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1.
Mech Ageing Dev ; 126(6-7): 648-54, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15888318

RESUMO

The effects of ageing on the metabolism of cholesterol were examined in three different organs (liver, aorta and brain) of 6-, 12- and 24-month-old male Sprague-Dawley rats. Ageing was associated with a significant increase in intracellular cholesterol esters in all three organs. Steady state mRNA levels of multidrug resistance protein (MDR) and acylCoA:cholesterol acyl transferase (ACAT), enzymes involved in cholesterol import and esterification, were also increased. By contrast, expression of mRNA for neutral cholesterol ester hydrolase (nCEH) and caveolin-1, proteins involved in cholesterol ester hydrolysis and export, were significantly reduced. Dietary restriction is the only intervention shown to extend lifespan and retard age-related declines in function in mammals. To further explore the possible correlation between changes in cholesterol esterification and ageing, we analysed cholesterol metabolism in liver, aorta, and brain of aged rats exposed to two dietary restriction regimens: intermittent (alternate-day) fasting (IF) and food intake restriction (60% of ad libitum feeding). Both dietary regimens attenuated the age-related changes in cholesterol esters and in the expression of genes involved in cholesterol metabolism. These results provide evidence that distinctive age-associated changes in intracellular cholesterol metabolism occur in rats. Furthermore, these modifications can be partially reversed by dietary restriction, a condition known to affect the ageing process. Age-related changes in cholesterol metabolism may play a role in triggering and/or aggravating senescence-related disorders characterized by altered cholesterol homeostasis.


Assuntos
Envelhecimento/metabolismo , Ésteres do Colesterol/metabolismo , Enzimas/biossíntese , Jejum/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Animais , Aorta/metabolismo , Encéfalo/metabolismo , Enzimas/genética , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
2.
Cell Prolif ; 35(3): 143-54, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12027950

RESUMO

Atherosclerosis is an inflammatory-fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth-muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose-monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD-normal (n = 5) and -deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]-thymidine incorporation) cholesterol synthesis and esterification ([14C]-acetate and [14C]-oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT-PCR) all increased following lectin stimulation in both normal and G6PD-deficient cells. However, these parameters were significantly lower in G6PD-deficient cells (P < 0.05). It is of interest that G6PD-deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD-deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.


Assuntos
Colesterol/metabolismo , Deficiência de Glucosefosfato Desidrogenase/enzimologia , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Leucócitos Mononucleares/enzimologia , Leucócitos Mononucleares/metabolismo , Adulto , Arteriosclerose/etiologia , Divisão Celular , Células Cultivadas , DNA/biossíntese , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos , Hidroximetilglutaril-CoA Redutases/biossíntese , Hidroximetilglutaril-CoA Redutases/genética , Cinética , Lipídeos/sangue , Masculino , RNA Mensageiro/biossíntese , Receptores de LDL/biossíntese , Receptores de LDL/genética
3.
Cell Prolif ; 32(1): 49-61, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10371303

RESUMO

A positive correlation between cholesterol esterification and growth rate potential was previously found in our laboratory during the growth of CEM and MOLT4 lymphoblastic cells. In the current study, we investigated whether the rates of cholesterol esters synthesis correlate with changes of acyl-CoAcholesterol acyltransferase (ACAT) mRNA levels and of other genes implied in cholesterol biosynthesis and uptake, such as 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase and low density lipoprotein (LDL) receptor. The results showed that the more rapid growing CEM cells had lower levels of expression of HMGCoA-reductase and LDL receptors compared to MOLT4. By contrast, ACAT mRNA levels were higher in CEM cells, further supporting the concept of a possible involvement of cholesterol esters in the regulation of cell growth and division. In this study, high levels of cholesterol esterification and of expression of ACAT gene were also associated with a markedly increased expression of multidrug resistance (MDR1) gene, suggesting that MDR1 activity might contribute to regulate the rate of cell growth and division by modulating intracellular cholesterol ester levels.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Ésteres do Colesterol/metabolismo , Leucemia de Células T , Animais , Divisão Celular/fisiologia , Colesterol/biossíntese , Primers do DNA , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Camundongos , RNA Mensageiro/análise , Receptores de LDL/genética , Receptores de LDL/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esterol O-Aciltransferase/genética , Esterol O-Aciltransferase/metabolismo , Células Tumorais Cultivadas/química , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/enzimologia
4.
J Med Chem ; 40(10): 1447-54, 1997 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-9154967

RESUMO

Novel compounds related to 2-(cyclohexylthio)-3,4-dihydro-5-methyl-6-(3-methylbenzyl)-4-ox opyrimidine (3c, MC 639) have been synthesized and tested as inhibitors of human immunodeficiency virus type-1 (HIV-1). Reaction of thiourea with ethyl arylmethylacetoacetates furnished 5-alkyl-6-(arylmethyl)-3,4-dihydro-2-mercapto-4-oxopyrimidines which were then alkylated at the sulfur atom to afford the required 2-alkylthio or 2-cycloalkylthio derivatives (S-DABOs). Chemical modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the aim of improving antiretroviral activity. In particular, replacement of the benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs, whereas N-3 alkylation and C=O transformation into C=S at position 4 of the pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower activity was generally observed when 1-naphthylmethyl was replaced by the isomeric 2-naphthylmethyl moiety. The most active compounds showed activity in the low micromolar range with EC50 values comparable to that of nevirapine.


Assuntos
Transcriptase Reversa do HIV/antagonistas & inibidores , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Linhagem Celular , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Pirimidinas/química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
5.
Cancer Lett ; 140(1-2): 53-8, 1999 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10403541

RESUMO

In the present study we examined gene expression and glucose-6-phosphate dehydrogenase (G6PD) activity in leukemic cells isolated from G6PD normal and deficient subjects. The results have shown that G6PD activity strongly increases in G6PD normal leukemic cells as well as in G6PD deficient leukemic cells when compared to peripheral blood mononuclear cells (PBMC). Higher levels of G6PD gene expression were observed in leukemic cells from G6PD deficient patients compared to G6PD normal. A similar pattern of gene expression was also observed for 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. These results support the hypothesis that G6PD deficient cell, in order to sustain their growth, must respond to the low activity of their mutant enzyme with an increase in quantity through an induction of gene expression.


Assuntos
Expressão Gênica , Deficiência de Glucosefosfato Desidrogenase/enzimologia , Glucosefosfato Desidrogenase/metabolismo , Leucemia/enzimologia , Adulto , Células Cultivadas , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Leucemia/metabolismo , Leucócitos Mononucleares/enzimologia , Leucócitos Mononucleares/metabolismo , Masculino , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Receptores de LDL/metabolismo
6.
Biochem Pharmacol ; 56(12): 1583-9, 1998 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9973178

RESUMO

Mutations at amino acid residues 161 (Q161L) and 208 (H208Y) of the reverse transcriptase (RT) have been identified in HIV-1 variants which are resistant to phosphonoformate (PFA). In the present study, we report on the biochemical properties of recombinant RTs (rRTs) carrying either one or both of the above mutations. We also report on their susceptibility to PFA and to nucleoside (NRTI) and non-nucleoside (NNRTI) RT inhibitors. Like the wild-type (wt) enzyme, mutant rRTs H208Y and Q161L/H208Y showed a preference for Mg2+ over Mn2+, whereas the Q161L rRT preferred Mn2+. The three mutant rRTs showed degrees of PFA resistance which differed according to the template-primer used, and steady-state kinetic studies revealed an inverse correlation between their degree of PFA resistance, affinity for deoxynucleoside triphosphates (dNTPs) and catalytic efficiency (kcat/Km ratio). These results indicated that HIV-1 rRTs bearing mutations at codons 161 and/or 208 had altered dNTP binding sites which led to a PFA-resistant phenotype. However, unlike the corresponding mutant viruses, which are hypersensitive to 3'-azido-3'-deoxythymidine (AZT), 11-cyclopropyl-5,-11-dihydro-4-methyl-6H-dipyridol[3,2-b:2',3',-e] diazepin-6-one (Nevirapine) and (+)-(5S)-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)-imidazo[4,5, 1-jk][1,4]benzodiazepin-2(1H)-thione. (TIBO R82150), the mutant RTs Q161L and Q161L/H208Y were resistant to 3'-azido-3'-deoxythymidine triphosphate (AZTTP) and as susceptible as the wt enzyme to Nevirapine and TIBO R82150. Overall, these results suggest that codons 161 and 208 of the HIV-1 RT gene are involved in substrate binding as well as in NRTI recognition, and provide more insights into the mechanism by which HIV-1 becomes resistant to PFA.


Assuntos
Resistência a Medicamentos/genética , Foscarnet/farmacologia , Transcriptase Reversa do HIV/genética , Inibidores da Transcriptase Reversa/farmacologia , Aminoácidos/química , Difosfatos/farmacologia , Relação Dose-Resposta a Droga , Estabilidade Enzimática/efeitos dos fármacos , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/química , Cinética , Mutagênese Sítio-Dirigida , Nevirapina/farmacologia , Proteínas Recombinantes/química , Zidovudina/farmacologia
7.
Obstet Gynecol ; 97(6): 916-20, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11384696

RESUMO

OBJECTIVE: To investigate the effect of nuchal translucency screening on use of prenatal diagnosis for chromosomal abnormalities in women aged 35 and older. METHODS: Two groups of women, referred to our center for prenatal karyotype diagnosis because of maternal age, were compared: one in 1995 and the other in 1999 after the introduction of nuchal translucency measurement. Each woman received nondirective genetic counseling, and for the 1999 group, nuchal translucency results were also discussed. Risks of transabdominal chorionic villi sampling (CVS) and amniocentesis, laboratory techniques, genetic results, and local experiences were discussed. Patient's decision to undergo prenatal diagnosis, acceptance of the nuchal translucency test (in the 1999 group), and the rate of chromosomal abnormalities diagnosed by transabdominal CVS and amniocentesis, were considered. RESULTS: Two hundred twenty-one of 982 (22%) women in the 1995 group and 421 of 1386 (30%) in the 1999 group, after nondirective genetic counseling declined invasive diagnosis (P <.05). In the 1999 cohort, 1088 of 1089 (99.9%) women of appropriate gestational age had nuchal translucency measurement. Among women seen in 1995, 214 opted for transabdominal CVS (31%) and 476 (69%) for amniocentesis. Nineteen abnormal karyotypes were detected, six by transabdominal CVS and 13 (68.5%) by amniocentesis. In 1999, 266 women (29%) opted for transabdominal CVS and 650 (71%) for amniocentesis. Twenty abnormal karyotypes were detected, 13 (65%) by transabdominal CVS and seven (35%) by amniocentesis (P <.05). CONCLUSION: Knowledge of nuchal translucency could lead to a decrease in the demand for invasive diagnosis and to a more frequent diagnosis by first-trimester transabdominal CVS.


Assuntos
Amostra da Vilosidade Coriônica/métodos , Aberrações Cromossômicas/diagnóstico , Idade Materna , Pescoço/anormalidades , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Diagnóstico Pré-Natal/estatística & dados numéricos , Aborto Terapêutico , Adulto , Amniocentese/métodos , Amniocentese/estatística & dados numéricos , Transtornos Cromossômicos , Feminino , Testes Genéticos , Humanos , Itália , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Pescoço/embriologia , Cooperação do Paciente , Gravidez , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Ultrassonografia
8.
Farmaco ; 52(5): 323-9, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9274003

RESUMO

Following the discovery of anti-HIV properties of suramin great efforts were devoted to design novel NNRT agents with the aims to find novel drugs for the clinical therapeutic management of AIDS. Sulfone and sulfonamide derivatives were studied by NCI at Bethesda as potential anti-HIV-1 agents and nitrophenyl phenyl sulfone (NPPS) was selected as lead compound for further investigations. At the same time Merck Laboratories discovered L-737,126, a potent indolyl aryl sulfone with inhibitory activity against reverse transcriptase. These studies stimulated novel search in the sulfone series and both diarylsulfones and cyclic sulfone derivatives were investigated. Our decennial interest in chemotherapeutic agents containing a pyrrole ring pulsed us to synthesize and test as anti-HIV-1 agents a number of pyrryl aryl sulfones (PASs), pyrrolobenzothiadiazepine (PBTDs) and pyrrolobenzothiazepine related sulfones. The new sulfone derivatives inhibit selectively HIV-1 and were inactive against HIV-2. Most of them were as active as, if not more active than, nevirapine.


Assuntos
Fármacos Anti-HIV/síntese química , Sulfonas/síntese química , Fármacos Anti-HIV/farmacologia , Relação Estrutura-Atividade , Sulfonas/farmacologia
9.
Farmaco ; 52(5): 281-2, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9273998

RESUMO

Acyclic glycosidopyrroles of type 3 were synthetized in good overall yields, according to the Scheme. When evaluated for antiviral activity against DNA and RNA viruses, only compound in which R1 = R2 = Ph, R3 = NH2 was found to inhibit the HIV-1 replication at concentrations that were not cytotoxic for MT-4 cells.


Assuntos
Antivirais/síntese química , Ganciclovir/análogos & derivados , Antivirais/farmacologia
11.
Farmaco ; 52(11): 667-72, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9550092

RESUMO

The series of 1-(1,3-dihydroxy-2-propoxy)methylpyrroles 2a-o were prepared in good overall yields according to Scheme I. When evaluated for antiviral activity against HIV-1, only compounds of the triphenyl series (R3 = NH2, N3, Br) were found to inhibit the HIV-1 replication at concentrations that were very not cytotoxic for MT-4 cells, with selectivity index 1.5-9.3. None of these compounds showed antibacterial or antifungal activity.


Assuntos
Fármacos Anti-HIV/farmacologia , Pirróis/farmacologia , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Chlorocebus aethiops , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Pirróis/síntese química , Pirróis/química , Células Vero , Replicação Viral/efeitos dos fármacos
13.
J Endocrinol Invest ; 20(5): 286-8, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9258809

RESUMO

Laron-type dwarfism (LTD) is an autosomal recessive disorder due to mutations in the GH receptor (GHR) gene. We report the case of a Sardinian boy affected by LTD in which we found by direct genomic sequencing a nonsense mutation in the fourth exon of the GHR gene (R43X) that determines a premature termination in the protein translation process. As the result of the absence of the extracellular portion of the GHR this patient had undetectable GH binding protein. This molecular defect is identical to that observed in other patients with LTD of mediterranean origin.


Assuntos
Nanismo/genética , Transtornos do Crescimento/genética , Mutação/genética , Receptores da Somatotropina/genética , Sequência de Bases , DNA/análise , DNA/química , Primers do DNA/química , Homozigoto , Humanos , Itália , Masculino , Reação em Cadeia da Polimerase
14.
Fetal Diagn Ther ; 15(3): 170-3, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10782003

RESUMO

OBJECTIVE: To evaluate the screening of chromosomal abnormalities by nuchal translucency (NT) measurement. METHODS: Assessment of risk for chromosomal abnormalities by NT and maternal age in 5,210 single fetuses with karyotype and outcome already known. RESULTS: Risk was > or =1 in 300 in 640 (12.2%) of all fetuses, in 575 (11.1%) of the normal fetuses, in 38 (80.8%) of the fetuses affected by trisomy 21, and in 65 (89%) of the fetuses affected by chromosomal abnormalities. Risk was > or =1 in 200 in 477 (9.1%) of all fetuses, in 418 (8.1%) of the normal fetuses, in 35 (74.4%) of the fetuses affected by trisomy 21, and in 59 (80.8%) of the fetuses affected by chromosomal abnormalities. Risk was > or =1 in 100 in 270 (5.1%) of all fetuses, in 216 (4.2%) of the normal fetuses, in 33 (70.2%) of the fetuses affected by trisomy 21, and in 54 (73.9%) of the fetuses affected by chromosomal abnormalities. CONCLUSIONS: Risk generated by NT and maternal age is effective in screening for chromosomal abnormalities.


Assuntos
Aberrações Cromossômicas , Idade Gestacional , Idade Materna , Pescoço/diagnóstico por imagem , Adulto , Cromossomos Humanos Par 18 , Síndrome de Down/diagnóstico , Feminino , Humanos , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Gravidez , Fatores de Risco , Trissomia , Síndrome de Turner/diagnóstico , Ultrassonografia
15.
Prenat Diagn ; 19(8): 758-60, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10451523

RESUMO

In Sardinia, fetal karyotyping for couples at risk for beta-thalassaemia is offered only to women >/=35 years and for specific risk of chromosomopathies. This policy is not easily accepted by the couples who incessantly request additional karyotyping. In order to select those at highest risk of chromosomal abnormalities among young women, fetal nuchal translucency (NT) thickness measurement was performed in 510 fetuses to assess the chromosomal risk before chorionic villus sampling. A risk >/=1/100 was judged positive and worthy of additional karyotyping. 126 cases interrupted the pregnancy after a result of homozygous beta-thalassaemia, hence 384 pregnancies were included in the study. 22 (5.7 per cent) fetuses were found NT positive. A total of three chromosomal abnormalities were detected. The NT test was positive in all three cases of chromosomopathies detected (100 per cent) and in 19 of 381 (4.98 per cent) normal karyotype fetuses. No features of major chromosomal abnormalities were reported among the newborns whose NT had resulted normal. These preliminary results have confirmed the efficacy of NT testing to assess the risk of trisomy 21 and other chromosomopathies and enhanced its utility in pregnancies already suited to sampling in the first-trimester for Mendelian disorders.


Assuntos
Doenças Fetais/diagnóstico por imagem , Ultrassonografia Pré-Natal , Talassemia beta/diagnóstico por imagem , Adulto , Aberrações Cromossômicas/diagnóstico por imagem , Aberrações Cromossômicas/embriologia , Transtornos Cromossômicos , Feminino , Doenças Fetais/embriologia , Humanos , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez , Talassemia beta/embriologia
16.
Ultrasound Obstet Gynecol ; 16(2): 197-9, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11117093

RESUMO

An unusually echogenic fetal pericardium was visualized using ultrasound at 21 weeks' gestation. Serial prenatal examinations revealed its progressive, spontaneous resolution. Follow-up examinations of the newborn and infant failed to demonstrate any clinical or echocardiographic abnormality. The occurrence of this unusual pericardial abnormality and its transient nature should be considered during sonographic examination of the fetus.


Assuntos
Ecocardiografia Doppler/métodos , Doenças Fetais/diagnóstico por imagem , Pericardite/diagnóstico por imagem , Pericárdio/anormalidades , Pericárdio/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Seguimentos , Idade Gestacional , Humanos , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Remissão Espontânea
17.
Prenat Diagn ; 20(9): 701-4, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11015696

RESUMO

The aim of this prospective study was to evaluate an umbilical artery pulsatility index (UAPI) in first trimester fetuses who present enlarged nuchal translucency (NT) measurements. UAPI was measured in 121 single fetuses with NT > or =95th centile, from 10+3 to 13+6 weeks (crown-rump length (CRL) > or =38 mm - < or =84 mm). In these fetuses there were 20 trisomy 21, and six other chromosomal abnormalities (three trisomy 18 and three monosomy X). Eighty-nine cases had normal karyotype and delivered a baby without evidence of congenital malformations. Five fetuses with normal karyotype assessed antenatally were excluded from the comparison, because of evidence of congenital malformation. A fetus with normal karyotype that was spontaneously miscarried at 14 weeks' after chorionic villus sampling was also excluded. UAPI of fetuses with enlarged NT was compared with those of 65 singleton fetuses with normal NT and normal karyotype, which were used to establish our terms of reference (5th centile, median and 95th centile). UAPI of 7/20 (35%) Down syndrome and 42/89 (47%) normal karyotype fetuses presenting enlarged NT were above the median, and respectively 2/20 (10%) and 14/89 (15.7%) were above 95th centile of normal NT and normal karyotype fetuses. No significant differences were demonstrated in the UAPI values amongst normal karyotype fetuses with normal NT or normal karyotype fetuses with an enlarged NT or trisomy 21 fetuses with an enlarged NT.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Pescoço/irrigação sanguínea , Fluxo Pulsátil , Ultrassonografia Pré-Natal , Artérias Umbilicais/fisiopatologia , Adulto , Velocidade do Fluxo Sanguíneo , Feminino , Sangue Fetal , Humanos , Pescoço/diagnóstico por imagem , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Artérias Umbilicais/diagnóstico por imagem
18.
Croat Med J ; 41(3): 266-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10962045

RESUMO

AIM: To evaluate the prevalence of increased nuchal translucency (NT) in multiple pregnancies and its relation to fetal karyotype and pregnancy outcome. METHODS: We measured fetal nuchal translucency (NT) in 6,338 women pregnant from 10+3 to 13+6 weeks by ultrasound and evaluated the prevalence of NT=95th centile in 115 multiple pregnancies, including 100 pairs of twins (70 dichorionic and 30 monochorionic placentas), 9 triplets, 5 quadruplets, and one quintuplet. Chorionicity, fetal karyotype, and pregnancy outcome were also evaluated in 400 singleton pregnancies. RESULTS: NT=95th centile in a single fetus was found in 10/70 cases of dichorionic twin pregnancies (14%), in two quadruplets, in 7/30 monochorionic twin pregnancies (23.3%), and in both fetuses in one dichorionic twin pregnancy. In the control group, NT=95th centile was found in 17/400 (4.2%) cases. In multiple pregnancies, two cases of trisomy 21 and one of 47, XXY were found. NT=95th centile was found in 2/2 fetuses with trisomy 21 (one dichorionic twin pregnancy and one tetrachorionic pregnancy), but not in the 47, XXY trisomy (trichorionic triplet pregnancy). A skeletal dysplasia and a Goldenhar syndrome were found among the 10 dichorionic pregnancies with increased NT. Three intrauterine deaths of both fetuses, one congenital heart disease, and a case of twin-to-twin transfusion occurred in 7 monochorionic pregnancies with increased NT. CONCLUSION: Increased NT in multiple pregnancies indicates fetuses at risk of chromosomal abnormalities and fetal malformation, and monochorionic twin pregnancies at higher risk of adverse outcome.


Assuntos
Anormalidades Congênitas/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Gravidez Múltipla , Ultrassonografia Pré-Natal , Adulto , Aberrações Cromossômicas/diagnóstico por imagem , Transtornos Cromossômicos , Feminino , Humanos , Gravidez , Resultado da Gravidez
19.
J Clin Ultrasound ; 29(7): 422-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11579407

RESUMO

This report describes the prenatal sonographic diagnosis of a case of Klippel-Trénaunay-Weber syndrome. The sonographic appearance of this disorder was characterized by the presence of multiple distorted cystic areas involving the right leg and abdomen and cardiomegaly with early fetal heart failure. Despite the prenatal detection of the extensive cutaneous and visceral involvement, the infant died soon after birth of high-output cardiac failure and Kasabach-Merritt syndrome.


Assuntos
Cardiomegalia/diagnóstico por imagem , Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagem , Ultrassonografia Pré-Natal , Abdome/patologia , Adulto , Débito Cardíaco Elevado , Feminino , Humanos , Perna (Membro)/patologia , Gravidez
20.
Biochem J ; 321 ( Pt 3): 603-8, 1997 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-9032443

RESUMO

CEM and MOLT4 are human T-cell lines isolated from patients with acute cell leukaemia. In culture they show important differences in cholesterol metabolism, CEM being less efficient at synthesizing cholesterol and having a lower activity of 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase. To investigate further the relationship between regulation of intracellular cholesterol metabolism at various steps and rate of cell growth, cholesterol synthesis, esterification and efflux were evaluated in CEM and MOLT4 cells at different times during exponential and stationary growth in vitro. It was shown that, although CEM cells have a lower rate of cholesterol synthesis, they grow at a faster rate than MOLT4 cells. However, CEM cells exhibit an increased capacity to esterify cholesterol associated with a decreased efflux of newly synthesized cholesterol into the medium. These results provide evidence for an association between the capability to synthesize and retain cell cholesterol esters and the growth rate potential.


Assuntos
Divisão Celular/fisiologia , Ésteres do Colesterol/metabolismo , Colesterol/metabolismo , Leucemia-Linfoma de Células T do Adulto/metabolismo , Acetatos/metabolismo , Colesterol/biossíntese , DNA/metabolismo , Óxido de Deutério/metabolismo , Formazans/metabolismo , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Sais de Tetrazólio/metabolismo , Células Tumorais Cultivadas
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