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1.
Environ Monit Assess ; 192(6): 352, 2020 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-32388656

RESUMEN

Understanding the tectonics at active sites of recent seismic activities in Nigeria is fundamental towards disaster mitigation and emergency planning. We apply geophysical techniques of gravity and magnetic methods to investigate crustal depths, subsurface geologic faults and fractures, and the overall subsurface interaction at Mpape region and environs. Estimated depths to the bottom of magnetic crust (basal depths) range between 11.0 and 11.4 km at the Mpape region and decrease further southward towards Guabe town. This signifies the depth range of the active crust within the region. Comparative deeper basal depths (15.0-16.2 km) were obtained at locations farther from Mpape-Guabe towns at Nasarawa, Rubochi, and Fuka regions, showing a more stable region away from Mpape region. Computed Moho depths from gravity data show deeper depths at the Mpape region (~ 34.1 km) suggesting that the active crust exists in the upper crust. Two-dimensional modeling analysis along a profile taken across the Mpape region shows a conspicuous subsurface basement intrusion at the Mpape region with deep faults and fractures reaching depths of 7-14 km. Shallow basal depths at the Mpape region resulting from significant subsurface intrusion and concentrated subsurface faults at the intruded region may be responsible for the instability of the Mpape region. The most affected area is located within the Mpape-Guabe towns. We recommend the establishment of seismic monitoring facilities in this area for effective monitoring and evaluation.


Asunto(s)
Terremotos , Monitoreo del Ambiente , Geología , Humanos , Nigeria
2.
Mol Cell Neurosci ; 54: 9-21, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23201237

RESUMEN

During their phase of developmental programmed cell death (PCD), neurons depend on target-released trophic factors for survival. After this period, however, they critically change as their survival becomes target-independent. The molecular mechanisms underlying this major transition remain poorly understood. Here, we investigated, which transcription factors (TFs) might be responsible for the closure of PCD. We used Purkinje cells as a model since their PCD is restricted to the first postnatal week in the mouse cerebellum. Transcriptome analysis of Purkinje cells during or after PCD allowed the identification of Krüppel like factor 9 (Klf9) as a candidate for PCD closure, given its high increase of expression at the end of the 1st postnatal week. Klf9 function was tested in organotypic cultures, through lentiviral vector-mediated manipulation of Klf9 expression. In absence of trophic factors, the Purkinje cell survival rate is of 40%. Overexpression of Klf9 during PCD dramatically increases the Purkinje cell survival rate from 40% to 88%, whereas its down-regulation decreases it to 14%. Accordingly, in organotypic cultures of Klf9 knockout animals, Purkinje cell survival rate is reduced by half as compared to wild-type mice. Furthermore, the absence of Klf9 could be rescued by Purkinje cell trophic factors, Insulin growth factor-1 and Neurotrophin3. Altogether, our results ascribe a clear role of Klf9 in Purkinje cell survival. Thus, we propose that Klf9 might be a key molecule involved in turning off the phase of Purkinje PCD.


Asunto(s)
Factores de Transcripción de Tipo Kruppel/genética , Células de Purkinje/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Cerebelo/citología , Cerebelo/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Ratones Noqueados , Neurotrofina 3/farmacología , Técnicas de Cultivo de Órganos , Células de Purkinje/fisiología , Factores de Transcripción/metabolismo , Transcripción Genética , Transcriptoma
3.
Virol J ; 6: 110, 2009 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-19619316

RESUMEN

Hepatitis C virus (HCV) infection is an important public health problem worldwide. Its association with, and predisposing nature for diabetes mellitus (DM) has been long established. This research was carried out to determine the prevalence of Hepatitis C virus (HCV) amongst people with possible genetic predisposition to diabetes mellitus living in and around Vom, Plateau State, Nigeria. 188 subjects were screened after they filled a structured questionnaire to determine some of their demographic data, social habits and possible risk factors. 5 ml of blood was collected from each subject and sera separated out. Biotech's third generation ELISA Kit for HCV antibodies was used for the screening. Liver enzyme analysis was carried out on positive samples to determine their disease status. A prevalence of 14.36% was recorded with the highest seropositive group being those in the age bracket of 18 - 37 years. 13(13.40%) of males and 14(15.38%) of females were sero-positive. Liver enzyme analysis of sero-positive subjects showed increased levels which may imply early onset of liver damage. These result showed that these individuals could later suffer diabetes which may be triggered by their HCV infection if not treated. This is not over-looking the economic significance of their ill health, assuming they progress to cirrhotic HCV or develop hepatocelluar carcinoma due to HCV chronicity.


Asunto(s)
Diabetes Mellitus/epidemiología , Hepatitis C/epidemiología , Adolescente , Adulto , Análisis Químico de la Sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Anticuerpos contra la Hepatitis C/sangre , Humanos , Pruebas de Función Hepática , Masculino , Nigeria/epidemiología , Estudios Seroepidemiológicos , Encuestas y Cuestionarios , Adulto Joven
4.
Cancers (Basel) ; 11(6)2019 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-31181810

RESUMEN

A greater understanding of the hypersensitivity and curability of testicular germ cell tumors (TGCTs) has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. The mechanisms of cisplatin hypersensitivity and resistance in embryonal carcinoma (EC), the stem cells of TGCTs, remain largely undefined. To study the mechanisms of cisplatin resistance we generated a large panel of independently derived, acquired resistant clones from three distinct parental EC models employing a protocol designed to match standard of care regimens of TGCT patients. Transcriptomics revealed highly significant expression changes shared between resistant cells regardless of their parental origin. This was dominated by a highly significant enrichment of genes normally repressed by H3K27 methylation and the polycomb repressive complex 2 (PRC2) which correlated with a substantial decrease in global H3K27me3, H2AK119 ubiquitination, and expression of BMI1. Importantly, repression of H3K27 methylation with the EZH2 inhibitor GSK-126 conferred cisplatin resistance to parental cells while induction of H3K27 methylation with the histone lysine demethylase inhibitor GSK-J4 resulted in increased cisplatin sensitivity to resistant cells. A gene signature based on H3K27me gene enrichment was associated with an increased rate of recurrent/progressive disease in testicular cancer patients. Our data indicates that repression of H3K27 methylation is a mechanism of cisplatin acquired resistance in TGCTs and that restoration of PRC2 complex function is a viable approach to overcome treatment failure.

5.
Mol Cell Biol ; 16(4): 1706-13, 1996 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8657146

RESUMEN

We isolated mouse cDNA clones (Arnt2) that are highly similar to but distinct from the aryl hydrocarbon receptor (AhR) nuclear translocator (Arnt). The composite cDNA covered a 2,443-bp sequence consisting of a putative 2,136-bp open reading frame encoding a polypeptide of 712 amino acids. The predicted Arnt2 polypeptide carries a characteristic basic helix-loop-helix (bHLH)/PAS motif in its N-terminal region with close similarity (81% identity) to that of mouse Arnt and has an overall sequence identity of 57% with Arnt. Biochemical properties and interaction of Arnt2 with other bHLH/PAS proteins were investigated by coimmunoprecipitation assays, gel mobility shift assays, and the yeast two-hybrid system. Arnt2 interacted with AhR and mouse Sim as efficiently as Arnt, and the Arnt2-AhR complex recognized and bound specifically the xenobiotic responsive element (XRE) sequence. Expression of Arnt2 successfully rescued XRE-driven reporter gene activity in the Arnt-defective c4 mutant of Hepa-1 cells. RNA blot analysis revealed that expression of Arnt2 mRNA was restricted to the brains and kidneys of adult mice, while Arnt mRNA was expressed ubiquitously. In addition, whole-mount in situ hybridization of 9.5-day mouse embryos showed that Arnt2 mRNA was expressed in the dorsal neural tube and branchial arch 1, while Arnt transcripts were detected broadly in various tissues of mesodermal and endodermal origins. These results suggest that Arnt2 may play different roles from Arnt both in adult mice and in developing embryos. Finally, sequence comparison of the currently known bHLH/PAS proteins indicates a division into two phylogenetic groups: the Arnt group, containing Arnt, Arnt2, and Per, and the AhR group, consisting of AhR, Sim, and Hif-1alpha.


Asunto(s)
ADN Complementario/genética , Secuencias Hélice-Asa-Hélice , Receptores de Hidrocarburo de Aril/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Clonación Molecular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Embrión de Mamíferos , Genes Reporteros , Ratones , Datos de Secuencia Molecular , Receptores de Hidrocarburo de Aril/metabolismo , Homología de Secuencia de Aminoácido , Factores de Transcripción/metabolismo
6.
Mol Cell Biol ; 16(10): 5865-75, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8927054

RESUMEN

From a cDNA library of mouse skeletal muscle, we have isolated mouse Sim1 (mSim1) cDNA encoding a polypeptide of 765 amino acids with striking amino acid identify in basic helix-loop-helix (89% identify) and PAS (89 % identify) domains to previously identified mSim2, although the carboxy-terminal third of the molecule did not show any similarity to mSim2 or Drosophila Sim (dSim). Yeast two-hybrid analysis and coimmunoprecipitation experiments demonstrated that both of the mSim gene products interacted with Arnt even more efficiently than AhR, a natural partner of Arnt, suggesting a functional cooperativity with Arnt. In sharp contrast with dSim having transcriptional-enhancing activity in the carboxy-terminal region, the two mSims possessed a repressive activity toward Arnt in the heterodimer complex. This is the first example of bHLH-PAS proteins with transrepressor activity, although some genetic data suggest that dSim plays a repressive role in gene expression (Z. Chang, D. Price, S. Bockheim, M. J. Boedigheimer, R. Smith, and A. Laughon, Dev. Biol. 160:315-322, 1993; D. M. Mellerick and M. Nirenberg, Dev. Biol. 171:306-316, 1995). Whole-mount in situ hybridization showed restricted and characteristic expression patterns of the two mSim mRNAs in various tissues and organs during embryogenesis, such as those for the somite, the nephrogenic cord, and the mesencephalon (for mSim1) and those for the diencephalon, branchial arches, and limbs (for mSim2). From sequence similarity and chromosomal localization, it is concluded that mSim2 is an ortholog of hSim2, which is proposed to be a candidate gene responsible for Down's syndrome. The sites of mSim2 expression showed an overlap with the affected regions of the syndrome, further strengthening involvement of mSim2 in Down's syndrome.


Asunto(s)
Mapeo Cromosómico , Regulación del Desarrollo de la Expresión Génica , Familia de Multigenes , Músculo Esquelético/metabolismo , Proteínas Represoras/biosíntesis , Secuencia de Aminoácidos , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Encéfalo/embriología , Encéfalo/metabolismo , Células COS , Línea Celular , Clonación Molecular , Proteínas de Unión al ADN/química , Drosophila , Proteínas de Drosophila , Desarrollo Embrionario y Fetal , Biblioteca de Genes , Secuencias Hélice-Asa-Hélice , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Ratones , Datos de Secuencia Molecular , Músculo Esquelético/embriología , Proteínas Nucleares/química , Sondas ARN , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes/biosíntesis , Proteínas Represoras/química , Homología de Secuencia de Aminoácido
7.
Food Chem Toxicol ; 43(2): 325-31, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15621345

RESUMEN

The objective of this study was to evaluate the developmental toxicity of 1-butanol in rats. Pregnant rats were given drinking water containing 1-butanol at 0.2%, 1.0% or 5.0% (316, 1454 or 5654 mg/kg/day) on days 0-20 of pregnancy. A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was found at 5.0%. No significant increase in the incidence of pre- and postimplantation embryonic loss was observed in any groups treated with 1-butanol. Fetal weight was significantly lowered at 5.0%. Although a significant increase in the incidence of fetuses with skeletal variations and decreased degree of ossification was found at 5.0%, no increase in the incidence of fetuses with external, skeletal and internal abnormalities was detected in any groups treated with 1-butanol. The data demonstrate that 1-butanol is developmental toxic only at maternal toxic doses. No evidence for teratogenicity of 1-butanol was noted in rats. Based on the significant decreases in maternal body weight gain and fetal weight, it is concluded that the no observed adverse effect levels (NOAELs) of 1-butanol for both dams and fetuses are 1.0% (1454 mg/kg/day) in rats.


Asunto(s)
1-Butanol/toxicidad , Anomalías Inducidas por Medicamentos/epidemiología , Desarrollo Fetal/efectos de los fármacos , Teratógenos/toxicidad , Anomalías Inducidas por Medicamentos/etiología , Administración Oral , Animales , Desarrollo Óseo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ingestión de Líquidos , Evaluación Preclínica de Medicamentos , Femenino , Peso Fetal/efectos de los fármacos , Masculino , Exposición Materna , Nivel sin Efectos Adversos Observados , Embarazo , Ratas , Factores de Tiempo , Aumento de Peso/efectos de los fármacos
8.
Pharmacogenetics ; 4(6): 349-54, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7704041

RESUMEN

A complete sequence of the Ah receptor gene was cloned from a mouse genomic library by using the Ah receptor cDNA as a probe. The Ah receptor gene is 37.5 kb long and is split into 11 exons by 10 introns. Sequence analysis of the 5' flanking region of the Ah receptor gene reveals that there is neither a TATA box nor a CAAT box in the promoter region. Instead, this gene has a few GC boxes and other enhancer elements in the 5' upstream flanking region. Southern blot analysis indicated that the Ah receptor gene is a unique gene.


Asunto(s)
Receptores de Hidrocarburo de Aril/genética , Animales , Secuencia de Bases , Clonación Molecular , ADN/genética , Cartilla de ADN/genética , ADN Complementario/genética , Elementos de Facilitación Genéticos , Exones , Biblioteca Genómica , Intrones , Ratones , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , ARN Mensajero/genética , Mapeo Restrictivo , Transcripción Genética
9.
Pharmacogenetics ; 5 Spec No: S149-53, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7581486

RESUMEN

Induction of cytochrome P4501A1 (CYP1A1) by certain xenobiotics is mediated by the Ah receptor/Arnt complex. The present knowledge about the molecular process of induction is summarized with special attention to our recent work on characterization of the polymorphic forms of the Ah receptor.


Asunto(s)
Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Polimorfismo Genético , Receptores de Hidrocarburo de Aril/genética , Xenobióticos/farmacología , Clonación Molecular , Inducción Enzimática/efectos de los fármacos , Humanos , Mutagénesis Sitio-Dirigida , Receptores de Hidrocarburo de Aril/química , Receptores de Hidrocarburo de Aril/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Xenobióticos/metabolismo
10.
J Biochem ; 116(4): 845-51, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7883760

RESUMEN

We isolated the human arylhydrocarbon receptor (AhR) cDNA from a human lung cDNA library, by using mouse AhR cDNA as a labeled probe. The nucleotide sequence of cloned human AhR cDNA is identical to the previously reported human AhR sequence [Dolwick et al. (1993), Mol. Pharmacol. 44, 911-917] from cell line HepG2. The overall amino acid identity with mouse AhR from cell line Hepa-1 is 72.5%. The human AhR expressed either in COS-7 cells or in a reticulocyte lysate in vitro translation system showed specific dioxin-binding activity and Arnt-dependent DNA-binding activity. Chromosomal localization of the AhR gene was determined to be chromosome 7p21 by fluorescent in situ hybridization and DNA blot hybridization using 23 human x mouse or Chinese hamster hybrid cell DNAs.


Asunto(s)
Cromosomas Humanos Par 7 , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Cricetinae , Cricetulus , Sondas de ADN , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , Expresión Génica , Humanos , Células Híbridas/fisiología , Hibridación Fluorescente in Situ , Ratones , Datos de Secuencia Molecular , Dibenzodioxinas Policloradas/metabolismo , Homología de Secuencia de Aminoácido
11.
Neurosci Res ; 25(3): 203-8, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8856716

RESUMEN

C6 glioma cells could be successively subcultured and maintained in serum- and growth factor-free medium (SF/GFF medium). C6 cell proliferation in SF/GFF medium was positively correlated with the initial cell density at plating. This correlation disappeared when the medium had been renewed early after cell adhesion (3 h after plating), suggesting that C6 cell growth depends on some diffusible factor in the medium before renewal, and that this factor is not secreted from C6 cells in the assay culture but is transferred from the cell suspension. The supernatant of trypsinized C6 cell suspension (SCS), trypsin-EDTA solution for routine cell harvesting use, and modified trypsin of protein sequencing grade all promoted C6 cell proliferation at, appropriate dilutions or concentrations under SF/GFF conditions. The growth promoting effects of SCS and trypsin-EDTA solution were completely inhibited by soybean trypsin inhibitor. These results demonstrate that the serine protease trypsin has a proliferative effect on C6 cells continuously subcultured in SF/GFF medium. In addition, it is suggested that trypsin used for cell dispersion is transferred from cell suspension into the culture, where it promotes C6 cell growth after passage in our SF/GFF subculture system.


Asunto(s)
Medio de Cultivo Libre de Suero/farmacología , Medios de Cultivo/farmacología , Glioma/patología , Tripsina/farmacología , Animales , División Celular/efectos de los fármacos , Medios de Cultivo/química , Sustancias de Crecimiento/análisis , Ratas , Células Tumorales Cultivadas
12.
Toxicology ; 86(3): 163-74, 1994 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-8128502

RESUMEN

The objective of this study was to determine the characterization of the developmental toxicity of di-n-butyl phthalate (DBP) in rats. Pregnant rats were given DBP by gastric intubation at a dose of 0.75, 1.0 or 1.5 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. Postimplantation loss was 100% for each period of dosing at 1.5 g/kg. A significant increase in the postimplantation loss was found in dams given DBP at doses of 0.75 and 1.0 g/kg regardless of the days of treatment. No evidence of teratogenicity was detected when DBP was given on days 10-12. Treatment on days 7-9 with DBP at doses of 0.75 and 1.0 g/kg caused a significant increase in the number of skeletal malformations such as deformity of the vertebral column in the cervical and thoracic regions and of the ribs, but neither external nor internal malformations. Treatment with DBP on days 13-15 at doses of 0.75 and 1.0 g/kg resulted in a significant increase in the incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The frequency of malformations increased as the dose of DBP was increased. The highest incidence of malformed fetuses occurred after treatment with DBP on days 13-15. It could be concluded that susceptibility to the teratogenicity of DBP varies with the developmental stage at the time of administration.


Asunto(s)
Anomalías Inducidas por Medicamentos , Dibutil Ftalato/toxicidad , Desarrollo Embrionario y Fetal/efectos de los fármacos , Animales , Huesos/anomalías , Huesos/efectos de los fármacos , Huesos/embriología , Fisura del Paladar/inducido químicamente , Relación Dosis-Respuesta a Droga , Pérdida del Embrión/inducido químicamente , Femenino , Muerte Fetal/inducido químicamente , Reabsorción del Feto/inducido químicamente , Masculino , Embarazo , Ratas , Ratas Wistar , Costillas/anomalías , Costillas/efectos de los fármacos , Costillas/embriología , Columna Vertebral/anomalías , Columna Vertebral/efectos de los fármacos , Columna Vertebral/embriología , Esternón/anomalías , Esternón/efectos de los fármacos , Esternón/embriología
13.
Toxicology ; 79(1): 11-9, 1993 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-8475496

RESUMEN

Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0.6, 0.75 or 1.0 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. While treatment with BBP on days 7-9 or 13-15 at doses of 0.75 and 1.0 g/kg was significantly teratogenic, no evidence of teratogenicity was detected when BBP was given on days 10-12. The incidence of malformed fetuses was proportional to the dose of BBP. Treatment on days 7-9 with BBP at doses of 0.75 g/kg and above caused a significant increase in the number of skeletal malformations, such as fusion of the cervical vertebral arches and deformity of the thoracic vertebrae, but neither external nor internal malformations. Treatment on days 13-15 with two higher doses of BBP resulted in a significantly increased incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The highest incidence of malformed fetuses occurred after treatment with BBP on days 13-15. It could be concluded that the susceptibility to the teratogenicity of BBP varies with the developmental stage at the time of administration.


Asunto(s)
Anomalías Inducidas por Medicamentos , Ácidos Ftálicos/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Femenino , Feto/efectos de los fármacos , Masculino , Embarazo , Ratas , Ratas Wistar , Reproducción/efectos de los fármacos
14.
Toxicology ; 73(1): 81-92, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1589881

RESUMEN

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 20 mg/kg on days 7-9, 10-12 or 13-15 of pregnancy or at a dose of 20 or 40 mg/kg on day 6, 7, 8 or 9 of pregnancy. While treatment with DBT on days 7-9 was significantly and highly teratogenic, no evidence of teratogenicity was detected when DBT was given on days 10-12 or 13-15. Treatment on day 7 or 8 with both doses of DBT, but neither on day 6 or 9, resulted in an increased incidence of fetuses with malformations. The highest incidence of malformed fetuses occurred after treatment on day 8. The incidence of malformed fetuses was proportional to the dose of DBT. Anomaly of tail, anal atresia, club foot, omphalocele, deformity of the vertebral column, defect of the ribs and anophthalmia or microphthalmia were predominantly observed. It could be concluded that, following maternal exposure to DBT in rats, developing offspring are not susceptible to teratogenic effects of DBT on day 6 and that day 7 is the earliest susceptible period, day 8 is the highest susceptible period and day 9 is no longer a susceptible period for teratogenesis of DBT.


Asunto(s)
Edad Gestacional , Compuestos Orgánicos de Estaño/toxicidad , Teratógenos/toxicidad , Animales , Femenino , Compuestos Orgánicos de Estaño/administración & dosificación , Embarazo , Ratas , Ratas Endogámicas
15.
Toxicology ; 96(3): 195-201, 1995 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-7900160

RESUMEN

The objective of this study was to further evaluate the developmental toxicity of tributyltin chloride (TBTCl) in rats. Pregnant rats were given TBTCl by gastric intubation at a dose of 25, 50 or 100 mg/kg on days 7-9, days 10-12 or days 13-15 of pregnancy. A significant increase in the incidence of post-implantation loss was found in the groups treated with TBTCl on days 7-9 at 25 and 50 mg/kg and on days 10-12 at 100 mg/kg, but not in the groups treated with TBTCl on days 13-15. No significant increase in the incidence of malformed fetuses was observed after treatment with TBTCl on days 7-9. A significant increase incidence of malformed fetuses was detected when TBTCl was given on days 10-12 at 100 mg/kg and on days 13-15 at 25, 50 and 100 mg/kg. The most predominant malformation was cleft palate. It could be concluded that the manifestation of deviant development induced by TBTCl varies with the developmental stage at the time of administration and TBTCl possesses teratogenic potential with developmental phase specificity.


Asunto(s)
Anomalías Inducidas por Medicamentos , Fisura del Paladar/inducido químicamente , Desarrollo Embrionario y Fetal/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Administración Oral , Animales , Pérdida del Embrión/inducido químicamente , Desarrollo Embrionario/efectos de los fármacos , Femenino , Muerte Fetal/inducido químicamente , Edad Gestacional , Intubación Gastrointestinal , Masculino , Embarazo , Distribución Aleatoria , Ratas , Ratas Wistar , Compuestos de Trialquiltina/administración & dosificación
16.
Toxicol Lett ; 125(1-3): 99-106, 2001 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-11701228

RESUMEN

The objective of this study was to determine the toxic effects of butyltin trichloride (BTCl) during early pregnancy. Following successful mating, female rats were given BTCl by gastric intubation at 0,56,226, or 903 mg/kg on days 0-3 or 4-7 of pregnancy. Female rats were sacrificed on day 20 of pregnancy and fetuses were examined for number, abnormality, mortality, and weight. The maternal body weight gain and food consumption during the administration period was significantly decreased after administration of BTCl at 903 mg/kg on days 0-3 or 4-7 of pregnancy. The pregnancy rate in the BTCl-treated groups was comparable to the control value, regardless of the days on which BTCl was given. The incidence of pre-implantation embryonic loss was not significantly affected after administration of BTCl on days 0-3 or 4-7. In females having implantations, the numbers of corpora lutea, implantations, and live fetuses and the incidences of pre- and postimplantation loss in the groups given BTCl on days 0-3 were comparable to the controls. Although a significant increase in the incidence of postimplantation loss was observed after administration of BTCl on days 4-7 at 56 mg/kg, this change was small and inconsistent across doses and seems unlikely to be toxicologically significant. A significant decrease in weight of female fetuses was found after administration of BTCl at 903 mg/kg on days 0-3 or 4-7. It could be concluded that BTCl treatment during early pregnancy is maternal and developmental toxic at 903 mg/kg.


Asunto(s)
Aborto Espontáneo/inducido químicamente , Feto/efectos de los fármacos , Compuestos Orgánicos de Estaño/toxicidad , Animales , Ingestión de Alimentos/efectos de los fármacos , Implantación del Embrión/efectos de los fármacos , Femenino , Embarazo , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacos
17.
Toxicol Lett ; 119(1): 79-84, 2001 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-11275424

RESUMEN

4-tert-Octylphenol (OP) is an alkylphenol that is an intermediate in the production of alkylphenol ethoxylates. OP has been reported to be the most potent estrogenic alkylphenol in vitro. In the present study, the effects of OP on initiation and maintenance of pregnancy were investigated in rats. Inseminated female rats were orally given OP at 0,15.6,31.3,62.5 and 125 mg/kg on day 0 through day 8 of pregnancy. Female rats were sacrificed on day 20 of pregnancy, and pregnancy outcome was determined. Decreases in body weight gain and food consumption on days 0-9 were found at 31.3 mg/kg and above, and at 15.6 mg/kg and above, respectively. The pregnancy rate was not adversely affected by OP administration during early pregnancy even at 125 mg/kg. The incidence of post-implantation loss per litter at 31.3 mg/kg and above was significantly higher than that in the control group. The body weights of live fetuses in the OP-treated groups were not significantly different from those in the control group. No increase in the incidence of fetuses with external malformations was found in any OP-treated group. We concluded that OP during early pregnancy caused post-implantation embryonic loss at doses that showed maternal toxicity.


Asunto(s)
Fenoles/toxicidad , Reproducción/efectos de los fármacos , Tensoactivos/toxicidad , Animales , Peso Corporal , Ingestión de Alimentos , Femenino , Masculino , Fenoles/administración & dosificación , Embarazo , Resultado del Embarazo , Ratas , Ratas Wistar , Tensoactivos/administración & dosificación , Útero/efectos de los fármacos , Útero/fisiología
18.
Toxicol Lett ; 58(3): 347-56, 1991 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1957330

RESUMEN

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 0, 2.5, 5.0, 7.5 or 10.0 mg/kg on days 7-15 of pregnancy. Maternal toxicity occurred in the 7.5 and 10.0 mg/kg groups as evidenced by a significant increase in maternal death and decrease in food consumption and body weight gain. The incidence of fetuses with malformations was roughly proportional to the dose of DBT, and was significantly increased in the 5.0, 7.5 and 10.0 mg/kg groups. Cleft jaw, ankyloglossia, defects of the mandible, fusion of the ribs and deformity of the vertebral column were predominantly found. It is concluded that DBT produced teratogenic effects in the absence of maternal toxicity.


Asunto(s)
Anomalías Inducidas por Medicamentos/fisiopatología , Intercambio Materno-Fetal , Compuestos Orgánicos de Estaño/toxicidad , Teratógenos/toxicidad , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Reabsorción del Feto/inducido químicamente , Masculino , Embarazo , Ratas , Ratas Endogámicas
19.
Toxicol Lett ; 63(2): 147-53, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1455446

RESUMEN

Pregnant rats were given glutaraldehyde (GA) by gastric intubation at a dose of 0, 25, 50 or 100 mg/kg on days 6-15 of pregnancy. Maternal toxicity occurred in the 100 mg/kg group as evidenced by a significant increase in maternal death and a significant decrease in maternal body weight gain and food consumption. A significantly lowered fetal weight was also found in the 100 mg/kg group. No significant change induced by GA was detected in the incidence of postimplantation loss. Morphologic examinations of fetuses revealed no evidence of teratogenicity of GA. It could be concluded that GA has no teratogenic effects on rat offspring even at a dose which induced severe maternal toxicity.


Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Glutaral/toxicidad , Animales , Animales Recién Nacidos , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Desarrollo Embrionario y Fetal/efectos de los fármacos , Femenino , Glutaral/administración & dosificación , Intubación Gastrointestinal , Intercambio Materno-Fetal , Mortalidad , Embarazo , Ratas , Ratas Wistar
20.
Toxicol Lett ; 89(3): 185-90, 1996 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-9001586

RESUMEN

The effect of tributyltin chloride (TBTCl) administered during early pregnancy on pregnancy maintenance was evaluated in rats. Inseminated females were orally administered TBTCl at a dose of 0, 8.1, 12.2 or 16.3 mg/kg on day 0 through day 7 of pregnancy. Females were sacrificed on day 20 of pregnancy and pregnancy outcome was determined. Pregnancy failure, which was evidenced by absence of implantation sites, was found in 0 of the 10, in 2 of the 11, in 10 of the 14 and in 10 of the 13 females at 0, 8.1, 12.2 and 16.3 mg/kg, respectively. The rate of pregnancy failure was significantly higher in the 12.2 and 16.3 mg/kg groups than that in the control group. In females with successful pregnancy, the numbers of corpora lutea, implantations and post-implantation loss per litter were comparable across all groups. No increase in the incidence of malformed fetuses was found in any TBTCl-treated groups. Thus it appears that TBTCl causes pregnancy failure after administration during very early pregnancy.


Asunto(s)
Desarrollo Embrionario/efectos de los fármacos , Fertilidad/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Pérdida del Embrión/inducido químicamente , Femenino , Feto/efectos de los fármacos , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Reproducción/efectos de los fármacos , Compuestos de Trialquiltina/administración & dosificación
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