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1.
BJOG ; 124 Suppl 3: 12-17, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28856855

RESUMO

OBJECTIVE: To evaluate the therapeutic effect and safety of ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment on symptomatic uterine fibroids in Black women. DESIGN: A feasibility study. SETTING: Gynaecological department in a teaching hospital in South Africa. POPULATION: Premenopausal women with uterus fibroids. METHODS: Twenty-six patients with 53 fibroids who underwent USgHIFU treatment were enrolled. The USgHIFU treatment information was recorded, including treatment time, sonication time and total energy. Adverse events were also observed and recorded during and after treatment. MAIN OUTCOME MEASURES: Safety and efficacy of USgHIFU for the treatment of uterine fibroids in Black women. RESULTS: The median volume of fibroids was 52.7 (interquartile range, 18.6-177.4) cm3 . According to USgHIFU treatment plan, total energy of 298.6 ± 169.3 kJ (range, 76.0-889.2) within treatment time of 90.3 ± 43.3 minutes (range, 14.0-208.0), in which sonication time of 774.0 ± 432.9 seconds (range, 190.0-2224.0) was used to ablate fibroids. The average ablation rate was 80.6 ± 9.7% (range, 46.5-94.5%). During the procedure, 69.2% of the patients reported lower abdominal pain, 57.7% sciatic/buttock pain, 38.5% burning skin, and 34.6% transient leg pain. No severe complications were observed. CONCLUSIONS: USgHIFU is feasible and safe to use to treat symptomatic uterine fibroids in Black women. TWEETABLE ABSTRACT: Multiple uterine fibroids are more frequently detected in Black women. USgHIFU is feasible and safe for the treatment of uterine fibroids in Black women.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Leiomioma/cirurgia , Neoplasias Uterinas/cirurgia , Adolescente , Adulto , População Negra/etnologia , Feminino , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Humanos , Leiomioma/etnologia , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Neoplasias Uterinas/etnologia , Adulto Jovem
2.
J Community Health ; 40(3): 431-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25319468

RESUMO

The National Action Plan to Improve Health Literacy emphasizes the importance of community-based opportunities for education, such as English as a second language (ESL) programs. It recommends collaborations among the adult literacy and ESL communities. However, limited attention has been given to researching the effectiveness of community-based interventions that combine ESL and health literacy. The purpose of this study was to explore the feasibility of using different community settings for improving health literacy among adult Spanish speakers through an English language program. The study used a pre-experimental, single arm pretest-posttest design, and implemented the Health Literacy and ESL Curriculum. A collaborative was established between the community and university researchers. Participants were recruited at three distinctive sites. Health literacy was assessed using the Spanish version of the Test of Functional Health Literacy in Adults (TOFHLA). Analysis included descriptive and paired-group t test. Forty-nine participants completed the intervention and post-tests (92% retention rate). Overall--all sites--posttest scores significantly improved for total TOFHLA, raw numeracy, and reading comprehension (p < 0.0001). Similarly, all three sites yielded significantly better mean differences for the total TOFHLA score while numeracy and reading comprehension significantly improved in some sites. Results suggest that community sites are viable venues for delivering health literacy/language instruction to Spanish speaking adults. The study also points to community engagement and ESL programs as two essential components of effective health literacy interventions among Spanish speakers.


Assuntos
Relações Comunidade-Instituição , Letramento em Saúde , Hispânico ou Latino/educação , Idioma , Adulto , Comportamento Cooperativo , Currículo , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New Mexico , Áreas de Pobreza , Características de Residência , Universidades
3.
Nature ; 506(7489): 463-6, 2014 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-24509711

RESUMO

The element abundance ratios of four low-mass stars with extremely low metallicities (abundances of elements heavier than helium) indicate that the gas out of which the stars formed was enriched in each case by at most a few--and potentially only one--low-energy supernova. Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae seems surprising, because it had been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron. What has remained unclear is the yield of iron from the first supernovae, because hitherto no star has been unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36-670839.3, which shows no evidence of iron (with an upper limit of 10(-7.1) times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass about 60 times that of the Sun (and that the supernova left behind a black hole). Taken together with the four previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yielded light-element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.

4.
Acta Anaesthesiol Scand ; 55(6): 713-21, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21615345

RESUMO

BACKGROUND: Central venous oxygen saturation (ScvO(2)) is suggested to reflect the adequacy of oxygen delivery, and the main objective of the present study was to determine whether ScvO(2) is associated with outcome in haemodynamically stabilized trauma patients. METHODS: Haemodynamically unstable trauma patients receiving a central venous line within 1 h of admission were eligible for inclusion in this prospective observational study. The mean arterial pressure (MAP), lactate and ScvO(2) were recorded at inclusion and every 6 h for 36 h or until lactate was <2.0 mmol/l and ScvO(2) was >75% in two consecutive measurements. Patients with a MAP of ≥70 mmHg were considered to be haemodynamically stabilized. The outcome measure was complications defined as infections, delta sequential organ failure assessment score of >0, and mortality. RESULTS: Fifty patients with a median new injury severity score of 27 (17-34) were analysed. Complications occurred in 33 patients. An association between ScvO(2) following resuscitation to MAP ≥70 mmHg and complications was detected with an odds ratio of 0.94 (95% confidence interval; 0.89-0.99). This association was also significant when adjusted for injury severity. The result implies that a low ScvO(2) value is associated with more complications. The optimal cut-off for ScvO(2) to discriminate between patients who did or did not develop complications was found to be 66.5% (56-86%). CONCLUSIONS: These data suggest that low ScvO(2) in haemodynamically stabilized patients is associated with a poor outcome and that ScvO(2) represents a potential endpoint of resuscitation in trauma patients.


Assuntos
Hemodinâmica , Oxigênio/sangue , Ferimentos e Lesões/sangue , Adulto , Cateterismo Venoso Central , Feminino , Humanos , Masculino , Estudos Prospectivos , Curva ROC , Resultado do Tratamento , Veias/metabolismo , Ferimentos e Lesões/fisiopatologia
5.
Int J Adolesc Med Health ; 5(3-4): 217-20, 2011 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-22912126
6.
Br J Cancer ; 97(3): 327-33, 2007 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-17637684

RESUMO

Tamoxifen (Tam) is effective for the treatment and prevention of breast cancer. However, it has toxic drawbacks and has limited-duration utility because, over time, human tumours become refractory to Tam. Recently, a new nontoxic peptide, alpha-fetoprotein-derived peptide (AFPep) has been proposed for the treatment and prevention of breast cancer. The purpose of this paper is to determine whether combining AFPep with Tam would increase efficacy and reduce toxicity in experimental models of breast cancer. Low doses of AFPep and Tam were more effective in combination than either agent alone against breast cancer growth in cell culture, in tumour-xenografted mice, and in carcinogen-exposed rats. alpha-Fetoprotein-derived peptide interfered with Tam-induced uterine hyperplasia in immature mice, and showed no toxic effects. Unlike Tam, AFPep did not inhibit binding of oestradiol (E(2)) to oestrogen receptor (ER). Thus, these two agents utilise different mechanisms to interfere with ER functionality, yet work cooperatively to reduce breast cancer growth and alleviate Tam's troubling toxicity of uterine hyperplasia and appear to be a rational combination for the treatment of ER-positive breast cancer.


Assuntos
Antineoplásicos Hormonais/farmacologia , Peptídeos/farmacologia , Tamoxifeno/farmacologia , Doenças Uterinas/prevenção & controle , alfa-Fetoproteínas/farmacologia , Animais , Antineoplásicos Hormonais/toxicidade , Linhagem Celular Tumoral , Feminino , Humanos , Hiperplasia/prevenção & controle , Camundongos , Coelhos , Tamoxifeno/toxicidade , Transplante Heterólogo , Doenças Uterinas/patologia , alfa-Fetoproteínas/química , alfa-Fetoproteínas/toxicidade
7.
J Intellect Disabil Res ; 49(Pt 2): 111-24, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15634320

RESUMO

BACKGROUND: Very little is known about the context of caregiving by parents of adults with autism or about the perceived impacts of continued patterns of co-residence vs. out-of-family living. In the present study, maternal assessments of residential status, involvement with adult children living in a non-family setting, and the impacts on mothers of their residential arrangements were examined. METHODS: Mothers from 133 families of adults (aged 22 years and older) with autism spectrum disorder (ASD) completed questionnaires as part of a longitudinal study on family caregiving. Mothers completed open-ended questions regarding the positive and negative aspects of their child's residential arrangement. Mothers also completed scaled questions regarding their satisfaction with their child's residential arrangement, the different ways in which people's lives change after a relative moves from the home, and the frequency of contact with their son or daughter. RESULTS: Mothers found co-residing with their adult child to be of greatest positive benefit to the family while those living apart found this residential arrangement of greatest benefit to the son or daughter with ASD. The greatest negative consequences for co-residing mothers were understood to fall on families, while mothers felt the majority of negative consequences for those that lived apart. There was a high level of contact and maternal involvement between the mother and adult child with ASD even after out-of-home placement. CONCLUSIONS: Residential status, as appraised by mothers, has varying impacts on the individual with ASD, on the family, and on mothers as individuals and caregivers. The present analysis suggests the multifaceted and highly contingent maternal experience associated with where her child with ASD lives. Among families whose children live elsewhere, there is an impressive amount of continued contact between these families and their son/daughter.


Assuntos
Transtorno Autístico/psicologia , Família , Habitação/estatística & dados numéricos , Mães , Tratamento Domiciliar , Meio Social , Adolescente , Adulto , Cuidadores , Demografia , Feminino , Seguimentos , Humanos , Masculino , Variações Dependentes do Observador , Inquéritos e Questionários
8.
J Pept Res ; 63(5): 409-19, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15140158

RESUMO

Asynthetic peptide that inhibits the growth of estrogen receptor positive (ER+) human breast cancers, growing as xenografts in mice, has been reported. The cyclic 9-mer peptide, cyclo[EMTOVNOGQ], is derived from alpha-fetoprotein (AFP), a safe, naturally occurring human protein produced during pregnancy, which itself has anti-estrogenic and anti-breast cancer activity. To determine the pharmacophore of the peptide, a series of analogs was prepared using solid-phase peptide synthesis. Analogs were screened in a 1-day bioassay, which assessed their ability to inhibit the estrogen-stimulated growth of uterus in immature mice. Deletion of glutamic acid, Glu1, abolished activity of the peptide, but glutamine (Gln) or asparagine (Asn) could be substituted for Glu1 without loss of activity. Methionine (Met2) was replaced with lysine (Lys) or tyrosine (Tyr) with retention of activity. Substitution of Lys for Met2 in the cyclic molecule resulted in a compound with activity comparable with the Met2-containing cyclic molecule, but with a greater than twofold increase in purity and corresponding increase in yield. This Lys analog demonstrated anti-breast cancer activity equivalent to that of the original Met-containing peptide. Therefore, Met2 is not essential for biologic activity and substitution of Lys is synthetically advantageous. Threonine (Thr3) is a nonessential site, and can be substituted with serine (Ser), valine (Val), or alanine (Ala) without significant loss of activity. Hydroxyproline (Hyp), substituted in place of the naturally occurring prolines (Pro4, Pro7), allowed retention of activity and increased stability of the peptide during storage. Replacement of the first Pro (Pro4) with Ser maintains the activity of the peptide, but substitution of Ser for the second Pro (Pro7) abolishes the activity of the peptide. This suggests that the imino acid at residue 7 is important for conformation of the peptide, and the backbone atoms are part of the pharmacophore, but Pro4 is not essential. Valine (Val5) can be substituted only with branched-chain amino acids (isoleucine, leucine or Thr); replacement by d-valine or Ala resulted in loss of biologic activity. Thus, for this site, the bulky branched side chain is essential. Asparagine (Asn6) is essential for activity. Substitution with Gln or aspartic acid (Asp), resulted in reduction of biologic activity. Removal of glycine (Gly8) resulted in a loss of activity but nonconservative substitutions can be made at this site without a loss of activity indicating that it is not part of the pharmacophore. Cyclization of the peptide is facilitated by addition of Gln9, but this residue does not occur in AFP nor is it necessary for activity. Gln9 can be replaced with Asn, resulting in a molecule with similar activity. These data indicate that the pharmacophore of the peptide includes side chains of Val5 and Asn6 and backbone atoms contributed by Thr3, Val5, Asn6, Hyp7 and Gly8. Met2 and Gln9 can be modified or replaced. Glu1 can be replaced with charged amino acids, and is not likely to be part of the binding site of the peptide. The results of this study provide information that will be helpful in the rational modification of cyclo[EMTOVNOGQ] to yield peptide analogs and peptidomimetics with advantages in synthesis, pharmacologic properties, and biologic activity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Peptídeos Cíclicos/farmacologia , Receptores de Estrogênio/metabolismo , alfa-Fetoproteínas/farmacologia , Sequência de Aminoácidos , Animais , Feminino , Humanos , Camundongos , Dados de Sequência Molecular , Células Tumorais Cultivadas
9.
Gac Sanit ; 17 Suppl 3: 9-14, 2003.
Artigo em Espanhol | MEDLINE | ID: mdl-14980182

RESUMO

A 1998 agreement between several states in the USA and the tobacco industry made millions of pages of internal documents available to the public. Many of these documents contain information that the industry would have preferred to keep confidential. Systematic review of these internal documents constitutes a valuable resource for international tobacco control, since they are available on the Internet and can be accessed from anywhere in the world. These documents provide relevant and useful information to antismoking activists and researchers. To facilitate their use, the present article presents the electronic archives of the tobacco industry's documents, describes methods for conducting searches, and identifies the documents with information on the industry's tactics for manipulating Spanish politics and society for its own commercial interests during the 1970s, 1980s, and 1990s.


Assuntos
Registros , Prevenção do Hábito de Fumar , Indústria do Tabaco , Humanos , Espanha
10.
Artigo em Inglês | MEDLINE | ID: mdl-12193904

RESUMO

Proliferative periostitis of Garré is described as a productive and proliferative inflammatory response of periosteum to infection or other irritation. This can be odontogenic or non-odontogenic in nature. This is a case report of an odontogenic periostitis resulting from periapical inflammation of endodontic origin. It was successfully treated by nonsurgical endodontics. Antibiotic therapy was not used during the treatment of this patient.


Assuntos
Necrose da Polpa Dentária/complicações , Doenças Mandibulares/etiologia , Periodontite Periapical/complicações , Periostite/etiologia , Criança , Necrose da Polpa Dentária/terapia , Infecção Focal Dentária/terapia , Humanos , Masculino , Doenças Mandibulares/terapia , Dente Molar , Periodontite Periapical/terapia , Periostite/terapia , Tratamento do Canal Radicular
11.
J Endod ; 28(4): 269-71, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12043860

RESUMO

Coronal leakage has been recognized as a cause of pulpal and periradicular disease. Although cleaning and shaping of the root canal system is considered paramount, obturation of the system is an important step in endodontic success. The purpose of this study was to evaluate coronal bacterial leakage in teeth obturated with the System B continuous wave of condensation technique, followed by an Obtura II backfill, versus teeth obturated using the lateral condensation technique. Sixty single-rooted bilaterally matched teeth were evaluated in this study. An anaerobic bacterial leakage model was used. Results indicate that microbial coronal leakage occurs more quickly using lateral condensation than with the System B continuous wave of condensation and Obtura II backfill. This difference was statistically significant (p < or = 0.05). However, there was no statistical difference between groups 1 and 2 in the numbers of teeth that demonstrated bacterial leakage at the end of the study.


Assuntos
Infiltração Dentária/microbiologia , Cavidade Pulpar/microbiologia , Obturação do Canal Radicular/métodos , Estudos de Casos e Controles , Quelantes/uso terapêutico , Distribuição de Qui-Quadrado , Desinfetantes/uso terapêutico , Ácido Edético/uso terapêutico , Guta-Percha/uso terapêutico , Humanos , Klebsiella pneumoniae/crescimento & desenvolvimento , Materiais Restauradores do Canal Radicular/uso terapêutico , Irrigantes do Canal Radicular/uso terapêutico , Obturação do Canal Radicular/instrumentação , Preparo de Canal Radicular/instrumentação , Preparo de Canal Radicular/métodos , Hipoclorito de Sódio/uso terapêutico , Estatísticas não Paramétricas
12.
J Pept Res ; 58(3): 246-56, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11576331

RESUMO

The peptide, EMTPVNPG, derived from alpha-fetoprotein, inhibits estrogen-stimulated growth of immature mouse uterus and estrogen-dependent proliferation of human breast cancer cells. However, the biological activities of the peptide diminish over time in storage, even when in the lyophilized state, probably because of peptide aggregation through hydrophobic interaction among monomers. Two analogs of EMTPVNPG were designed with the intent of minimizing aggregation and retaining biological activity during prolonged storage. EMTOVNOG, where O is 4-hydroxyproline, is a linear peptide generated by substituting 4-hydroxyproline for the two prolines, thereby increasing peptide hydrophilicity. This analog exhibited a dose-dependent inhibition of estrogen-stimulated growth of immature mouse uterus similar to that of EMTPVNPG (maximal activity at 1 microg/mouse). A second analog, cyclo-(EMTOVNOGQ), a hydrophilic, cyclic analog with increased conformational constraint, was as potent as the other peptides in its inhibition of estrogen-dependent growth of immature mouse uterus, and had an expanded effective dose range. Both linear and cyclized hydroxyproline-substituted analogs exhibited indefinite shelf-life. Furthermore, both analogs inhibited the estrogen-dependent growth of MCF-7 human breast cancer growing as a xenograft in SCID mice. These analogs may become significant, novel agents for the treatment of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/prevenção & controle , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Receptores de Estrogênio/antagonistas & inibidores , Útero/efeitos dos fármacos , Substituição de Aminoácidos , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias da Mama/induzido quimicamente , Divisão Celular/efeitos dos fármacos , Desenho de Fármacos , Estrogênios/efeitos adversos , Estrogênios/farmacologia , Feminino , Humanos , Camundongos , Camundongos SCID , Conformação Molecular , Útero/crescimento & desenvolvimento , Ensaios Antitumorais Modelo de Xenoenxerto , alfa-Fetoproteínas/química
13.
J Pept Res ; 57(6): 539-46, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11437957

RESUMO

A 34-amino acid portion of the third domain of alpha-fetoprotein possesses antigrowth and anticancer activities. Three analogs of this sequence were chemically synthesized, in which the two cysteines of the original sequence were replaced by alanines, glycines or serines. The original cysteine and alanine peptides formed trimers at 0.20 g/L in pH 7.4 phosphate buffer, and the glycine and serine peptides formed dimers. Trimer preparations were more potent in inhibiting estrogen-induced growth in the mouse uterine assays than the two dimeric oligomers. Of salient importance is that the alanine peptide retained its trimeric form in solution much longer than the cysteine peptide. Antigrowth assays were performed starting with stock solutions at a peptide concentration of 0.20 g/L, because at very high peptide concentration (8.0 g/L) the peptides aggregated extensively. All the peptides, although differing in biological activity, had almost identical secondary structures. Unlike alpha-fetoprotein, the three peptides have low amounts of alpha-helix. Trifluoroethanol has the ability to convert peptides into a helical conformation when they have a propensity for that structure. At trifluoroethanol concentrations of 20% and higher, the alanine and glycine peptides were changed into highly helical structures.


Assuntos
Antineoplásicos/síntese química , Peptídeos/química , Peptídeos/farmacologia , alfa-Fetoproteínas/química , alfa-Fetoproteínas/farmacologia , Alanina/análogos & derivados , Alanina/química , Animais , Cromatografia em Gel , Cisteína/análogos & derivados , Cisteína/química , Relação Dose-Resposta a Droga , Epitopos , Estrogênios/metabolismo , Feminino , Glicina/análogos & derivados , Glicina/química , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Estrutura Secundária de Proteína , Serina/análogos & derivados , Serina/química , Fatores de Tempo , Útero/efeitos dos fármacos
14.
J Pept Res ; 57(1): 29-38, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11168886

RESUMO

A 34-amino acid synthetic peptide was derived from the third domain of human alpha-fetoprotein, and the peptide was shown to inhibit estrogen-stimulated growth. Under certain conditions, however, the peptide lost growth-inhibitory activity. A biophysical study of the peptide was undertaken with a goal of obtaining completely reliable preparations. The peptide was studied using gel-filtration column chromatography as a function of peptide concentration and age of solution, and was found to exhibit complex aggregation behaviors. During the early period (0-3 h) after dissolving lyophilized peptide into pH 7.4 buffer, solutions were composed mostly of trimers. At higher peptide concentrations (> or = 3.0 g/L), the trimers aggregated extensively to a large aggregate (minimum size approximately 102 peptides). At 5.0-8.0 g/L, these large aggregates increased in size (up to approximately 146 peptides) until trimers were largely exhausted from solution. During the later times (>3 h) after sample preparation, the trimeric oligomer of the peptide dissociated slowly to form dimers for samples at 0.10-3.0 g/L. After their build-up, a very small number of dimers associated to form hexamers. Disulfide bonds stabilized the dimers as indicated by the conversion of dimers to trimers upon the addition of a reducing agent, and the failure of dimers to form in the presence of reducing agent. Reducing agent did not affect trimer or large aggregate formation. Trimers were found to be active in an assay monitoring inhibition of estrogen-stimulated growth, whereas dimers and large aggregates were inactive. The two cysteines in the peptide were modified to either S-methylcysteine or S-(2-aminoethyl)cysteine, and both derivatives showed significant growth-inhibition activity. A serine analog in which both cysteines were replaced had very different aggregation behavior than the cysteine peptide and lacked its growth inhibitory ability. Peptide aggregation is critically important in establishing the ability of the peptide to inhibit growth and have anticancer activity, but the state of its two cysteines is of little influence.


Assuntos
Antineoplásicos/síntese química , Peptídeos/química , Peptídeos/farmacologia , alfa-Fetoproteínas/química , alfa-Fetoproteínas/farmacologia , Acetilcisteína/análogos & derivados , Acetilcisteína/química , Animais , Cromatografia em Gel , Cisteína/análogos & derivados , Cisteína/química , Dissulfetos , Relação Dose-Resposta a Droga , Epitopos , Estrogênios/metabolismo , Feminino , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Biossíntese Peptídica , Estrutura Terciária de Proteína , Fatores de Tempo , Útero/efeitos dos fármacos
15.
Biochim Biophys Acta ; 1501(1): 33-43, 2000 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-10727847

RESUMO

Alpha-fetoprotein (AFP) is a major serum protein produced during fetal development. Experimental findings suggest that AFP has antiestrotrophic activity and that it can be developed as a therapeutic agent to treat existing estrogen-dependent breast cancer or to prevent premalignant foci from developing into breast cancer. The antiestrotrophic activity of AFP was reported to be localized to a peptide consisting of amino acids 447-480, a 34-mer peptide termed P447. A series of parsings and substitutions of amino acids in the P447 sequence was intended to identify the shortest analog which retained antiestrotrophic activity. Peptides related to P447 were generated using solid phase peptide synthesis. Several shorter peptides, including an 8-mer called P472-2 (amino acids 472-479, peptide sequence EMTPVNPG), retained activity, whereas peptides shorter than eight amino acid residues were inactive. The dose-related antiestrotrophic activity of AFP-derived peptides was determined in an immature mouse uterine growth assay that measures their ability to inhibit estradiol-stimulated uterine growth. In this assay, the maximal inhibitory activities exhibited by peptide P472-2 (49%), by peptide P447 (45%), and by intact AFP (35-45%) were comparable. The octapeptide P472-2 was also active against estradiol-stimulated growth of T47D human breast cancer cells in culture. These data suggest that peptide P472-2 is the minimal sequence in AFP, which retains the antiestrotrophic activity found with the full-length molecule. The synthetic nature and defined structure of this 8-mer peptide suggest that it can be developed into a new drug which opposes the action of estrogen, perhaps including the promotional effects of estradiol in the development of human breast cancer.


Assuntos
Moduladores de Receptor Estrogênico/química , Peptídeos/química , alfa-Fetoproteínas/metabolismo , Sequência de Aminoácidos , Animais , Peso Corporal/efeitos dos fármacos , Neoplasias da Mama , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Desenho de Fármacos , Estradiol/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Feminino , Humanos , Camundongos , Dados de Sequência Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Peptídeos/síntese química , Peptídeos/farmacologia , Estrutura Secundária de Proteína , Útero/efeitos dos fármacos , Útero/crescimento & desenvolvimento , alfa-Fetoproteínas/química , alfa-Fetoproteínas/farmacologia
16.
Nurs Health Care Perspect ; 21(2): 76-80, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11143612

RESUMO

The recommendation that future practitioners have the competency to work effectively in interdisciplinary teams is not new, but educating students for this type of practice remains a challenge for the health care professions (1-4). Early interdisciplinary teams usually worked in parallel. There were no common goals, but each group's goals stemmed from its professional education (5). In the traditional model, medical doctors were the "team leaders." Current recommendations challenge health professions educators "to move beyond traditional discipline-bound educational models to future-oriented interdisciplinary teaching/learning models" (6). Taking this recommendation seriously, educators from the University of South Florida (USF) formed a team to develop a model to guide the education of students from four health professions. Our goal was to model, by our philosophy, actions, and words, the art of teaching as an interdisciplinary team. This article describes the first phase of the process and four critical steps--establishing a common goal, developing a team process, creating a model to guide our interactions, and developing support networks within the community.


Assuntos
Bacharelado em Enfermagem/organização & administração , Modelos Educacionais , Equipe de Assistência ao Paciente , Humanos , Relações Interprofissionais
17.
Biochim Biophys Acta ; 1427(2): 307-14, 1999 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-10216247

RESUMO

Previous studies have shown that alpha-fetoprotein (AFP) interferes with estrogen (E2)-stimulated growth, including E2-stimulated breast cancer growth. In an effort to localize the antiestrotrophic portion of the molecule, the C-terminal one-third (200 amino acids) of human AFP, known as Domain III, was produced in a baculovirus expression system as a fusion protein containing an amino terminal histidine tag. The histidine tag was included to facilitate purification by metal ion affinity chromatography. The purified recombinant Domain III fusion protein was functionally similar to full-length natural AFP isolated from human cord sera or from cultured human hepatoma cells (HepG2) in that they all produced significant and quantitatively similar inhibition of E2-stimulated growth of immature mouse uterus. Furthermore, the dose-response profiles of the recombinant Domain III AFP and natural full-length AFP were similar. Preincubation of either protein in a molar excess of E2 lowered the minimally effective antiestrotrophic dose and produced a difference spectrum consistent with a change in conformation. These findings indicate that the antiestrotrophic activity of AFP is contained within the third domain of the molecule, and they have obvious implications for the production of biologically active peptides derived from this portion of the AFP molecule.


Assuntos
Antagonistas de Estrogênios/química , alfa-Fetoproteínas/química , Animais , Baculoviridae/genética , Sítios de Ligação , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Antagonistas de Estrogênios/farmacologia , Estrogênios/farmacologia , Feminino , Histidina/química , Humanos , Camundongos , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/química , Proteínas Recombinantes/química , Espectrofotometria Ultravioleta , Útero/efeitos dos fármacos , Útero/crescimento & desenvolvimento , alfa-Fetoproteínas/biossíntese , alfa-Fetoproteínas/genética
18.
Clin Cancer Res ; 4(11): 2877-84, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9829755

RESUMO

Alpha-fetoprotein (AFP) is a transport protein that has growth-regulatory properties in many different tissues. It is known to interfere with responses stimulated by estrogen. The purpose of this study was to determine whether human AFP would inhibit the growth of human breast cancer. AFP was isolated from the culture supernatant of human hepatoma cells (HepG2) grown in serum-free medium and was purified by immunoaffinity chromatography. Human breast cancers were grown as xenografts under the kidney capsule of severe combined immunodeficient mice. The minimum inhibitory dose of AFP against estradiol (E2)-stimulated growth of human MCF-7 breast cancer xenografts was 10 microg/mouse/day, and maximum inhibition (no growth) was achieved with 100 microg/mouse/day. Daily treatment was required to sustain inhibition. This 100-microg dose of AFP also inhibited xenograft growth of E2-dependent T47 human breast carcinoma. Estrogen receptor-negative MDA MB 231 and BT20 human breast carcinoma xenografts were not inhibited by AFP (100 microg/mouse/day). Elevation in serum E2 occurred during AFP treatment. AFP did not compete with agonists for the estrogen receptor. These laboratory results are consistent with the findings of a literature search, which consistently showed an association between elevated pregnancy levels of AFP and subsequent reduced risk for breast cancer later in life. We conclude that AFP can inhibit growth of estrogen-dependent breast cancer and warrants further development as an agent for the treatment and perhaps even the prevention of human breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , alfa-Fetoproteínas/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Carcinoma Hepatocelular/química , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estrogênios/fisiologia , Humanos , Neoplasias Hepáticas/química , Camundongos , Camundongos SCID , Transplante de Neoplasias , Transplante Heterólogo , Células Tumorais Cultivadas , alfa-Fetoproteínas/isolamento & purificação
19.
Acta Ophthalmol Scand ; 76(4): 405-12, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9716325

RESUMO

PURPOSE: To study aqueous flare longitudinally in patients with Fuchs' heterochromic uveitis (FHU) and for comparison in another group with iris atrophy (non FHU). METHODS: A new laser flare meter was used. Iris angiography was performed in most FHU patients. RESULTS: The flare values in the affected eyes in the FHU group were always higher compared to the normal eyes and rather constant over time. Cataract surgery did not permanently change the flare values. Systemic - but not local steroid therapy caused normalization of the flare. Iris angiography displayed leakage in all FHU eyes. Leakage from original vessels dominated although some newly-formed leaking vessels were observed. CONCLUSIONS: The results support the notion that FHU is a low grade, chronic, stable disease. Leaking iris vessels, original or newly-formed, are probably the source of the increased flare. Our hypothesis is that inflammation plays a major part. Atrophy per se does not enhance flare.


Assuntos
Humor Aquoso/metabolismo , Angiofluoresceinografia , Iridociclite/metabolismo , Iris/irrigação sanguínea , Iris/patologia , Adulto , Idoso , Atrofia/metabolismo , Atrofia/patologia , Permeabilidade Capilar , Extração de Catarata , Doença Crônica , Feminino , Fluorofotometria/instrumentação , Fluorofotometria/métodos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Iridociclite/patologia , Masculino , Pessoa de Meia-Idade
20.
Breast Cancer Res Treat ; 45(2): 169-79, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9342442

RESUMO

Alpha-fetoprotein (AFP) isolated from rodent amniotic fluid or human cord sera, upon incubation with a molar excess of estradiol, is converted to a form which inhibits estrogen-stimulated tissue growth. The purpose of this study was to determine whether recombinant human AFP produced in an E. coli expression system retained this function. The recombinant protein was similar to the natural protein isolated from pooled human cord sera in all functional aspects evaluated. It was detected by monoclonal and polyclonal antibodies to the natural protein. Following exposure to estradiol, it was converted to an inhibitor of estrogen-stimulated growth of immature mouse uterus yielding a dose/response curve similar to that of the natural protein. It inhibited the growth of estrogen-dependent (MCF-7) but not estrogen-independent (MDA-MB-231) breast cancer xenografts with the same schedule dependency and resultant histological changes as the natural protein. Availability of large quantities of homogeneous, biologically active recombinant human AFP will facilitate further studies of structure/function, mechanism, and therapeutic potential of this agent as a regular of breast cancer growth.


Assuntos
Neoplasias da Mama/patologia , alfa-Fetoproteínas/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Estrogênios/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos ICR , Camundongos SCID , Proteínas Recombinantes/farmacologia , Transplante Heterólogo , Útero/efeitos dos fármacos , alfa-Fetoproteínas/isolamento & purificação
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