Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
1.
Hum Reprod ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890127

RESUMO

In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients' hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize 'success' and 'failure' in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop 'plan(s) B', to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.

2.
Ecotoxicology ; 30(4): 705-710, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761023

RESUMO

Among the new contaminants relevant for environment, one of the most significant roles is played by pharmaceuticals like antibiotic products for either human or veterinary use. Their presence could cause serious damage to bacteria and microfauna, like nematodes. Within the widely investigated nematodes, very little is known about the interaction between antibiotics and entomopathogenic nematodes (EPN). EPNs have been used for biological control of crops, due to their ability to penetrate arthropod pests and kill their hosts thanks to a complex symbiotic mechanism with specific gram-negative bacteria. Tetracycline is an antibiotic used in human and veterinary medicine, both for therapeutic purposes and for the growth of livestock. Since its action against gram-negative bacteria is documented, we verified in this study the survival, growth and pathogenicity of two species of EPNs, Steinernema vulcanicum and S. feltiae. All tests were performed with tetracycline in 1% ethanol solution and up to 300 mg/L. Apparently, this incubation did not harm the vitality of EPNs. Both S. vulcanicum as S. feltiae recovered their vitality and entomopathogenic ability after 48 h. Moreover, the latter EPN species did not grow nor reproduce in the hemolymph of the Greater Wax Moth, Galleria mellonella, and their endosymbionts did not grow on MacConkey Agar. Our results suggest that the first EPN species has always retained all its abilities and that endosymbionts have acquired resistance to tetracycline, while experiments with the second EPN species provided some contrasting results in time that will require further investigations.


Assuntos
Mariposas , Rabditídios , Animais , Antibacterianos/toxicidade , Bactérias , Humanos , Tetraciclinas
3.
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
4.
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
5.
J Helminthol ; 89(3): 359-66, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24721783

RESUMO

An investigation was carried out on the distribution and biodiversity of steinernematid and heterorhabdtid entomopathogenic nematodes (EPN) in nine regions of Italy in the period 1990-2010. More than 2000 samples were collected from 580 localities and 133 of them yielded EPN specimens. A mapping of EPN distribution in Italy showed 133 indigenous EPN strains belonging to 12 species: 43 isolates of Heterorhabditis bacteriophora, 1 of H. downesi, 1 of H. megidis, 51 of Steinernema feltiae, 12 of S. affine, 4 of S. kraussei, 8 of S. apuliae, 5 of S. ichnusae, 3 of S. carpocapsae, 1 of S. vulcanicum, 3 of Steinernema 'isolate S.sp.MY7' of 'S. intermedium group' and 1 of S. arenarium. Steinernematids are more widespread than heterorhabditids and S. feltiae and H. bacteriophora are the most commonly encountered species. Sampling sites were grouped into 11 habitats: uncultivated land, orchard, field, sea coast, pinewood, broadleaf wood, grasslands, river and lake borders, caves, salt pan and moist zones; the soil texture of each site was defined and the preferences of habitat and soil texture of each species was assessed. Except for the two dominant species, S. feltiae and H. bacteriophora, EPN occurrence tends to be correlated with a specific vegetation habitat. Steinernema kraussei, H. downesi and H. megidis were collected only in Sicily and three of the species recently described - S. apuliae, S. ichnusae and S. vulcanicum - are known only from Italy and seem to be endemic.


Assuntos
Biodiversidade , Nematoides/classificação , Nematoides/isolamento & purificação , Rabditídios/parasitologia , Animais , DNA de Helmintos , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Ecossistema , Itália , Dados de Sequência Molecular , Nematoides/genética , Análise de Sequência de DNA
6.
Eur Rev Med Pharmacol Sci ; 24(17): 9112-9115, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32965001

RESUMO

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. PATIENTS AND METHODS: We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. RESULTS: At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. CONCLUSIONS: Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Valsartana/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Combinação de Medicamentos , Ecocardiografia , Humanos , Dose Máxima Tolerável , Distrofia Muscular de Duchenne/fisiopatologia , Valsartana/administração & dosagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
7.
J Clin Invest ; 93(2): 776-87, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8113411

RESUMO

Eosinophils and T lymphocytes are thought to be involved in allergic airway inflammation. Both cells express the alpha 4 beta 1-integrin, very late antigen-4 (VLA-4, CD49d/CD29); alpha 4-integrins can promote cellular adhesion and activation. Therefore, we examined the in vivo effects of a blocking anti-alpha 4 monoclonal antibody, HP 1/2, on antigen-induced early and late bronchial responses, airway hyperresponsiveness, inflammatory cell influx, and peripheral leukocyte counts in allergic sheep. Sheep blood lymphocytes, monocytes, and eosinophils expressed alpha 4 and bound HP 1/2. In control sheep, Ascaris antigen challenge produced early and late increases in specific lung resistance of 380 +/- 42% and 175 +/- 16% over baseline immediately and 7 h after challenge, respectively, as well as airway hyperresponsiveness continuing for 14 d after antigen challenge. Treatment with HP 1/2 (1 mg/kg, i.v.) 30 min before antigen challenge did not affect the early increase in specific lung resistance but inhibited the late-phase increase at 5-8 h by 75% (P < 0.05) and inhibited the post-antigen-induced airway hyperresponsiveness at 1, 2, 7, and 14 d (P < 0.05, for each time). Intravenous HP 1/2 given 2 h after antigen challenge likewise blocked late-phase airway changes and postchallenge airway hyperresponsiveness. Airway administration of HP 1/2 (16-mg dose) was also effective in blocking these antigen-induced changes. Response to HP 1/2 was specific since an isotypic monoclonal antibody, 1E6, was ineffective by intravenous and aerosol administration. Inhibition of leukocyte recruitment did not totally account for the activity of anti-alpha 4 antibody since HP 1/2 neither diminished the eosinopenia or lymphopenia that followed antigen challenge nor consistently altered the composition of leukocytes recovered by bronchoalveolar lavage. Because airway administration of HP 1/2 was also active, HP 1/2 may have inhibited cell activation. Reduction of platelet-activating factor-induced eosinophil peroxidase release from HP 1/2-treated eosinophils supports such a mechanism. These findings indicate a role for alpha 4-integrins in processes that lead to airway late phase responses and persisting airway hyperresponsiveness after antigen challenge.


Assuntos
Antígenos de Helmintos/imunologia , Brônquios/fisiologia , Integrinas/fisiologia , Leucócitos/fisiologia , Linfócitos/fisiologia , Fenômenos Fisiológicos Respiratórios , Aerossóis , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Antígenos de Helmintos/administração & dosagem , Ascaris/imunologia , Brônquios/imunologia , Eosinófilos/imunologia , Eosinófilos/fisiologia , Citometria de Fluxo , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Injeções Intravenosas , Integrina alfa4 , Integrinas/imunologia , Leucócitos/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/fisiologia , Linfócitos/imunologia , Sistema Respiratório/imunologia , Sistema Respiratório/fisiopatologia , Ovinos , Fatores de Tempo
8.
Clin Ter ; 158(5): 409-19, 2007.
Artigo em Italiano | MEDLINE | ID: mdl-18062347

RESUMO

AIM: The aim of the present study is to obtain comprehensive epidemiological data of the incidence of oral and dental health conditions in an Italian homogeneous population of schoolchildren. MATERIALS AND METHODS: The study has been performed on schoolchildren born, living and attending the primary school in Matera, Basilicata, Southern Italy. Such data have been compared with the alimentary habits of the participants to the study, as well as with the social-economic family situations and with the social-environmental data. RESULTS: The data show a marked difference in the habits of oral hygiene, and in the health status of the oral structures also, based on both the sex and the environment of life. CONCLUSIONS: Such differences in the prevalence of caries among various urban areas and the behavioural habits related to sex and age ratios may be very useful findings for future regional prevention programs.


Assuntos
Cárie Dentária/epidemiologia , Comportamento Alimentar , Higiene Bucal/estatística & dados numéricos , Pobreza , Classe Social , População Urbana/estatística & dados numéricos , Criança , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Higiene Bucal/métodos , Prevalência , Saúde da População Urbana/estatística & dados numéricos
9.
Biomech Model Mechanobiol ; 16(3): 1035-1047, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28070737

RESUMO

Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.


Assuntos
Anti-Hipertensivos/farmacologia , Modelos Cardiovasculares , Consumo de Oxigênio/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Simulação por Computador , Humanos , Hipertensão , Oxigênio/metabolismo
10.
Radiat Prot Dosimetry ; 170(1-4): 446-50, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27103642

RESUMO

Monte Carlo (MC) methods are numerical simulation techniques that can be used to extend the scope of calibrations performed in in vivo monitoring laboratories. These methods allow calibrations to be carried out for a much wider range of body shapes and sizes than would be feasible using physical phantoms. Unfortunately, nowadays, this powerful technique is still used mainly in research institutions only. In 2013, EURADOS and the in vivo monitoring laboratory of Karlsruhe Institute of Technology (KIT) organized a 3-d training course to disseminate knowledge on the application of MC methods for in vivo monitoring. It was intended as a hands-on course centered around an exercise which guided the participants step by step through the calibration process using a simplified version of KIT's equipment. Only introductory lectures on in vivo monitoring and voxel models were given. The course was based on MC codes of the MCNP family, widespread in the community. The strong involvement of the participants and the working atmosphere in the classroom as well as the formal evaluation of the course showed that the approach chosen was appropriate. Participants liked the hands-on approach and the extensive course materials on the exercise.


Assuntos
Monitoramento de Radiação/instrumentação , Monitoramento de Radiação/métodos , Contagem Corporal Total/instrumentação , Calibragem , Radioisótopos de Césio , Simulação por Computador , Alemanha , Humanos , Capacitação em Serviço , Cooperação Internacional , Radioisótopos do Iodo , Pulmão/efeitos da radiação , Método de Monte Carlo , Imagens de Fantasmas , Radioisótopos de Potássio , Monitoramento de Radiação/normas , Contagem Corporal Total/métodos , Contagem Corporal Total/normas
11.
J Clin Oncol ; 20(7): 1918-22, 2002 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11919252

RESUMO

PURPOSE: To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs). MATERIALS AND METHODS: Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period. RESULTS: One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported. CONCLUSION: Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Criopreservação/normas , Fibrinolíticos/economia , Fibrinolíticos/uso terapêutico , Ativador de Plasminogênio Tecidual/economia , Ativador de Plasminogênio Tecidual/uso terapêutico , Trombose Venosa/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Custo-Benefício , Estudos de Viabilidade , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Ativador de Plasminogênio Tecidual/efeitos adversos , Estados Unidos , Trombose Venosa/etiologia
12.
Clin Ter ; 156(5): 227-30, 2005.
Artigo em Italiano | MEDLINE | ID: mdl-16382971

RESUMO

During the last years the importance of the correct nutritional assessment as a part of the therapeutic process of the human pathologies has a greatly increased relevance. Still more in oncology, such relationship among nutritional assessment and good result of the therapeutic treatment have a fundamental importance. Among the neoplastic diseases those of the head and the neck result to be particularly aggressive, both for their nature and for the particular anatomical organization of such body areas, and the affected patients also need a precise evaluation of the nutritional assessment to obtain an optimal therapeutic result. On the basis of such premises and to their own clinical experience, the authors describe the main nutritional problems of the patients with tumours of the head and the neck and the possible therapeutic solutions.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Desnutrição/prevenção & controle , Estado Nutricional , Apoio Nutricional , Nutrição Enteral , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Desnutrição/fisiopatologia , Fenômenos Fisiológicos da Nutrição , Necessidades Nutricionais , Nutrição Parenteral , Fatores de Risco
13.
Endocrinology ; 128(4): 1849-56, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2004604

RESUMO

Rat proenkephalin was overexpressed in Chinese hamster ovary cells using the dihydrofolate reductase-coupled genetic amplification method. About 2 mg purified protein could be obtained from 250 ml conditioned medium; multiple successive harvests could be obtained from the same roller bottle. Degradation of proenkephalin released into the conditioned medium was reduced significantly in the presence of 2% fetal bovine serum. Forty-eight percent of recombinant proenkephalin was glycosylated; glycosylation could be entirely prevented by the addition of tunicamycin. Two-dimensional isoelectric focusing experiments showed that recombinant proenkephalin exhibited considerable charge heterogeneity, with two major unglycosylated isoelectric forms and six or seven glycosylated isoelectric forms. The estimated isoelectric points of the major unglycosylated proenkephalins were 6.0 and 6.1, while glycosylated proenkephalins ranged in pI from 5.7-6.1. Some of this isoelectric heterogeneity is due to phosphorylation; [32P] orthophosphate was readily incorporated into serine residues within newly synthesized proenkephalin.


Assuntos
Encefalinas/metabolismo , Precursores de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Linhagem Celular , Encefalinas/genética , Glicosilação , Focalização Isoelétrica , Ponto Isoelétrico , Peso Molecular , Fosfatos/metabolismo , Fosforilação , Fosfosserina/metabolismo , Precursores de Proteínas/genética , Ratos , Proteínas Recombinantes/metabolismo , Transfecção , Tunicamicina/farmacologia
14.
J Med Chem ; 42(5): 920-34, 1999 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-10072689

RESUMO

Integrin alpha4beta1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of alpha4beta1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide "cap" strategy. One inhibitor, BIO-1211, was approximately 10(6)-fold more potent than the starting peptide and exhibited tight-binding properties (koff = 1.4 x 10(-4) s-1, KD = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of alpha4beta1, and it stimulated expression of ligand-induced epitopes on the integrin beta1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.


Assuntos
Antialérgicos/síntese química , Hiper-Reatividade Brônquica/prevenção & controle , Integrinas/antagonistas & inibidores , Oligopeptídeos/síntese química , Receptores de Retorno de Linfócitos/antagonistas & inibidores , Animais , Antialérgicos/química , Antialérgicos/metabolismo , Antialérgicos/farmacologia , Sítios de Ligação , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/imunologia , Carbacol/toxicidade , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Desenho de Fármacos , Epitopos , Fibronectinas/química , Fibronectinas/fisiologia , Humanos , Integrina alfa4beta1 , Integrinas/metabolismo , Células Jurkat , Cinética , Ligantes , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacologia , Receptores de Retorno de Linfócitos/metabolismo , Ovinos , Relação Estrutura-Atividade , Molécula 1 de Adesão de Célula Vascular/fisiologia
15.
J Neuroendocrinol ; 9(5): 355-61, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9181489

RESUMO

Male and female Long-Evans adult rats were adrenalectomized and sacrificed 6 weeks later to determine whether dentate gyrus damage would differ in females and males. A subset of adrenalectomized rats of both sexes had significantly reduced dentate gyrus volumes compared to the same sex SHAM operated rats. The remainder of the male and female adrenalectomized rats which did not have clear dentate gyrus damage had significantly larger dentate gyrus volumes compared to the same sex SHAM rats. The dentate gyrus volumes of all adrenalectomized rats were significantly correlated with two indices of residual hormonal levels (Na+/K+ ratios and body weight gain 6 weeks after surgery), indicating that endogenous corticosterone levels may be a determining factor in the response of the dentate gyrus to adrenalectomy. These dentate gyrus volumetric changes could not be attributed to tissue shrinkage as there were no changes in CA3 volumes in any of the groups. These results suggest that long-term adrenalectomy can result in either increased or decreased dentate gyrus volumes and that the adrenal steroid levels of each individual adrenalectomized rat may be the factor determining the direction of the dentate gyrus volumetric response.


Assuntos
Glândulas Suprarrenais/fisiologia , Giro Denteado/patologia , Adrenalectomia , Análise de Variância , Animais , Contagem de Células , Feminino , Masculino , Ratos , Fatores de Tempo
16.
Ann N Y Acad Sci ; 796: 113-23, 1996 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-8906218

RESUMO

Evidence for a central role for the integrins alpha 4 beta 1 and alpha 4 beta 7 in leukocyte pathophysiology is rapidly accumulating. Five distinct alpha 4 mAbs, each able to block alpha 4-dependent adhesion in vitro, show beneficial effects in vivo in six different species, and in a wide variety of organ systems, including colon, lung, skin, neural tissue, pancreas, peritoneum, and the vessel wall. In particular, a clear role for these integrins in lung pathophysiology is implied on the basis of in vivo studies in four different species. Although several issues remain to be resolved, including the relative importance of alpha 4 beta 1 and alpha 4 beta 7, and the relative roles of their counterligands, VCAM1, fibronectin, and MAdCAM, the data argue that alpha 4 integrins will likely be critical to both the normal physiology and pathology of the lung in man. To this end, we (Adams, Lin, Lobb, and Gill, unpublished data) and others have generated peptidomimetic small molecule antagonists of VLA4 based on the connecting segment 1 (CS1) peptide sequence of fibronectin that are potent blockers of integrin adhesive function in vitro and show efficacy in vivo. We have found that our inhibitors are excellent blockers of both murine contact hypersensitivity, and of the LPR and AHR in the sheep allergic airways model (Abraham, Lobb, Adams, and Gill, unpublished data), and are therefore possible candidates for clinical intervention in human asthma. The use of the VCAM-Ig fusion protein as a probe for high-affinity alpha 4 integrins has further enhanced our understanding of alpha 4 integrin function in the lung. While integrin upregulation in vitro has been observed many times, and high affinity (as opposed to avidity) of integrins seen in vitro in several systems, in vivo proof of integrin upregulation to a high-affinity state has been difficult to obtain in the absence of selective probes. Our data provide key information in this regard and strongly argue not only that integrin upregulation does indeed occur in vivo, but also that it is in fact obligatory for the leukocyte pathologies we have examined to date. Further studies are clearly warranted to further examine mechanisms of action, and to confirm and extend these studies, both with the alpha 4 integrins and with other integrin families. In summary, our studies of alpha 4 integrins continue to provide novel insights into the pathophysiology of integrin function and into future directions for drug discovery.


Assuntos
Integrinas/fisiologia , Pulmão/fisiopatologia , Receptores de Retorno de Linfócitos/fisiologia , Animais , Asma/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Modelos Animais de Doenças , Cobaias , Humanos , Integrina alfa4beta1 , Masculino , Camundongos , Proteínas Recombinantes de Fusão/farmacologia , Ovinos , Molécula 1 de Adesão de Célula Vascular/farmacologia
17.
Ann N Y Acad Sci ; 612: 90-7, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2291578

RESUMO

This paper reviews the molecular pathology of a heterogeneous group of beta-thalassemia heterozygotes which may be referred to as atypical beta-thalassemia. This group includes four different categories of heterozygous beta-thalassemia, which are characterized, respectively, by (1) normal MCV and MCH; (2) normal Hb A2; (3) normal MCV, MCH, and Hb A2 and imbalanced globin chain synthesis only or, (4) the presence of clinical manifestations. The first group is represented by a limited proportion of double heterozygotes for alpha- and beta-thalassemia. The second group includes two categories. One category is double heterozygotes for delta- and beta-thalassemia with the delta-thalassemia mutation in cis or in trans to beta-thalassemia. A number of delta-thalassemia mutations which produce this phenotype by interacting with beta-thalassemia have been described. The other category within the second group is heterozygotes for some mild beta(+)-thalassemia mutations. Within the third group, conclusive evidence for a mutation within the beta-globin gene cluster producing the silent beta-thalassemia phenotype has been obtained solely for a C----T substitution at -101 within the CACCC box of the beta-globin gene. Possible candidates are the complex rearrangements (-T, +ATA; -T, +ATATA) found at position -530 from the cap site. In the group of thalassemic hemoglobinopathies, a series of mutations mostly located in the third exon and producing elongated or truncated molecules have been recently reported. Most of the mutations are silent at the protein level, produce inclusion bodies in peripheral erythrocytes, and show a dominant transmission pattern or occur sporadically.


Assuntos
Triagem de Portadores Genéticos , Globinas/genética , Mutação , Talassemia/genética , Códon/genética , Feminino , Humanos , Masculino , Linhagem , Regiões Promotoras Genéticas , Talassemia/sangue
18.
Science ; 164(3876): 132, 1969 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-5774184
19.
Med Sci Sports Exerc ; 31(12): 1807-12, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10613432

RESUMO

PURPOSE: This study determined gender differences in voluntary reporting of lower extremity musculoskeletal injuries among U.S, Marine Corps (USMC) recruits, and it examined the association between these differences and the higher injury rates typically found among women trainees. METHODS: Subjects were 176 male and 241 female enlisted USMC recruits who were followed prospectively through 11 wk (men) and 12 wk (women) of boot camp training. Reported injuries were measured by medical record reviews. Unreported injuries were determined by a questionnaire and a medical examination administered at the completion of training. RESULTS: Among female recruits the most commonly reported injuries were patellofemoral syndrome (10.0% of subjects), ankle sprain (9.1%), and iliotibial band syndrome (5.8%); the most common unreported injuries were patellofemoral syndrome (2.1%), metatarsalgia (1.7%), and unspecified knee pain (1.7%). Among male recruits iliotibial band syndrome (4.0% of subjects), ankle sprain (2.8%), and Achilles tendinitis/bursitis (2.8%) were the most frequently reported injuries; shin splints (4.6%), iliotibial band syndrome (4.0%), and ankle sprain (2.8%) were the most common unreported diagnoses. Female recruits were more likely to have a reported injury than male recruits (44.0% vs 25.6%, relative risk (RR) = 1.72, 95% confidence interval (CI) 1.29-2.30), but they were less likely to have an unreported injury (11.6% vs 23.9%, RR = 0.49, 95% CI 0.31-0.75). When both reported and unreported injuries were measured, total injury rates were high for both sexes (53.5% women, 45.5% men, RR = 1.18, 95% CI 0.96-1.44), but the difference between the rates was not statistically significant. CONCLUSIONS: Our results indicate that the higher injury rates often found in female military trainees may be explained by gender differences in symptom reporting.


Assuntos
Sistema Musculoesquelético/lesões , Adolescente , Adulto , Atitude , Feminino , Humanos , Masculino , Militares , Fatores Sexuais , Inquéritos e Questionários , Estados Unidos/epidemiologia , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/psicologia
20.
Dig Liver Dis ; 32(7): 598-602, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11142558

RESUMO

BACKGROUND: Quite often subjects affected by chronic hepatitis C virus infection have no clinical signs of liver disease and serum aminotransferase values never go beyond the upper limit of normal. Yet these subjects, defined "asymptomatic HCV carriers", often have active viral replication and various degrees of histological damage. AIMS: To verify, in a population of antibody to hepatitis C virus carriers, if normal serum aminotransferase values in hepatitis C virus-RNA positive differed considerably from those in hepatitis C virus-RNA negative subjects. SUBJECTS/METHODS: We followed 24 anti-hepatitis C virus-positive subjects (15 hepatitis C virus-RNA positive and 9 negative) by measuring alanine and aspartate aminotransferase levels at 3-month intervals for a median of 40 months (range 6-77). RESULTS: Determinations resulted repeatedly and rigorously within the normal range in all participants. Alanine aminotransferase values were higher in hepatitis C virus-RNA positives than in negatives (mean +/- SD: 0.609+/-0.172 vs 0.434+/-0.153 times the upper limit of normal; p

Assuntos
Hepatite C Crônica/sangue , Transaminases/sangue , Carga Viral , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Portador Sadio/sangue , Portador Sadio/diagnóstico , Feminino , Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA