Larissa Coutinho - Academia.edu (original) (raw)
Papers by Larissa Coutinho
Advances in Clinical Chemistry
Human Reproduction Update
BACKGROUND Despite intense research, it remains intriguing why hormonal therapies in general and ... more BACKGROUND Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis. OBJECTIVE AND RATIONALE We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments. SEARCH METHODS We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment. OUTCOMES Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase ...
Clinics in Mother and Child Health
Introduction: Thrombophilias are associated with venous thromboembolism. According to reports, ut... more Introduction: Thrombophilias are associated with venous thromboembolism. According to reports, uteroplacental thrombosis can lead to preeclampsia, intrauterine growth restriction (IUGR), placental abruption (PA) and even to fetal death. The Brazilian Ministry of Health recommends the application of heparin treatment-associated, or not, with ASA to pregnant women diagnosed with thrombophilia, based on its type. However, many studies have not been able to confirm the beneficial effects of heparin use on maternal and fetal health. Methods: The current research is a case-control study comprising pregnant women treated at the Obstetrics Service of Federal University of Juiz de Fora and at the Medical School of Barbacena, who used heparin in the current pregnancy due to previously diagnosed thrombophilia. Current pregnancy associated with heparin use was named 'case', whereas previous pregnancy without heparin use was named 'control'. Thus, 47 cases (current pregnancy) and 32 controls were selected (1,4 cases: 1,0 control). Results: Association between heparin and miscarriage, intrauterine fetal death and preeclampsia were analyzed. Results showed that heparin acted as protective factor against miscarriage (OR=0.04; CI=0.01-0.14; p<0.0001), intrauterine fetal death (OR=0.01; CI=0.01-0.11; but heparin use did not reduce the frequency of preeclampsia cases (OR=0.35; CI=0.07-1.6; p=0.17). Conclusion: Based on the current results, the early heparin application to pregnant women with thrombophilia was able to reduce the number of miscarriage, intrauterine death, but did not reduce the frequency of preeclampsia.
Clinics in Mother and Child Health
Introduction: Doppler flowmetry of uterine arteries allows identifying women at risk of developin... more Introduction: Doppler flowmetry of uterine arteries allows identifying women at risk of developing preeclampsia (PE), mainly early preeclampsia; it also facilitates the timely use of prophylaxis. Minidose Acetylsalicylic Acid (ASA) can help preventing/delaying preeclampsia development, as well as reducing its severity and the risk of complications. However, not all patients can use this medication; therefore, it is necessary finding clinical alternatives for pregnant women who do not tolerate ASA, as well as evaluating the possibility of increasing this prophylaxis with new drugsthe use of omega 3 is one of these alternatives. Thus, it is possible assuming that omega use by pregnant women could reduce the vascular resistance of uterine arteries and facilitate placentation. The aim of the current study is to evaluate uterine artery resistance and pulsatility indices, as well as bilateral notch in pregnant women presenting identifiable risk factor for PE development, who use omega 3 in association, or not, with ASA. Methodology: The current research is a randomized-controlled, non-blind, parallel, two-arm, open-label preventive clinical trial. Patients were divided into two groups: group 1-use of ASA; and group 2-use of ASA+omega 3. Omegabased supplementations comprised doses of 400 mg/day in gelatin capsules, at DHA: EPA ratios 2.5:1 and 5.0:1. Results: Patients' mean age was 33.48+4.68 years. Mean pregnancies and childbirths were 1.93+1.30 and 0.59 ± 0.37, respectively. Results of uterine artery Doppler flowmetry were associated with omega and/or ASA use; patients who used ASA in association with omega (ASA+omega) recorded the highest uterine artery resistance and pulsatility indices-results were statistically significant. The comparison between ASA use in association, or not, with omega did not show difference in PE, prematurity, oligohydramnios, IUGR or hospitalization in neonatal ICU frequency. There were no cases of fetal death or Hellp Syndrome in either groups. Conclusion: The omega 3 use in association with ASA has increased the uterine artery resistance and pulsatility indices of the investigated patients; however, it did not make any difference in primary and secondary outcomes.
Clinics in Mother and Child Health
Introduction: It is possible assuming that thrombophilias can change the optimal placental functi... more Introduction: It is possible assuming that thrombophilias can change the optimal placental function, as well as lead to infarctions, impaired maternal-fetal exchange mechanisms and even to fetal death. Placental hypoxia determines a vicious cycle comprising oxidative stress, vasoconstriction and impaired fetal oxygenation. Prophylactic heparin use throughout pregnancy has been recommended in some thrombophilia cases because it acts on the coagulation cascade. However, although heparin does not cross the placental barrier and is safe for the fetus, not all patients can use it. Its administration route (parenteral) is not practical and even its prophylactic use is not necessarily harmless, as seen in different thrombocytopenia, gastrointestinal and cerebral bleeding reports. Thus, finding clinical alternatives for these pregnant women would help significantly improving the current medical practice. The use of essential fatty acids (EFAs) is a new perspective that appears to be applicable in daily medical practice, because it facilitates the blood flow and tissue oxygenation, since they reduce vascular resistance and platelet aggregation. Methods: This study is a randomized, controlled, unblind, parallel, three-arm, open-label prevention trial conducted with pregnant women diagnosed with thrombophilia, who were treated in the Obstetrics Services of University Hospitals belonging to UFJF and to Medical School of Barbacena. All the patients were divided in two groups: Group 1=Hereditary thrombophilia patients who used 40 mg of heparin/day (enoxaparin) from the 6th pregnancy week on; Group 2 Patients with acquired or hereditary thrombophilias associated with risk factors for preeclampsia, according to ACOG19 (chronic kidney disease, previous diabetes mellitus, chronic arterial hypertension and collagenoses). Results: The current study assessed 38 pregnant women. Patients' mean age was 32.9 ± 5.0 years. The pulsatility index in the second gestational trimester (24 to 28 weeks) was compared based on treatments. Patients treated with the H+ASA+omega association recorded the lowest pulsatility index; however, there was not statistically significant difference between groups (p>0.05). Uterine artery resistance index in the second gestational trimester (24 to 28 weeks) was also compared based on treatments. Patients treated with the H+ASA+omega association recorded the best resistance index, however, there was not statistically significant difference between groups (p>0.05). The group treated only with heparin recorded the lowest fetal weight, although there was not statistically significant difference between groups. Conclusion: Our results are preliminary, and a crude evaluation of the data shows a decrease in the pulsatility and resistance indices of the uterine art. With the increase of patients in the analysis, we hope that the statistical results can demonstrate this improvement of placental flow.
Gynecological Endocrinology
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 23, 2015
Activin A is a growth factor that stimulates decidualization and is abundantly expressed in endom... more Activin A is a growth factor that stimulates decidualization and is abundantly expressed in endometrial proliferative disorders. Nevertheless, whether it directly affects endometrial cell survival is still unknown. This study investigated the effects of activin A on total death and apoptosis rates and on tumor necrosis factor (TNF) release by human endometrial stromal cells (HESC). We performed a controlled prospective in vitro study using primary HESC cultures obtained from healthy reproductive age women (n = 11). Cells were treated with medium alone (control) or activin A (25 ng/mL) or activin A (25 ng/mL) and its antagonist follistatin (250 ng/mL). Apoptosis and total cell death were measured by flow cytometry, while TNF concentrations in culture media were quantified by ELISA. Activin A decreased the percentage of apoptotic/dead cells from 31% to 22% (p < 0.05, paired t-test) and reduced TNF levels in culture medium by 14%, but there was no linear correlation between TNF rele...
Revista brasileira de ginecologia e obstetrícia : revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2008
Camptomelic dysplasia belongs to a heterogeneous and rare group of lethal skeletal dysplasias, ch... more Camptomelic dysplasia belongs to a heterogeneous and rare group of lethal skeletal dysplasias, characterized by abnormal development of bones and cartilages. It is caused by a mutation in gene Sox9 (SRY-like HMG [high-mobility group] BOX 9) of chromosome 17 and it is transmitted as an autosomal dominant trait. Its main characteristics are the shortening and bowing of the long bones, principally the lower limbs. It is also associated with other severe skeletal and extraskeletal malformations. Karyotype study may reveal sex reversal. The majority of carriers die during the fetal and early neonatal periods. Ultrasound is essential to elucidate a prenatal diagnosis.
Revista Brasileira de Ginecologia e Obstetrícia, 2008
Relato de caso Resumo A displasia camptomélica pertence a um grupo heterogêneo e raro de displasi... more Relato de caso Resumo A displasia camptomélica pertence a um grupo heterogêneo e raro de displasias esqueléticas letais, que se caracterizam pelo desenvolvimento anormal dos ossos e das cartilagens. É causada por uma mutação no gene Sox9 (SRY-like HMG [high-mobility group] BOX 9) do cromossomo 17 e transmitida pela via autossômica dominante. Apresenta como principais características o encurtamento e o encurvamento dos ossos longos, principalmente nos membros inferiores. Também está associada a outras graves malformações esqueléticas e extra-esqueléticas. O estudo do cariótipo pode revelar incompatibilidade entre o genótipo e o fenótipo genital. A maioria dos portadores morre nos períodos fetal e neonatal precoce. A ultra-sonografia é essencial para a elucidação diagnóstica pré-natal.
Revista Brasileira de Ginecologia e Obstetrícia, 2010
Artigo original Resumo OBJETIVOS: avaliar a evolução da adequação do processo de atendimento às g... more Artigo original Resumo OBJETIVOS: avaliar a evolução da adequação do processo de atendimento às gestantes usuárias do Sistema Único de Saúde (SUS) e consolidar metodologia para monitoramento da assistência pré-natal. MÉTODOS: estudo de séries temporais múltiplas, com auditoria em cartões de gestantes que realizaram pré-natal em município do Sudeste brasileiro (Juiz de Fora, Minas Gerais) nos semestres iniciais de 2002 e 2004 (370 e 1.200 cartões, respectivamente) e utilizaram o SUS no atendimento ao parto a termo (p ≤ 0,05). Obedeceu-se a uma sequência em três níveis complementares: utilização do pré-natal (início e número de atendimentos) no nível 1; utilização do pré-natal e procedimentos clínicoobstétricos obrigatórios em uma consulta pré-natal [aferições de pressão arterial (PA), peso, altura uterina (AU), idade gestacional (IG), batimentos cardiofetais (BCFs) e apresentação fetal] no nível 2; e utilização, procedimentos clínico-obstétricos obrigatórios e exames laboratoriais básicos, segundo o Programa de Humanização no Pré-natal e Nascimento/PHPN [tipagem ABO/Rh, hemoglobina/hematócrito (Hb/Htc), VDRL, glicemia e exame comum de urina] no nível 3. RESULTADOS: confirmou-se a alta cobertura pré-natal (99%), aumento da média de consultas/gestante (6,4 versus 7,2%) e decréscimo da idade gestacional na primeira consulta (17,4 versus 15,7 semanas). Aumentaram significativamente os registros adequados dos procedimentos e exames (exceções: apresentação fetal e tipagem sanguínea):
Revista Brasileira de …, 2003
Advances in Clinical Chemistry
Human Reproduction Update
BACKGROUND Despite intense research, it remains intriguing why hormonal therapies in general and ... more BACKGROUND Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis. OBJECTIVE AND RATIONALE We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments. SEARCH METHODS We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment. OUTCOMES Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase ...
Clinics in Mother and Child Health
Introduction: Thrombophilias are associated with venous thromboembolism. According to reports, ut... more Introduction: Thrombophilias are associated with venous thromboembolism. According to reports, uteroplacental thrombosis can lead to preeclampsia, intrauterine growth restriction (IUGR), placental abruption (PA) and even to fetal death. The Brazilian Ministry of Health recommends the application of heparin treatment-associated, or not, with ASA to pregnant women diagnosed with thrombophilia, based on its type. However, many studies have not been able to confirm the beneficial effects of heparin use on maternal and fetal health. Methods: The current research is a case-control study comprising pregnant women treated at the Obstetrics Service of Federal University of Juiz de Fora and at the Medical School of Barbacena, who used heparin in the current pregnancy due to previously diagnosed thrombophilia. Current pregnancy associated with heparin use was named 'case', whereas previous pregnancy without heparin use was named 'control'. Thus, 47 cases (current pregnancy) and 32 controls were selected (1,4 cases: 1,0 control). Results: Association between heparin and miscarriage, intrauterine fetal death and preeclampsia were analyzed. Results showed that heparin acted as protective factor against miscarriage (OR=0.04; CI=0.01-0.14; p<0.0001), intrauterine fetal death (OR=0.01; CI=0.01-0.11; but heparin use did not reduce the frequency of preeclampsia cases (OR=0.35; CI=0.07-1.6; p=0.17). Conclusion: Based on the current results, the early heparin application to pregnant women with thrombophilia was able to reduce the number of miscarriage, intrauterine death, but did not reduce the frequency of preeclampsia.
Clinics in Mother and Child Health
Introduction: Doppler flowmetry of uterine arteries allows identifying women at risk of developin... more Introduction: Doppler flowmetry of uterine arteries allows identifying women at risk of developing preeclampsia (PE), mainly early preeclampsia; it also facilitates the timely use of prophylaxis. Minidose Acetylsalicylic Acid (ASA) can help preventing/delaying preeclampsia development, as well as reducing its severity and the risk of complications. However, not all patients can use this medication; therefore, it is necessary finding clinical alternatives for pregnant women who do not tolerate ASA, as well as evaluating the possibility of increasing this prophylaxis with new drugsthe use of omega 3 is one of these alternatives. Thus, it is possible assuming that omega use by pregnant women could reduce the vascular resistance of uterine arteries and facilitate placentation. The aim of the current study is to evaluate uterine artery resistance and pulsatility indices, as well as bilateral notch in pregnant women presenting identifiable risk factor for PE development, who use omega 3 in association, or not, with ASA. Methodology: The current research is a randomized-controlled, non-blind, parallel, two-arm, open-label preventive clinical trial. Patients were divided into two groups: group 1-use of ASA; and group 2-use of ASA+omega 3. Omegabased supplementations comprised doses of 400 mg/day in gelatin capsules, at DHA: EPA ratios 2.5:1 and 5.0:1. Results: Patients' mean age was 33.48+4.68 years. Mean pregnancies and childbirths were 1.93+1.30 and 0.59 ± 0.37, respectively. Results of uterine artery Doppler flowmetry were associated with omega and/or ASA use; patients who used ASA in association with omega (ASA+omega) recorded the highest uterine artery resistance and pulsatility indices-results were statistically significant. The comparison between ASA use in association, or not, with omega did not show difference in PE, prematurity, oligohydramnios, IUGR or hospitalization in neonatal ICU frequency. There were no cases of fetal death or Hellp Syndrome in either groups. Conclusion: The omega 3 use in association with ASA has increased the uterine artery resistance and pulsatility indices of the investigated patients; however, it did not make any difference in primary and secondary outcomes.
Clinics in Mother and Child Health
Introduction: It is possible assuming that thrombophilias can change the optimal placental functi... more Introduction: It is possible assuming that thrombophilias can change the optimal placental function, as well as lead to infarctions, impaired maternal-fetal exchange mechanisms and even to fetal death. Placental hypoxia determines a vicious cycle comprising oxidative stress, vasoconstriction and impaired fetal oxygenation. Prophylactic heparin use throughout pregnancy has been recommended in some thrombophilia cases because it acts on the coagulation cascade. However, although heparin does not cross the placental barrier and is safe for the fetus, not all patients can use it. Its administration route (parenteral) is not practical and even its prophylactic use is not necessarily harmless, as seen in different thrombocytopenia, gastrointestinal and cerebral bleeding reports. Thus, finding clinical alternatives for these pregnant women would help significantly improving the current medical practice. The use of essential fatty acids (EFAs) is a new perspective that appears to be applicable in daily medical practice, because it facilitates the blood flow and tissue oxygenation, since they reduce vascular resistance and platelet aggregation. Methods: This study is a randomized, controlled, unblind, parallel, three-arm, open-label prevention trial conducted with pregnant women diagnosed with thrombophilia, who were treated in the Obstetrics Services of University Hospitals belonging to UFJF and to Medical School of Barbacena. All the patients were divided in two groups: Group 1=Hereditary thrombophilia patients who used 40 mg of heparin/day (enoxaparin) from the 6th pregnancy week on; Group 2 Patients with acquired or hereditary thrombophilias associated with risk factors for preeclampsia, according to ACOG19 (chronic kidney disease, previous diabetes mellitus, chronic arterial hypertension and collagenoses). Results: The current study assessed 38 pregnant women. Patients' mean age was 32.9 ± 5.0 years. The pulsatility index in the second gestational trimester (24 to 28 weeks) was compared based on treatments. Patients treated with the H+ASA+omega association recorded the lowest pulsatility index; however, there was not statistically significant difference between groups (p>0.05). Uterine artery resistance index in the second gestational trimester (24 to 28 weeks) was also compared based on treatments. Patients treated with the H+ASA+omega association recorded the best resistance index, however, there was not statistically significant difference between groups (p>0.05). The group treated only with heparin recorded the lowest fetal weight, although there was not statistically significant difference between groups. Conclusion: Our results are preliminary, and a crude evaluation of the data shows a decrease in the pulsatility and resistance indices of the uterine art. With the increase of patients in the analysis, we hope that the statistical results can demonstrate this improvement of placental flow.
Gynecological Endocrinology
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, Jan 23, 2015
Activin A is a growth factor that stimulates decidualization and is abundantly expressed in endom... more Activin A is a growth factor that stimulates decidualization and is abundantly expressed in endometrial proliferative disorders. Nevertheless, whether it directly affects endometrial cell survival is still unknown. This study investigated the effects of activin A on total death and apoptosis rates and on tumor necrosis factor (TNF) release by human endometrial stromal cells (HESC). We performed a controlled prospective in vitro study using primary HESC cultures obtained from healthy reproductive age women (n = 11). Cells were treated with medium alone (control) or activin A (25 ng/mL) or activin A (25 ng/mL) and its antagonist follistatin (250 ng/mL). Apoptosis and total cell death were measured by flow cytometry, while TNF concentrations in culture media were quantified by ELISA. Activin A decreased the percentage of apoptotic/dead cells from 31% to 22% (p < 0.05, paired t-test) and reduced TNF levels in culture medium by 14%, but there was no linear correlation between TNF rele...
Revista brasileira de ginecologia e obstetrícia : revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2008
Camptomelic dysplasia belongs to a heterogeneous and rare group of lethal skeletal dysplasias, ch... more Camptomelic dysplasia belongs to a heterogeneous and rare group of lethal skeletal dysplasias, characterized by abnormal development of bones and cartilages. It is caused by a mutation in gene Sox9 (SRY-like HMG [high-mobility group] BOX 9) of chromosome 17 and it is transmitted as an autosomal dominant trait. Its main characteristics are the shortening and bowing of the long bones, principally the lower limbs. It is also associated with other severe skeletal and extraskeletal malformations. Karyotype study may reveal sex reversal. The majority of carriers die during the fetal and early neonatal periods. Ultrasound is essential to elucidate a prenatal diagnosis.
Revista Brasileira de Ginecologia e Obstetrícia, 2008
Relato de caso Resumo A displasia camptomélica pertence a um grupo heterogêneo e raro de displasi... more Relato de caso Resumo A displasia camptomélica pertence a um grupo heterogêneo e raro de displasias esqueléticas letais, que se caracterizam pelo desenvolvimento anormal dos ossos e das cartilagens. É causada por uma mutação no gene Sox9 (SRY-like HMG [high-mobility group] BOX 9) do cromossomo 17 e transmitida pela via autossômica dominante. Apresenta como principais características o encurtamento e o encurvamento dos ossos longos, principalmente nos membros inferiores. Também está associada a outras graves malformações esqueléticas e extra-esqueléticas. O estudo do cariótipo pode revelar incompatibilidade entre o genótipo e o fenótipo genital. A maioria dos portadores morre nos períodos fetal e neonatal precoce. A ultra-sonografia é essencial para a elucidação diagnóstica pré-natal.
Revista Brasileira de Ginecologia e Obstetrícia, 2010
Artigo original Resumo OBJETIVOS: avaliar a evolução da adequação do processo de atendimento às g... more Artigo original Resumo OBJETIVOS: avaliar a evolução da adequação do processo de atendimento às gestantes usuárias do Sistema Único de Saúde (SUS) e consolidar metodologia para monitoramento da assistência pré-natal. MÉTODOS: estudo de séries temporais múltiplas, com auditoria em cartões de gestantes que realizaram pré-natal em município do Sudeste brasileiro (Juiz de Fora, Minas Gerais) nos semestres iniciais de 2002 e 2004 (370 e 1.200 cartões, respectivamente) e utilizaram o SUS no atendimento ao parto a termo (p ≤ 0,05). Obedeceu-se a uma sequência em três níveis complementares: utilização do pré-natal (início e número de atendimentos) no nível 1; utilização do pré-natal e procedimentos clínicoobstétricos obrigatórios em uma consulta pré-natal [aferições de pressão arterial (PA), peso, altura uterina (AU), idade gestacional (IG), batimentos cardiofetais (BCFs) e apresentação fetal] no nível 2; e utilização, procedimentos clínico-obstétricos obrigatórios e exames laboratoriais básicos, segundo o Programa de Humanização no Pré-natal e Nascimento/PHPN [tipagem ABO/Rh, hemoglobina/hematócrito (Hb/Htc), VDRL, glicemia e exame comum de urina] no nível 3. RESULTADOS: confirmou-se a alta cobertura pré-natal (99%), aumento da média de consultas/gestante (6,4 versus 7,2%) e decréscimo da idade gestacional na primeira consulta (17,4 versus 15,7 semanas). Aumentaram significativamente os registros adequados dos procedimentos e exames (exceções: apresentação fetal e tipagem sanguínea):
Revista Brasileira de …, 2003