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1.
Andrologia ; 39(4): 117-23, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17683459

RESUMO

The spermatogenic effects of levonorgestrel butanoate were studied in adult male bonnet monkeys when administered alone and in combination with testosterone buciclate. Levonorgestrel butanoate (0.25, 1.0 and 2.5 mg kg(-1)) given as two injections on days 0 and 60 (groups II, III, IV) resulted in thickening and folding of the basement membrane and disruption of cell associations in groups III and IV (on day 120). In group II, no apparent changes in testicular histology were observed. When these doses of levonorgestrel butanoate were combined with 40 mg of testosterone buciclate (groups V, VI, VII), maximum changes were seen in group VI in which all stages of spermatogenesis were absent on day 120 except for a small number of spermatogonia. The changes caused by lower dose (group V) and higher dose (group VII) of levonorgestrel butanoate were less prominent than in group VI. A significant decrease in the number of dark A (Ad) and B spermatogonia was observed in all groups except for Ad spermatogonia on day 120 in group V, B spermatogonia on day 60 in group IV and B spermatogonia on day 120 in group III. A significant decrease in pachytene spermatocytes was seen on day 120 in groups V only. Early spermatids showed a significant decrease only in groups V and VII on day 120 of treatment. Advanced spermatids were suppressed significantly in group IV on day 60 and in groups IV and V on day 120. These data indicate that levonorgestrel butanoate (1.0 mg kg(-1)) in combination with 40 mg of testosterone buciclate was the most effective treatment in suppressing spermatogenesis. The site of action of this combination regimen is at the level of renewing Ad spermatogonia.


Assuntos
Norgestrel/análogos & derivados , Testosterona/análogos & derivados , Animais , Quimioterapia Combinada , Macaca radiata , Masculino , Norgestrel/administração & dosagem , Norgestrel/farmacologia , Espermátides/efeitos dos fármacos , Espermatócitos/efeitos dos fármacos , Testosterona/administração & dosagem , Testosterona/farmacologia
2.
Appl Nurs Res ; 17(4): 297-300, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15573339

RESUMO

Peripheral-inserted central catheters (PICCs) offer a successful alternative to peripheral venipuncture for long term medication therapy. When catheters become occluded, the nurse must intervene to avoid delayed or missed treatments. Pharmacological interventions are costly and not without risks. The purpose of this exploratory study was to test a mechanical percussive POP technique to restore patency. Thirty PICC catheters were clotted with human blood and incubated for 8 hours in a 35 degrees saline bath. Using the percussive POP technique, a 10-mL syringe with 1 mL of saline restored patency in 86% of the occluded catheters. The safety and effectiveness of the POP technique in vitro was established.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Percussão/métodos , Segurança , Cloreto de Sódio/administração & dosagem , Irrigação Terapêutica/métodos , Trombose/prevenção & controle , Fenômenos Biomecânicos , Cateterismo Venoso Central/enfermagem , Cateterismo Periférico/enfermagem , Pesquisa em Enfermagem Clínica , Desenho de Equipamento , Falha de Equipamento , Humanos , Percussão/instrumentação , Percussão/enfermagem , Fatores de Risco , Sucção , Seringas/normas , Irrigação Terapêutica/instrumentação , Irrigação Terapêutica/enfermagem , Trombose/etiologia , Resultado do Tratamento
3.
Int J Androl ; 23(2): 95-105, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10762435

RESUMO

Levonorgestrel butanoate, 0.25, 1.0 and 2.5 mg/kg, administered as two injections 60 days apart (groups II, III, IV), failed to suppress spermatogenesis consistently and uniformly in adult bonnet monkeys (group size, n=6) compared to controls (group I). Levonorgestrel butanoate at the same doses combined with two simultaneous injections of 40 mg testosterone buciclate (groups V, VI, VII), consistently suppressed spermatogenesis in the period 60-240 days and in most animals to azoospermia or severe oligozoospermia (<5 x 106/mL) during days 90-210. The degree and duration of suppression were greatest in group VI. Sperm motility declined in all treated animals and spermatozoa in the semen of animals from groups V and VI lost all progressive motility in the period 60-150 and 60-210 days, respectively. The changes in testosterone levels were similar in groups V and VI, increasing within 24 h after the combined injection to reach a peak by day 28 followed by a sharp decrease until day 67. The second injection increased testosterone levels by a lesser degree to peak levels on day 81. In group VII, testosterone levels decreased until day 59 after the first injection but increased to a maximum on day 81 after the second injection followed by a gradual decrease until day 150 to below baseline values. Peak levels of serum levonorgestrel were observed 1-7 days after injection of levonorgestrel butanoate alone. Clearance of the drug was slow, being detectable in the circulation until day 330 of the 360 day study period in the high dose group. Dose-response increases to peak levels of levonorgestrel were attained on day 7 in groups V, VI and VII, after the first injection. After the second injection, peak levels were seen on day 61 in groups V and VI and on day 81 in group VII. Levonorgestrel was no longer detectable in blood in groups V and VI by days 210 and 300, respectively, but small circulating amounts remained in group VII at the conclusion of the study on day 360. This study indicates that when levonorgestrel butanoate is combined with a long-acting androgen and injected at two-monthly intervals, effective and reversible suppression of spermatogenesis is achieved.


Assuntos
Norgestrel/análogos & derivados , Espermatogênese/efeitos dos fármacos , Testosterona/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Macaca radiata , Masculino , Norgestrel/farmacologia , Sêmen/efeitos dos fármacos , Contagem de Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/farmacologia
4.
Int J Gynaecol Obstet ; 67 Suppl 2: S111-6, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10661748

RESUMO

One approach to fertility regulation for which there is still a large unmet need is a once-a-month method that can be taken at the end of the luteal phase as a menses-inducer. Such a method would have a number of logistical and economic advantages for many women over other currently available methods. However, to be acceptable, menses-inducers of this type must not produce disturbances in subsequent menstrual cycles that would lead to unpredictable menstrual patterns or advance or delay subsequent ovulations. A number of structural and functional factors associated with the cyclical development and demise of the endometrium and corpus luteum in fertile and infertile women have been identified and the opportunity is now presented for interfering with implantation by disrupting the function of these factors at the local level in these tissues without systemic involvement or prolonged activity. The Rockefeller Foundation and WHO are supporting six centers and investigators around the world, as an international collaborative research initiative, to investigate the molecular biology of these factors and the effect on fertility of their manipulation. It is intended that promising leads identified and selected in this way will be developed into new products with industry.


Assuntos
Indutores da Menstruação , Comportamento Cooperativo , Feminino , Fundações , Humanos , Apoio à Pesquisa como Assunto , Estados Unidos , Organização Mundial da Saúde
5.
Int J Androl ; 21(1): 8-12, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9639146

RESUMO

Following clinical trials conducted in China in the 1970s, gossypol was proposed as a drug for male contraceptive use. This review summarizes the extensive investigations on formal animal toxicology and on the recovery of fertility in men after stopping gossypol treatment which led to the decision by the Special Programme of Research, Development and Research Training in Human Reproduction (HRP) at the World Health Organization (WHO), that gossypol would not be acceptable as an antifertility drug. It is concluded that the assessment of gossypol reinforces the mandatory requirement that future contraceptive drugs must be developed by the established routes of appropriate animal toxicology and phased clinical studies.


PIP: There have been reports that studies conducted in China confirm the efficacy of gossypol as a male antifertility drug. This paper presents the extensive investigations on formal animal toxicology and on the recovery of male fertility after cessation of gossypol use. Studies conducted by the International Organization for Chemical Sciences in Development showed that 40 of the 70 highly purified, novel structural forms of gossypol were no more active than gossypol. Experiments conducted on Sprague-Dawley rats and cynomolgous monkeys confirm that either (-) or (+) gossypol is too toxic to be developed for human contraception. Among the side effects associated with the use of gossypol, the most serious was hypokalemic paralysis, although differences in reported incidences could be attributed to the regional differences in dietary intake of potassium and genetic predisposition. On the other hand, studies that examine the risk of permanent sterility among healthy reproductive males were confirmed by two separate studies, which found an incidence of 25% irreversible sterility. The failure of recovery among those who stopped gossypol use could be attributed to longer treatment, greater total dose of gossypol, smaller testicular volume, and elevated follicle stimulating hormone concentrations. The cessation of clinical studies on gossypol because of increased risk in irreversible testicular damage and low therapeutic ratio is recommended.


Assuntos
Anticoncepcionais Masculinos/efeitos adversos , Gossipol/efeitos adversos , Acetatos/efeitos adversos , Animais , Humanos , Hipopotassemia/etiologia , Infertilidade Masculina/etiologia , Masculino , Oligospermia , Ratos , Risco
6.
BioDrugs ; 8(6): 457-68, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18031108

RESUMO

The advent of immunocontraceptives represents the first truly novel approach to the development of family planning methods in over 30 years. Such products would have many advantages over existing contraceptives in that they would not elicit metabolic disturbances, would provide long-acting (i.e. 6 to 12 months) protection from pregnancy, be easy to administer, be economical to manufacture and distribute, and could, depending on their composition, be used by either men or women. Several lines of research and development currently in progress are aimed at the development of safe and effective immunocontraceptives based on reproductive hormones, components of the gametes (sperm and ova) and products of the early pre-implantation conceptus. The only prototype immunocontraceptives to have reached the stage of clinical trials in women are those based on the hormone human chorionic gonadotropin, and in men that based on follicle-stimulating hormone. However, extensive research is also underway on immunocontraceptives based on sperm and ovum components for use by women, and on immunocontraceptives based on sperm components and gonadotropin-releasing hormone for use by men. Before such preparations can be made available for wide-scale use, further research is needed on ways to overcome genetically determined variations in individual immune responses so that protective responses of a predetermined duration can be elicited in all recipients. It is anticipated that these technical problems can be solved and the clinical testing of lead products will be completed in the next decade. Almost all of the financial support for the research and development of immunocontraceptives has been provided by academic institutions and public sector agencies. In general, the pharmaceutical industry has not been willing to engage in new contraceptive development, largely because of concerns about product liability claims, anticipated low profitability and/or the risk of negative publicity. Therefore, the further development, manufacture and distribution of immunocontraceptives will probably require the collaboration of public sector agencies, governments and industry in order to overcome the current paucity of effort being put into the development and provision of new, safe, effective and acceptable methods of family planning. The purpose of this review is to provide information on the current status of research and development of potential immunocontraceptives and to attempt to stimulate pharmaceutical companies to reassess their positions with regard to the development, manufacture and distribution of these products.

10.
Immunol Today ; 16(10): 502-3, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7576057
11.
Hum Reprod ; 9(2): 267-72, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8027282

RESUMO

The possibility of using the immune system to provide protection against an unwanted pregnancy has been postulated since the very early days of modern immunology. During the past two decades or more, a major goal-directed research effort, involving several independent groups of investigators, has been underway with the objective of developing birth control vaccines suitable for use by men and women at all stages of their reproductive lives. The most advanced work in this area is concerned with the development of a vaccine directed against human chorionic gonadotrophin (HCG), a hormone that is produced by the peri-implantation embryo and that is essential for successful implantation and the establishment of early pregnancy. These studies have reached the stage of clinical testing of a number of prototype vaccines based on different parts of the HCG molecule. No adverse side effects have been observed or reported in these clinical trials and larger scale clinical studies are being planned to assess further the safety, efficacy and acceptability of these preparations. Research is also underway to develop improved versions of these HCG vaccines that will offer 12-18 months protection following a single injection. The stage is set for the introduction, by the turn of this century, of the first totally new method of family planning in four decades.


Assuntos
Gonadotropina Coriônica/imunologia , Anticoncepção/métodos , Imunização , Vacinas/imunologia , Sequência de Aminoácidos , Autoanticorpos/biossíntese , Autoanticorpos/sangue , Ensaios Clínicos como Assunto , Feminino , Humanos , Tolerância Imunológica , Dados de Sequência Molecular
13.
Scand J Immunol Suppl ; 11: 111-7, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1514024

RESUMO

Although the number of family planning methods currently available to couples has never been greater, the range and type of options are still not adequate to meet the widely varying personal needs and demands of individuals worldwide. Birth control vaccines offer a number of theoretical attractions although the development, preclinical and clinical testing of such vaccines pose a number of unique problems requiring novel solutions. If the on-going studies in this area are successful, a valuable new family planning method may be available by the end of the current decade.


PIP: Research on immunization against self-antigens as a means of controlling normal physiological processes, such as those involved in reproduction, has not been extensive. Candidates for antifertility vaccines include molecules that are tissue-specific proteins expressed on the mature gametes (sperm and/or ovum) and the trophectoderm of the preimplantation embryo and, to a lesser extent, the pituitary gonadotropin, follicle stimulating hormone. The most advanced work in this area involves the development of vaccines based on human chorionic gonadotropin (hCG), the hormone that is produced in, and secreted by, the trophectoderm of the preimplantation embryo. The WHO Task Force on Vaccines for Fertility Regulation has conducted studies in connection with its anti-hCG vaccine development program since the early 1970s. The various stages of clinical testing of a novel antifertility vaccine begin with Phase I to determine the safety of the preparation in humans. Phase I studies usually involve about 50 subjects allocated sequentially to increasing dose groups, and take 1-2 years to complete. The principal purpose of a Phase II clinical trial of an antifertility vaccine is to determine the efficacy of a selected dose of vaccine in healthy, fertile volunteers. Phase II studies typically involve 100-200 subjects and take 2-3 years to complete. A Phase III clinical trial determines efficacy and safety in the general population by recruiting more than 1000 subjects, and it may take 4-6 years to complete. The development process from prototype to final product may require modifications for scientific or medical reasons, such as large differences in individual immune responses or the appearance of unacceptable side effects of low incidence, or for practical reasons, such as quality assurance and formulation needs when scaling up production from experimental quantities to large-scale manufacture.


Assuntos
Anticoncepção Imunológica/métodos , Vacinas , Animais , Feminino , Humanos , Masculino
14.
Geneva; World Health Organization; 1992. 171 p. ilus.
Monografia em Inglês | PAHO | ID: pah-10844

RESUMO

The Special Programme of Research, Development and Research Training in Human Reproduction was established by WHO in 1972 to coordinate, promote, conduct, and evaluate international research in human reproduction. The Programme brings together administrators, policy-makers, scientists, clinicians and the community to identify priorities for research and for the strengthening, in developing countries, of research institutions. It marshals the scientific community to conduct research in human reproduction and to evaluate the results of research. The Programme also ensures coordination of efforts in this field and in the exchange of information, joint planning, and joint activities among national, nongovernmental, and international agencies involved in institution strengthening and research in human reproduction and family planning


Assuntos
Anticoncepção , Serviços de Planejamento Familiar , Reprodução , Nível de Saúde
15.
Stat Med ; 10(2): 177-90, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2052798

RESUMO

Since the mid 1970s, the World Health Organization's Special Programme of Research, Development and Research Training in Human Reproduction, through its Task Force on Vaccines for Fertility Regulation, has been supporting and coordinating the development of a birth control vaccine based on a synthetic peptide representing part of the beta subunit of human chorionic gonadotrophin (beta-hCG). The majority of this work has been carried out in the laboratories of Dr V.C. Stevens at Ohio State University. This hCG vaccine has recently been tested for tolerability and immunogenicity in a phase I clinical trial, and a preliminary evaluation of the vaccine's efficacy in fertile women volunteers is currently being planned. This paper describes the preclinical and clinical testing of this vaccine and the problems and challenges presented by this novel preparation. These have included the need to carry out safety and efficacy studies in the baboon, and the difficulties of designing appropriate preclinical toxicity and immunosafety studies and clinical trial protocols in the absence of previous experience with vaccines of this type.


Assuntos
Gonadotropina Coriônica , Serviços de Planejamento Familiar/métodos , Vacinas Sintéticas , Animais , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos
16.
Hum Reprod ; 6(1): 166-72, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1874951

RESUMO

Over the past 18 years, the WHO Task Force on Vaccines for Fertility Regulation has been supporting basic and clinical research on the development of birth control vaccines directed against the gametes or the preimplantation embryo. These studies have involved the use of advanced procedures in peptide chemistry, hybridoma technology and molecular genetics as well as the evaluation of a number of novel approaches in general vaccinology. As a result of this international, collaborative effort, a prototype anti-HCG vaccine is now undergoing clinical testing, raising the prospect that a totally new family planning method may be available before the end of the current decade.


PIP: The WHO Task Force on Vaccines for Fertility Regulation is one of several Task Forces, consisting of international, multidisciplinary groups of scientists and clinicians collaborating in research on specific goals, established in 1972. Its accomplishments are reviewed here. The Task Force convened a meeting in 1974 to select criteria for tissues and molecules capable of mounting antifertility responses. These molecules had to be restricted to the target tissue, sequestered in the reproductive tract, present transiently, and chemically characterized. Some of the antigens considered were sperm enzymes and membranes, as well as a data bank of sera naturally immunized against sperm. Other were anti-ovum and placenta molecules such as zona pellucida, the SP-1 placental antigen, and the placental hormones chorionic somatotrophin and human chorionic gonadotropin (hCH). Trophoblast-derived monoclonal antibodies and gene libraries are being screened. Anti-hCH is the vaccine composed of a portion of the beta subunit complexed to a carrier antigen, diphtheria toxoid, in a water- oil emulsion with an adjuvant has been tested in a phase I clinical trial in 1986-1988. A Phase II trial is being planned to see if the immune response in women is large enough to be capable of preventing pregnancy. Further improvements in the vaccine are being envisioned, such as incorporation of the peptide carrier conjugate and immune stimulant into biodegradable microspheres, hopefully to produce a longer-lasting immunity and a more stable vaccine. While the WHO Task Force on Vaccines for Fertility Regulation has been forced to cut back on some avenues of research, its success has stimulated other centers to take up several important projects, e.g. the sperm LDH and zona pellucida vaccines.


Assuntos
Anticoncepção Imunológica/história , Organização Mundial da Saúde , Animais , Gonadotropina Coriônica/imunologia , Anticoncepção Imunológica/métodos , História do Século XX , Humanos , Masculino , Óvulo/imunologia , Placenta/imunologia , Lactogênio Placentário/imunologia , Espermatozoides/imunologia
17.
Lancet ; 1(8598): 1295-8, 1988 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-2453766

RESUMO

A birth control vaccine incorporating a synthetic peptide antigen representing the aminoacid sequence 109-145 of the C-terminal region of the beta subunit of human chorionic gonadotropin (hCG-beta) was submitted to a phase 1 clinical trial. Thirty surgically sterilised female volunteers, divided into five equal groups for different vaccine doses, received two intramuscular injections six weeks apart. Over a six-month follow-up there were no important adverse reactions, and potentially contraceptive levels of antibodies to hCG developed in all subjects. In the highest vaccine dose group, the results gave promise of a contraceptive effect of six months' duration.


PIP: A Phase I clinical trial of the immunogenicity and safety of a vaccine against the C-terminal region of the beta subunit of human chorionic gonadotropin (hCG-B) demonstrated a dose-related immune response. The antigen was a synthetic peptide of the C 109-145 region of hCG-B, conjugated to diphtheria toxoid, and administered in a water-soluble synthetic adjuvant in a saline-oil emulsion. This vaccine had been previously tested for toxicity in laboratory animals and for immunogenicity, safety and contraceptive effectiveness in baboons. 30 previously sterilized women were given 2 injections 6 weeks apart, ranging from 50 to 1000 mcg of the antigen. Each woman tested free of HLA B27 antigen and reacted negative to the diphtheria toxoid skin test. Based on calculated contraceptive antibody binding level of 0.52 nmol/l, all subjects mounted an effective antibody response for at least 6 months. 2 subjects in the group given 1000 mcg who were followed for 9 and 10 months maintained this level of antibody. 12 women showed an anamnestic response to diphtheria toxoid, while 8 did not. The only adverse reactions were mild, transient pain at the injection site. Several women who received unstable adjuvant experienced more severe myalgia. Menstrual changes appeared in 5 subjects: early menopause in 1, spotting in 3 and menorrhagia in 1 woman. Only transient positive findings were seen in some sera screened for autoantibodies. This preliminary trial indicates that anti-hCG vaccine is a hopeful reversible contraceptive.


Assuntos
Anticorpos/imunologia , Gonadotropina Coriônica/imunologia , Fragmentos de Peptídeos/imunologia , Vacinas , Organização Mundial da Saúde , Adulto , Autoanticorpos/imunologia , Gonadotropina Coriônica Humana Subunidade beta , Anticoncepção Imunológica/métodos , Reações Cruzadas , Toxoide Diftérico , Avaliação de Medicamentos , Feminino , Humanos
18.
J Reprod Immunol ; 10(3): 231-57, 1987 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3585867

RESUMO

Two WHO-sponsored workshops were recently held to obtain a consensus view from researchers active in the field of reproductive immunology on the current status of the application of monoclonal antibodies to studies of molecular events underlying reproduction and to determine the feasibility of using this approach to identify trophoblast- or sperm-specific antigens that might represent suitable candidates for the development of antifertility vaccines. A total of 66 mouse monoclonal antibodies reacting with human sperm and 45 monoclonal antibodies reacting with human trophoblast membrane components were submitted by 29 laboratories. These were evaluated in coded form by 42 laboratories with the appropriate expertise in biochemistry, immunohistology and tests of reproductive cell function. The majority of both anti-sperm and anti-trophoblast monoclonal antibodies cross-reacted with cellular elements in non-reproductive tissues. However, at least five monoclonal antibodies (two anti-trophoblast and three anti-sperm) appeared to demonstrate sufficient specificity to warrant further investigation as reagents for the identification of antifertility vaccine candidates.


Assuntos
Anticorpos Monoclonais , Espermatozoides/imunologia , Trofoblastos/imunologia , Coriocarcinoma/imunologia , Reações Cruzadas , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Gravidez , Sêmen/imunologia , Teratoma/imunologia , Organização Mundial da Saúde
19.
J Reprod Immunol ; 8(4): 271-8, 1985 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2422369

RESUMO

In an attempt to identify appropriate antigens for birth control vaccines, the Task Force on Immunological Methods for Fertility Regulation under WHO's Special Programme of Research, Development and Research Training in Human Reproduction carried out an investigation of naturally occurring immune responses to reproductive tract antigens which were consistently associated with infertility. Large volumes of sera from subjects satisfying the criteria for one of 16 different clinical categories (listed in Table 1) were collected and samples were subsequently assessed, under code, by investigators with experience in the detection of antibodies to antigens involved in the reproductive process. Sera from 329 persons were included in the study and 20 laboratories examined the sera for antibodies to sperm, zona pellucida, and trophoblast or trophoblast products. In addition, antibodies to certain microbial antigens and to various leucocyte and organ antigens were investigated. The results of these studies are presented in the following papers.


Assuntos
Epitopos/análise , Serviços de Planejamento Familiar/métodos , Ovário/imunologia , Espermatozoides/imunologia , Testículo/imunologia , Útero/imunologia , Vacinas/imunologia , Anticorpos/análise , Epitopos/imunologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Imunização Passiva/métodos , Infertilidade Feminina/sangue , Infertilidade Feminina/imunologia , Infertilidade Masculina/sangue , Infertilidade Masculina/imunologia , Cooperação Internacional , Masculino , Testes Sorológicos , Vacinas/administração & dosagem , Organização Mundial da Saúde
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