASURES: This study calculated directly standardised mortality rates by mean neighbourhood income and estimated relative mortality ratios comparing the two lowest socioeconomic groups with the two highest socioeconomic groups for all and cause specific mortality by country of origin and sex. MAIN RESULTS: Socioeconomic differences in total mortality were comparatively large in Dutch, (RR = 1.49, CI = 1.46 to 1.52), Surinamese (1.32, 1.19 to 1.46), and Antillean/Aruban men (1.56, 1.29 to 1.89) and in Dutch (1.39, 135 to 1.42) and Surinamese women (1.27, 1.11 to 1.46). They were comparatively small among Turkish (1.10, 0.99 to 1.23) and Moroccan men (1.10, 0.97 to 1.26) and among Turkish (1.13, 0.97 to 1.33), Moroccan (1.12, 0.93 to 1.35) and Antillean/Aruban women (1.03, 0.80 to 1.33). The mortality differences among the Dutch were partly attributable to inequalities in mortality from cardiovascular diseases, whereas among Antillean/Aruban men external causes strongly contributed to the mortality differences. The small differences among Turkish and Moroccan men were due to a lack of inequalities for cardiovascular diseases and small inequalities for the other causes. CONCLUSIONS: The impact of socioeconomic status on mortality differed between ethnic groups living in the Netherlands. Maintaining small socioeconomic inequalities in mortality among Turkish and Moroccans men and women and among Antillean/Aruban women could prevent future increases in overall mortality in these groups.
Assuntos
Etnicidade/estatística & dados numéricos , Mortalidade/tendências , Doenças Cardiovasculares/mortalidade , Causas de Morte/tendências , Estudos de Coortes , Feminino , Humanos , Renda/estatística & dados numéricos , Masculino , Marrocos/etnologia , Países Baixos/epidemiologia , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Suriname/etnologia , Turquia/etnologia , Índias Ocidentais/etnologiaRESUMO
Of the two homologous forms of glutamic acid decarboxylase, GAD65 and GAD67, only GAD65 is a common target of autoimmunity. Epitope profiles of autoantibodies to GAD65 (GADA) in 140 type 1 diabetes, adult-onset diabetes mellitus (AODM), and thyroid diseases (TD) were studied. Probes were GAD65, GAD65/67 hybrids (displaying separately GAD65 residues 1-95, 96-444, and 445-585), delta GAD65 (a truncated GAD65 spanning residues 69-585), and GAD67. delta GAD65 and GAD65 detected 137 and 125 positive patients, respectively. The hybrids reacted with 113 sera and in 3 cases disclosed cryptic epitopes. Eighteen patients reacted with GAD67, indicating GAD65-GAD67 cross-reactivity. Most patients recognized both middle and C-terminal epitopes, had low reactivity against N-terminal epitopes, and seldom displayed reactivity limited to the N or C terminus. Compared with type 1 and AODM, TD patients showed a greater prevalence of multiple reactivity and higher incidence of GAD67 positivity.
Assuntos
Autoanticorpos/imunologia , Epitopos/imunologia , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/imunologia , Engenharia de Proteínas , Diabetes Mellitus Tipo 1/imunologia , HumanosRESUMO
The apoptotic process evoked by efferent duct ligation in the testes of adult rats was followed for 10 days by differential staining for haematoxylin-eosin, periodic acid-Schiff and a modified trichrome technique in optical microscopy and by ultrastructural localization of acid phosphatase. Round spermatids showed the first effects of efferent duct ligation. At day 3 after ligation, annular clumps of chromatin with typical apoptotic characteristics appeared against the nuclear membrane of these cells. Afterwards, membranous structures and a wide separation between the two layers of the nuclear membrane were observed but nuclear fragmentation did not occur and apoptotic granules were not seen. Cytoplasmic components were also altered, and severely damaged organoids and empty vacuoles lacking acid phosphatase reaction were frequently seen. On day 2 after efferent duct ligation, multinucleated giant cells appeared, which displayed similar characteristics as spermatids and showed no acid phosphatase reaction. Although abnormal spermatids and multinucleated giant cells were surrounded by the cytoplasm of Sertoli cells, neither lysosomal acid phosphatase nor phagocytic activity was detected. It is concluded that efferent duct ligation specifically affects round immature spermatids eliciting a partial nuclear apoptotic response that is not accompanied by autophagic or heterophagic activity and without lysosomal participation in Sertoli cells.
Assuntos
Células Gigantes/citologia , Espermátides/citologia , Testículo/citologia , Fosfatase Ácida/metabolismo , Animais , Apoptose , Células Gigantes/ultraestrutura , Histocitoquímica/métodos , Ligadura , Masculino , Microscopia Eletrônica , Ratos , Ratos Wistar , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/ultraestrutura , Espermátides/ultraestrutura , Testículo/metabolismoAssuntos
Átrios do Coração/anormalidades , Ramos Subendocárdicos/patologia , Pré-Escolar , Ecocardiografia Transesofagiana , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Ultrassonografia Doppler em CoresRESUMO
Solvent-induced directional aggregation of human carbonic anhydrase II (hCA) was studied by small angle X-ray scattering and fluorescence and fourth-derivative ultraviolet absorption spectroscopy. We propose that hCA at 5 mg ml(-1) in pure water forms head-to-tail oligomers built up, on average, by four to five monomers. At higher protein concentrations, the oligomers associate pair-wise and side-by-side. Spectroscopic evidence suggests that the subunits forming the aggregates are tightly folded, but with a structure that differs, at least locally, from the native state. A more complex aggregation pattern was observed under solvent conditions that favor the removal of zinc from the enzyme-active site, conditions under which the subunits are significantly less compact than in water. hCA may provide a useful model to investigate the effects of additives and genetic manipulation on protein aggregation.
Assuntos
Anidrases Carbônicas/química , Espalhamento de Radiação , Sítios de Ligação , Escherichia coli/química , Humanos , Concentração de Íons de Hidrogênio , Dobramento de Proteína , Espectrometria de Fluorescência , Espectrometria por Raios X , Espectrofotometria Ultravioleta , Raios Ultravioleta , Água/química , Raios X , Zinco/químicaRESUMO
Most insulin-dependent diabetes mellitus patients gen-erate conformational autoantibodies to the islet-cell 65-kDa variant of human glutamate decarboxylase (GAD65), and several immunochemical tests for the early detection of type-1 diabetes rely on GAD65 antibody (GADA) assessment using properly folded recombinant GAD65 as the antigen. In addition, preventive therapies based on tolerization by GAD65 administration may be available in the near future. Therefore, there exists a strong interest in a facile and economically sound expression procedure for this antigen. Several attempts to produce, in native form, wild-type GAD65 in Escherichia coli have failed. However, this difficulty was recently surmounted in our laboratory by expressing GAD65 as a fusion protein with thioredoxin [Papouchado, Valdez, Ghiringhelli, Poskus and Ermácora (1997) Eur. J. Biochem. 246, 350-359]. In this work, a new GAD65 hybrid gene was prepared by joining engineered cDNA obtained from human and rat tissues. The new gene was modified additionally to finally code for human GAD65 with a single amino-acid substitution: Met-161-->Thr. This change impeded the co-expression of a 48-kDa by-product from an internal translation site. Also, a second 58-kDa by-product was identified as a GAD65 C-terminal proteolytic fragment that co-purifies with thioredoxin-M161T GAD65. The new GAD65 variant was expressed and easily purified, yielding an antigen that performed equally or better than wild-type GAD65 in the reference radiobinding assay for GADA. The procedure provides an inexpensive source of large amounts of fully active and immunochemically competent GAD65.
Assuntos
Escherichia coli/genética , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Humanos , Metionina , Dados de Sequência Molecular , Engenharia de Proteínas/métodos , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , TreoninaRESUMO
The direct effect of cyclophosphamide (CY) on bone marrow and liver stromal cells of DBA/2 and C57BL/6 mice after a single intraperitoneal dose of 300 mg/kg, was assessed. Ultrastructural observations were carried out 2,4,6,12,18, and 24 h and 2,3,5,7,10,15,22 and 30 days after CY in femoral bone marrow and liver fixed by immersion or vascular perfusion. A massive depletion of hemopoietic cells was observed in bone marrow as early as 12 h after CY treatment, and normality was recovered only after 10 days. Among stromal cells, sinus endothelial cells, reticular cells, and macrophages were particularly sensitive to CY and showed severe damage as soon as 2 h after treatment. There was also an important dilatation of sinusoids, and the presence of mature red cells in the hemopoietic parenchyma, and macrophages and immature cells in the lumen and in circulating blood demonstrated the loss of integrity of the endothelium. In the liver, injured cells showing vesiculation and disruption of endothelial and Kupffer cells of sinusoids were evident 6 h after CY. The alterations caused by CY were transient. Although recovery of the hemopoietic cells in bone marrow and liver was achieved by day 10, the stromal cells showed damage even 15 days after CY, and a return to normality was only reached on day 30. Thus, the effect of CY on stromal cells, that was longer lasting than the effect on the hemopoietic compartment, demonstrated a higher recovery capacity of hemopoiesis with respect to stromal cells. These results demonstrate that recovery of hemopoiesis occurred even while the severe damage inflicted by CY to the stromal cells remained unrepaired.
Assuntos
Medula Óssea/efeitos dos fármacos , Ciclofosfamida/farmacologia , Imunossupressores/farmacologia , Fígado/efeitos dos fármacos , Células Estromais/ultraestrutura , Animais , Medula Óssea/ultraestrutura , Células da Medula Óssea , Contagem de Leucócitos , Fígado/citologia , Fígado/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Células Estromais/efeitos dos fármacosRESUMO
The effect of a single dose of 300 mg/kg of cyclophosphamide (CY) on the ultrastructure of the basal area of lower incisor teeth was investigated in two strains of mice (DBA/2 and C57BL/6) which are very differently affected by the delayed toxicity of CY. As in the rat, CY produced necrosis in the primitive mesenchymal cells and preodontoblasts of the pulp. Moreover, important changes were noticed in the associated layers of the enamel organ (presumptive stratum intermedium cells and stellate reticulum); thus, most of the cells displayed degenerative changes including extensive vacuolization, cytoplasm sequestration and variable nuclear alterations ranging from relative integrity to complete disorganization. In contrast, non-dividing columnar odontoblasts and ameloblasts were not affected by the drug. The alterations appeared as early as 21 hours after CY and progressed in the following 2 and 3 days. Normality of the formative tooth end was regained 7 days after CY. These results indicate that in addition to the effect on the pulp, CY produces severe cytopathological changes in the cells of the stratum intermedium and stellate reticulum of the enamel organ. The different sensitivity of DBA/2 and C57BL/6 mice to the delayed toxicity of CY does not seem to be related to its effect on odontogenesis since both strains showed the same response to CY in this respect.
Assuntos
Antineoplásicos Alquilantes/toxicidade , Ciclofosfamida/toxicidade , Incisivo/efeitos dos fármacos , Incisivo/ultraestrutura , Odontogênese/efeitos dos fármacos , Animais , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/ultraestrutura , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Microscopia Eletrônica , Especificidade da EspécieRESUMO
Early and delayed toxicity of a single dose of 300 mg kg-1 cyclophosphamide (CP) was investigated in male DBA/2 and C57BL/6 mice. Early toxicity (up to 30 days after CP administration) resulted in 36.6% lethality in DBA/2 and no mortality in C57BL/6 mice. Delayed toxicity (after 30 days) occurred primarily in DBA/2 mice, resulting in a survival of 3% in DBA/2 and 93% in C57BL/6 mice on day 125 after CP administration. Early modifications brought about by CP in erythrocytes and leucocytes, and spleen and liver indexes (mg organ g-1 body wt.) were rather similar in DBA/2 and C57BL/6 strains. However, CP treatment caused a profound cell depletion in DBA/2 bone marrow owing, in part, to the fact that the number of cells in bone marrow of normal DBA/2 mice was much lower than that in normal C57BL/6 mice. Furthermore, the thymus index (mg organ g-1 body wt.) decreased sooner in DBA/2 than in C57BL/6 animals and no sign of recovery was evident in the former even after 10 days, whereas recovery in the latter started on day 5 after injection. Differential sensitivity of DBA/2 and C57BL/6 strains to CP could be due to differences in activation and/or inactivation of the drug, or to the increased effect of CP on DBA/2 bone marrow resulting in damage to pre-T cells that normally participate in thymus recovery.