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1.
Ultrasound Obstet Gynecol ; 60(5): 632-639, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35638182

RESUMO

OBJECTIVE: To describe the incidence, clinical features and perinatal outcome of late-onset fetal growth restriction (FGR) associated with genetic syndrome or aneuploidy, structural malformation or congenital infection. METHODS: This was a retrospective multicenter cohort study of patients who attended one of four tertiary maternity hospitals in Italy. We included consecutive singleton pregnancies between 32 + 0 and 36 + 6 weeks' gestation with either fetal abdominal circumference (AC) or estimated fetal weight < 10th percentile for gestational age or a reduction in AC of > 50 percentiles from the measurement at an ultrasound scan performed between 18 and 32 weeks. The study group consisted of pregnancies with late-onset FGR and a genetic syndrome or aneuploidy, structural malformation or congenital infection (anomalous late-onset FGR). The presence of congenital anomalies was ascertained postnatally in neonates with abnormal findings on antenatal investigation or detected after birth. The control group consisted of pregnancies with structurally and genetically normal fetuses with late-onset FGR. Composite adverse perinatal outcome was defined as the presence of at least one of stillbirth, 5-min Apgar score < 7, admission to the neonatal intensive care unit (NICU), need for respiratory support at birth, neonatal jaundice and neonatal hypoglycemia. The primary aims of the study were to assess the incidence and clinical features of anomalous late-onset FGR, and to compare the perinatal outcome of such cases with that of fetuses with non-anomalous late-onset FGR. RESULTS: Overall, 1246 pregnancies complicated by late-onset FGR were included in the study, of which 120 (9.6%) were allocated to the anomalous late-onset FGR group. Of these, 11 (9.2%) had a genetic syndrome or aneuploidy, 105 (87.5%) had an isolated structural malformation, and four (3.3%) had a congenital infection. The most frequent structural defects associated with late-onset anomalous FGR were genitourinary malformations (28/105 (26.7%)) and limb malformation (21/105 (20.0%)). Compared with the non-anomalous late-onset FGR group, fetuses with anomalous late-onset FGR had an increased incidence of composite adverse perinatal outcome (35.9% vs 58.3%; P < 0.01). Newborns with anomalous, compared to those with non-anomalous, late-onset FGR showed a higher frequency of need for respiratory support at birth (25.8% vs 9.0%; P < 0.01), intubation (10.0% vs 1.1%; P < 0.01), NICU admission (43.3% vs 22.6%; P < 0.01) and longer hospital stay (median, 24 days (range, 4-250 days) vs 11 days (range, 2-59 days); P < 0.01). CONCLUSIONS: Most pregnancies complicated by anomalous late-onset FGR have structural malformations rather than genetic abnormality or infection. Fetuses with anomalous late-onset FGR have an increased incidence of complications at birth and NICU admission and a longer hospital stay compared with fetuses with isolated late-onset FGR. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Ultrassonografia Pré-Natal , Feminino , Gravidez , Recém-Nascido , Humanos , Lactente , Estudos de Coortes , Incidência , Retardo do Crescimento Fetal , Idade Gestacional , Feto , Aneuploidia
2.
J Biol Regul Homeost Agents ; 33(1 Suppl. 1): 29-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30966730

RESUMO

A new developed collagen matrix CM-10826 (CM) of porcine origin designed to be used as oral soft tissue substitute was investigated before and after implantation by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). In a case series biopsy specimens were harvested from thirteen patients at 10, 20, 30, 43 days after abutment surgery for uncovering dental implants. The in vivo histological evaluations of each patient were performed via micro-coring of newly formed oral mucosa in the area covered by CM (test side) or left uncovered (control). Results showed that CM can be integrated in connective and epithelial tissues within 10 days, can be completely resorbed within 20 days and it is able to reduce inflammatory infiltrates and to stimulate both fibroblast/epithelial cell proliferation and neo-angiogenesis. Generally it seems to be superior in promoting soft tissue healing compared to that induced by secondary intention healing. Furthermore, it is able to act as a scaffold for soft-tissue regeneration, allowing the proliferation of keratinocytes from the wound edges and favoring neovascularization and growth of connective tissue in the mesh of porous layer. It appears that a CM might function in oral surgery as a substitute for autologous grafts and to avoid secondary intention healing in soft tissue defects.


Assuntos
Colágeno , Cicatrização , Animais , Autoenxertos , Tecido Conjuntivo , Gengiva , Humanos , Suínos
3.
J Biol Regul Homeost Agents ; 31(2 Suppl. 2): 91-97, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28702969

RESUMO

Collagen Matrix (CM) 10826 is a nanostructured bi-layered collagen membrane obtained from type I and III porcine collagen, which in vitro has shown to have the potential to be a substitute and/or stimulant for soft oral tissue regeneration. The objective of this study was to evaluate the in vivo potential and safety of this membrane for soft tissue regeneration in the early stage of wound healing. Two soft tissue wounds (test and control) were created on the back skin of 5 rabbits (female New Zealand White Rabbits specific pathogen free). All wounds were protected by a special poly-tetra-fluoro-ethylene (PTFE) healing camera. On each rabbit on the test side CM-10826 was used, while on the control side conventional treatment (an autologous pedicle graft) was performed. The healing process was observed clinically after 2 and 6 days, and Magnetic Resonance Imaging (MRI) was performed after this period. After 7 days, animals were sacrificed and specimens were analyzed with light optic microscopy (LM), Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These in vivo trials on rabbits confirmed that CM-10826 is well tolerated, without signs of histological inflammatory reaction and proved to be able to accelerate the spontaneous repair of the skin defect taken as the control. The light-optic and ultra-microscopy of serial biopsies showed that the new matrix is biocompatible and is able to function as a scaffold inducing soft tissue regeneration. In conclusion this study demonstrates that CM-10826 promote early soft tissue regeneration and suggests it is a potential constituent for human autologous keratinocytes seeded derma bioequivalent. It protects the wound from injuries and bacterial contamination accelerating healing process. As a clinical relevance, we consider that the quality of life of patients will be improved avoiding the use of major autologous grafts, reducing the hospitalization time and morbidity.

4.
AJNR Am J Neuroradiol ; 38(7): 1399-1404, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28495950

RESUMO

BACKGROUND AND PURPOSE: Carotid webs are intraluminal shelf-like filling defects at the carotid bulb with recently recognized implications in patients with recurrent ischemic stroke. We sought to determine whether carotid webs are an under-recognized cause of "cryptogenic" ischemic stroke and to estimate their prevalence in the general population. MATERIALS AND METHODS: A retrospective review of neck CTA studies in young patients with cryptogenic stroke over the past 6 years (n = 33) was performed to determine the prevalence of carotid webs compared with a control group of patients who received neck CTA studies for reasons other than ischemic stroke (n = 63). RESULTS: The prevalence of carotid webs in the cryptogenic stroke population was 21.2% (95% CI, 8.9%-38.9%). Patients with symptomatic carotid webs had a mean age of 38.9 years (range, 30-48 years) and were mostly African American (86%) and women (86%). In contrast, only 1.6% (95% CI, 0%-8.5%) of patients in the control group demonstrated a web. Our findings demonstrate a statistically significant association between carotid webs and ischemic stroke (OR = 16.7; 95% CI, 2.78-320.3; P = .01). CONCLUSIONS: Carotid webs exhibit a strong association with ischemic stroke, and their presence should be suspected in patients lacking other risk factors, particularly African American women.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Artérias Carótidas/anormalidades , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Adolescente , Adulto , Negro ou Afro-Americano , Isquemia Encefálica/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Angiografia Cerebral , Feminino , Lateralidade Funcional , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
5.
G Chir ; 35(9-10): 229-34, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25419589

RESUMO

Cystic adventitial disease (CAD) is a rare vascular disease that causes a localized stenosis or occlusion in absence of alterations of blood vessels in other sites of the body. CAD is predominantly located to the popliteal artery, although cases have been described involving other arteries. Typically it affects young men with minimal cardiovascular risk factors, presenting a short history of progressive claudication. Imaging is based on US, CTA and MRA. Suspected diagnosis is confirmed at the time of the surgery. We report two cases of CAD involving the popliteal artery. In the first case a 59 year-old man was treated by resection of the popliteal artery and a reversed saphenous vein was used to restore circulation. In the second case a 53 year-old man was treated by resection of the popliteal artery and a cryo-preserved arterial graft was used to restore circulation. We also made a review of the literature on this subject.


Assuntos
Arteriopatias Oclusivas , Artéria Poplítea , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
6.
Minerva Stomatol ; 2014 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-24423738

RESUMO

Background: The success of implant therapy depends on the availability of an adequate bone volume in the edentulous site. In the case of posterior bone atrophy, the increase of the alveolar ridge is a prerequisite for the optimal placement of endosseous implants. Purpose: The purpose of this research is to analyze in Literature the success of bone grafts in posterior atrophic edentulous mandible. Materials and methods: The Literature analysis includes only relevant articles specifically on the topic. The following parameters were evaluated: the type of materials used, the average gain expressed in millimeters, the success of the grafts over time and their complications, the outcome of the grafts according of the materials used and the survival rate of endosseous implants over time. Results: Autologous, homologous and heterologous materials were used for the grafts, either separately or in combination. However autologous bone, obtained from the mandible, was preferentially used for grafts in atrophic posterior mandible. Membranes could be also associated to the grafts. The gain in the alveolar ridge was achieved both horizontally and vertically, and usually reflected the surgeon's effort to meet patient's needs. Conclusions: A review of literature reveals that the intraoral autologous bone graft is the most used and allows to achieve the best result in restoring posterior atrophic mandible.

7.
Minerva Stomatol ; 62(8 Suppl 1): 45-53, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23903445

RESUMO

AIM: Ankyloglossia, commonly known as tongue-tie, is a congenital oral anomaly characterized by a short lingual frenulum that may contribute to feeding, speech and mechanical problems. The purpose of this study is to compare the advantages of laser vis-à-vis conventional frenectomy in both intra- and post-surgical phases. METHODS: This study took into consideration two patients, who were respectively 9 and 10-year-old. The first one underwent a common surgical procedure. A Nd:Yap laser device with a micropulsed wavelength of 1340 nm and power of 8 watts was used for the second. The postsurgical discomfort and healing characteristics were evaluated. RESULTS: The results indicated that the Nd:Yap laser has the following advantages when compared to the conventional frenectomy: 1) soft tissue cutting was efficient, with no bleeding, giving a clear operative field; 2) there was no need to use sutures; 3) the surgery was less time-consuming; 4) there was no postsurgical infection and no need for analgesics or antibiotics; 5) wound contraction and scarring were decreased or eliminated; 6) despite the initial slowness of the healing process, the complete and final recovery was faster. CONCLUSIONS: Considering the above elements, it is possible to assert that the laser frenectomy has a series of unquestionable advantages if compared to the conventional surgical technique.

8.
Q J Nucl Med Mol Imaging ; 57(2): 161-70, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23822991

RESUMO

Internal dosimetry was developed as a basis for 131I-mIBG treatment at an early stage and has continued to develop for over the last 20 years. Whole-body dosimetry was introduced to prevent hematological toxicity. It will be the basis for a forthcoming European multicentre trial, in which the activity of a second administration is determined according to the results calculated from the first. Lesion dosimetry has also been performed in a small number of centres. The major goal of dosimetry now is to establish dose-effect correlation studies, which will be the basis for individualized treatment planning. The aim of this paper is to analyse previously published studies and to consider the potential for improvement in order to obtain a stronger predictive power of dosimetry. The intrinsic radiobiological limits of dosimetry are also illustrated. Due to the development and dissemination of methods of internal dosimetry and radiobiology over the last two decades, and to the increasing availability of quantitative 124I PET imaging, dosimetry could provide in the near future a more systematic basis for standardization and individualization of mIBG therapy. This will however require a number of multicentre trials which are performed under good instrumental and scientific methodology.


Assuntos
3-Iodobenzilguanidina/uso terapêutico , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/radioterapia , Paraganglioma/diagnóstico por imagem , Paraganglioma/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Medicina de Precisão , Cintilografia , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/métodos
9.
Free Radic Res ; 47(6-7): 507-10, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23566300

RESUMO

Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with pathological lesions of Alzheimer's disease (AD), suggesting that oxidative stress is a major component in the disease. Here, we examined the HNE-cross-linking modifications by using an antibody specific for a lysine-lysine cross-link. Since in a prior study we noted no immunolabeling of neuritic plaques or neurofibrillary tangles but instead found strong labeling of axons, we focused this study on axons. Axonal labeling was examined in mouse sciatic nerve, and immunoblotting showed the cross-link was restricted to neurofilament heavy and medium subunits, which while altering migration, did not indicate larger NF aggregates, indicative of intermolecular cross-links. Examination of mice at various ages showed the extent of modification remaining relatively constant through the life span. These findings demonstrate lipid-cross-linking peroxidation primarily involves lysine-rich neurofilaments and is restricted to intramolecular cross-links.


Assuntos
Aldeídos/química , Proteínas de Neurofilamentos/química , Proteínas de Neurofilamentos/metabolismo , Nervo Isquiático/metabolismo , Animais , Anticorpos/imunologia , Fluorescência , Lisina/química , Lisina/imunologia , Camundongos , Camundongos Endogâmicos , Nervo Isquiático/química , Nervo Isquiático/citologia
10.
Curr Alzheimer Res ; 8(6): 639-42, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21605042

RESUMO

Mainstream thinking is dominated by the notion that the aggregation of specific proteins within neurons, and their subsequent formation into cytoplasmic and extracellular lesions, directly elicits neuronal dysfunction and death. Current dogma, for example, maintains that phosphorylated tau protein, the major component of neurofibrillary tangles, is a central mediator of disease pathogenesis. In this article, we challenge this classic notion by proposing that tau phosphorylation represents a compensatory response mounted by neurons against oxidative stress that serves a protective function. This concept provides a better understanding of the mechanisms underlying disease pathophysiology and also provides a window for therapeutic intervention.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Emaranhados Neurofibrilares/metabolismo , Estresse Oxidativo/fisiologia , Proteínas tau/metabolismo , Doença de Alzheimer/patologia , Encéfalo/patologia , Humanos , Emaranhados Neurofibrilares/patologia , Neurônios/metabolismo , Neurônios/patologia , Fosforilação
12.
Arthritis Rheum ; 62(5): 1504-12, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20131286

RESUMO

OBJECTIVE: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays a role in blastocyst implantation and is down-regulated in preeclampsia and in hypertensive pregnancy disorders associated with defective extravillous trophoblast invasion. Defective placentation and severe preeclampsia are also features of the antiphospholipid syndrome (APS). The purpose of this study was to investigate whether abnormal HB-EGF expression plays a pathogenic role in antiphospholipid antibody (aPL)-mediated defective placentation. METHODS: HB-EGF expression in placental tissue was evaluated by Western blotting and messenger RNA analysis in normal and APS placentae. Polyclonal IgG fractions or monoclonal beta(2)-glycoprotein I-dependent aPL and their respective controls were investigated for the following 4 features: their binding to human trophoblast monolayers, as determined by cell enzyme-linked immunosorbent assay (ELISA); their effect on HB-EGF expression by Western blotting in trophoblast cell extracts as well as by ELISA as a protein secreted in the culture supernatants; their inhibitory effect on in vitro trophoblast invasiveness, as evaluated by Matrigel assay; and their inhibitory effect on matrix metalloproteinase (MMP) levels, as measured by gelatin zymography. Experiments were also performed in the presence of serial concentrations of heparin or recombinant HB-EGF. RESULTS: Placental APS tissue displayed reduced expression of HB-EGF. Polyclonal and monoclonal aPL bound to trophoblast monolayers and significantly reduced the in vitro synthesis and secretion of HB-EGF. Heparin inhibited aPL binding and restored HB-EGF expression in a dose-dependent manner. Addition of recombinant HB-EGF reduced the in vitro aPL-induced inhibition of Matrigel invasiveness as well as MMP-2 levels. CONCLUSION: These preliminary findings suggest that the reduction of aPL-mediated HB-EGF represents an additional mechanism that is responsible for the defective placentation associated with APS and that heparin protects from aPL-induced damage by inhibiting antibody binding.


Assuntos
Síndrome Antifosfolipídica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Doenças Placentárias , Adulto , Anticorpos Antifosfolipídeos/imunologia , Anticorpos Antifosfolipídeos/farmacologia , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticoagulantes/farmacologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/metabolismo , Síndrome Antifosfolipídica/patologia , Western Blotting , Células Cultivadas , Regulação para Baixo/imunologia , Feminino , Expressão Gênica/imunologia , Heparina de Baixo Peso Molecular/farmacologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Projetos Piloto , Doenças Placentárias/imunologia , Doenças Placentárias/metabolismo , Doenças Placentárias/patologia , Gravidez , RNA Mensageiro/metabolismo , Trofoblastos/citologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/imunologia , beta 2-Glicoproteína I/imunologia
13.
Neuropathol Appl Neurobiol ; 34(4): 457-65, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17995921

RESUMO

AIMS: The literature and teachings instruct that neurones in the adult brain are fully differentiated, quiescent cells that never divide. Somewhat surprisingly, and counter to such dogma, susceptible neurones in Alzheimer disease display an activated cell cycle phenotype. However, whether this leads to a coordinated procession through the cell cycle is unclear, particularly whether neurones enter anaphase and beyond. To begin to address this issue, in this study we sought to determine whether nuclear division occurs in these neurones. METHODS: We examined a series of 101 archived, routinely stained hippocampal sections collected at post mortem for neuropathological evaluation for evidence of neuronal binucleation. RESULTS: We report for the first time, binucleated neurones within the hippocampus in cases of Alzheimer disease but not in control cases (P < 0.05). CONCLUSIONS: While a relatively rare event, occurring once every 20,000 neurones, this morphological evidence that neuronal cells within the cortical regions of the adult human brain in Alzheimer disease contain two nuclei supports the hypothesis that neuronal cells can re-enter into a coordinated cell cycle that culminates in nuclear division.


Assuntos
Doença de Alzheimer/patologia , Hipocampo/patologia , Neurônios/patologia , Neurônios/ultraestrutura , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Masculino
14.
CNS Neurol Disord Drug Targets ; 6(6): 411-23, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18220780

RESUMO

Neuronal death is a common feature in neurodegenerative diseases including Alzheimer disease (AD) and Parkinson disease (PD). This occurs over years, not the minutes of classically defined apoptosis, and neurons show both responses of apoptosis and regeneration, evidenced by accumulated oxidative insult and attempts at cell cycle re-entry. There is recent evidence suggesting that several known gene mutations in causing familial AD (amyloid beta protein precursor, presenilin-1, or presenilin-2 gene) and familial PD (Parkin, PINK-1, or DJ-1 gene) are associated with increased oxidative stress. Also, several known genetic (e.g. Apolipoprotein Eepsilon4 variant) and environmental (e.g. metals or pesticides exposure) risk factors of sporadic AD and/or PD are associated with increased oxidative stress. In concord, patients at the preclinical stages of AD and PD as well as cellular and animal models of the diseases provide consistent evidence that oxidative insult is a significant early event in the pathological cascade of AD and PD. In contrast to the general aspects of the pathological hallmarks, aggregation of the disease-specific proteins such as amyloid-beta, tau, and alpha-synuclein may act as a compensatory (survival) response against the oxidative insult via the mechanism that the disease-specific structures sequester redox-active metals. Expanding knowledge of the molecular mechanisms of organism longevity indicates that pro-longevity gene products such as forkhead transcription factors and sirtuins are involved in the insulin-like signaling pathway and oxidative stress resistance against aging. An enhancement of the pro-longevity signaling (e.g. caloric restriction) may be a promising approach as anti-oxidative strategy against age-associated neurodegenerative diseases.


Assuntos
Doença de Alzheimer/fisiopatologia , Neurônios/fisiologia , Estresse Oxidativo/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Alzheimer/patologia , Animais , Morte Celular/fisiologia , Sobrevivência Celular/fisiologia , Humanos , Doença de Parkinson/patologia
15.
Placenta ; 28(4): 298-304, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16750851

RESUMO

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.


Assuntos
Anticoagulantes/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Trofoblastos/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/enzimologia , Coriocarcinoma/patologia , Relação Dose-Resposta a Droga , Expressão Gênica , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , RNA Mensageiro/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Trofoblastos/citologia , Trofoblastos/enzimologia , Células Tumorais Cultivadas
16.
Br J Cancer ; 92(11): 1984-8, 2005 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-15900298

RESUMO

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988-June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994-1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted.


Assuntos
Neuroblastoma/tratamento farmacológico , Neuroblastoma/radioterapia , Transplante de Células-Tronco , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Neuroblastoma/patologia , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
17.
Ann Rheum Dis ; 64(3): 462-7, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15256379

RESUMO

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.


Assuntos
Síndrome Antifosfolipídica/imunologia , Autoanticorpos/fisiologia , Morte Fetal/imunologia , Glicoproteínas/imunologia , Trofoblastos/metabolismo , Sítios de Ligação/genética , Adesão Celular/imunologia , Células Cultivadas , Gonadotropina Coriônica/biossíntese , Gonadotropina Coriônica/genética , Meios de Cultura , Meios de Cultura Livres de Soro , Feminino , Regulação da Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Mutagênese Sítio-Dirigida , Fosfolipídeos/metabolismo , RNA Mensageiro/genética , beta 2-Glicoproteína I
18.
Neurology ; 63(3): 436-42, 2004 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-15304573

RESUMO

BACKGROUND: The increase of the 14-3-3 protein in CSF is used as a diagnostic test in Creutzfeldt-Jakob disease (CJD), but the sensitivity and specificity of the 14-3-3 test are disputed. One reason for the dispute may be the recently established heterogeneity of sporadic CJD. The relationship between CSF 14-3-3 protein and sporadic CJD subtypes, distinguished by electrophoretic mobility of proteinase K-resistant prion protein (PrP(Sc)) and genotype at codon 129 of the prion protein gene, has not been elucidated. METHODS: The authors examined the 14-3-3 protein test in 90 patients with sporadic CJD. PrP(Sc) type (type 1 or type 2) and the genotype at polymorphic codon 129 were determined in each patient. Mutations were excluded by prion gene sequencing. RESULTS: The authors' findings indicate that the sensitivity of the 14-3-3 test is higher in patients with molecular features of the classic sporadic CJD than in patients with the nonclassic CJD subtypes. The difference appears to be related to the PrP(Sc) type and not to the codon 129 genotype. Disease duration before 14-3-3 testing might also have an influence because it was shorter in classic sporadic CJD. CONCLUSION: The Creutzfeldt-Jakob disease clinical subtype should be considered when interpreting results of the 14-3-3 test.


Assuntos
Proteínas 14-3-3/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Idoso , Amiloide/genética , Biomarcadores , Códon/genética , Síndrome de Creutzfeldt-Jakob/classificação , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/química , Fenótipo , Proteínas PrPSc/genética , Proteínas Priônicas , Príons , Precursores de Proteínas/genética , Sensibilidade e Especificidade
19.
J Submicrosc Cytol Pathol ; 36(3-4): 225-40, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15906597

RESUMO

Many factors play a role in the development of atherosclerotic lesions. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia (FH). FH is a genetic disease characterized by a deficiency, and/or mutation, of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells (EC), a high level of low density lipoprotein in the plasma, and early, spontaneous development of atherosclerosis and skin xanthoma. In this review we describe Watanabe heritable hyperlipidemic (WHHL) rabbits, which represent such an animal model for human FH. This strain of the rabbits is characterized by a genetic deficiency or mutation of functional LDL receptors and develops severe atherosclerosis, which is pathologically similar to familial homozygous hyperlipidemic patients. The most completely characterized animal model is the Watanabe rabbit, a model of homozygous and heterozygous type IIa hypercholesterolemia related to an LDL receptor deficiency. Additional manipulation such as aortic injury in this rabbit model induces the development of atherosclerotic lesions that are structurally similar to those found in humans. Thus, this model of hypercholesterolemia fulfils the above criteria set, i.e. it is able to provide new insights for a better understanding of the pathogenesis of atherosclerosis and for testing new treatment strategies.


Assuntos
Arteriosclerose/patologia , Hiperlipoproteinemia Tipo II/patologia , Receptores de LDL/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Arteriosclerose/genética , Arteriosclerose/metabolismo , Modelos Animais de Doenças , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/metabolismo , Coelhos , Receptores de LDL/deficiência , Receptores de LDL/genética
20.
Prenat Diagn ; 22(1): 42-7, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11810649

RESUMO

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified.


Assuntos
Contratura/complicações , Anormalidades Craniofaciais/complicações , Retardo do Crescimento Fetal/complicações , Deformidades Congênitas dos Membros/complicações , Pulmão/anormalidades , Diagnóstico Pré-Natal , Adulto , Amniocentese , Contratura/diagnóstico , Anormalidades Craniofaciais/diagnóstico , Feminino , Retardo do Crescimento Fetal/diagnóstico , Idade Gestacional , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Masculino , Músculo Esquelético/patologia , Poli-Hidrâmnios , Gravidez , Medula Espinal/patologia , Ultrassonografia Pré-Natal
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