Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
1.
Eur J Med Chem ; 117: 321-34, 2016 Jul 19.
Article in English | MEDLINE | ID: mdl-27161176

ABSTRACT

In this work, we present and discuss a comprehensive set of both newly and previously synthesized compounds belonging to 5 distinct molecular classes of linear aromatic N-polycyclic systems that efficiently inhibits bovine viral diarrhea virus (BVDV) infection. A coupled in silico/in vitro investigation was employed to formulate a molecular rationale explaining the notable affinity of all molecules to BVDV RNA dependent RNA polymerase (RdRp) NS5B. We initially developed a three-dimensional common-feature pharmacophore model according to which two hydrogen bond acceptors and one hydrophobic aromatic feature are shared by all molecular series in binding the viral polymerase. The pharmacophoric information was used to retrieve a putative binding site on the surface of the BVDV RdRp and to guide compound docking within the protein binding site. The affinity of all compounds towards the enzyme was scored via molecular dynamics-based simulations, showing high correlation with in vitro EC50 data. The determination of the interaction spectra of the protein residues involved in inhibitor binding highlighted amino acids R295 and Y674 as the two fundamental H-bond donors, while two hydrophobic cavities HC1 (residues A221, I261, I287, and Y289) and HC2 (residues V216, Y303, V306, K307, P408, and A412) fulfill the third pharmacophoric requirement. Three RdRp (K263, R295 and Y674) residues critical for drug binding were selected and mutagenized, both in silico and in vitro, into alanine, and the affinity of a set of selected compounds towards the mutant RdRp isoforms was determined accordingly. The agreement between predicted and experimental data confirmed the proposed common molecular rationale shared by molecules characterized by different chemical scaffolds in binding to the BVDV RdRp, ultimately yielding compound 6b (EC50 = 0.3 µM; IC50 = 0.48 µM) as a new, potent inhibitor of this Pestivirus.


Subject(s)
Diarrhea Viruses, Bovine Viral/drug effects , Polycyclic Aromatic Hydrocarbons/metabolism , RNA-Dependent RNA Polymerase/metabolism , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Binding Sites/genetics , Bovine Virus Diarrhea-Mucosal Disease/drug therapy , Bovine Virus Diarrhea-Mucosal Disease/prevention & control , Cattle , Diarrhea Viruses, Bovine Viral/enzymology , Hydrogen Bonding , Models, Molecular , Polycyclic Aromatic Hydrocarbons/pharmacology , RNA-Dependent RNA Polymerase/drug effects
5.
Ultrasound Obstet Gynecol ; 28(1): 77-81, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16795127

ABSTRACT

OBJECTIVES: To perform a qualitative assessment of the pulsed Doppler waveform profile at the level of left atrioventricular valve inflow in first-trimester fetuses with increased nuchal translucency thickness (NT), in order to compare those with trisomy 21 and those with normal karyotype. METHODS: This was a review of 285 consecutive fetuses with increased NT. Pulsed Doppler velocity waveforms of left atrioventricular valve inflow were recorded. The E-wave, A-wave and velocity profile in the aorta were displayed. Cases were classified into two patterns: Pattern A included those in which the E-wave velocity crossed the A-wave before the baseline in all waveforms; Pattern B included those in which the lowest E-wave velocity crossed the baseline but not the A-wave in at least one of the profiles. The karyotype was determined and the frequency of occurrence of Patterns A or B in fetuses with normal karyotype and those with trisomy 21 were compared. RESULTS: Of the 285 cases, 230 were assigned to Pattern A and 55 to Pattern B. There were 47 cases of trisomy 21, 22 had other chromosomal abnormalities, and 212 had a normal karyotype; in four cases the karyotype was unknown. Among the 212 karyotypically normal fetuses, five had heart defects, five had other structural defects, three suffered spontaneous intrauterine death and one was terminated. Pattern A was found in 200/212 (94.3%) cases with normal karyotype, in 12/47 (25.5%) cases with trisomy 21, and in 17/22 (77.3%) cases with other chromosomal abnormalities. Pattern B was found in 12/212 (5.7%) cases with normal karyotype, in 35/47 (74.5%) cases with trisomy 21 (chi-square test, P < 0.001), and in 5/22 (22.7%) cases with other chromosomal abnormalities. CONCLUSIONS: Intracardiac Doppler qualitative assessment of left valve inflow in first-trimester fetuses with increased NT shows differences between normal and trisomy 21 fetuses, probably reflecting differences in myocardial function.


Subject(s)
Down Syndrome , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/genetics , Nuchal Translucency Measurement , Adult , Blood Flow Velocity , Chi-Square Distribution , Echocardiography, Doppler, Pulsed , Female , Heart Defects, Congenital/physiopathology , Humans , Karyotyping , Pregnancy , Pregnancy Trimester, First
7.
J Clin Ultrasound ; 29(7): 422-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11579407

ABSTRACT

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.


Subject(s)
Cardiomegaly/diagnostic imaging , Klippel-Trenaunay-Weber Syndrome/diagnostic imaging , Ultrasonography, Prenatal , Abdomen/pathology , Adult , Cardiac Output, High , Female , Humans , Leg/pathology , Pregnancy
8.
Obstet Gynecol ; 97(6): 916-20, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11384696

ABSTRACT

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.


Subject(s)
Chorionic Villi Sampling/methods , Chromosome Aberrations/diagnosis , Maternal Age , Neck/abnormalities , Patient Acceptance of Health Care/statistics & numerical data , Prenatal Diagnosis/statistics & numerical data , Abortion, Therapeutic , Adult , Amniocentesis/methods , Amniocentesis/statistics & numerical data , Chromosome Disorders , Female , Genetic Testing , Humans , Italy , Middle Aged , Neck/diagnostic imaging , Neck/embryology , Patient Compliance , Pregnancy , Pregnancy Trimester, First , Prenatal Diagnosis/methods , Retrospective Studies , Risk Assessment , Risk Factors , Sensitivity and Specificity , Ultrasonography
9.
Ultrasound Obstet Gynecol ; 18(6): 649-51, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11844208

ABSTRACT

OBJECTIVE: To examine the distribution of fetal nuchal translucency thickness in normal and chromosomally abnormal fetuses in Sardinia and to determine the effectiveness of screening by a combination of fetal nuchal translucency and maternal age. METHODS: Fetal nuchal translucency thickness and crown-rump length were measured at 10-14 weeks of gestation in 12 495 pregnancies. A reference range of fetal nuchal translucency thickness for crown-rump length was determined from the 10 001 singleton pregnancies with known normal pregnancy outcome. The median nuchal translucency thickness for crown-rump length was determined by regression analysis of the calculated median values of nuchal translucency thickness for each 0.1 mm interval in crown-rump length. The proportions of unaffected fetuses and those with trisomy 21 or other chromosomal defects with nuchal translucency thickness > 1.5 and 2.0 multiples of the regressed normal median for crown-rump length were calculated. The distribution of estimated risks based on maternal age and fetal nuchal translucency thickness according to The Fetal Medicine Foundation software were also determined and the sensitivity and false-positive rates were calculated. RESULTS: In the 10 001 normal pregnancies, the median fetal nuchal translucency thickness increased with crown-rump length (median nuchal translucency thickness = 0.3496 + 0.018 x crown-rump length) (r2 = 0.4411). In the singleton pregnancies, there were 64 fetuses with trisomy 21 and 46 with other chromosomal defects. The fetal nuchal translucency thickness was > 1.5 multiples of the median in 510 (5%) of the normal fetuses, in 52 (81%) of the trisomy 21 fetuses and in 33 (72%) of those with other chromosomal defects. The respective values for nuchal translucency thickness > 2.0 multiples of the median were 195 (2%), 41 (64%) and 32 (70%). In 184 multiple pregnancies, there were four fetuses with chromosomal abnormalities and in three of these the nuchal translucency thickness was > 1.5 multiples of the median. Screening by a combination of maternal age and fetal nuchal translucency thickness with a risk cut-off of 1 in 300 identified 90% of trisomy 21 pregnancies and 85% of all other chromosomal defects for a false-positive rate of 9%. CONCLUSION: Screening for chromosomal defects by measurement of nuchal translucency thickness identifies 80% of fetuses with trisomy 21 for a false-positive rate of 5%. In our population with a median maternal age of 33 years, screening by a combination of maternal age and fetal nuchal translucency thickness with a risk cut-off of 1 in 300 identified 90% of trisomy 21 pregnancies for a false-positive rate of 9%.


Subject(s)
Down Syndrome/diagnostic imaging , Neck/embryology , Ultrasonography, Prenatal , Crown-Rump Length , Down Syndrome/epidemiology , Female , Humans , Italy/epidemiology , Mass Screening , Maternal Age , Pregnancy , Risk Factors
10.
Ultrasound Obstet Gynecol ; 16(2): 159-62, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11117087

ABSTRACT

OBJECTIVES: To evaluate the sonographic appearances and prenatal natural history of congenital cystic adenomatoid malformation of the lung. METHODS: In each case a detailed examination of the thoracic lesion and a complete fetal survey was performed. The pregnancies that elected to continue were followed to term. RESULTS: A total of 26 cases were identified. The pregnancy was electively terminated in nine cases (35%). All the remaining 17 pregnancies ended in liveborn infants (100%). The lesion disappeared completely in three fetuses (18%). Of the 14 infants in whom the lesion was confirmed at birth nine required surgery in the neonatal or post-natal period. Five children did not undergo surgery. CONCLUSIONS: Conservative management appears to be an adequate medical practice in cases of isolated congenital unilateral cystic adenomatoid malformation of the lung, in the absence of hydrops and/or acute polyhydramnios.


Subject(s)
Cystic Adenomatoid Malformation of Lung, Congenital/diagnostic imaging , Pregnancy Outcome , Ultrasonography, Prenatal/methods , Adult , Cystic Adenomatoid Malformation of Lung, Congenital/mortality , Cystic Adenomatoid Malformation of Lung, Congenital/surgery , Female , Follow-Up Studies , Humans , Pregnancy , Sensitivity and Specificity , Survival Analysis , Treatment Outcome , Ultrasonography, Doppler, Color/methods
11.
Ultrasound Obstet Gynecol ; 16(2): 197-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11117093

ABSTRACT

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.


Subject(s)
Echocardiography, Doppler/methods , Fetal Diseases/diagnostic imaging , Pericarditis/diagnostic imaging , Pericardium/abnormalities , Pericardium/diagnostic imaging , Ultrasonography, Prenatal/methods , Adult , Female , Follow-Up Studies , Gestational Age , Humans , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, Second , Remission, Spontaneous
13.
Prenat Diagn ; 20(9): 701-4, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11015696

ABSTRACT

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.


Subject(s)
Chromosome Aberrations , Chromosome Disorders , Neck/blood supply , Pulsatile Flow , Ultrasonography, Prenatal , Umbilical Arteries/physiopathology , Adult , Blood Flow Velocity , Female , Fetal Blood , Humans , Neck/diagnostic imaging , Pregnancy , Pregnancy Trimester, First , Prospective Studies , Umbilical Arteries/diagnostic imaging
14.
Croat Med J ; 41(3): 266-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10962045

ABSTRACT

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.


Subject(s)
Congenital Abnormalities/diagnostic imaging , Neck/diagnostic imaging , Pregnancy, Multiple , Ultrasonography, Prenatal , Adult , Chromosome Aberrations/diagnostic imaging , Chromosome Disorders , Female , Humans , Pregnancy , Pregnancy Outcome
15.
Fetal Diagn Ther ; 15(3): 170-3, 2000.
Article in English | MEDLINE | ID: mdl-10782003

ABSTRACT

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.


Subject(s)
Chromosome Aberrations , Gestational Age , Maternal Age , Neck/diagnostic imaging , Adult , Chromosomes, Human, Pair 18 , Down Syndrome/diagnosis , Female , Humans , Karyotyping , Klinefelter Syndrome/diagnosis , Pregnancy , Risk Factors , Trisomy , Turner Syndrome/diagnosis , Ultrasonography
17.
Prenat Diagn ; 19(8): 758-60, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10451523

ABSTRACT

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.


Subject(s)
Fetal Diseases/diagnostic imaging , Ultrasonography, Prenatal , beta-Thalassemia/diagnostic imaging , Adult , Chromosome Aberrations/diagnostic imaging , Chromosome Aberrations/embryology , Chromosome Disorders , Female , Fetal Diseases/embryology , Humans , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, First , beta-Thalassemia/embryology
19.
Ultrasound Obstet Gynecol ; 12(1): 19-22, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9697279

ABSTRACT

OBJECTIVE: The aim of this study was to assess the application of iliac bone length measurement in screening for Down's syndrome. DESIGN: Measurement of fetal iliac bone length was prospectively carried out in 609 pregnant women at the time of amniocentesis, and correlated with the results of karyotype analysis. SUBJECTS: Following exclusion of cases with chromosomal abnormalities other than trisomy 21, cases with intrauterine growth impairment or structural abnormalities and cases with incomplete follow-up, 466 karyotypically normal fetuses and 14 fetuses with trisomy 21 were included in the analysis. METHODS: Centiles, standard deviations, expected values by means of linear regression analysis of the iliac bone, in relation to the biparietal diameter, were calculated in the normal fetuses. In order to identify pregnancies at risk for trisomy 21, where a 'longer' than normal iliac bone was expected, three cut-offs previously proposed by other authors and three new criteria were employed. Sensitivity, false-positive rate and likelihood ratio were calculated to assay the different cut-off criteria. RESULTS: Eleven of the 14 (79%) fetuses affected by trisomy 21 had an iliac bone length greater than the 50th centile of normal values. The most useful threshold was an iliac bone length > or = 2 SD of the normal (29% sensitivity and 2% false-positive rate). CONCLUSIONS: This study confirms that fetuses with Down's syndrome tend to have a longer iliac bone length measurement than those with normal karyotype. However, due to the different methods used in different centers, the application of this measurement does not offer sufficiently convincing results for it to be used when screening for Down's syndrome.


Subject(s)
Down Syndrome/diagnostic imaging , Ilium/diagnostic imaging , Mass Screening , Ultrasonography, Prenatal , Adult , Anthropometry , Down Syndrome/genetics , Female , Humans , Infant, Newborn , Karyotyping , Observer Variation , Pregnancy , Prospective Studies , Reference Values , Sensitivity and Specificity
20.
Croat Med J ; 39(2): 220-3, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9575281

ABSTRACT

AIM: To investigate feasibility, safety, and efficacy of in utero transplantation of hemopoietic stem cells. METHODS: A 10-week fetus was found to have b-thalassemia major after prenatal diagnosis by chorionic villus sampling and DNA analysis. The couple asked for prenatal treatment and, after extensive genetic counseling and local Ethical Committee approval, CD34+ hematopoietic progenitor cells purified from paternal bone marrow were injected to the fetus intraperitoneally, under ultrasound guidance. RESULTS: A healthy 3.5 kg fetus was spontaneously delivered with no clinical or laboratory signs of graft-versus-host-disease. Analysis of the cord blood by high-pressure liquid chromatography revealed the absence of adult HbA, typical of b-thalassemic patients. Analysis of the Hb chain synthesis showed no clear signs of b-chain presence. CONCLUSIONS: In utero transplantation of hematopoietic progenitor cells was not successful for b-thalassemia. Caution should be taken when considering other applications than immunodeficiency diseases.


Subject(s)
Fetal Diseases/therapy , Hematopoietic Stem Cell Transplantation , beta-Thalassemia/therapy , Adult , Feasibility Studies , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Pregnancy
SELECTION OF CITATIONS
SEARCH DETAIL
...