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1.
Neuroepidemiology ; 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38295773

ABSTRACT

Native American individuals are more frequently affected by cerebrovascular diseases including stroke and vascular cognitive decline. The aim of this study is to determine stroke risk factors that are most prevalent in Wisconsin Native Americans and to examine how education at the community and individual level as well as intensive health wellness coaching may influence modification of stroke risk factors. Additionally, we will investigate the role novel stroke biomarkers may play in stroke risk in this population. This paper details the aims and methods employed in the "Stroke Prevention in the Wisconsin Native American Population" (clinicaltrials.gov identifier: NCT04382963) study including participant health assessments, clinical ultrasound exam of the carotid arteries, cognitive testing battery and structure and execution of the coaching program.

2.
Brain Inj ; 37(8): 697-705, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37317533

ABSTRACT

PURPOSE: To identify life satisfaction trajectories at 1-10 years post-traumatic brain injury (TBI) and examine which demographic and injury characteristics at the time of injury are associated with those trajectories. METHODS: Participants included 1,051 Hispanic individuals from the multi-site, longitudinal TBI Model Systems (TBIMS) database. Individuals were enrolled after sustaining a TBI and while undergoing inpatient rehabilitation at a TBIMS site; they were included if they completed the Satisfaction with Life Scale during one or more follow-up data collections at 1, 2, 5, or 10 years after TBI. RESULTS: A linear (straight-line) movement of life satisfaction trajectories was the best fit to the data. Across the overall sample, life satisfaction increased over time, with higher trajectories for Hispanic individuals who had been partnered at baseline, born outside the US and experienced a nonviolent injury cause. There were no significant interactions between time and any of these main effect predictors, suggesting no differential change over time in life satisfaction trajectories as a function of these characteristics. CONCLUSIONS: Results revealed increases in life satisfaction over time among Hispanic individuals with TBI and shed light on critical risks and protective factors that may inform targeted rehabilitation services with this underserved group.


Subject(s)
Brain Injuries, Traumatic , Hispanic or Latino , Personal Satisfaction , Humans , Databases, Factual , Hispanic or Latino/psychology , Inpatients
3.
J Hum Hypertens ; 36(10): 882-886, 2022 10.
Article in English | MEDLINE | ID: mdl-35082377

ABSTRACT

While evidence-based medicine has contributed enormously to the uniformity and rationale of patient care, it is necessary that we anticipate changes in order to implement their rapid translation to practice. The purpose of this review is to expose three issues regarding cardiovascular health in women, including milestones to reflect the pace at which these are incorporated into public policies. Two of these matters, as changes in the thresholds of normal blood pressure in gestation and in nonpregnant women, need further evidence and deserve to be retrospectively analyzed in high-quality databases. The third subject derives from the association of remote cardiovascular complications of hypertensive pregnancies, an example of the unnecessary delay of more than two decades to install a wide prevention strategy when the health system is not on the watch.


Subject(s)
Hypertension , Pregnancy Complications, Cardiovascular , Blood Pressure/physiology , Female , Humans , Hypertension/diagnosis , Pregnancy , Retrospective Studies
4.
J Endocr Soc ; 5(10): bvab073, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34377881

ABSTRACT

PURPOSE: Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades. METHODS: Demographic, clinical, biochemical, and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980-2019 period. Data were organized into 4 periods by decade. RESULTS: Age at diagnosis, gender, tumor size and percentage of bilaterality, percentage of paragangliomas, and metastases remained stable across the 4 decades. The proportion of genetic testing and incidentalomas increased in recent decades (all P < 0.001). Therefore, we compared PPGLs diagnosed as incidentalomas (36%) with those clinically suspected (64%). Incidentalomas had fewer adrenergic symptoms (38 vs. 62%; P < 0.001) and lower rates of hypertension (64% vs. 80%; P = 0.01) and hypertensive crisis (28% vs. 44%; P = 0.02); also, they had lower functionality (79% vs. 100%; P = 0.01) and lower catecholamines levels (8.4-fold vs. 12.5-fold above upper cutoffs; P = 0.04). Regarding management of all PPGLs over the decades, we observed significant increases in both perioperative doxazosin dose (P = 0.003) and laparoscopic approach rates (P < 0.001), along with a decrease in the length of hospital stays (P = 0.007). CONCLUSIONS: We observed a change in the clinical presentation of PPGL in recent decades, with a marked increase in incidental cases and milder symptoms. The implementation of a multidisciplinary program for adrenal disorders in our institution has translated into more timely diagnoses, more genetic testing, and improvements in perioperative management.

6.
Andes Pediatr ; 92(2): 263-267, 2021 Apr.
Article in Spanish | MEDLINE | ID: mdl-34106166

ABSTRACT

INTRODUCTION: Both premature birth and low birth weight compromise nephron development. The lower nephron endowment is subjected to compensatory hyperfiltration that overloads the glomeruli and leads to the vicious circle of progressive deterioration of renal function. OBJECTIVE: To emphasize the risk of renal involvement in this susceptible population by describing the case of a patient with long-term follow-up. CLINICAL CASE: Low-weight premature newborn, who presented at 3 years of age severe hypertension, which was controlled with different types of antihypertensive drugs. However, 10 years later subnephrotic proteinuria was detected; a renal biopsy confirmed a focal and segmental glome rulosclerosis. Despite blocking the renin-angiotensin system for 23 years, his renal function progres sively deteriorated, until requiring chronic hemodialysis during the last 3 years. CONCLUSION: It is essential to increase the awareness of the risk of renal damage in premature and low weight newborns in order to establish management that covers from gestation to adult life and to achieve an individual and epidemiological impact on renal health.


Subject(s)
Glomerulosclerosis, Focal Segmental/etiology , Infant, Premature, Diseases , Adolescent , Adult , Child, Preschool , Disease Progression , Glomerulosclerosis, Focal Segmental/diagnosis , Glomerulosclerosis, Focal Segmental/pathology , Humans , Hypertension/drug therapy , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Kidney/pathology , Male , Proteinuria/diagnosis , Proteinuria/etiology , Time Factors
8.
Reprod Sci ; 27(8): 1648-1655, 2020 08.
Article in English | MEDLINE | ID: mdl-32430711

ABSTRACT

INTRODUCTION: The pleiotropic kininogen-kallikrein-kinin system is upregulated in pregnancy and localizes in the uteroplacental unit. To identify the systemic and local participation of the bradykinin type 2 receptor (B2R), this was antagonized by Bradyzide (BDZ) during 2 periods: from days 20 to 34 and from days 20 to 60 in pregnant guinea pigs. METHODS: Pregnant guinea pigs received subcutaneous infusions of saline or BDZ from gestational day 20 until sacrifice on day 34 (Short B2R Antagonism [SH-B2RA]) or on day 60 (Prolonged B2R Antagonism [PR-B2RA]). In SH-BDZA, systolic blood pressure was determined on day 34, while in PR-BDZA it was measured preconceptionally, at days 40 and 60. On gestational day 60, plasma creatinine, uricemia, proteinuria, fetal, placental and maternal kidney weight, and the extent of trophoblast invasion were evaluated. RESULTS: The SH-B2RA increased systolic blood pressure on day 34 and reduced trophoblast myometrial invasion, spiral artery remodeling, and placental sufficiency. The PR-B2RA suppressed the normal blood pressure fall observed on days 40 and 60; vascular transformation, placental efficiency, urinary protein, serum creatinine, and uric acid did not differ between the groups. The proportion of all studied mothers with lost fetuses was greater under BDZ infusion than in controls. CONCLUSION: The increased systolic blood pressure and transient reduction in trophoblast invasion and fetal/placental weight in the SH-B2R blockade and the isolated impact on blood pressure in the PR-B2R blockade indicate that bradykinin independently modulates systemic hemodynamics and the uteroplacental unit through cognate vascular and local B2R receptors.


Subject(s)
Blood Pressure/physiology , Bradykinin Receptor Antagonists/pharmacology , Bradykinin/metabolism , Receptor, Bradykinin B2/metabolism , Trophoblasts/metabolism , Animals , Blood Pressure/drug effects , Bradykinin/antagonists & inhibitors , Female , Guinea Pigs , Placenta/drug effects , Placenta/metabolism , Pregnancy , Pyrrolidines/pharmacology , Thiosemicarbazones/pharmacology , Trophoblasts/drug effects
9.
Rev. chil. cardiol ; 38(2): 132-145, ago. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1042607

ABSTRACT

ANTECEDENTES: Desde 1995 hasta la fecha la asociación entre patologías derivadas los embarazos hipertensivos y las enfermedades cardiovasculares ha generado un gran volumen de potentes evidencias epidemiológicas y clínicas. OBJETIVOS: Los propósitos de esta revisión son varios. Mostrar la consistencia y magnitud de la evidencia científica. Integrar los riesgos/enfermedades cardiovasculares y los problemas obstétricos a través de la disfunción endotelial. Preconizar el seguimiento postparto de la hipertensa embarazada, como una ventana de oportunidad para beneficiar la salud de las mujeres y sus hijos. Incluir la historia obstétrica como factor de riesgo de enfermedad coronaria. Proponer cuestionarios adaptables a las prácticas locales para facilitar la pronta incorporación de los índices de riesgo obstétrico y cardiovascular en dos etapas de la vida de una mujer. CONCLUSIÓN: Ha llegado el momento para que los equipos obstétricos, cardiológicos y pacientes jueguen un rol en la prevención de los riesgos y enfermedades cardiovasculares.


BACKGROUND: From 1995 onwards the association between hypertensive pregnancies and cardiovascular disease has generated a great volume of epidemiologic and clinical evidence. OBJECTIVES: The purposes of this review are several. To demonstrate the consistence and weight of the scientific evidence. To integrate cardiovascular risks/ diseases and obstetric complications through the link of endothelial dysfunction. To advocate postpartum follow-up after a hypertensive pregnancy as a window of opportunity to benefit the health of mothers and offsprings. To include the obstetrical history as a risk factor for coronary disease. To propose questionnaires adaptable to local practices to incorporate cardiovascular and obstetrical indexes into two stages of a woman's lifetime. CONCLUSION: The time has come for obstetrical teams, cardiologists and patients to play a preventive role regarding cardiovascular risks and diseases.


Subject(s)
Humans , Female , Pregnancy , Pre-Eclampsia/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Heart Disease Risk Factors , Pregnancy Complications/diagnosis , Surveys and Questionnaires , Women's Health , Risk Assessment/methods , Hypertension, Pregnancy-Induced/epidemiology
10.
Reprod Sci ; : 1933719119833494, 2019 Mar 05.
Article in English | MEDLINE | ID: mdl-30836849

ABSTRACT

INTRODUCTION:: The pleiotropic kininogen-kallikrein-kinin system is upregulated in pregnancy and localizes in the uteroplacental unit. To identify the systemic and local participation of the bradykinin type 2 receptor (B2R), this was antagonized by Bradyzide (BDZ) during 2 periods: from days 20 to 34 and from days 20 to 60 in pregnant guinea pigs. METHODS:: Pregnant guinea pigs received subcutaneous infusions of saline or BDZ from gestational day 20 until sacrifice on day 34 (Short B2R Antagonism [SH-B2RA]) or on day 60 (Prolonged B2R Antagonism [PR-B2RA]). In SH-BDZA, systolic blood pressure was determined on day 34, while in PR-BDZA it was measured preconceptionally, at days 40 and 60. On gestational day 60, plasma creatinine, uricemia, proteinuria, fetal, placental and maternal kidney weight, and the extent of trophoblast invasion were evaluated. RESULTS:: The SH-B2RA increased systolic blood pressure on day 34 and reduced trophoblast myometrial invasion, spiral artery remodeling, and placental sufficiency. The PR-B2RA suppressed the normal blood pressure fall observed on days 40 and 60; vascular transformation, placental efficiency, urinary protein, serum creatinine, and uric acid did not differ between the groups. The proportion of all studied mothers with lost fetuses was greater under BDZ infusion than in controls. CONCLUSION:: The increased systolic blood pressure and transient reduction in trophoblast invasion and fetal/placental weight in the SH-B2R blockade and the isolated impact on blood pressure in the PR-B2R blockade indicate that bradykinin independently modulates systemic hemodynamics and the uteroplacental unit through cognate vascular and local B2R receptors.

13.
Integr Blood Press Control ; 10: 17-23, 2017.
Article in English | MEDLINE | ID: mdl-28894390

ABSTRACT

The potent and now longstanding evidence of the association between placentation-related disorders and cardiovascular disease should be translated into clinical practice in order to introduce a preventive approach to future obstetric and cardiovascular diseases. The purpose of this review is to integrate cardiovascular risk/disease and obstetric complications, which are linked by endothelial dysfunction, as windows of opportunity for improving women's health. Questionnaires adaptable to local practices are proposed to incorporate cardiovascular and obstetrical indexes into two stages of a woman's lifetime.

14.
Rev Chilena Infectol ; 34(2): 151-155, 2017 Apr.
Article in Spanish | MEDLINE | ID: mdl-28632830

ABSTRACT

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1) The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2) The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3) Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians' interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients' ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.


Subject(s)
Academies and Institutes , Clinical Trials as Topic/legislation & jurisprudence , Drugs, Investigational , Government Regulation , Biomedical Research/legislation & jurisprudence , Biomedical Research/standards , Chile , Clinical Trials as Topic/standards , Humans
15.
Entramado ; 13(1)jun. 2017.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1534395

ABSTRACT

Un líder posibilita la transformación de las capacidades individuales, convirtiéndolas en fortalezas organizacionales para ponerlas al servicio de la organización y con ello, permitir su sostenibilidad y perdurabilidad. La universidad en el siglo XXI afronta grandes retos, para continuar aportando al desarrollo de la sociedad, desde del cumplimiento de sus funciones misionales: investigación, docencia y extensión. Para enfrentar esos retos, el Liderazgo Transformacional en la gerencia universitaria, incide en la transformación organizacional que posibilita la resolución de problemas relacionados con la financiación institucional, la calidad en la educación, el incremento de la cobertura, o el relacionamiento con la sociedad, entre otros. Este artículo presenta el resultado de un estudio cuantitativo, racional y positivista, que demuestra teóricamente la importancia del Liderazgo Transformacional para enfrentar los problemas y retos derivados del cambio en la gerencia universitaria. Además, mediante la aplicación de la propuesta teórica a un análisis de caso de una universidad concreta, se caracteriza el Liderazgo Transformacional existente, desde la percepción de los seguidores. Para el desarrollo de la investigación, en términos metodológicos, se utilizaron las teorías del Liderazgo Transformacional y la gerencia de las instituciones de educación superior, el juicio de expertos, y la aplicación del formulario Inventario de Prácticas del Liderazgo de Kouzes y Posner -IPL-. Con estas herramientas, se logró validar las hipótesis guía, comprobando la necesidad de utilizar el Liderazgo Transformacional en el proceso de la gerencia universitaria.


A leader enables the transformation of individual capacities, converting them organizational strengths to put them at the service of the organization and thereby allow its sustainability and durability. The University in the XXI Century faces great challenges to continue contributing to the development of society, based on the fulfillment of its missionary functions: Research, teaching and extension. Transformational Leadership stands out as one of the best tools for university management to allow the organizational transformation that leads to solve problems such as financing quality in education, increased coverage, and relationships with society, among others. This work, through a quantitative, rational positivist study aimed to demonstrate theoretically the importance of Transformational Leadership in university management to face change and university transformation; And on the other hand, through a case analysis, characterize the Transformational Leadership present in the University, from the perception of the followers. For this purpose, theories of transformational leadership and management of higher education institutions, expert judgment, and the application of the Leadership Practices Inventory form of Kouzes and Posner -IPL- were used. Among the main results, the guiding hypotheses were validated, confirming the need to use Transformational Leadership in the process of the university management.


Este artigo tem por objetivo analisar a expansão da influência da China na América Latina nos campos econômico e militar bem como os Estados Unidos reagiu a este. Pois será utilizada a metodologia do estudo de caso-Venezuela, Bolívia e Equador, já que é onde a China tem uma forte presença e, especialmente, porque são países, como a potência asiática, têm um anti-política americano ou soberanista que busca consolidar uma ordem mundial multipolar A principal constatação é que a China não representa uma séria ameaça para os EUA no curto prazo, e de fato, a expansão da sua influência na região tem sido percebida pelo governo dos EUA como uma oportunidade. Isto é devido a várias razões: China tem implementado uma política cautelosa e pragmática que visa consolidar as suas metas nacionais sem desafiar diretamente a hegemonia dos EUA na região, reforçada por restrições internas que levam a liderança chinesa a optar por uma atitude menos ativista na atitude reorganização político-militar do mundo. Por outro lado, graças aos Estados Unidos, que está em uma fase de declínio de sua hegemonia na região, preferem promover os seus interesses em um quadro de cooperação e não de confronto, na esperança de tirar proveito desta nova situação.

16.
Rev. chil. infectol ; 34(2): 151-155, abr. 2017.
Article in Spanish | LILACS | ID: biblio-844459

ABSTRACT

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1) The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2) The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3) Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians’ interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients’ ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.


En Chile los tratamientos de alto costo requeridos por seleccionadas condiciones médicas son financiados por el Estado, de acuerdo a la Ley 20.85, que se hizo efectiva en noviembre de 2015. Un reglamento de esta ley -actualmente en discusión por el Senado- incluye la regulación de los ensayos clínicos y plantea importantes aspectos que van a poner en riesgo la realización de investigaciones clínicas avanzadas: 1) El control exclusivo y mandatorio otorgado al Instituto de Salud Pública durante todas las etapas de los ensayos y la vigilancia de las instituciones que los realizan, que sobrepasa las atribuciones de los Comités de Ética Científica Institucionales; 2) El período de hasta 10 años después de la aparición de cualquier efecto adverso, durante el cual se asume causado por el medicamento o dispositivo evaluado en el ensayo, mientras no se demuestre lo contrario en un proceso judicial; 3) Los participantes de los estudios tienen derecho a continuar con el tratamiento recibido durante el estudio una vez terminado este, financiado por las entidades que patrocinan los estudios y mientras el fármaco o dispositivo se consideren útil. Estamos de acuerdo con la necesidad de contar con un Registro Nacional de Ensayos Clínicos. Sin embargo, predecimos que los aspectos críticos del reglamento causarán dificultades y procesos judiciales innecesarios, lo que limitará el interés de los clínicos en realizar investigación. Proponemos que el reglamento debe modificarse a fin de excluir responsabilidades sobre eventos asociados con la evolución natural de la condición clínica, el envejecimiento del paciente, comorbilidades y eventos clínicos no predecibles cuando se aceptó el estudio. Recomendamos que el acceso gratuito posterior al estudio debe constituir una decisión conjunta del paciente y su médico tratante, considerando los riesgos y la carga a que se expuso el paciente, o al riesgo vital secundario a la suspensión del tratamiento del estudio mientras no esté disponible en el mercado nacional.


Subject(s)
Humans , Drugs, Investigational , Clinical Trials as Topic/legislation & jurisprudence , Government Regulation , Academies and Institutes , Chile , Clinical Trials as Topic/standards , Biomedical Research/legislation & jurisprudence , Biomedical Research/standards
17.
Pregnancy Hypertens ; 6(1): 30-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26955769

ABSTRACT

The bradykinin type 2 receptor (B2R), main effector of the pleiotropic kallikrein-kinin system (KKS), has been localized in the key sites related to placentation in human, rat and guinea pig utero-placental units. The present study was directed to characterize the content, the cellular and subcellular localization of B2R in the villi and basal plate of placentas from normal and preeclamptic pregnancies by means of western blotting, immunohistochemistry and immunoelectron microscopy. The protein content of B2R was demonstrated in both placental zones. The villous placenta of normal and preeclamptic pregnancies expressed B2R in syncytiotrophoblast and fetal endothelium; the basal plate displayed B2R in extravillous trophoblasts and decidual cells. Lastly, immunogold electron microscopy revealed B2R in fetal endothelium, syncytiotrophoblast, extravillous cytotrophoblasts and decidual cells; in all cell types the receptor was mainly located in the cytosol and nucleus. The protein content of placental homogenates and the immunoreactivity in the different cells types did not differ between both study groups; however the abundance of nuclear immunogold B2R positive beads in extravillous trophoblasts was greater in the normal than in the preeclamptic placentas. The purpose of describing nuclear B2R in the utero-placental unit, and its increment in normal extravillous trophoblasts, is to stimulate the study of the functional pathways that may be relevant to understand the local role of the B2R in normal and preeclamptic gestation.


Subject(s)
Cell Nucleus/chemistry , Placenta/chemistry , Pre-Eclampsia/metabolism , Receptor, Bradykinin B2/analysis , Uterus/chemistry , Adult , Biomarkers/analysis , Blotting, Western , Case-Control Studies , Cell Nucleus/ultrastructure , Chorionic Villi/chemistry , Decidua/chemistry , Endothelial Cells/chemistry , Female , Humans , Immunohistochemistry , Microscopy, Electron , Placenta/ultrastructure , Pre-Eclampsia/diagnosis , Pregnancy , Trophoblasts/chemistry , Uterus/ultrastructure , Young Adult
18.
Biomed Res Int ; 2014: 280497, 2014.
Article in English | MEDLINE | ID: mdl-25295255

ABSTRACT

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22-24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.


Subject(s)
Atherosclerosis/genetics , Fetal Growth Retardation/genetics , Hypercholesterolemia/genetics , Receptors, LDL/genetics , Animals , Atherosclerosis/etiology , Atherosclerosis/pathology , Dietary Supplements , Disease Models, Animal , Embryonic Development/drug effects , Embryonic Development/genetics , Female , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/pathology , Fetus/drug effects , Humans , Hypercholesterolemia/pathology , Male , Mice , Mice, Knockout , Pregnancy , Pregnancy, Animal , Receptors, LDL/metabolism , Vitamin E/administration & dosage
19.
Reprod Biol Endocrinol ; 12: 49, 2014 Jun 04.
Article in English | MEDLINE | ID: mdl-24893657

ABSTRACT

BACKGROUND: The opposing renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) are upregulated in pregnancy and localize in the utero-placental unit. To test their participation as counter-regulators, circulating angiotensin II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS balance during the period of maximal trophoblast invasion and placental development would provoke increased blood pressure, defective trophoblast invasion and a preeclampsia-like syndrome. METHODS: Pregnant guinea-pigs received subcutaneous infusions of AII (200 µg/kg/day), the B2R antagonist Bradyzide (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non-pregnant cycling animals were included in a control group (C NP) or received AII + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined during cycle in C NP, and on the last day of infusion, and 6 and 26 days thereafter in the remaining groups. Twenty six days after the infusions blood and urine were extracted, fetuses, placentas and kidneys were weighed, and trophoblast invasion of spiral arteries was defined in the utero-placental units by immunocytochemistry. RESULTS: Systolic blood pressure transiently rose in a subgroup of the pregnant females while receiving AII + BDZ infusion, but not in AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ-treated pregnant and non-pregnant females. Aborted and dead fetuses were increased in dams that received AII and AII + BDZ. The fetal/placental weight ratio was reduced in litters of AII + BDZ-treated mothers. All groups that received interventions during pregnancy showed reduced replacement of endothelial cells by extravillous trophoblasts in lateral and myometrial spiral arteries. CONCLUSIONS: The acute effects on fetal viability, and the persistently impaired renal/placental sufficiency and incomplete arterial remodeling implicate the RAS and KKS in the adaptations in pregnancy. The results partially confirm our hypothesis, as a preeclampsia-like syndrome was not induced. We demonstrate the feasibility of characterizing systemic and local modifications in pregnant guinea-pig, supporting its use to study normal placentation and related disorders.


Subject(s)
Disease Models, Animal , Kallikrein-Kinin System , Placenta/blood supply , Placentation , Pre-Eclampsia/physiopathology , Renin-Angiotensin System , Vascular Remodeling , Angiotensin II/administration & dosage , Angiotensin II/metabolism , Angiotensin II/pharmacology , Animals , Bradykinin B2 Receptor Antagonists/administration & dosage , Bradykinin B2 Receptor Antagonists/pharmacology , Feasibility Studies , Female , Fetal Development/drug effects , Guinea Pigs , Infusions, Subcutaneous , Kallikrein-Kinin System/drug effects , Kidney/drug effects , Kidney/pathology , Kidney/physiopathology , Organ Size/drug effects , Placenta/drug effects , Placenta/pathology , Placentation/drug effects , Pre-Eclampsia/blood , Pre-Eclampsia/chemically induced , Pregnancy , Pregnancy Maintenance/drug effects , Pyrrolidines/administration & dosage , Pyrrolidines/pharmacology , Receptor, Bradykinin B2/chemistry , Receptor, Bradykinin B2/metabolism , Renin-Angiotensin System/drug effects , Thiosemicarbazones/administration & dosage , Thiosemicarbazones/pharmacology , Uterus/blood supply , Uterus/drug effects , Uterus/pathology , Vascular Remodeling/drug effects
20.
Rev Med Chil ; 141(2): 237-47, 2013 Feb.
Article in Spanish | MEDLINE | ID: mdl-23732498

ABSTRACT

The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.


Subject(s)
Hypertension , Menopause/physiology , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Female , Humans , Hypertension/drug therapy , Hypertension/etiology , Hypertension/physiopathology , Hypertension, Pregnancy-Induced/physiopathology , Pregnancy , Sex Factors
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