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Biomedical subjects

A Caruso

Publications and source records attributed to A Caruso.

At least 19 recordsLinked to original sources
PubMed2007

Gadolinium periconceptional exposure: pregnancy and neonatal outcome.

BACKGROUND: Gadolinium derivatives are ionic paramagnetic contrast agents used to enhance magnetic resonance images, labeled as a pregnancy category C by the Food and Drug Administration because of a lack of epidemiological studies concerning first-trimester exposure. METHODS: Prospective cohort study to determine whether gadolinium derivatives exposure in periconceptional period is a risk factor for pregnancy or fetal development. RESULTS: We report the outcome of 26 pregnant women exposed to gadolinium derivatives in the first trimester without adverse effect on pregnancy and neonatal outcome. CONCLUSIONS: Currently, this study represents the only prospective investigation of gadolinium derivatives in pregnancy, but more data are necessary to exclude a teratogenic risk.

Abnormalities, Drug-Induced↗
PubMed2006

Pathogenic role of anti-beta2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin.

Most of the clinical manifestations of the antiphospholipid syndrome (APS) can be related to thrombotic events; however, placental thrombosis cannot explain all of the pregnancy complications that occur in women with this syndrome. In this regard, it has been hypothesized that antiphospholipid (aPL) antibodies can directly attack trophoblasts, but it is still unclear what pathogenetic mechanisms play a role and which aPL antibodies subpopulations are involved. Although it has been assumed that aPL antibodies are directed against anionic phospholipids (PLs), current advances in the field suggest that antibodies to PL-binding plasma protein such as beta2-glycoprotein-I (beta2-GPI) are the clinically relevant aPL antibodies. It appears that following the attachment of beta2-GPI to PLs, both molecules undergo conformational changes that result in the exposure of cryptic epitopes within the structure of beta2-GPI allowing the subsequent binding of antibodies. aPL antibodies detected by anti-beta2-GPI assays are associated with fetal loss. However, there is still debate on how the antibodies might induce the obstetrical manifestations. The significantly improved outcome of pregnancies treated with heparin has stimulated interest in the drug's mechanisms of action. Several mechanisms could explain its beneficial effects, because in addition to a direct effect of heparin on the coagulation cascade, it might protect pregnancies by reducing the binding of aPL antibodies, reducing inflammation, facilitating implantation and/or inhibiting complement activation. Further investigations are needed to better understand how aPL antibodies induce obstetric complications and to better clarify the functional role of heparin in the human placenta leading to more successful therapeutic options.

Animals↗
PubMed2006

Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid.

Cultured mouse D3 embryonic stem (ES) cells differentiating into embryoid bodies (EBs) expressed several Wnt isoforms, nearly all isotypes of the Wnt receptor Frizzled and the Wnt/Dickkopf (Dkk) co-receptor low-density lipoprotein receptor-related protein (LRP) type 5. A 4-day treatment with retinoic acid (RA), which promoted neural differentiation of EBs, substantially increased the expression of the Wnt antagonist Dkk-1, and induced the synthesis of the Wnt/Dkk-1 co-receptor LRP6. Recombinant Dkk-1 applied to EBs behaved like RA in inducing the expression of the neural markers nestin and distal-less homeobox gene (Dlx-2). Recombinant Dkk-1 was able to inhibit the Wnt pathway, as shown by a reduction in nuclear beta-catenin levels. Remarkably, the antisense- or small interfering RNA-induced knockdown of Dkk-1 largely reduced the expression of Dlx-2, and the neuronal marker beta-III tubulin in EBs exposed to RA. These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells.

Animals↗
PubMed2006

The first case of mitoxantrone exposure in early pregnancy.

Mitoxantrone is an antineoplastic agent considered a potential human teratogen because of its mechanism of action and is classified by the US Food and Drug Administration in pregnancy category risk D. In the literature there are only four cases of women exposed to the drug in late pregnancy. We report the first case of mitoxantrone therapy in the first trimester and during the pregnancy. A 41-year-old woman affected with multiple sclerosis, conceived during therapy and continued mitoxantrone until 29 weeks and 3 days of her pregnancy. She delivered by cesarean section at 39 weeks a growth restricted female baby weighing 1950g without evidence of congenital malformations.

Adult↗
PubMed2006

Proteoglycan synthesis in bovine articular cartilage explants exposed to different low-frequency low-energy pulsed electromagnetic fields.

OBJECTIVE: To investigate the role of pulsed electromagnetic field (PEMF) exposure parameters (exposure length, magnetic field peak amplitude, pulse frequency) in the regulation of proteoglycan (PG) synthesis of bovine articular cartilage explants. METHODS: Bovine articular cartilage explants were exposed to a PEMF (75 Hz; 2 mT) for different time periods: 1, 4, 9, 24 h. Then, cartilage explants were exposed for 24 h to PEMFs of different magnetic field peak amplitudes (0.5, 1, 1.5, 2 mT) and different frequencies (2, 37, 75, 110 Hz). PG synthesis of control and exposed explants was determined by Na2-35SO4 incorporation. RESULTS: PEMF exposure significantly increased PG synthesis ranging from 12% at 4 h to 17% at 24 h of exposure. At all the magnetic field peak amplitude values, a significant PG synthesis increase was measured in PEMF-exposed explants compared to controls, with maximal effect at 1.5 mT. No effect of pulse frequency was observed on PG synthesis stimulation. CONCLUSIONS: The results of this study show the range of exposure length, PEMF amplitude, pulse frequency which can stimulate cartilage PG synthesis, and suggest optimal exposure parameters which may be useful for cartilage repair in in vivo experiments and clinical application.

Animals↗
PubMed2006

Inherited and acquired thrombophilia: pregnancy outcome and treatment.

Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An extensive literature review highlights the role of inherited and acquired thrombophilic disorders in spontaneous abortion, both early and late, recurrent or isolate, in intrauterine growth retardation, in placenta abruption, in pre-eclampsia and in venous thromboembolism. We have particularly focused attention on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS) deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C resistance. Appropriate treatment can improve pregnancy outcome without teratogenic effects.

Abortion, Spontaneous↗
PubMed2006

Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors.

Heparin is used widely for the prevention of pregnancy loss in pregnant women with thrombophilia. However, it is still unknown if heparin may be able to affect trophoblast functions. Therefore, we investigated the hypothesis that low-molecular weight heparin (LMWH) might regulate in vitro trophoblast invasiveness and placental production of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs). In the first-trimester placental tissue, the MMP-9 expression was observed in both villous and extravillous cytotrophoblast cells, and MMP-2 mainly in villous cytotrophoblast. In human choriocarcinoma cells (JAR), MMP-2 was the dominant form. Heparin significantly enhanced both pro-MMPs and the active forms, and increased Matrigel invasiveness of extravillous trophoblast and choriocarcinoma cells. In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.

Anticoagulants↗
PubMed2006

Rubella infection in pregnancy.

Rubella is the first virus demonstrated as a teratogen. There is a high risk to develop congenital rubella syndrome (CRS) if the infection occurs in the first part of pregnancy, particularly in women without specific immunological protection. Specific therapies to prevent CRS are not available. Many developed countries have specific vaccination programs and maternal rubella is rare. However, in developing countries or where campaigns of rubella surveillance and preconceptional vaccination are inadequate, there are still cases of CRS registered despite primary possibilities of prevention. Maternal infection is not indicative of vertical transmission in 100% of cases, and damage does not necessarily occur in all cases of fetal infection. This is the reason why an adequate prenatal counselling is mandatory, particularly in cases of proven maternal infection. Advanced prenatal diagnostic techniques, invasive or not, should be offered to the women especially in order to distinguish the cases without fetal damage. Prevention of voluntary interruption of pregnancy for the latter or in case of maternal false IgM rubella antibody positivity or IgM "chronic carrier" patients is mandatory. World wide, the aim is to perform an adequate primary prevention through vaccination of childbearing age women without specific immunological protection.

Female↗
PubMed2006

Teratological risk evaluation and prevention of voluntary abortion.

AIM: Many women exposed to completely innocuous agents during pregnancy have a high perception of adverse effects to such an extent that they may interrupt their pregnancy. The objective of our study is to evaluate the importance of the perception of the risk level in making the decision to end the pregnancy and the relevance that a teratology consultation can have in preventing unmotivated terminations of pregnancy METHODS: We carried out a survey on 350 women in Rome who voluntarily interrupted their pregnancy to evaluate the prevalence due to presumed teratogen. Contemporarily we studied the pregnancy outcomes, the clinical, the psychological and the socio-economic factors of 142 women who contacted our Teratology Information Service (TIS) in the 1(st)trimester of pregnancy because suspected of teratogen exposure: 72 decided to terminate their pregnancy, whereas 70 were used as a control group. RESULTS: On 350 women who voluntarily interrupted their pregnancy, 4 cases (1.4%) reported exposure to a suspected teratogen, but our evaluation determined only 1 case. On 72 women decided to terminate their pregnancy and who contacted our TIS, after counselling 73% continued their pregnancy with respect to 97% of the control group. Those women who interrupted their pregnancy did so because of personal reasons independently to or the type of exposure or the risk attributed by us. CONCLUSIONS: From our data it appears that a percentage of voluntary abortions is related to suspected teratogen exposure and that TIS are effective in the prevention of this kind of voluntary abortions caused by groundless fears.

Abnormalities, Drug-Induced↗
PubMed2005

[Postpartum hemorrhage].

Postpartum hemorrhage, frequently due to uterine atony, is an important cause of maternal death and morbidity. The knowledge of causes, of antenatal and intrapartum risk factors and of physiopathological changes in hemodynamics and coagulation during pregnancy are essential for the management of the condition. At the present time, many efforts are made to organize a multidisciplinary approach to this complication of delivery involving clinical and laboratory staffs, since the rapid correction of hypovolemia, the diagnosis and treatment of defective coagulation, the surgical and pharmacological control of bleeding are mandatory. Several medical options have been developed and the surgical management includes traditional and newer conservative procedures with variable success rates. The developments in the treatment of postpartum hemorrhage may reduce hysterectomy that is to be considered the last resort to resolve the hemorrhage in some cases. In the modern management of postpartum hemorrhage protocols and guidelines should be available in every delivery room.

Embolization, Therapeutic↗
PubMed2005

Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues.

Relatively few attempts have been made in the past to isolate and expand lymphatic endothelial cells (LECs). Recently this task has become feasible thanks to the identification of new lymphatic markers such as Podoplanin, Lyve-1, Prox-1 and D2-40. Using a two-step purification method based on the sorting of endothelial cells with Ulex Europaeus Agglutinin 1-coated beads followed by purification with monoclonal antibody D2-40, we were able to purify and in vitro expand human derived LECs from tissues such as lymph node, spleen, thymus, palatine tonsil and iliac lymphatic vessels. The isolated LECs were expanded on collagen type 1 and fibronectin coated flasks for up to 8-10 passages and then analyzed for phenotypic and functional properties. LECs were able to form a capillary like network, when seeded on Cultrex BME, indicating their capability to form lymphatic vessels in vitro. Comparative studies were performed, and we found that specific lymphatic and vascular markers were differentially expressed by LECs prepared from different sources, clearly demonstrating the phenotypic heterogeneity of LECs from different organs and different segments of the lymphatic vasculature. We here propose a new technique to make available ready sources of abundant well-characterized human LECs to examine normal profiles and behavior to compare with abnormal conditions.

Biomarkers↗
PubMed2004

Effect of folic acid on homocysteine-induced trophoblast apoptosis.

In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 micromol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.

Apoptosis↗
PubMed2004

Pathogenic role of anti-beta 2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterisation of beta 2-glycoprotein I binding to trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies in vitro.

BACKGROUND: Antiphospholipid antibodies reacting with beta2-glycoprotein I (beta 2GPI) have been associated with recurrent fetal loss and pregnancy complications. OBJECTIVE: To investigate whether specific mutations in the phospholipid binding site of beta 2GPI might affect its binding to trophoblast and in turn the anti-beta 2GPI antibody induced functional effects. METHODS: beta 2GPI adhesion to trophoblast was evaluated as human monoclonal IgM or polyclonal IgG anti-beta 2GPI antibody binding to trophoblast monolayers cultured (1) in complete medium; (2) in serum-free medium; (3) after serum starvation in the presence of purified human beta 2GPI; or (4) in the presence of beta 2GPI with single or multiple mutations in the amino acid loop Cys(281)-Lys-Asn-Lys-Glu-Lys-Lys-Cys(288). The effect of anti-beta 2GPI binding to trophoblast was evaluated as chorionic gonadotropin (hCG) mRNA expression, and protein release by RT-PCR and radioimmunoassay, respectively. RESULTS: beta 2GPI adhesion to trophoblast and its consequent recognition by the specific antibodies were inversely proportional to the mutation number in the phospholipid binding site. Anti-beta 2GPI antibodies reduced gonadotropin release, hormone dependent hCG mRNA expression, and protein synthesis in the presence of beta 2GPI, while the addition of the mutants or the absence of beta 2GPI had no effect. CONCLUSIONS: beta 2GPI binds to trophoblast in vitro through its fifth domain, as reported for endothelial cells, and can be recognised by anti-beta 2GPI antibodies; the antibody binding downregulates trophoblast hCG synthesis and secretion. Such a mechanism might contribute to defective placentation in women with fetal loss associated with the antiphospholipid syndrome.

Antiphospholipid Syndrome↗
PubMed2004

The mGlu5 metabotropic glutamate receptor is expressed in zones of active neurogenesis of the embryonic and postnatal brain.

Metabotropic glutamate (mGlu) receptors have been implicated in the regulation of developmental plasticity. Here, we examined the expression of mGlu1a-b, -2, -3, -4a-b, and -5a receptor subtypes from embryonic day 12 (E12) to the early and late postnatal life. While all transcripts (with the exception of mGlu4 mRNA) were detected prenatally, only the mGlu5 receptor protein was found in detectable amounts in the embryonic brain. Immunohistochemical analysis showed that the mGlu5 receptor was mainly expressed by cells surrounding the ventricles at E15, whereas it was more diffusely expressed at E18. In the postnatal life, besides its classical expression sites, the mGlu5 receptor was found in zones of active neurogenesis such as the external granular layer (EGL) of the cerebellar cortex and the subventricular zone. In these regions, the presence of actively proliferating progenitor cells was detected by BrdU staining. No other subtype (among those we have examined) was found to be expressed in regions enriched of BrdU(+) cells. These data suggest a role for mGlu5 receptors in the early brain development and in basic cellular processes such as proliferation and/or differentiation.

Animals↗
PubMed2004

Activation of Fas receptor is required for the increased formation of the disialoganglioside GD3 in cultured cerebellar granule cells committed to apoptotic death.

Apoptosis was induced in cultured cerebellar granule cells by lowering extracellular K+ concentrations (usually from 25 to 10 mM). The apoptotic phenotype was preceded by an early and transient increase in the intracellular levels of the disialoganglioside, GD3, which behaves as a putative pro-apoptotic factor. We examined whether activation of Fas receptor mediates the increase in GD3 formation in granule cells committed to die. Degenerating granule cells showed increased expression of both Fas receptor and its ligand (Fas-L), at times that coincided with the increase in GD3 levels and the induction of GD3 synthase mRNA. Addition of neutralizing anti-Fas-L antibodies reduced the extent of 'low-K+'-induced apoptosis and abolished the increase in GD3 levels and GD3 synthase mRNA. Similar reductions were observed in cultures prepared from gld or lpr mice, which harbor loss-of-function mutations of Fas-L and Fas receptor, respectively. In addition, exogenous application of soluble Fas-L further enhanced both the increase in GD3 formation and cell death in cultured granule cells switched from 25 into 10 mM K+. We conclude that activation of Fas receptor is entirely responsible for the increase in GD3 levels and contributes to the development of apoptosis by trophic deprivation in cultured cerebellar granule cells.

Animals↗
PubMed2004

Testosterone amplifies excitotoxic damage of cultured oligodendrocytes.

An overactivation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptors has been implicated in the pathophysiology of oligodendrocyte damage in demyelinating disorders of the CNS. We decided to examine the effect of testosterone on excitotoxic death of oligodendrocytes because a gender difference exists in the incidence and disease course of multiple sclerosis. Short-term pure cultures of oligodendrocytes (4 days in vitro) were exposed to a brief pulse with kainate or AMPA + cyclothiazide for the induction of excitotoxicity. Exposure to testosterone enantate was slightly toxic per se and amplified both AMPA and kainate toxicity. Testosterone treatment induced all gene targets of p53, and amplified the induction of these genes induced by kainate. The effect of testosterone was mediated by the activation of androgen receptors and was resistant to the aromatase inhibitors, dl-aminoglutethimide and 4-hydroxyandrost-4-ene-3,17-dione. Testosterone treatment also potentiated the stimulation of 45Ca2+ influx induced by AMPA + cyclothiazide or kainate without changing the expression of the glutamate receptor (GluR) 1, -2/3, and -4 subunits of AMPA receptors or the GluR6/7 subunits of kainate receptors. We conclude that testosterone amplifies excitotoxic damage of oligodendrocytes acting at an early step of the death cascade triggered by AMPA/kainate receptors.

Animals↗