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1.
J Assist Reprod Genet ; 36(6): 1135-1142, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31077010

RESUMO

PURPOSE: To explore the association between patient-centered communication, patients' satisfaction, and retention in care in assisted reproductive technology (ART) visits. METHODS: ART visits at eight Italian clinics were videotaped and coded using the Roter Interaction Analysis System, which includes a Patient-Centered Index (PCI), a summary "patient-centered communication" ratio. After the visit, patients completed a satisfaction questionnaire (SATQ). After 3 months, patients were asked about their retention in care. Spearman correlations and Mann-Whitney tests were used to test associations between the study variables; the open-ended item of SATQ was analyzed through content analysis. RESULTS: Eighty-five visits were videotaped (involving 28 gynecologists and 160 patients). PCI score (µ = 0.51 ± 0.28) revealed a more disease-oriented communication during the visit. Patients reported high levels of satisfaction with the visit and identified in the information provision or in the doctor's humanity or kindness the main reasons of satisfaction. At the follow-up, the majority of the couples declared to have followed the clinicians' recommendations and to have remained related to the ART center. No associations were found among the study variables, except for a lower male satisfaction among couples who declared to have changed ART clinic. CONCLUSIONS: Contrary to what was expected, the style of physician-patient communication was not found to be associated with patient satisfaction and retention in care. However, patients were highly satisfied and engaged. The actual meaning of a communication that is "patient-centered" in the ART context might be wider, including the couples' need for information, as suggested by qualitative findings.


Assuntos
Satisfação do Paciente , Assistência Centrada no Paciente , Técnicas de Reprodução Assistida/psicologia , Retenção nos Cuidados , Adolescente , Adulto , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Técnicas de Reprodução Assistida/tendências , Inquéritos e Questionários
2.
Ann Ig ; 30(5 Supple 2): 36-44, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30374510

RESUMO

BACKGROUND: Appropriate perioperative antibiotic prophylaxis has been shown to be an effective measure for preventing surgical site infections and to avoid complications including increased antimicrobial resistance. The objective of the present study was to evaluate the appropriateness of perioperative antibiotic prophylaxis in two Italian hospitals. STUDY DESIGN: In 2016 a survey was prospectively carried out at two hospitals (identified as A and B) and all patients who underwent a surgical operation were enrolled. METHODS: For each patient, perioperative antibiotic prophylaxis data were collected and appropriateness of perioperative antibiotic prophylaxis was assessed according to the national guidelines (SNLG-17, 2011). RESULTS: During the study period, 107 and 467 operations were included. Compliance to perioperative antibiotic prophylaxis according to indication was 72.3% (hospital A) and 77.9% (hospital B). Perioperative antibiotic prophylaxis was administered <60 min before the skin incision in 89.1% of surgical procedures in hospital A and in 78.4% in hospital B. In hospital A, the recommended molecule of antibiotic was correctly administered in 87.8% of surgeries (n= 36), while, in hospital B, the antibiotic was correctly administered only in 9.8% of surgeries. Antibiotic prophylaxis was not extended postoperatively or did not exceed 24 hours after the end of the surgery in 99% and 8.9% of the procedures in hospital A and B, respectively. CONCLUSION: Our study found an overall low compliance to perioperative antibiotic prophylaxis mainly regarding antibiotic choice and total duration of prophylaxis. The Italian Study Group of Hospital Hygiene - Italian Society of Hygiene, Preventive Medicine and Public Health, together with the National Association of Hospital Physician, promoted the implementation of the project "Choosing wisely - Hospital Hygiene", and, among the list of the 5 procedures with the highest evidence of inappropriateness, the timing and the duration of administration of perioperative antibiotic prophylaxis have been included and a multicenter study has been launched to evaluate the appropriateness of perioperative antibiotic prophylaxis components in all the participating Italian hospitals.


Assuntos
Antibioticoprofilaxia/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Criança , Esquema de Medicação , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/normas , Hospitais , Humanos , Itália , Masculino , Erros de Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Projetos Piloto , Qualidade da Assistência à Saúde/normas , Qualidade da Assistência à Saúde/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adulto Jovem
3.
Hum Reprod ; 33(5): 877-886, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29635461

RESUMO

STUDY QUESTION: What are the characteristics of doctor-couple communication content during actual ART visits? SUMMARY ANSWER: Physicians were mainly focused on providing biomedical information, while communication content from couples had a 2-fold focus on providing biomedical information and on positive talk. WHAT IS KNOWN ALREADY: Communication aspects in ART seem crucial for clinical decision-making, retention in care and critical conversations with couples due to low treatment success rates. However, no studies have been carried out on the actual interaction between the doctor and the couple in this context. STUDY DESIGN, SIZE, DURATION: This observational study involved 28 clinicians and 160 patients referred to eight Italian ART clinics during a one-year recruitment period. PARTICIPANTS/MATERIALS, SETTING, METHODS: ART visits at eight Italian clinics were videotaped. The visits were coded using the Roter Interaction Analysis System (RIAS), particularly focusing on RIAS composite categories, verbal dominance and patient-centeredness score. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 85 visits were eligible for analysis (62% acceptance rate), involving 28 clinicians and 160 patients (including 75 couples). The average visit duration was 37 ± 17.7 min. The mean verbal dominance was 1.9 ± 0.86 (range: 0.72-5.74). Physicians mainly focused on providing biomedical information. Communication content from couples had a 2-fold focus on providing biomedical information and on positive talk. The mean of patient centeredness index (PCI) was 0.51 (SD = 0.28; range 0.08-1.77); visits in which the doctor was a woman or the treatment indication was for heterologous fertilization showed higher PCI scores. Overall, females accounted for 67% of all patient talk. Taking this imbalance into account as expected frequencies for each composite category, males reported significantly more utterances in almost all of the socioemotional categories. LIMITATIONS, REASONS FOR CAUTION: These results are preliminary and observational and only regard Italy. Communication during visits may have been biased since the professionals who agreed to participate showed an interest in communication issues. Another limitation is a possible Hawthorne effect due to the fact that participants were aware of being videotaped. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that ART physicians mainly adopted an informative model of communication and a more disease-oriented approach. Findings revealed the complexity of communication content during ART consultations, given its triadic characteristic in which the third party is also a patient; clinicians should be aware of this complex aspect and of the specific male and female perspectives to be taken into account. The results could be useful for training ART professionals. STUDY FUNDING/COMPETING INTEREST(S): This study was possible thanks to an unconditional grant from Ferring Spa to the Department of Health Sciences, University of Milan. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Comunicação , Relações Médico-Paciente , Técnicas de Reprodução Assistida , Adulto , Feminino , Humanos , Itália , Masculino , Gravidez , Resultado do Tratamento
4.
Neurosci Lett ; 629: 234-240, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27235580

RESUMO

Alzheimer's disease has become one of the most impacting disorders since world population is rapidly aging. MicroRNA-125b plays a crucial role in many cellular processes and pathologies, but, to date, its role in Alzheimer's disease is controversial. In this study, we demonstrated, for the first time, that the down regulation of miR-125b is a key event for the neurotoxic effect of Aß treatment in cortical neurons. Moreover, we found that 17ß-estradiol treatment protects neurons from the Aß-peptide induced neurotoxicity by increasing miR-125b expression that, in turn, decreased the expression, both at gene and protein levels, of the pro-apoptopic proteins Bak1 and p53. Overall, our data reveal miR-125b as a novel neuro-protector miRNA in Alzheimer's disease.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/toxicidade , Apoptose , Estradiol/administração & dosagem , MicroRNAs/metabolismo , Fragmentos de Peptídeos/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/fisiologia
5.
Oncogene ; 35(36): 4741-51, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-26876201

RESUMO

Deregulated Notch signaling is associated with T-cell Acute Lymphoblastic Leukemia (T-ALL) development and progression. Increasing evidence reveals that Notch pathway has an important role in the invasion ability of tumor cells, including leukemia, although the underlying molecular mechanisms remain mostly unclear. Here, we show that Notch3 is a novel target protein of the prolyl-isomerase Pin1, which is able to regulate Notch3 protein processing and to stabilize the cleaved product, leading to the increased expression of the intracellular domain (N3IC), finally enhancing Notch3-dependent invasiveness properties. We demonstrate that the combined inhibition of Notch3 and Pin1 in the Notch3-overexpressing human leukemic TALL-1 cells reduces their high invasive potential, by decreasing the expression of the matrix metalloprotease MMP9. Consistently, Pin1 depletion in a mouse model of Notch3-induced T-ALL, by reducing N3IC expression and signaling, impairs the expansion/invasiveness of CD4(+)CD8(+) DP cells in peripheral lymphoid and non-lymphoid organs. Notably, in in silico gene expression analysis of human T-ALL samples we observed a significant correlation between Pin1 and Notch3 expression levels, which may further suggest a key role of the newly identified Notch3-Pin1 axis in T-ALL aggressiveness and progression. Thus, combined suppression of Pin1 and Notch3 proteins may be exploited as an additional target therapy for T-ALL.


Assuntos
Progressão da Doença , Peptidilprolil Isomerase de Interação com NIMA/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch3/biossíntese , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Leucêmica da Expressão Gênica , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptor Notch3/genética , Transdução de Sinais/genética
7.
Cell Death Dis ; 5: e1472, 2014 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-25321479

RESUMO

Numb asymmetrically segregates at mitosis to control cell fate choices during development. Numb inheritance specifies progenitor over differentiated cell fates, and, paradoxically, also promotes neuronal differentiation, thus indicating that the role of Numb may change during development. Here we report that Numb nuclear localization is restricted to early thymocyte precursors, whereas timed appearance of pre-T-cell receptor (pre-TCR) and activation of protein kinase Cθ promote phosphorylation-dependent Numb nuclear exclusion. Notably, nuclear localization of Numb in early thymocyte precursors favors p53 nuclear stabilization, whereas pre-TCR-dependent Numb nuclear exclusion promotes the p53 downmodulation essential for further differentiation. Accordingly, the persistence of Numb in the nucleus impairs the differentiation and promotes precursor cell death. This study reveals a novel regulatory mechanism for Numb function based on its nucleus-cytosol shuttling, coupling the different roles of Numb with different stages of T-cell development.


Assuntos
Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células Precursoras de Linfócitos T/citologia , Células Precursoras de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Morte Celular , Diferenciação Celular , Núcleo Celular/metabolismo , Células HEK293 , Humanos , Isoenzimas/metabolismo , Camundongos , Modelos Biológicos , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Quinase C/metabolismo , Proteína Quinase C-theta , Estabilidade Proteica , Proteólise , Transdução de Sinais , Frações Subcelulares/metabolismo
8.
Leukemia ; 28(12): 2324-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24727676

RESUMO

Notch signaling deregulation is linked to the onset of several tumors including T-cell acute lymphoblastic leukemia (T-ALL). Deregulated microRNA (miRNA) expression is also associated with several cancers, including leukemias. However, the transcriptional regulators of miRNAs, as well as the relationships between Notch signaling and miRNA deregulation, are poorly understood. To identify miRNAs regulated by Notch pathway, we performed microarray-based miRNA profiling of several Notch-expressing T-ALL models. Among seven miRNAs, consistently regulated by overexpressing or silencing Notch3, we focused our attention on miR-223, whose putative promoter analysis revealed a conserved RBPjk binding site, which was nested to an NF-kB consensus. Luciferase and chromatin immunoprecipitation assays on the promoter region of miR-223 show that both Notch and NF-kB are novel coregulatory signals of miR-223 expression, being able to activate cooperatively the transcriptional activity of miR-223 promoter. Notably, the Notch-mediated activation of miR-223 represses the tumor suppressor FBXW7 in T-ALL cell lines. Moreover, we observed the inverse correlation of miR-223 and FBXW7 expression in a panel of T-ALL patient-derived xenografts. Finally, we show that miR-223 inhibition prevents T-ALL resistance to γ-secretase inhibitor (GSI) treatment, suggesting that miR-223 could be involved in GSI sensitivity and its inhibition may be exploited in target therapy protocols.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas F-Box/genética , Regulação Leucêmica da Expressão Gênica , MicroRNAs/genética , NF-kappa B/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células , Análise por Conglomerados , Dipeptídeos/farmacologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Proteína 7 com Repetições F-Box-WD , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Camundongos Transgênicos , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos
9.
Curr Mol Med ; 14(1): 34-44, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24236458

RESUMO

The Notch receptors have attracted considerable attention for their ability to control cellular functions that regulate embryo development and tissue homeostasis. Notch receptors act by controlling the expression of a specific set of target genes. If Notch signaling system can be so simple, and yet so complex in its pleiotropic effects, then a sophisticated network of regulatory mechanisms is required to maintain the control over the initiation, activity and termination of this signaling pathway. A multitude of regulatory mechanisms has been discovered that controls the interaction of Notch receptors with their ligands, the assembling of a Notch transcriptional activation complex and the termination of Notch signals. The intracellular and extracellular domains of the Notch receptors are synthesized as single proteins, pairing with each other during their trafficking through the exocytotic route. The mechanisms operating in the phase preceding the generation of the heterodimeric signal-competent Notch receptors can be as elaborate and physiologically important as those operating downstream of Notch receptor activation. These regulatory mechanisms, which are essential to understand the role of Notch signaling in human physiology and pathology are reviewed here.


Assuntos
Receptores Notch/metabolismo , Transdução de Sinais , Acetilação , Animais , Humanos , Ligantes , Fosforilação , Proteólise , Ubiquitinação
10.
Leukemia ; 27(2): 485-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22846929
11.
Oncogene ; 31(33): 3807-17, 2012 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-22120716

RESUMO

Post-translational modifications of Notch3 and their functional role with respect to Notch3 overexpression in T-cell leukemia are still poorly understood. We identify here a specific novel property of Notch3 that is acetylated and deacetylated at lysines 1692 and 1731 by p300 and HDAC1, respectively, a balance impaired by HDAC inhibitors (HDACi) that favor hyperacetylation. By using HDACi and a non-acetylatable Notch3 mutant carrying K/R(1692-1731) mutations in the intracellular domain, we show that Notch3 acetylation primes ubiquitination and proteasomal-mediated degradation of the protein. As a consequence, Notch3 protein expression and its transcriptional activity are decreased both in vitro and in vivo in Notch3 transgenic (tg) mice, thus impairing downstream signaling upon target genes. Consistently, Notch3-induced T-cell proliferation is inhibited by HDACi, whereas it is enhanced by the non-acetylatable Notch3-K/R(1692-1731) mutant. Finally, HDACi-induced Notch3 hyperacetylation prevents in vivo growth of T-cell leukemia/lymphoma in Notch3 tg mice. Together, our findings suggest a novel level of Notch signaling control in which Notch3 acetylation/deacetylation process represents a key regulatory switch, thus representing a suitable druggable target for Notch3-sustained T-cell acute lymphoblastic leukemia therapy.


Assuntos
Leucemia de Células T/etiologia , Receptores Notch/fisiologia , Acetilação , Animais , Células HEK293 , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Leucemia de Células T/tratamento farmacológico , Ativação Linfocitária , Camundongos , Complexo de Endopeptidases do Proteassoma/fisiologia , Receptor Notch3 , Linfócitos T/imunologia , Ubiquitinação
12.
J Intellect Disabil Res ; 54(12): 1104-15, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20977517

RESUMO

BACKGROUND: Previous research suggests that individuals with autism spectrum disorder (ASD) have a reduced preference for viewing social stimuli in the environment and impaired facial identity recognition. METHODS: Here, we directly tested a link between these two phenomena in 13 ASD children and 13 age-matched typically developing (TD) controls. Eye movements were recorded while participants passively viewed visual scenes containing people and objects. Participants also completed independent matching tasks for faces and objects. RESULTS AND CONCLUSIONS: Behavioural data showed that participants with ASD were impaired on both face- and object-matching tasks relative to TD controls. Eye-tracking data revealed that both groups showed a strong bias to orient towards people. TD children spent proportionally more time looking at people than objects; however, there was no difference in viewing times between people and objects in the ASD group. In the ASD group, an individual's preference for looking first at the people in scenes was associated with level of face recognition ability. Further research is required to determine whether a causal relationship exists between these factors.


Assuntos
Síndrome de Asperger/psicologia , Atenção , Transtornos Globais do Desenvolvimento Infantil/psicologia , Discriminação Psicológica , Reconhecimento Psicológico , Percepção Social , Adolescente , Síndrome de Asperger/fisiopatologia , Estudos de Casos e Controles , Criança , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Movimentos Oculares , Face , Feminino , Humanos , Masculino , Reconhecimento Visual de Modelos , Valores de Referência
13.
Oncogene ; 29(10): 1463-74, 2010 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-19966856

RESUMO

Notch3 and pTalpha signaling events are essential for T-cell leukemogenesis and characterize murine and human T-cell acute lymphoblastic leukemia. Genetic ablation of pTalpha expression in Notch3 transgenic mice abrogates tumor development, indicating that pTalpha signaling is crucial to the Notch3-mediated leukemogenesis. Here we report a novel direct interaction between Notch3 and pTalpha. This interaction leads to the recruitment and persistence of the E3 ligase protein c-Cbl to the lipid rafts in Notch3-IC transgenic thymocytes. Conversely, deletion of pTalpha in Notch3 transgenic mice leads to cytoplasmic retention of c-Cbl that targets Notch3 protein to the proteasomal-degradative pathway. It appears that protein kinase C theta (PKCtheta), by regulating tyrosine and serine phosphorylation of Cbl, is able to control its function. We report here that the increased Notch3-IC degradation correlates with higher levels of c-Cbl tyrosine phosphorylation in Notch3-IC/pTalpha(-/-) double-mutant thymocytes, which also display a decreased PKCtheta activity. Our data indicate that pTalpha/pre-T-cell receptor is able to regulate the different subcellular localization of c-Cbl and, by regulating PKCtheta activity, is also able to influence its ubiquitin ligase activity upon Notch3 protein.


Assuntos
Leucemia de Células T/metabolismo , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Western Blotting , Linhagem Celular , Espaço Intracelular/metabolismo , Isoenzimas/metabolismo , Leucemia de Células T/genética , Leucemia de Células T/patologia , Microdomínios da Membrana/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Modelos Biológicos , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Proteína Quinase C/metabolismo , Proteína Quinase C-theta , Proteínas Proto-Oncogênicas c-cbl/genética , Interferência de RNA , Receptor Notch3 , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores Notch/genética , Timo/metabolismo , Timo/patologia , Transfecção , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
14.
J Med Primatol ; 38 Suppl 1: 17-23, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19863674

RESUMO

The National Primate Research Centers (NPRCs) established Working Groups (WGs) for developing resources and mechanisms to facilitate collaborations among non-human primate (NHP) researchers. Here we report the progress of the Genome Banking and the Genetics and Genomics WGs in developing resources to advance the exchange, analysis and comparison of NHP genetic and genomic data across the NPRCs. The Genome Banking WG has established a National NHP DNA bank comprising 1250 DNA samples from unrelated animals and family trios from the 10 NHP species housed within the NPRC system. The Genetics and Genomics WG is developing SNP arrays that will provide a uniform, highly informative, efficient and low-cost method for rhesus and long-tailed macaque genotyping across the eight NPRCs. This WG is also establishing a Biomedical Informatics Research Network-based portal for shared bioinformatics resources including vital statistics, genotype and population data and information on the National NHP DNA bank.


Assuntos
Genômica/organização & administração , Primatas/genética , Animais , National Institutes of Health (U.S.) , Estados Unidos
15.
Hum Reprod ; 20(8): 2224-8, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15817586

RESUMO

BACKGROUND: The new Italian law, passed in 2004, regulating assisted reproduction technology imposes that no more than three oocytes can be fertilized at one time and that all embryos obtained must be transferred simultaneously. Oocyte cryopreservation is allowed while embryo cryostorage is banned. The aim of this study was to evaluate the clinical impact of these limitations. METHODS: Seven Italian infertility centres were invited to collect data on IVF cycles performed over the first 4 months of application of the new legislation. As a control, all centres provided data on cycles performed in the same solar period, 1 year before. RESULTS: Data from 1861 cycles were obtained, 961 in the pre-law period and 900 in the post-law period. Pregnancy rate per oocyte retrieval and rate of multiple pregnancies in the pre- and post-law periods were 27.0 and 24.2% (P=0.18) and 25.8 and 20.9% (P=0.11) respectively. However, the prohibition to freeze embryos does appear to have markedly reduced the cumulative rate of success. CONCLUSIONS: The rate of success of IVF-ICSI cycles using fresh embryos is not significantly influenced by the new legislation while the prohibition to freeze embryos seems to result in a more relevant impact.


Assuntos
Criopreservação , Fertilização in vitro/legislação & jurisprudência , Injeções de Esperma Intracitoplásmicas/legislação & jurisprudência , Adulto , Coleta de Dados , Transferência Embrionária/estatística & dados numéricos , Feminino , Fertilização in vitro/estatística & dados numéricos , Humanos , Incidência , Itália/epidemiologia , Oócitos , Gravidez , Taxa de Gravidez , Gravidez Múltipla/estatística & dados numéricos , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos
16.
Acta Neurol Scand ; 108(5): 323-6, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14616301

RESUMO

OBJECTIVES: Previous papers have mainly demonstrated the presence and the frequency of cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis. The purpose of this study was to investigate subjects with the relapsing-remitting form of the disease and mild clinical disability (EDSS < or = 3.5), so as to quantify this deficit when the illness does not yet interfere with daily living and the ability to work. METHODS: Fifty patients and 50 healthy controls were submitted to a wide neuropsychological battery, including Wechsler Memory Scale I- (WMS), Benton Visual Retention Test D- (BVRT), Raven Coloured Progressive Matrices (RCPM), Kohs' test (KT), Judgement of Lines Orientation H- (JLO), Facial Recognition (FR) and Aachner Aphasie Test (AAT). They also underwent Clinical Depression Scale (CDQ) and State-Trait Anxiety Inventory (STAI). RESULTS: The results show the presence of significant memory impairment on both WMS (P = 0.000) and BVRT (P = 0.000) in patients compared with controls. Patients were also impaired in abstract reasoning and problem-solving deficit (KT P = 0.003; RCPM P = 0.000) and in FR (P = 0.019). Cognitive decline correlated with illness duration (r = 0.761), but was independent of EDSS (r = 0.085). CONCLUSION: Cognitive decline was present even when physical disability was not yet severe, but it was mild and did not limit patients' ability to work. The cognitive impairment outlined was of the subcortical type and correlated with illness duration. This study emphasizes the importance of cognitive examination in clinical practice. It is suggested that a complete neurological examination include tests on memory and abstract reasoning.


Assuntos
Transtornos Cognitivos/diagnóstico , Esclerose Múltipla Recidivante-Remitente/complicações , Adulto , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Índice de Gravidade de Doença , Análise e Desempenho de Tarefas
17.
Bioorg Med Chem Lett ; 11(8): 969-72, 2001 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-11327602

RESUMO

The 5,5-disubstitutedpyrimidine-2,4,6-triones represent a new class of MMP inhibitors showing selectivity for the gelatinases A and B, collagenase-3, and human neutrophil collagenase. The SAR presented here is in good agreement with an X-ray structure of compound 5 bound to the catalytic domain of stromelysin-1. While of the barbiturate structural class, compound 5 did not show any toxic or sedative effects.


Assuntos
Inibidores de Metaloproteinases de Matriz , Pirimidinonas/farmacologia , Animais , Colagenases/metabolismo , Cristalografia por Raios X , Humanos , Concentração Inibidora 50 , Metaloproteinase 13 da Matriz , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Camundongos , Pirimidinonas/síntese química , Relação Estrutura-Atividade
18.
Protein Sci ; 10(5): 923-6, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11316871

RESUMO

A new class of matrix metalloproteinase (MMP) inhibitors has been identified by screening a collection of compounds against stromelysin. The inhibitors, 2,4,6-pyrimidine triones, have proven to be potent inhibitors of gelatinases A and B. An X-ray crystal structure of one representative compound bound to the catalytic domain of stromelysin shows that the compounds bind at the active site and ligand the active-site zinc. The pyrimidine triones mimic substrates in forming hydrogen bonds to key residues in the active site, and provide opportunities for placing appropriately chosen groups into the S1' specificity pocket of MMPS: A number of compounds have been synthesized and assayed against stromelysin, and the variations in potency are explained in terms of the binding mode revealed in the X-ray crystal structure.


Assuntos
Metaloproteinase 3 da Matriz/química , Inibidores de Metaloproteinases de Matriz , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Sítios de Ligação , Cristalografia por Raios X , Ligação de Hidrogênio , Concentração Inibidora 50 , Metaloproteinase 3 da Matriz/metabolismo , Modelos Moleculares , Inibidores de Proteases/síntese química , Inibidores de Proteases/metabolismo , Conformação Proteica , Relação Estrutura-Atividade , Zinco/metabolismo
19.
Dement Geriatr Cogn Disord ; 11(5): 239-44, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10940674

RESUMO

Apolipoprotein E (ApoE) genotypes, presenilin 1 (PS-1) and alpha(1)-antichymotrypsin (ACT) polymorphism and the association of the genotypes were examined in patients with Alzheimer's disease (AD, n = 121) or vascular dementia (VD, n = 68) in comparison with elderly controls (n = 125). The frequency of the ApoE epsilon 4 allele was significantly increased both in late-onset AD (0.35) and in VD (0.17); the frequency of ApoE epsilon 2 was significantly reduced in AD, but it was similar in VD and controls. The presence of the allele 1 of PS-1 intronic polymorphism was not associated with AD or VD and was not influenced by the ApoE genotypes. Also, the frequency of allele A of the intronic polymorphism of ACT was similar in AD, VD and controls and it was not altered by ApoE or PS-1 genotypes. The results confirm the association between ApoE epsilon 4 and AD and indicate an increase in ApoE epsilon 4 in Vd, too. A potential protective role of ApoE epsilon 2 is also suggested for late-onset AD but not for VD. No association was shown between ACT allele A and PS-1 allele 1 in AD or VD.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Demência Vascular/genética , Proteínas de Membrana/genética , Polimorfismo Genético/genética , alfa 1-Antitripsina/genética , Idoso , Alelos , Feminino , Genótipo , Humanos , Masculino , Presenilina-1
20.
J Med Chem ; 43(11): 2135-48, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10841792

RESUMO

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.


Assuntos
Apresentação de Antígeno , Dipeptídeos/farmacologia , Antígenos HLA-DR/química , Mimetismo Molecular , Ligação Competitiva , Carboidratos/química , Catepsina B/metabolismo , Divisão Celular/efeitos dos fármacos , Cristalografia por Raios X , Dipeptídeos/síntese química , Dipeptídeos/química , Humanos , Metilação , Modelos Moleculares , Biossíntese Peptídica , Conformação Proteica , Relação Estrutura-Atividade , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos
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