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1.
Prostaglandins Leukot Essent Fatty Acids ; 198-199: 102594, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37957091
2.
Artigo em Inglês | MEDLINE | ID: mdl-37121179

RESUMO

Sickle cell disease (SCD) induces red blood cell sickling, which causes debilitating symptoms including vaso-occlusion and inflammation. We investigated a food enriched with omega-3 fatty acids to determine its effect on certain factors: blood cell membrane fatty acid composition (including anti-inflammatory elements-docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-and the pro-inflammatory, arachidonic acid (AA)); the inflammation biomarker, C-reactive protein (CRP); and vaso-occlusive crisis (VOC) pain. Ten adults with SCD ingested the food, daily, for 28 days. Evaluated measures included blood cell membrane fatty acid ratios (AA vs omega-3 (DHA+EPA)), CRP (mg/L) levels, and Visual Analogue Scale (VAS) scores (a VOC assessment). The food was well tolerated and led to a statistically significant CRP reduction (39%). However, changes in omega-3 fatty acid ratios and VAS scores were not significant. Overall, while the omega-3-enriched food reduced inflammation, larger, blinded studies are needed to assess its effectiveness on other measures.


Assuntos
Anemia Falciforme , Ácidos Graxos Ômega-3 , Compostos Orgânicos Voláteis , Adulto , Humanos , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Proteína C-Reativa/metabolismo , Inflamação , Ácidos Graxos , Ácido Araquidônico
4.
Toxicol Pathol ; 46(2): 224-246, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29471779

RESUMO

Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack distinctive features indicative of lysosomal or cellular dysfunction, making it difficult to consistently interpret and assign adverse dose levels. To help address this issue, the European Society of Toxicologic Pathology organized a workshop where representative types of lysosomal accumulation induced by pharmaceuticals and environmental chemicals were presented and discussed. The expert working group agreed that the diversity of lysosomal accumulations requires a case-by-case weight-of-evidence approach and outlined several factors to consider in the adversity assessment, including location and type of cell affected, lysosomal contents, severity of the accumulation, and related pathological effects as evidence of cellular or organ dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation, or fibrosis were generally considered to be adverse, while those found in isolation (without morphologic or functional consequences) were not. Workshop examples highlighted the importance of thoroughly characterizing the biological context of lysosomal effects, including mechanistic data and functional in vitro readouts if available. The information provided here should facilitate greater consistency and transparency in the interpretation of lysosomal effects.


Assuntos
Lisossomos/efeitos dos fármacos , Lisossomos/patologia , Fenômenos Toxicológicos , Animais
5.
J Clin Endocrinol Metab ; 89(7): 3337-44, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15240612

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age associated with obesity. It may involve dysregulation of ghrelin, a hormone implicated in appetite regulation. The effect of diet composition on ghrelin is unclear. Overweight women with and without PCOS were randomized to a high-protein (40% carbohydrate, 30% protein; 10 PCOS, six non-PCOS) or standard protein diet (55% carbohydrate, 15% protein; 10 PCOS, six non-PCOS) for 12 wk of energy restriction and 4 wk of weight maintenance. Diet composition had no effect on fasting or postprandial ghrelin or measures of satiety. Non-PCOS subjects had a 70% higher fasting baseline ghrelin (P = 0.011), greater increase in fasting ghrelin (57.5 vs. 34.0%, P = 0.033), and greater maximal decrease in postprandial ghrelin after weight loss (-144.1 +/- 58.4 vs. -28.9 +/- 14.2 pg/ml, P = 0.02) than subjects with PCOS. Subjects with PCOS were less satiated (P = 0.001) and more hungry (P = 0.007) after a test meal at wk 0 and 16 than subjects without PCOS. Appetite regulation, as measured by subjective short-term hunger and satiety and ghrelin homeostasis, may be impaired in PCOS.


Assuntos
Dieta , Obesidade/complicações , Hormônios Peptídicos/sangue , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/fisiopatologia , Resposta de Saciedade , Adulto , Glicemia/análise , Composição Corporal , Peso Corporal , Restrição Calórica , Proteínas Alimentares/administração & dosagem , Jejum/sangue , Feminino , Grelina , Homeostase , Humanos , Insulina/sangue , Pessoa de Meia-Idade , Medição da Dor , Cooperação do Paciente , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/psicologia , Período Pós-Prandial , Análise de Regressão
6.
J Clin Endocrinol Metab ; 88(2): 812-9, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12574218

RESUMO

Overweight women with polycystic ovary syndrome (PCOS) were randomized to a high protein (HP; 40% carbohydrate and 30% protein; n = 14) or a low protein (LP; 55% carbohydrate and 15% protein) diet (n = 14). The intervention consisted of 12 wk of energy restriction (approximately 6000 kJ/d), followed by 4 wk of weight maintenance. Pregnancies (two HP and one LP); improvements in menstrual cyclicity, lipid profile, and insulin resistance (as measured by the homeostasis model); and decreases in weight (7.5%) and abdominal fat (12.5%) occurred independently of diet composition. Improvements in menstrual cyclicity were associated with greater decreases in insulin resistance and fasting insulin (P = 0.011). On the LP diet, high density lipoprotein cholesterol decreased 10% during energy restriction (P = 0.008), and the free androgen index increased 44% in weight maintenance stages (P = 0.027). Weight loss leads to improvements in cardiovascular and reproductive parameters potentially mediated by improvements in surrogate measures of insulin resistance. An HP weight loss diet may result in minor differential endocrine and metabolic improvements.


Assuntos
Dieta com Restrição de Proteínas , Obesidade/dietoterapia , Obesidade/metabolismo , Ovulação/fisiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/dietoterapia , Adulto , Glicemia , Composição Corporal , Carboidratos da Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Metabolismo Energético , Exercício Físico , Feminino , Hirsutismo/dietoterapia , Hirsutismo/metabolismo , Humanos , Insulina/sangue , Lipídeos/sangue , Gravidez , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Redução de Peso
7.
Can J Vet Res ; 64(4): 229-31, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11041501

RESUMO

The uterine tubes from 405 ewes, collected at an abattoir, were assessed grossly and microscopically for abnormalities that correlated with serological evidence of exposure to Chlamydophila abortus. Gross lesions were found in 41 ewes and 86 had microscopic lesions. Enzyme immunoassay (EIA) of serum was used as an indication of exposure of individual ewes to C. abortus; 52 were found to be positive. Chi-squared analysis indicated no association between EIA-positive animals and lesions of the uterine tube.


Assuntos
Aborto Animal/microbiologia , Infecções por Chlamydophila/veterinária , Chlamydophila/patogenicidade , Tubas Uterinas/microbiologia , Matadouros , Aborto Animal/etiologia , Animais , Infecções por Chlamydophila/complicações , Tubas Uterinas/patologia , Feminino , Gravidez , Útero/microbiologia , Útero/patologia
8.
J Tissue Viability ; 10(4): 140-3, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11949301

RESUMO

This case study illustrates the role of the Podiatrist in the primary health care team and how a multidisciplinary approach to treatment promotes successful diagnosis and treatment regimes. It also outlines the role for chemical lumbar sympathectomies in treating critical lower limb ischaemia, a procedure regarded as having been superseded by more effective treatments but which proved to be the treatment of choice in this case. The subject of this case study presented at a community podiatry clinic exhibiting the signs of acute ischaemia, together with two recently developed ulcers on her right foot. After further vascular investigations, including angiograms and doppler studies, a blockage in the popliteal artery was revealed. Due to anatomically slender arteries, angioplasty and by-pass surgery were contra indicated. A chemical lumbar sympathectomy was performed in an attempt to increase blood flow to the tissues and to reduce the extreme pain being experienced by the patient. This proved successful, allowing the lesions to heal and also the collateral circulation to develop, resulting in a re-vascularized, viable foot.


Assuntos
Pé/irrigação sanguínea , Isquemia/terapia , Perna (Membro)/irrigação sanguínea , Equipe de Assistência ao Paciente , Fenol/administração & dosagem , Podiatria , Encaminhamento e Consulta , Soluções Esclerosantes/administração & dosagem , Simpatectomia Química/métodos , Feminino , Pé/patologia , Úlcera do Pé/patologia , Humanos , Relações Interprofissionais , Região Lombossacral , Pessoa de Meia-Idade , Dor/etiologia , Manejo da Dor , Fenol/uso terapêutico , Fluxo Sanguíneo Regional , Soluções Esclerosantes/uso terapêutico , Resultado do Tratamento
9.
Am J Physiol ; 277(5): L881-6, 1999 11.
Artigo em Inglês | MEDLINE | ID: mdl-10564171

RESUMO

Ascent to high altitude leads to pulmonary edema formation in some individuals. Recent laboratory evidence supports the hypothesis that hypoxia may impair the function of the alveolar epithelium and thus augment edema accumulation via reduced clearance of lung liquid. We investigated the effect of hypobaric hypoxia on epithelial sodium transport in adult Sprague-Dawley rats by measuring the nasal transepithelial potential difference (PD) as an index of airway sodium transport. Baseline PDs were similar to those previously reported in other species. Administration of amiloride resulted in a significant fall in nasal PD, as did ouabain administration for 24 h (-27.8 vs. -18.8 mV; P = 0.001; n = 5 rats). Exposure to hypobaric hypoxia (0.5 atm) for 24 h caused a significant fall in nasal PD (-23.7 vs. -18.8 mV; P = 0.002; n = 15 rats), which was not additive to the changes in nasal PD produced by amiloride or ouabain. We conclude that subacute exposure to moderate hypobaric hypoxia can inhibit sodium transport by the airway epithelium in rats.


Assuntos
Células Epiteliais/metabolismo , Hipóxia/metabolismo , Cavidade Nasal/citologia , Sódio/metabolismo , Doença da Altitude/metabolismo , Amilorida/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Diuréticos/farmacologia , Inibidores Enzimáticos/farmacologia , Masculino , Cavidade Nasal/metabolismo , Ouabaína/farmacologia , Edema Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Hum Reprod ; 13(6): 1502-5, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9688382

RESUMO

Obesity affects ovulation, response to fertility treatment, pregnancy rates and outcome. In this prospective study, a weight loss programme was assessed to determine whether it could help obese infertile women, irrespective of their infertility diagnosis, to achieve a viable pregnancy, ideally without further medical intervention. The subjects underwent a weekly programme aimed at lifestyle changes in relation to exercise and diet for 6 months; those that did not complete the 6 months were treated as a comparison group. Women in the study lost an average of 10.2 kg/m2, with 60 of the 67 anovulatory subjects resuming spontaneous ovulation, 52 achieving a pregnancy (18 spontaneously) and 45 a live birth. The miscarriage rate was 18%, compared to 75% for the same women prior to the programme. Psychometric measurements also improved. None of these changes occurred in the comparison group. The cost savings of the programme were considerable. Prior to the programme, the 67 women had had treatment costing a total of A$550,000 for two live births, a cost of A$275,000 per baby. After the programme, the same women had treatment costing a total of A$210,000 for 45 babies, a cost of A$4600 per baby. Thus weight loss should be considered as a first option for women who are infertile and overweight.


Assuntos
Peso Corporal , Infertilidade Feminina/fisiopatologia , Indução da Ovulação , Redução de Peso , Adulto , Feminino , Humanos , Infertilidade Feminina/terapia , Obesidade/fisiopatologia , Gravidez , Resultado da Gravidez
11.
J Psychosom Obstet Gynaecol ; 17(2): 125-8, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8819023

RESUMO

We report on a group program for obese infertile women. Sixty-four women completed the 24-week program, which included exercise, information about healthy eating and group discussion sessions. Their mean initial weight was 101.9 +/- 18.14 kg. The mean weight loss on completion of the program was 5.2 +/- 5.11 kg (p < 0.0001). There was significant improvement on ratings of self-esteem and depression. Changes to life-style and health which are known to improve fertility may be a useful precursor to invasive, high technology infertility treatment procedures.


Assuntos
Infertilidade/complicações , Obesidade/terapia , Redução de Peso , Ansiedade/psicologia , Depressão/psicologia , Dieta , Exercício Físico , Feminino , Humanos , Infertilidade/psicologia , Obesidade/complicações , Obesidade/psicologia , Autoimagem , Apoio Social
12.
Epilepsy Res ; 24(1): 47-55, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8800634

RESUMO

The development and standardisation of an inventory for measuring anti-epileptic drug effects on cognition and affect is described. The Side Effect and Life Satisfaction inventory (SEALS) was derived from symptoms and side-effects reported by a patient population. It was administered to 45 patients on two occasions and test-retest reliability was demonstrated. It was administered to 923 patients with epilepsy. An underlying factor structure was produced by principal components analysis, consisting of five sub-scales which were stable when data from males and females were analysed separately or together. Validity was evaluated by comparing inventory scores of patients undergoing a number of treatment trials to show that the inventory was sensitive to treatment differences when other variables were controlled. Patients taking two or more anti-epileptic drugs had poorer SEALS scores than those taking a single drug. Patients taking vigabatrin and one other AED had poorer scores than those taking lamotrigine (LTG) and one other AED. A comparison of changes from baseline to week 4 of a double blind comparison of carbamazepine (CBZ) and LTG showed significantly greater improvement in SEALS scores for patients taking LTG, and significantly poorer scores in those patients taking CBZ who dropped out of the study, than in those who continued. It is concluded that SEALS is a valid and reliable tool for use in anti-epileptic drug trials.


Assuntos
Anticonvulsivantes/efeitos adversos , Comportamento/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/psicologia , Transtornos do Humor/induzido quimicamente , Transtornos do Humor/psicologia , Adolescente , Adulto , Afeto/efeitos dos fármacos , Envelhecimento/psicologia , Anticonvulsivantes/uso terapêutico , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Método Duplo-Cego , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Fadiga/induzido quimicamente , Fadiga/psicologia , Feminino , Humanos , Relações Interpessoais , Lamotrigina , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Triazinas/efeitos adversos , Triazinas/uso terapêutico
13.
Gen Hosp Psychiatry ; 18(3): 192-5, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8739012

RESUMO

Thirty-seven women with a mean initial weight of 98.5 +/- 18.7 kg completed a group treatment program for obese, infertile women. The program lasted for 24 weeks and included regular exercise and group discussion of topics such as coping with the psychological impact of infertility, developing healthy eating patterns, and the effects of obesity on reproductive physiology. There was significant weight loss (mean weight loss 6.2 +/- 4.5 kg, p < 0.001) and improvement on measures of self-esteem, anxiety, depression, and general health. Twenty-nine women became pregnant during the follow-up period (21-36 months). Two women were avoiding pregnancy, so only six who had completed the group program and wished to become pregnant had not conceived by the end of the follow-up period. A further five women did not complete the program as they became pregnant while attending the group. Our results suggest that active measures to improve mood and self-esteem, along with better nutrition and weight reduction through diet and exercise, can produce considerable improvement in the outcome of treatment for infertility in obese women.


Assuntos
Infertilidade Feminina/psicologia , Obesidade/psicologia , Psicoterapia de Grupo , Adaptação Psicológica , Adulto , Terapia Combinada , Dieta Redutora/psicologia , Exercício Físico/psicologia , Feminino , Fertilização in vitro/psicologia , Seguimentos , Humanos , Infertilidade Feminina/terapia , Obesidade/terapia , Inventário de Personalidade , Gravidez , Autoimagem , Resultado do Tratamento
14.
Int J Eat Disord ; 19(2): 209-12, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8932560

RESUMO

OBJECTIVE: To evaluate the usefulness of dexfenfluramine as an adjunct to a group treatment program for obese infertile women. METHOD: Twenty-one obese infertile women were referred by the Reproductive Medicine Unit. They attended a 24-week group program which included exercise and educational sessions. Dexfenfluramine and placebo were given, each for 12 weeks, in a double-blind crossover design. RESULTS: Dexfenfluramine treatment was not associated with greater loss of weight. The mean weight loss during dexfenfluramine treatment was 3.21 kg (SD 3.09) and during placebo was 3.31 kg (SD 3.15). Self-esteem, anxiety, and depression ratings all improved significantly over the 24 weeks. DISCUSSION: The group treatment program appeared to be equally effective with or without dexfenfluramine. Previous studies have found dexfenfluramine to be effective in combination with individual treatment, but it has not previously been evaluated as an adjunct to group treatment. It is unclear whether dexfenfluramine may be less effective in combination with group treatment programs, or whether its usefulness is restricted in this particular population of obese patients. No differences were found associated with the order in which active and placebo treatments were given. Patients showed improvement in self-esteem and reduction in depression and anxiety, but dexfenfluramine treatment was not associated with any difference in these measures, compared to placebo.


Assuntos
Depressores do Apetite/uso terapêutico , Fenfluramina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Obesidade/tratamento farmacológico , Adulto , Depressores do Apetite/efeitos adversos , Terapia Combinada , Método Duplo-Cego , Exercício Físico/psicologia , Feminino , Fenfluramina/efeitos adversos , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/psicologia , Obesidade/complicações , Obesidade/psicologia , Psicoterapia de Grupo , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos
15.
Hum Reprod ; 10(10): 2705-12, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8567797

RESUMO

Obesity can affect ovulation and the chances of pregnancy. In this prospective study, a weight loss programme was assessed to determine whether it could help infertile overweight anovulatory women to establish ovulation and assist in achieving pregnancy, ideally without further medical intervention. The subjects acted as their own historical controls. They underwent a weekly programme of behavioural change in relation to exercise and diet over 6 months; those who did not complete the 6 months were treated as the comparison group. Women in the study group lost an average of 6.3 kg, with 12 of the 13 subjects resuming ovulation and 11 becoming pregnant, five of these spontaneously. Fitness, diet and psychometric measurements all improved. Fasting insulin and testosterone concentrations dropped significantly, while sex hormone binding globulin concentrations rose. None of these changes occurred in the comparison group. Thus, weight loss with a resultant improvement in ovulation, pregnancy outcome, self-esteem and endocrine parameters is the first therapeutic option for women who are infertile and overweight.


Assuntos
Anovulação/terapia , Infertilidade Feminina/terapia , Obesidade/terapia , Ovulação , Resultado da Gravidez , Redução de Peso , Adulto , Anovulação/etiologia , Dieta , Exercício Físico , Feminino , Humanos , Infertilidade Feminina/etiologia , Obesidade/complicações , Aptidão Física , Gravidez , Estudos Prospectivos
17.
Clin Exp Immunol ; 80(2): 219-24, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2357848

RESUMO

Children from an area of Africa endemic for the large roundworm of humans, Ascaris lumbricoides, were found to vary considerably in the specificity of their serum IgG response to the internal antigens of the parasite. This was particularly noticeable for responses to a 14-kD protein (ABA-1) of the parasite that has previously been shown to be the subject of a strong IgE antibody response in infected animals. The possibility that this heterogeneity in immune repertoire has a genetic basis was explored in inbred mice infected with Ascaris suum. This showed that no strain responded to all the potential antigens, that the recognition profiles of strains bearing independent haplotypes were unique, and only H-2-identical strains had responses of similar specificities. Major histocompatability complex (MHC) restriction was confirmed using H-2-congenic animals on BALB and B10 backgrounds, which responded according to their H-2 haplotype. It is likely, therefore, that it is the MHC which controls the repertoire to Ascaris antigens in infected people. If this is so, then there will be implications for immunopathology associated with ascariasis, and possibly also for resistance and susceptibility to infection.


Assuntos
Anticorpos Anti-Helmínticos/biossíntese , Especificidade de Anticorpos/genética , Antígenos de Helmintos/imunologia , Ascaris/imunologia , Antígenos H-2/fisiologia , Animais , Ascaríase/imunologia , Humanos , Camundongos , Camundongos Endogâmicos
18.
J Immunol ; 143(7): 2349-56, 1989 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-2778320

RESUMO

Humans vary considerably in the antigen specificity of their immune responses to parasitic nematodes, and in the infection loads of individuals living in the same environment. The possibility that the former has a genetic basis operating through repertoire control of the immune system was investigated using infection of mice with the nematode Ascaris. The specificity of the antibody response was examined using excretory/secretory (ES) materials of the parasite as target Ag. No strain of mouse was found to recognize all of the potentially antigenic components of ES, and the Ag recognition patterns varied considerably from strain to strain. Using H-2 congenic mice on both the BALB and B10 backgrounds, it was established that the antigen recognition patterns were MHC-determined. Focusing on one particular component of ES, of Mr 14,000, only H-2s strains responded in IgG. This MHC restriction of the repertoire was confined to infection, and broke down under adjuvant-assisted immunization with the purified protein. The Mr 14,000 molecule was also found to be a potent allergen in a passive cutaneous anaphylaxis assay, and the IgE response to it was also restricted to H-2s. This haplotype was, however, a low IgE responder on the SJL background. There is, therefore, MHC control of the specificity of the immune response to this molecule, but non-MHC control of the amplitude of the IgE antibody response to it. Hybrids between responder and nonresponder strains (BALB/c x SJL)F1, responded to the Mr 14,000, but their responses to other ES components could not be predicted from the response patterns of parental strains. For example, the BALB/c parent responded to a 118-kDa component, but the SJL parent and the F1 progeny did not. Moreover, the response to a 41-kDa Ag was substantially down-regulated in the F1, whereas both parental strains responded vigorously. This new model system, therefore, has implications for MHC control of responses to the allergens of pathogens, and for the complex immunoregulation in heterozygotes in the context of infection.


Assuntos
Alérgenos/imunologia , Anticorpos Anti-Helmínticos/biossíntese , Antígenos de Helmintos/imunologia , Ascaris/imunologia , Antígenos H-2/genética , Animais , Anticorpos Anti-Helmínticos/análise , Cruzamentos Genéticos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Coelhos
20.
Proc Natl Acad Sci U S A ; 86(2): 408, 1989 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2911587
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