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1.
Prenat Diagn ; 32(3): 252-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22430723

ABSTRACT

OBJECTIVES: Human tissues are usually studied using a series of two-dimensional visualizations of in vivo or cutout specimens. However, there is no precise anatomical description of some of the processes of human fetal development. The purpose of our study is to develop a quantitative description of the normal axial skeleton by means of high-resolution three-dimensional magnetic resonance (MR) images, collected from six normal 20-week-old human fetuses fixed in formaldehyde. METHODS: Fetuses were collected after spontaneous abortion and subsequently fixed with formalin. They were imaged using a 1.5 T MR scanner with an isotropic spatial resolution of 200 µm. The correct tissue discrimination between ossified and cartilaginous bones was confirmed by comparing the images achieved by MR scans and computerized axial tomographies. The vertebral column was segmented out from each image using a specially developed semi-automatic algorithm. RESULTS: Vertebral body dimensions and inter-vertebral distances were larger in the lumbar region, in agreement with the beginning of the ossification process from the thoracolumbar region toward the sacral and cephalic ends. CONCLUSION: In this article, we demonstrate the feasibility of using MR images to study the ossification process in formalin-fixed fetal tissues. A quantitative description of the ossification centers of vertebral bodies and arches is presented.


Subject(s)
Aborted Fetus/diagnostic imaging , Bone and Bones/diagnostic imaging , Bone and Bones/embryology , Magnetic Resonance Imaging , Osteogenesis/physiology , Pregnancy Trimester, Second , Aborted Fetus/anatomy & histology , Aborted Fetus/drug effects , Aborted Fetus/embryology , Abortion, Spontaneous/diagnostic imaging , Body Patterning/physiology , Bone Density/physiology , Bone and Bones/anatomy & histology , Bone and Bones/physiology , Female , Femur/anatomy & histology , Femur/diagnostic imaging , Formaldehyde/pharmacology , Gestational Age , Humans , Magnetic Resonance Imaging/methods , Male , Organ Size , Pregnancy , Radiography
2.
Contraception ; 81(4): 328-30, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20227550

ABSTRACT

BACKGROUND: Induced fetal demise by intraamniotic injection of digoxin is an alternative to methods using intracardiac or umbilical vein injection. This study was designed to evaluate the effectiveness of intraamniotic injection and the timing of fetal demise after injection. STUDY DESIGN: Twenty-two women had ultrasonic fetal cardiac assessments 1, 2, 4 and 20 to 24 h after intraamniotic injection of 1.5 mg digoxin. RESULTS: Fetal cardiac activity was absent in 21/21 women assessed at least 20 h after injection. One woman had agonal (40 bpm) fetal cardiac activity at 14 h. Most women had fetal cardiac activity 4 h after injection. Signs of toxicity were not seen. CONCLUSION: Intraamniotic injection of digoxin 1.5 mg is effective at causing fetal demise by 20 to 24 h. However, for most women, fetal demise is not obtained within 4 h.


Subject(s)
Aborted Fetus/drug effects , Abortifacient Agents, Nonsteroidal/administration & dosage , Abortion, Induced/methods , Digoxin/administration & dosage , Abortifacient Agents, Nonsteroidal/adverse effects , Amniotic Fluid , Digoxin/adverse effects , Female , Heart Rate, Fetal/drug effects , Humans , Injections , Pregnancy
3.
Placenta ; 30(6): 491-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19395083

ABSTRACT

Infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolytic-Uremic Syndrome (HUS) have become relevant in public health since STEC is considered as one of the most important emergent pathogens. STEC infection may either be asymptomatic or begin with watery diarrhea associated with hemorrhagic colitis and HUS. The major virulence factor of STEC is Shiga toxin type 1 or 2 (Stx1, Stx2) although strains that express only Stx2 are highly prevalent. Up to now, it has not been established whether STEC infection affect pregnant women. In this study, we evaluated the effect of Stx2 on maternal lethality, fetal status and delivery time by injecting Stx2 in rats in the late stage of pregnancy. Stx2 induced fetal resorption, placental abruption, intrauterine hemorrhage and fetal death at 1-2 days post-injection in a dose-dependent manner. With 2ng Stx2/g body weight, placentas and fetuses presented extensive necrotic areas, while uteri and kidneys showed normal histology. Immunolocalization of Stx2 was observed in placentas and fetuses. With 4 and 6ng Stx2/g body weight maternal death was also observed. Those rats that survived after Stx2-treatment were able to become pregnant and deliver normal pups at term. Our results show, for the first time, that the preterm labor with fetal death observed in treated rats may be a consequence of the action of Stx2 on the feto-maternal unit. Although there are no reports of Stx2 effects in human pregnancy, we speculate that STEC infections could be one of the causes not yet determined of fetal morbimortality.


Subject(s)
Fetal Death/chemically induced , Premature Birth/chemically induced , Shiga Toxin 2/pharmacology , Aborted Fetus/drug effects , Animals , Female , Gestational Age , Injections, Intraperitoneal , Male , Pregnancy , Premature Birth/mortality , Rats , Rats, Sprague-Dawley , Shiga Toxin 2/administration & dosage , Shiga Toxin 2/metabolism , Survival Analysis , Uterus/metabolism , Uterus/pathology
4.
Drug Chem Toxicol ; 26(3): 147-68, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12953656

ABSTRACT

The developmental toxicity of methyl ethyl ketoxime (MEKO), an industrial antioxidant used primarily as an antiskinning agent in alkyd paint, was investigated in rats and rabbits. Following preliminary dose range finding studies, groups of 25 pregnant rats or 18 pregnant rabbits were dosed by gavage with aqueous solutions of MEKO at 0, 60, 200, or 600 mg/kg (rats) or 0, 8, 14, 24, or 40 mg/kg (rabbits) on gestation days 6-15 or 6-18, respectively. In rats, dose-dependent clinical signs of maternal toxicity including reduced body weight gains were noted at 200 and 600 mg/kg. At 60 mg/kg and above enlarged spleens were observed at necropsy. The preliminary study found methemoglobin formation and reticulocytosis indicative of anemia at these dose levels. No treatment-related gestational effects, malformations or developmental variations were observed in the rats. In rabbits, 3 females aborted and 8 females were found dead at 40 mg/kg between gestation days 11 and 24. Clinical signs of maternal toxicity were present in surviving doses at this dose level. Body weight gains were reduced at 24 and 40 mg/kg. The preliminary study indicated maternal hematological effects in the rabbits similar to the rats at dose levels as low as 10 mg/kg. MEKO was not considered to have produced any treatment-related gestational effects, malformations or developmental variations in the rabbit at dose levels at or below 24 mg/kg. Because of excessive maternal mortality and abortions at the 40 mg/kg dose level, only 6 rabbits produced litters. The severe maternal toxicity and limited number of litters precluded a full assessment of developmental toxicity at 40 mg/kg. Nonetheless, MEKO did not appear to be teratogenic to the rabbit at this dose level.


Subject(s)
Abnormalities, Drug-Induced/etiology , Butanones/toxicity , Environmental Pollutants/toxicity , Oximes/toxicity , Reproduction/drug effects , Abnormalities, Drug-Induced/embryology , Aborted Fetus/abnormalities , Aborted Fetus/drug effects , Anemia/chemically induced , Animals , Behavior, Animal/drug effects , Butanones/administration & dosage , Dose-Response Relationship, Drug , Embryonic and Fetal Development/drug effects , Environmental Pollutants/administration & dosage , Female , Fetal Resorption/chemically induced , Oximes/administration & dosage , Pregnancy , Pregnancy Complications/chemically induced , Rabbits , Rats , Rats, Sprague-Dawley , Reticulocyte Count
5.
Int J Dev Neurosci ; 21(3): 117-24, 2003 May.
Article in English | MEDLINE | ID: mdl-12711349

ABSTRACT

The neuroprotective activity of a novel N-acylprolyl-containing dipeptide analog of the nootropic 2-oxo-1-pyrrolidine acetamide (Piracetam) designated as GVS-111 (DVD-111/Noopept) was tested in two in vitro models of neuronal degeneration mediated by oxidative stress: normal human cortical neurons treated with H(2)O(2), and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H(2)O(2) for 1h resulted in morphological and structural changes consistent with neuronal apoptosis and in the degeneration of more than 60% of the neurons present in the culture. GVS-111 significantly increased neuronal survival after H(2)O(2)-treatment displaying a dose-dependent neuroprotective activity from 10nM to 100 microM, and an IC(50) value of 1.21+/-0.07 microM. GVS-111 inhibited the accumulation of intracellular free radicals and lipid peroxidation damage in neurons treated with H(2)O(2) or FeSO(4), suggesting an antioxidant mechanism of action. GVS-111 exhibited significantly higher neuroprotection compared to the standard cognition enhancer Piracetam, or to the antioxidants Vitamin E, propyl gallate and N-tert-butyl-2-sulpho-phenylnitrone (s-PBN). In DS cortical cultures, chronic treatment with GVS-111 significantly reduced the appearance of degenerative changes and enhanced neuronal survival. The results suggest that the neuroprotective effect of GVS-111 against oxidative damage and its potential nootropic activity may present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders.


Subject(s)
Cerebral Cortex/pathology , Dipeptides/pharmacology , Down Syndrome/pathology , Neurons/drug effects , Neurons/pathology , Aborted Fetus/drug effects , Aborted Fetus/pathology , Aborted Fetus/physiopathology , Antioxidants/pharmacology , Apoptosis/drug effects , Cells, Cultured , Cerebral Cortex/drug effects , Cerebral Cortex/embryology , Cerebral Cortex/physiopathology , Down Syndrome/embryology , Down Syndrome/physiopathology , Female , Ferrous Compounds/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Pregnancy , Reference Values
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