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1.
Pediatr Dev Pathol ; 27(2): 139-147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38098271

RESUMO

In fetal circulation, oxygenated blood from the placenta flows through the umbilical vein into the ductus venosus (DV), then enters the inferior vena cava, and subsequently reaches the right atrium of the heart. The DV serves as a shunt, allowing this oxygen-rich blood to bypass the liver. The absence of the DV (ADV), also known as agenesis of the DV, is a rare congenital anomaly. Without a DV, blood from the umbilical vein must follow alternative routes to the heart. In ADV cases, blood from the umbilical vein must follow 1 of 2 primary drainage patterns: either an extrahepatic shunt or an intrahepatic shunt. This report details the antenatal ultrasound and postmortem findings of 2 fetuses diagnosed with ADV by prenatal imaging studies. The first case involved a fetus with a persistent right umbilical vein connected directly to the suprahepatic IVC, accompanied by early obliteration of the left umbilical vein and true agenesis of the DV. This fetus also had additional congenital anomalies. In contrast, the second case involved a fetus with a normal left umbilical vein that entered the liver. However, despite an ultrasound diagnosis of "absence" of the DV, a DV was present, though markedly hypoplastic and probably minimally functional or non-functional. In this case, blood from the umbilical vein likely followed an alternate intrahepatic route through the portal and hepatic veins, before reaching the heart (intrahepatic shunt). These contrasting cases emphasize the heterogeneity of vascular anomalies and embryologic origins captured by the term "ADV." Additionally, the terminology of "absence" or "agenesis" may be misleading in some purported ADV cases. Specifically, in the second case, the DV was not absent; it was markedly hypoplastic instead. This also appears to be the first reported case of a hypoplastic DV in a fetus. Both cases underscore the importance of effective collaboration and clear communication between maternal-fetal medicine specialists and pathologists.


Assuntos
Feto , Ultrassonografia Pré-Natal , Feminino , Gravidez , Humanos , Feto/irrigação sanguínea , Veias Umbilicais/diagnóstico por imagem , Veia Cava Inferior/diagnóstico por imagem , Autopsia
2.
J Obstet Gynaecol Can ; 45(10): 102154, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37730302

RESUMO

OBJECTIVE: Fetal growth restriction is a common obstetrical complication that affects up to 10% of pregnancies in the general population and is most commonly due to underlying placental diseases. The purpose of this guideline is to provide summary statements and recommendations to support a clinical framework for effective screening, diagnosis, and management of pregnancies that are either at risk of or affected by fetal growth restriction. TARGET POPULATION: All pregnant patients with a singleton pregnancy. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in this guideline should increase clinician competency to detect fetal growth restriction and provide appropriate interventions. EVIDENCE: Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library through to September 2022 using appropriate controlled vocabulary via MeSH terms (fetal growth retardation and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Grey literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, radiologists, and other health care providers who care for pregnant patients. TWEETABLE ABSTRACT: Updated guidelines on screening, diagnosis, and management of pregnancies at risk of or affected by FGR. SUMMARY STATEMENTS: RECOMMENDATIONS: Prediction of FGR Prevention of FGR Detection of FGR Investigations in Pregnancies with Suspected Fetal Growth Restriction Management of Early-Onset Fetal Growth Restriction Management of Late-Onset FGR Postpartum management and preconception counselling.


Assuntos
Apêndice , Medicina , Feminino , Gravidez , Humanos , Recém-Nascido , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/terapia , Placenta , Recém-Nascido Pequeno para a Idade Gestacional
3.
J Obstet Gynaecol Can ; 45(10): 102155, 2023 10.
Artigo em Francês | MEDLINE | ID: mdl-37730301

RESUMO

OBJECTIF: Le retard de croissance intra-utérin est une complication obstétricale fréquente qui touche jusqu'à 10 % des grossesses dans la population générale et qui est le plus souvent due à une pathologie placentaire sous-jacente. L'objectif de la présente directive clinique est de fournir des déclarations sommaires et des recommandations pour appuyer un protocole clinique de dépistage, diagnostic et prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. POPULATION CIBLE: Toutes les patientes enceintes menant une grossesse monofœtale. BéNéFICES, RISQUES ET COûTS: La mise en application des recommandations de la présente directive devrait améliorer la compétence des cliniciens quant à la détection du retard de croissance intra-utérin et à la réalisation des interventions indiquées. DONNéES PROBANTES: La littérature publiée a été colligée par des recherches effectuées jusqu'en septembre 2022 dans les bases de données PubMed, Medline, CINAHL et Cochrane Library en utilisant un vocabulaire contrôlé au moyen de termes MeSH pertinents (fetal growth retardation and small for gestational age) et de mots-clés (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Seuls les résultats de revues systématiques, d'essais cliniques randomisés ou comparatifs et d'études observationnelles ont été retenus. La littérature grise a été obtenue par des recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Obstétriciens, médecins de famille, infirmières, sages-femmes, spécialistes en médecine fœto-maternelle, radiologistes et autres professionnels de la santé qui prodiguent des soins aux patientes enceintes. RéSUMé POUR TWITTER: Mise à jour de la directive sur le dépistage, le diagnostic et la prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS: Prédiction du retard de croissance intra-utérin Prévention du retard de croissance intra-utérin Détection du retard de croissance intra-utérin Examens en cas de retard de croissance intra-utérin soupçonné Prise en charge du retard de croissance intra-utérin précoce Prise en charge du retard de croissance intra-utérin tardif Prise en charge du post-partum et consultations préconception.

4.
Chem Sci ; 14(2): 362-371, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36687351

RESUMO

The in vitro to in vivo translation of metal-based cytotoxic drugs has proven to be a significant hurdle in their establishment as effective anti-cancer alternatives. Various nano-delivery systems, such as polymeric nanoparticles, have been explored to address the pharmacokinetic limitations associated with the use of these complexes. However, these systems often suffer from poor stability or involve complex synthetic procedures. To circumvent these problems, we report here a simple, one-pot procedure for the preparation of covalently-attached Ru-polylactide nanoparticles. This methodology relies on the ring-opening polymerization of lactide initiated by a calcium alkoxide derivative formed from calcium bis(trimethylsilyl amide) and a hydroxyl-bearing ruthenium complex. This procedure proceeds with high efficiency (near-quantitative incorporation of Ru in the polymer) and enables the preparation of polymers with varying molecular weights (2000-11000 Da) and high drug loadings (up to 68% w/w). These polymers were formulated as narrowly dispersed nanoparticles (110 nm) that exhibited a slow and predictable release of the ruthenium payload. Unlike standard encapsulation methods routinely used, the release kinetics of these nanoparticles is controlled and may be adjusted on demand, by tuning the size of the polymer chain. In terms of cytotoxicity, the nanoparticles were assessed in the ovarian cancer cell line A2780 and displayed potency comparable to cisplatin and the free drug, in the low micromolar range. Interestingly, the activity was maintained when tested in a cisplatin-resistant cell line, suggesting a possible orthogonal mechanism of action. Additionally, the internalization in tumour cells was found to be significantly higher than the free ruthenium complex (>200 times in some cases), clearly showcasing the added benefit in the drug's cellular permeation and accumulation of the drug. Finally, the in vivo performance was evaluated for the first time in mice. The experiments showed that the intravenously injected nanoparticles were well tolerated and were able to significantly improve the pharmacokinetics and biodistribution of the parent drug. Not only was the nanosystem able to promote an 18-fold increase in tumour accumulation, but it also allowed a considerable reduction of drug accumulation in vital organs, achieving, for example, reduction levels of 90% and 97% in the brain and lungs respectively. In summary, this simple and efficient one-pot procedure enables the generation of stable and predictable nanoparticles capable of improving the cellular penetration and systemic accumulation of the Ru drug in the tumour. Altogether, these results showcase the potential of covalently-loaded ruthenium polylactide nanoparticles and pave the way for its exploitation and application as a viable tool in the treatment of ovarian cancer.

5.
Am J Obstet Gynecol MFM ; 5(2): 100815, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36400421

RESUMO

BACKGROUND: Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. OBJECTIVE: This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. STUDY DESIGN: This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. RESULTS: Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. CONCLUSION: This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.


Assuntos
Pré-Eclâmpsia , Gravidez , Recém-Nascido , Humanos , Feminino , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Estudos Prospectivos , Medição de Risco , Fator de Crescimento Placentário , Canadá , Aspirina/uso terapêutico , Aneuploidia
6.
Obstet Gynecol ; 139(6): 1155-1167, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35675615

RESUMO

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.


Assuntos
Doenças do Recém-Nascido , Morte Perinatal , Feminino , Retardo do Crescimento Fetal/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Morte Perinatal/etiologia , Gravidez , Gravidez de Gêmeos , Estudos Prospectivos , Estudos Retrospectivos , Natimorto/epidemiologia , Gêmeos
7.
Am J Perinatol ; 39(3): 329-336, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34775579

RESUMO

OBJECTIVE: The objective of this study is to assess the effect of the lockdown measures during the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes of women who were not affected by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: We used data from the perinatal health program and neonatal databases to conduct a cohort analysis of pregnancy outcomes during the COVID-19 lockdown in the Calgary region, Canada. Rates of preterm birth were compared between the lockdown period (March 16 to June 15, 2020) and the corresponding pre-COVID period of 2015 to 2019. We also compared maternal and neonatal characteristics of preterm infants admitted to neonatal intensive care units (NICUs) in Calgary between the two periods. FINDINGS: A total of 4,357 and 24,160 live births occurred in the lockdown and corresponding pre-COVID period, respectively. There were 366 (84.0 per 1,000 live births) and 2,240 (92.7 per 1,000 live births) preterm births in the lockdown and corresponding pre-COVID period, respectively (p = 0.07). Rates of very preterm and very-low-birth-weight births were lower in the lockdown period compared with the corresponding pre-COVID period (11.0 vs. 15.6 and 9.0 vs. 14.4 per 1,000 live births, p = 0.02 and p = 0.005, respectively). There was no difference in spontaneous stillbirth between the two periods (3.7 vs. 4.1 per 1,000 live birth, p = 0.71). During the lockdown period, the likelihood of multiple births was lower (risk ratio [RR] 0.73, 95% confidence interval [CI]: 0.60-0.88), while gestational hypertension and clinical chorioamnionitis increased (RR 1.24, 95%CI: 1.10-1.40; RR 1.33, 95%CI 1.10-1.61, respectively). CONCLUSION: Observed rates of very preterm and very-low-birth-weight births decreased during the COVID-19 lockdown. Pregnant women who delivered during the lockdown period were diagnosed with gestational hypertension and chorioamnionitis more frequently than mothers in the corresponding pre-COVID period. KEY POINTS: · Lockdown measures to reduce COVID-19 transmission were associated with a lower rate of preterm birth.. · Mental and physical wellbeing of pregnant women were significantly affected by the lockdown measures.. · A comprehensive public health plan to relieve psychosocial stress during pregnancy is required..


Assuntos
Nascido Vivo/epidemiologia , Nascimento Prematuro/epidemiologia , Quarentena , Adulto , COVID-19 , Canadá/epidemiologia , Corioamnionite/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Pandemias , Gravidez , Gravidez Múltipla , Estudos Retrospectivos
8.
J Obstet Gynaecol Can ; 43(6): 769-780.e1, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33631321

RESUMO

OBJECTIVE: To describe evidence-based practice for managing the labour, delivery, and postpartum care of people with physical disabilities in Canada. TARGET POPULATION: This guideline addresses the needs of people with physical disabilities, with a focus on conditions that affect strength and mobility, as well as those that affect neurological or musculoskeletal function or structure. Although aspects of this guideline may apply to people with solely intellectual, developmental, or sensory disabilities (e.g., hearing and vision loss), the needs of this population are beyond the scope of this guideline. OUTCOMES: Safe and compassionate care for people with physical disabilities who are giving birth. BENEFITS, HARMS, AND COSTS: Implementation of this guideline will improve health care provider awareness of specific complications people with physical disabilities may experience during labour, delivery, and the postpartum period and therefore increase the likelihood of a safe birth. EVIDENCE: A literature review was conducted using MEDLINE (474), Embase (36), and the Cochrane Central Register of Controlled Trials (CENTRAL; 28) databases. The results have been filtered for English language, publication date of 2013 to present, observational studies, systematic reviews, meta-analyses, and guidelines and references in these publications were also reviewed. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: Maternal-fetal medicine specialists, obstetricians, family physicians, nurses, midwives, neurologists, physiatrists, and those who care for people with physical disabilities.


Assuntos
Pessoas com Deficiência , Trabalho de Parto , Cuidado Pré-Concepcional/normas , Complicações na Gravidez , Cuidado Pré-Natal/normas , Canadá , Parto Obstétrico , Feminino , Humanos , Cuidado Pós-Natal , Período Pós-Parto , Gravidez , Sociedades Médicas
10.
Adv Mater ; 32(47): e2003294, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33073433

RESUMO

Ru(II) polypyridyl complexes are compounds of great interest in cancer therapy due to their unique photophysical, photochemical, and biological properties. For effective treatment, they must be able to penetrate tumor cells effectively and selectively. The development of nanoscale carriers capable of delivering Ru(II) polypyridyl complexes has the potential to passively or selectively enhance their cellular uptake in tumor cells. Many different strategies have been explored to incorporate Ru(II) polypyridyl complexes into a variety of nanosized constructs, ranging from organic to inorganic materials. Herein, recent developments in nanomaterials loaded with Ru(II) polypyridyl complexes are highlighted. Their rational design, preparation, and physicochemical properties are described, and their potential applications in cancer therapy are eventually discussed.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Nanomedicina/métodos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Piridinas/química , Rutênio/química , Animais , Humanos
11.
Pharmaceutics ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066200

RESUMO

Antimicrobial photodynamic therapy (aPDT) also known as photodynamic inactivation (PDI) is a promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria. This therapy relies on the use of a molecule called photosensitizer capable of generating, from molecular oxygen, reactive oxygen species including singlet oxygen under light irradiation to induce bacteria inactivation. Ru(II) polypyridyl complexes can be considered as potential photosensitizers for aPDT/PDI. However, to allow efficient treatment, they must be able to penetrate bacteria. This can be promoted by using nanoparticles. In this work, ruthenium-polylactide (RuPLA) nanoconjugates with different tacticities and molecular weights were prepared from a Ru(II) polypyridyl complex, RuOH. Narrowly-dispersed nanoparticles with high ruthenium loadings (up to 53%) and an intensity-average diameter < 300 nm were obtained by nanoprecipitation, as characterized by dynamic light scattering (DLS). Their phototoxicity effect was evaluated on four bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa) and compared to the parent compound RuOH. RuOH and the nanoparticles were found to be non-active towards Gram-negative bacterial strains. However, depending on the tacticity and molecular weight of the RuPLA nanoconjugates, differences in photobactericidal activity on Gram-positive bacterial strains have been evidenced whereas RuOH remained non active.

12.
Chem Sci ; 11(10): 2657-2663, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34084324

RESUMO

Ruthenium complexes have attracted a lot of attention as potential photosensitizers (PSs) for photodynamic therapy (PDT). However, some of these PSs are unsuitable for PDT applications due to their low cellular uptake, which is possibly the consequence of their relatively low degree of lipophilicity, which prevents them from penetrating into tumor cells. Here, we report the simple one-pot synthesis of ruthenium-containing nanoconjugates from a non-cell-penetrating, non-phototoxic ruthenium(ii) polypyridyl complex (RuOH), by a drug-initiated ring-opening polymerization of lactide through the formation of a zinc initiator. These conjugates were then formulated into nanoparticles by nanoprecipitation and characterized by means of nuclear magnetic resonance spectroscopy (NMR), matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS) and dynamic light scattering (DLS). Finally, their photo-therapeutic activity (λ exc = 480 nm, 3.21 J cm-2) in cancerous human cervical carcinoma (HeLa) and non-cancerous retinal pigment epithelium (RPE-1) cells was tested alongside that of RuOH and their cellular uptake in HeLa cells was assessed by confocal microscopy and inductively coupled plasma - mass spectrometry (ICP-MS). All nanoparticles showed improved photophysical properties including luminescence and singlet oxygen generation, enhanced cellular uptake and, capitalizing on this, an improved photo-toxicity. Overall, this study demonstrates how it is possible to transform a non-phototoxic PDT PS into an active PS using an easy, versatile polymerization technique.

13.
Eur J Pharm Biopharm ; 142: 281-290, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279918

RESUMO

Poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)), an upper critical solution temperature (UCST)-type copolymer in water, was synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization and used as a macro-RAFT agent for the polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) to yield amphiphilic diblock P(AAm-co-AN)-b-POEGMA copolymer. A series of copolymers with different AN content was obtained allowing to finely tune the UCST behavior (cloud point (Tt-UCST) from 35 to 78 °C). Addition of the POEGMA block did not modify the Tt-UCST regardless its Mn but provided a lower critical solution temperature behavior at high temperature. Nanoparticles were then formulated by the nanoprecipitation technique revealing that copolymers with higher Tt-UCST yield smaller, better-defined nanoparticles. Eventually, doxorubicin (Dox) was encapsulated into nanoparticles made from the copolymer having a Tt-UCST close to mild hyperthermia (~43 °C). Surprisingly, Dox encapsulation increased Tt-UCST and gave smaller nanoparticles as opposed to their unloaded counterparts. The dilution of the suspension also led to a decrease of Tt-UCST. No obvious hyperthermia effect was observed on the cytotoxicity of Dox-loaded nanoparticles. Our study highlighted the influence of macromolecular engineering, drug encapsulation and nanoparticle dilution on UCST behavior, important features often overlooked despite their crucial impact in the development of thermosensitive nanoscale drug delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Febre/tratamento farmacológico , Nanopartículas/administração & dosagem , Nanopartículas/química , Polímeros/química , Tecnologia Farmacêutica/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Metacrilatos/administração & dosagem , Metacrilatos/química , Polimerização/efeitos dos fármacos , Temperatura , Água/química
14.
Am J Perinatol ; 34(6): 585-592, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27919118

RESUMO

Objective Angiogenesis is essential for normal lung development. The objective of our study was to test the hypothesis that preeclampsia, an antiangiogenic state, is a risk factor for bronchopulmonary dysplasia (BPD). Design Prospective cohort study of infants less than 32 weeks' gestation born to mothers with preeclampsia between January 2007 and June 2010 at a single tertiary care center. Their BPD outcome was compared with infants born to the next two normotensive mothers with a ± 1 week gestational age difference. BPD was defined as oxygen dependency at 36 weeks' postmenstrual age. Multivariable binary regression was used to estimate the risk ratio (RR) of BPD with preeclampsia exposure and adjust for confounders. Results Of 102 infants in the preeclampsia group, 23 (23%) developed BPD and of the 217 infants in the normotensive group, 56 (26%) developed BPD. On multivariable binary regression modeling, preeclampsia was not a risk factor for development of BPD (RR: 0.5, 95% confidence interval [CI]: 0.20-1.20). Surfactant use, Score for Neonatal Acute Physiology Perinatal Extension-II score, sepsis, blood transfusion, and intrauterine growth restriction (IUGR) were significant risk factors for BPD. Conclusion In our cohort, preeclampsia was not a significant risk factor for BPD. IUGR infants of preeclamptic and normotensive mothers were at higher risk for BPD.


Assuntos
Displasia Broncopulmonar/epidemiologia , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Pré-Eclâmpsia/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Alberta , Displasia Broncopulmonar/etiologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Gravidez , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Fatores de Risco
15.
BMJ Open Ophthalmol ; 1(1): e000049, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29354703

RESUMO

OBJECTIVE: To evaluate the relationship between pre-eclampsia and development of retinopathy of prematurity (ROP) in infants with birth weight of <1500 g and/or gestation <31 weeks. METHODS: A retrospective cohort study comprising infants born to mothers with pre-eclampsia between January 2007 and June 2010 at a single tertiary care centre. Their ROP outcome was compared with infants born to the next two normotensive mothers with a ±1 week gestational age difference. Pearson χ2 test was used for categorical variables and Mann-Whitney U test was used for continuous variables. Multivariable regression was used to estimate the OR of ROP with prenatal pre-eclampsia exposure and adjust for confounders. RESULTS: Of the 97 infants in the pre-eclampsia group, 27 (27%) developed ROP and of the 185 infants in the normotensive group, 50 (27%) developed ROP. On multivariable regression modelling, pre-eclampsia was not a risk factor for the development of ROP (OR 1.4, 95% CI 0.46 to 4.1). Gestational age, intrauterine growth restriction and blood transfusion were significant risk factors for the development of ROP. CONCLUSIONS: In our cohort, pre-eclampsia was not a significant risk factor for the development of ROP. Intrauterine growth restricted infants of pre-eclamptic and normotensive mothers were at higher risk of ROP.

16.
Epilepsia ; 49(9): 1619-26, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18435756

RESUMO

PURPOSE: We aimed to evaluate the effect of epilepsy on the reproductive hormones levels among female patients, and to investigate the frequency of catamenial pattern of seizures. METHODS: A total of 42 female patients with epilepsy and 21 healthy females (control group) were included. Subjects were at least 2 years postmenarche with regular cycles. Symptoms of premenstrual syndrome (PMS) were assessed using calendar of premenstrual experience scoring. Patients were evaluated for catamenial pattern of seizures. Levels of FSH, LH, estradiol (E), and progesterone (P) were assessed for all subjects in the three phases of the cycles. Pelvi-abdominal ultrasound was performed near time of ovulation, to follow up size of mature follicle. RESULTS: Symptoms of PMS were not different in patients and controls, or in patients with and those without catamenial tendency. In both perimenstrual (M) and midluteal phases, FSH and P levels were lower and E/P ratio higher in patients group. There was a catamenial pattern of seizures in 31% of patients (53.8% M C(1); 46.15% inadequate luteal phase C(3)pattern). Patients with C(3)pattern showed lower P levels in the midluteal phase compared to patients with noncatamenial pattern, to those with C(1)pattern or to controls. Patients with C(1)pattern had lower P levels than controls in the M phase. CONCLUSION: There was evident disruption in the reproductive hormones in female patients with epilepsy with lower FSH and P levels and higher E/P ratio. A total of 31% of patients showed catamenial pattern of seizures (C(1)and C(3)patterns) that was significantly related to P withdrawal.


Assuntos
Epilepsia/fisiopatologia , Estradiol/fisiologia , Hormônio Foliculoestimulante/fisiologia , Hormônio Luteinizante/fisiologia , Progesterona/fisiologia , Adolescente , Eletroencefalografia , Epilepsia/diagnóstico , Feminino , Humanos , Reprodução
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