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1.
J Biol Chem ; 291(53): 26958-26969, 2016 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-27875293

RESUMEN

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema are hallmark features of several brain pathologies, including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1ß (IL-1ß) that is up-regulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability, but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain. In these studies, rat brain microvascular endothelial cell monolayers exposed to calpain inhibitors (calpain inhibitor III and calpastatin) or transfected with calpain-1 siRNA demonstrated attenuation of IL-1ß-induced monolayer hyperpermeability. Calpain inhibition led to protection against IL-1ß-induced loss of zonula occludens-1 (ZO-1) at the tight junctions and alterations in F-actin cytoskeletal assembly. IL-1ß treatment had no effect on ZO-1 gene (tjp1) or protein expression. Calpain inhibition via calpain inhibitor III and calpastatin decreased IL-1ß-induced calpain activity significantly (p < 0.05). IL-1ß had no detectable effect on intracellular calcium mobilization or endothelial cell viability. Furthermore, calpain inhibition preserved BBB integrity/permeability in a mouse controlled cortical impact model of TBI when studied using Evans blue assay and intravital microscopy. These studies demonstrate that calpain-1 acts as a mediator of IL-1ß-induced loss of BBB integrity and permeability by altering tight junction integrity, promoting the displacement of ZO-1, and disorganization of cytoskeletal assembly. IL-1ß-mediated alterations in permeability are neither due to the changes in ZO-1 expression nor cell viability. Calpain inhibition has beneficial effects against TBI-induced BBB hyperpermeability.


Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Calpaína/antagonistas & inhibidores , Permeabilidad de la Membrana Celular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Glicoproteínas/farmacología , Animales , Lesiones Traumáticas del Encéfalo/etiología , Lesiones Traumáticas del Encéfalo/metabolismo , Calpaína/genética , Calpaína/metabolismo , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Interleucina-1beta/toxicidad , Ratones , Ratones Endogámicos C57BL , ARN Interferente Pequeño/genética , Ratas
2.
Am J Perinatol ; 33(14): 1337-1356, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27159203

RESUMEN

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.


Asunto(s)
Quimiocinas/metabolismo , Hormonas/metabolismo , Inflamación/fisiopatología , Complicaciones del Embarazo/inmunología , Receptores Toll-Like/metabolismo , Diabetes Gestacional/inmunología , Femenino , Retardo del Crecimiento Fetal/inmunología , Humanos , Inmunidad Celular , Inmunidad Innata , Recién Nacido , Obesidad/inmunología , Preeclampsia/inmunología , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/inmunología
3.
Mol Cell Biochem ; 405(1-2): 81-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25863494

RESUMEN

Diabetes in pregnancy is associated with microvascular complications and a higher incidence of preeclampsia. The regulatory signaling pathways involving nitric oxide, cGMP, and cGMP-dependent protein kinase (PKG) have been shown to be down-regulated under diabetic conditions and contribute to the pathogenesis of vascular complications in diabetes. The present study was undertaken to investigate how high glucose concentrations regulate PKG expression in cytotrophoblast cells (CTBs). Human CTBs (Sw. 71) were treated with 45, 135, 225, 495, or 945 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (10 µM SB203580) or 10 µM rosiglitazone. After treatment, the cell lysates were subjected to measure the expression of protein kinase G1α (PKG1α), protein kinase G1ß (PKG1ß), soluble guanylate cyclase 1α (sGC1α), and soluble guanylate cyclase 1 ß (sGC1ß) by Western blot. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test. The expressions of PKG1α, PKG1ß, sGC1α, and sGC1ß were significantly down-regulated (p < 0.05) in CTBs treated with >135 mg/dL glucose compared to basal (45 mg/dL). The hyperglycemia-induced down-regulation of cGMP and cGMP-dependent PKG were attenuated by the SB203580 or rosiglitazone pretreatment. Exposure of CTBs to excess glucose down-regulates cGMP and cGMP-dependent PKG, contributing to the development of vascular complications in diabetic mothers during pregnancy. The attenuation of hyperglycemia-induced down-regulation of PKG proteins by SB203580 or rosiglitazone pretreatment further suggests the involvement of stress signaling mechanisms in this process.


Asunto(s)
Proteína Quinasa Dependiente de GMP Cíclico Tipo I/metabolismo , GMP Cíclico/metabolismo , Regulación hacia Abajo/fisiología , Hiperglucemia/metabolismo , Primer Trimestre del Embarazo/metabolismo , Trofoblastos/metabolismo , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Femenino , Glucosa/metabolismo , Guanilato Ciclasa/metabolismo , Humanos , Imidazoles/farmacología , Embarazo , Primer Trimestre del Embarazo/efectos de los fármacos , Piridinas/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Rosiglitazona , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Guanilil Ciclasa Soluble , Tiazolidinedionas/farmacología , Trofoblastos/efectos de los fármacos
4.
Microcirculation ; 21(2): 187-95, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24372803

RESUMEN

OBJECTIVE: Microvascular hyperpermeability that occurs due to breakdown of the BBB is a major contributor of brain vasogenic edema, following IR injury. In microvascular endothelial cells, increased ROS formation leads to caspase-3 activation following IR injury. The specific mechanisms, by which ROS mediates microvascular hyperpermeability following IR, are not clearly known. We utilized an OGD-R in vitro model of IR injury to study this. METHODS: RBMEC were subjected to OGD-R in presence of a caspase-3 inhibitor Z-DEVD, caspase-3 siRNA or an ROS inhibitor L-AA. Cytochrome c levels were measured by ELISA and caspase-3 activity was measured fluorometrically. TJ integrity and cytoskeletal assembly were studied using ZO-1 immunofluorescence and rhodamine phalloidin staining for f-actin, respectively. RESULTS: OGD-R significantly increased monolayer permeability, ROS formation, cytochrome c levels, and caspase-3 activity (p < 0.05) and induced TJ disruption and actin stress fiber formation. Z-DEVD, L-AA and caspase-3 siRNA significantly attenuated OGD-R-induced hyperpermeability (p < 0.05) while only L-AA decreased cytochrome c levels. Z-DEVD and L-AA protected TJ integrity and actin cytoskeletal assembly. CONCLUSIONS: These results suggest that OGD-R-induced hyperpermeability is ROS and caspase-3 dependent and can be regulated by their inhibitors.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Permeabilidad Capilar , Caspasa 3/metabolismo , Células Endoteliales/metabolismo , Glucosa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Barrera Hematoencefálica/patología , Barrera Hematoencefálica/fisiopatología , Edema Encefálico/metabolismo , Edema Encefálico/patología , Edema Encefálico/fisiopatología , Hipoxia de la Célula , Células Cultivadas , Ratas , Ratas Sprague-Dawley
5.
Cureus ; 16(2): e53512, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38440038

RESUMEN

BACKGROUND: Premedication in neonates undergoing elective intubation effectively minimizes the negative physiological events of bradycardia, systemic hypertension, intracranial hypertension, and hypoxia. Premedication decreases procedure-related pain and discomfort. This study aimed to evaluate the current practice of pre-intubation medications for non-emergent intubations in preterm and term neonates in the United States. STUDY DESIGN: A cross-sectional survey (Appendix) was sent via e-mail to all level 3 and 4 Neonatal Intensive Care Units (NICUs) of the Organization of Neonatal Perinatal Medicine Training Program Directors (ONTPD), NICU directors with pediatric residency only, and Baylor Scott and White Health, Mednax, and Envision health services systems. RESULTS: Of 170 responses, 41% (69/168) routinely premedicate, 38% (64/168) premedicate under specific circumstances, and 21% (35/168) do not administer any routine pre-intubation medications. Only 46% (77/168) of units had a written policy. The most frequently used drugs were fentanyl (68%, 116/170), atropine (39%, 66/170), midazolam (38%, 64/170), and morphine (26%, 45/170). 21% (36/170) used a two-drug combination, and 38% (64/170) used a three-drug combination. The most commonly used two-drug combination was atropine and fentanyl, and the most common three-drug combination was atropine, fentanyl, and a paralytic agent. CONCLUSION:  Despite the well-documented benefits of premedication for NICU intubations, as aligned with AAP recommendations, the US lags behind other nations, with stagnant rates since 2006. This disparity persists despite a rise in written policies, which exhibit significant content variations. The authors advocate for the adoption of standardized, AAP-aligned policies across all NICUs in the US. Continued research is vital to monitor the progress of this crucial practice and address any underlying barriers to implementation.

6.
Cureus ; 16(5): e59634, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38832150

RESUMEN

Background Despite evidence suggesting improved outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), data on the impact of temperature variability during cooling and its association with clinical outcomes remain limited. Objective To compare the efficacy and ease of use of two different cooling systems, the Arctic Sun (Medivance, Inc., Louisville, CO) vs. the Blanketrol III (Gentherm Medical, Cincinnati, OH) on achieving TH, temperature variability, and clinical outcomes in neonates with HIE undergoing TH. Methods This study was conducted at the Baylor Scott and White Medical Center's Level IV NICU. The study employed a retrospective cohort design, comparing infants treated with the Arctic Sun device (from December 2020 to August 2021) to a historical cohort treated with the Blanketrol system (from January 2017 to November 2020). Both groups were evaluated for clinical characteristics, patients' outcomes, and ease of use of the cooling devices. Ease of use was assessed through a self-developed survey administered to NICU nurses. Core body temperatures throughout the cooling course were documented at four-hour intervals, including induction, maintenance, and rewarming phases. Results Twenty-two infants were cooled using the Arctic Sun system, and 44 infants were cooled with the Blanketrol device. Median birth weight and gestational age were comparable. There were no significant differences in one-minute and five-minute appearance, pulse, grimace, activity, and respiration (APGAR) scores. The Arctic Sun group had a significantly higher rate of maternal morbidities, including diabetes and placental abruption. Although the median temperature achieved with both devices was 33.5°C, temperature variability was significantly greater with the Blanketrol device (p = 0.03). Thrombocytopenia rates were statistically different between the groups (9% in Arctic Sun vs. 38% in Blanketrol, p = 0.001). Although the Blanketrol group had higher rates of disseminated intravascular coagulation (48% vs. 37%), hypercalcemia (23% vs. 5%), and subcutaneous fat necrosis (7% vs. 5%), these differences were not statistically significant. A nurses' survey on ease of use revealed a strong preference for the Arctic Sun cooling system. Over 85% of nurses found it easier to learn and set up and required less manual intervention than the Blanketrol device. Conclusions Gel adhesive pad-based TH is a potentially superior modality to traditional water-circulating cooling devices. These pads offer advantages in user-friendliness, improved temperature control precision, and potentially reduced adverse event profiles.

7.
Cureus ; 15(9): e45541, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37868372

RESUMEN

Background This study evaluates the long-term risk of autism spectrum disorder (ASD) in infants with intraventricular hemorrhage (IVH) using the Modified Checklist for Autism in Toddlers-Revised with Follow-Up (M-CHAT-R/F) screening tool. Methods This retrospective cohort study compared IVH (exposed) infants across all gestational age groups with no-IVH (non-exposed) infants admitted to level IV neonatal intensive care unit (NICU). The M-CHAT-R/F screening tool was used to assess the ASD risk at 16-30 months of age. Discharge cranial ultrasound (CUS) findings also determined the ASD risk. Descriptive statistics comprised median and interquartile range for skewed continuous data and frequencies and percentages for categorical variables. Comparisons for non-ordinal categorical measures in bivariate analysis were carried out using the χ2 test or Fisher exact test. Results Of the 334 infants, 167 had IVH, and 167 had no IVH. High ASD risk (43% vs. 20%, p = 0.044) and cerebral palsy (19% vs. 5%, p = 0.004) were significantly associated with severe IVH. Infants with CUS findings of periventricular leukomalacia had 3.24 odds of developing high ASD risk (odds ratios/OR: 3.24, 95% confidence interval/CI: 0.73-14.34), and those with hydrocephalus needing ventriculoperitoneal (VP) shunt had 4.75 odds of developing high ASD risk (OR: 4.75, 95% CI: 0.73-30.69). Conclusion Severe IVH, but not mild IVH, increased the risk of ASD and cerebral palsy. This study demonstrates the need for timely screening for ASD in high-risk infants. Prompt detection leads to earlier treatment and better outcomes.

8.
Proc (Bayl Univ Med Cent) ; 36(5): 572-577, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37614853

RESUMEN

Background: Preeclampsia (PreE), the de novo onset of hypertension and proteinuria at 20 weeks of gestation, is a leading cause of maternal and fetal morbidity and mortality. This study compared inflammatory biomarkers in PreE and normal pregnancies using paired samples of mothers and neonates. Methods: Twenty normal pregnant and 27 PreE patients were monitored for biomarkers, neonatal outcomes, and placental morphologies. Fetal and maternal serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble endoglin (sENG), and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured by enzyme-linked immunosorbent assay. Results: Placental thickness was 25 mm in early PreE subjects compared to 32 mm in late PreE subjects (P < 0.05). Placental volume was 296 cm3 in early PreE compared to 393 cm3 in late PreE (P < 0.05). The average hospital stay for PreE babies was longer (20 ± 5 days) compared to babies from normal pregnancies (2 ± 1 days; P < 0.05). PreE babies had a lower Ponderal index (2.28 ± 0.3) than those from normal pregnancies (2.95 ± 0.2; P < 0.05). sENG and sFLT-1 had cord values like the maternal values, while VEGF and PlGF did not. Conclusion: PreE alters the intrauterine environment by activating chemical mediators that result in maternal and fetal complications.

9.
Pediatrics ; 151(4)2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36960655

RESUMEN

BACKGROUND AND OBJECTIVES: Infants and children are at increased risk of severe influenza virus infection and its complications. Influenza vaccine effectiveness (VE) varies by age, influenza season, and influenza virus type/subtype. This study's objective was to examine the effectiveness of inactivated influenza vaccine against outpatient influenza illness in the pediatric population over 9 influenza seasons after the 2009 A(H1N1) pandemic. METHODS: During the 2011-2012 through the 2019-2020 influenza seasons at outpatient clinics at 5 sites of the US Influenza Vaccine Effectiveness Network, children aged 6 months to 17 years with an acute respiratory illness were tested for influenza using real-time, reverse-transcriptase polymerase chain reaction. Vaccine effectiveness was estimated using a test-negative design. RESULTS: Among 24 148 enrolled children, 28% overall tested positive for influenza, 3017 tested positive for influenza A(H3N2), 1459 for influenza A(H1N1)pdm09, and 2178 for influenza B. Among all enrollees, 39% overall were vaccinated, with 29% of influenza cases and 43% of influenza-negative controls vaccinated. Across all influenza seasons, the pooled VE for any influenza was 46% (95% confidence interval, 43-50). Overall and by type/subtype, VE against influenza illness was highest among children in the 6- to 59-month age group compared with older pediatric age groups. VE was lowest for influenza A(H3N2) virus infection. CONCLUSIONS: Analysis of multiple seasons suggested substantial benefit against outpatient illness. Investigation of host-specific or virus-related mechanisms that may result in differences by age and virus type/subtype may help further efforts to promote increased vaccination coverage and other influenza-related preventative measures.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Lactante , Niño , Humanos , Preescolar , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Subtipo H3N2 del Virus de la Influenza A , Eficacia de las Vacunas , Vacunación , Vacunas de Productos Inactivados , Estaciones del Año , Estudios de Casos y Controles , Virus de la Influenza B
10.
Artículo en Inglés | MEDLINE | ID: mdl-36239587

RESUMEN

OBJECTIVE: To determine the effect of preeclampsia on the development of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Retrospective cohort study of infants' ≤32 weeks' gestation admitted to a level-IV single center neonatal intensive care unit from 2014 to 2016. Infants with major congenital anomalies, death or transfer before 28 days were excluded. Infants were stratified by maternal preeclampsia status. Demographic, clinical, and laboratory data were reviewed. Logistic regression was used to examine predictors for BPD. MAIN OUTCOME MEASURE: The primary outcome was BPD incidence. RESULTS: 432 infants met inclusion criteria; 22% developed BPD, of which, 16% had severe BPD. Thirty-eight percent of infants were born to preeclamptic mothers, with 23% of those infants developing BPD. Infants born to preeclamptic mothers were delivered by cesarean section (88% vs. 60%; p<0.0001) more often and had lower birthweight (Median=1265g, IQR 910-1555 vs. Median=1388g, IQR 959-1752; p=0.008) compared to infants born to non-preeclamptic mothers. Higher incidence of intrauterine growth restriction was noted in pre-eclampsia group,24% vs 8%, p=0.0001). Gestational age, length of stay and days on ventilator were all associated with the development of BPD. In multivariable logistic regression, preeclampsia was not a risk factor for development of BPD (OR 1.12 [0.68, 1.83]). CONCLUSIONS: Preeclampsia was not a significant risk factor for development of BPD nor the severity of BPD in infants' ≤32 weeks' gestation. IUGR infants with or without preeclampsia mothers were at higher risk for BPD.

11.
Vaccine ; 39(12): 1788-1796, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33597114

RESUMEN

BACKGROUND: In the United States (U.S.), annual influenza vaccination has been recommended for all persons aged ≥6 months with the Healthy People 2020 coverage target of 70%. However, vaccination coverage has remained around 42-49% during the past eight influenza seasons. We sought to quantify influenza vaccination coverage and factors associated with vaccination in persons seeking outpatient medical care for an acute respiratory illness (ARI). METHODS: We enrolled outpatients aged ≥6 months with ARI from >50 U.S. clinics from 2011 to 2012 through 2018-2019 influenza seasons and tested for influenza with molecular assays. Vaccination status was based on documented receipt of the current season's influenza vaccine. We estimated vaccination coverage among influenza-negative study participants by study site, age, and season, and compared to state-level influenza coverage estimates in the general population based on annual immunization surveys. We used multivariable logistic regression to examine factors independently associated with receipt of influenza vaccines. RESULTS: We enrolled 45,424 study participants with ARI who tested negative for influenza during the study period. Annual vaccination coverage among influenza-negative ARI patients and the general population in the participating states averaged 55% (range: 47-62%), and 52% (range: 46-54%), respectively. Among enrollees, coverage was highest among adults aged ≥65 years (82%; range, 80-85%) and lowest among adolescents aged 13-17 years (38%; range, 35-41%). Factors significantly associated with non-vaccination included non-White race, no college degree, exposure to cigarette smoke, absence of high-risk conditions, and not receiving prior season influenza vaccine. CONCLUSIONS: Influenza vaccination coverage over eight seasons among outpatients with non-influenza respiratory illness was slightly higher than coverage in the general population but 15% lower than national targets. Increased efforts to promote vaccination especially in groups with lower coverage are warranted to attain optimal health benefits of influenza vaccine.


Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Adolescente , Adulto , Anciano de 80 o más Años , Humanos , Lactante , Gripe Humana/prevención & control , Pacientes Ambulatorios , Vigilancia de la Población , Estaciones del Año , Estados Unidos , Vacunación , Cobertura de Vacunación
12.
Obstet Gynecol Surv ; 74(2): 111-125, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30756125

RESUMEN

IMPORTANCE: Pregnancy is getting more and more complex due to increasing number of complications that may affect fetal outcomes. The introduction of newer "proteomics and metabolomics" technologies in the field of obstetrics and gynecology may allow physicians to identify possible associated etiologies that affect the mother during pregnancy and lead to associated complications affecting the offspring. OBJECTIVE: The principal objective of this review article is to provide a comprehensive evaluation of the use of proteomics and metabolomics in complicated pregnancies. Future studies that incorporate data from multiple technologies may allow the development of an integrated biological system approach to maternal genomes, proteomes, and metabolomes in pregnancy. EVIDENCE ACQUISITION AND RESULTS: We conducted a substantial MEDLINE, EBSCOhost, and Cochrane database search for all the relevant articles containing use of "omics" technologies in pregnancy. We identified 197 relevant articles, following standardized systematic review process along with grading systems; 69 eligible articles were identified. CONCLUSION/RELEVANCE: We sought to provide a comprehensive review in this emerging field of "omics" in pregnancy and associated complications. This article focuses mainly on use of proteomics and metabolomics identification techniques and possible interventions for early pregnancy complications to improve neonatal outcomes.


Asunto(s)
Metabolómica/métodos , Complicaciones del Embarazo/metabolismo , Proteómica/métodos , Femenino , Humanos , Embarazo
13.
Sci Rep ; 9(1): 133, 2019 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-30644421

RESUMEN

Hydrogen peroxide (H2O2) plays an important role physiologically as the second messenger and pathologically as an inducer of oxidative stress in injury, ischemia and other conditions. However, it is unclear how H2O2 influences various cellular functions in health and disease differentially, particularly in the blood-brain barrier (BBB). We hypothesized that the change in cellular concentrations of H2O2 is a major contributor in regulation of angiogenesis, barrier integrity/permeability and cell death/apoptosis in BBB endothelial cells. Rat brain microvascular endothelial cells were exposed to various concentrations of H2O2 (1 nM to 25 mM). BBB tight junction protein (zonula ocludens-1; ZO-1) localization and expression, cytoskeletal organization, monolayer permeability, angiogenesis, cell viability and apoptosis were evaluated. H2O2 at low concentrations (0.001 µM to 1 µM) increased endothelial cell tube formation indicating enhanced angiogenesis. H2O2 at 100 µM and above induced monolayer hyperpermeability significantly (p < 0.05). H2O2 at 10 mM and above decreased cell viability and induced apoptosis (p < 0.05). There was a decrease of ZO-1 tight junction localization with 100 µm H2O2, but had no effect on protein expression. Cytoskeletal disorganizations were observed starting at 1 µm. In conclusion H2O2 influences angiogenesis, permeability, and cell death/apoptosis in a tri-phasic and concentration-dependent manner in microvascular endothelial cells of the blood-brain barrier.


Asunto(s)
Barrera Hematoencefálica/patología , Células Endoteliales/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Animales , Barrera Hematoencefálica/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Endoteliales/patología , Neovascularización Patológica/inducido químicamente , Permeabilidad/efectos de los fármacos , Ratas , Uniones Estrechas/efectos de los fármacos
14.
J Investig Med ; 66(4): 728-732, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29170244

RESUMEN

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan's post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.


Asunto(s)
Diabetes Gestacional/patología , Preeclampsia/patología , Adulto , Peso al Nacer , Estudios Transversales , Diabetes Gestacional/fisiopatología , Diástole , Femenino , Edad Gestacional , Humanos , Preeclampsia/fisiopatología , Embarazo , Estudios Retrospectivos , Sístole
15.
Proc (Bayl Univ Med Cent) ; 30(4): 459-460, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28966466

RESUMEN

Congenital midline nasal anomalies are rare, with a prevalence of 1 in 20,000 to 40,000 births and with 5% to 7% of them being nasal glioma. Differential diagnoses of nasal anomalies include nasal dermoid cysts, gliomas, encephaloceles, nasal polyps, and some other rare anomalies. Due to current medical technological advancements, most of these anomalies are easily correctable, though delaying management may lead to fatal effects. This report describes two cases-one of nasal glioma and one of nevus lipomatosus cutaneous superficialis-that presented as respiratory distress in a newborn. Approximately 10 to 20 cases of these two conditions have been described; notably, this is the second documented case of nevus lipomatosus cutaneous superficialis with nasal presentation.

16.
BMC Res Notes ; 10(1): 42, 2017 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-28086969

RESUMEN

BACKGROUND: In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. METHODS: We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. RESULTS: A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. CONCLUSIONS: Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population.


Asunto(s)
Sistemas de Administración de Bases de Datos , Humanos , Recién Nacido
17.
J Natl Med Assoc ; 98(2): 261-4, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16708512

RESUMEN

OBJECTIVE: To evaluate the effects of topical emollient therapy on fluid intake, urine output, serum electrolytes, glucose, bilirubin and other outcome measures of neonates < or = 27 weeks' gestational age (GA) with birthweight (BW) <1,000 g. METHODS: We reviewed medical records of 18 infants treated with topical emollient Aquaphor, and 36 BW- and GA-matched control infants that were not treated with similar topical emollient. RESULTS: Characteristics of the study and control infants were similar: BW: 698 +/- 144 g vs. 732 +/- 134 g, GA: 25.5 +/- 1.33 weeks vs. 25 +/- 1.6 weeks and Score for Neonatal Acute Physiology (SNAP) 14.3 +/- 5.1 vs. 14.6 +/- 7.8, respectively. Fluid intake was lower and urine output was significantly better in Aquaphor-treated infants during the first two weeks of life. Peak serum potassium and bilirubin values were also lower in the study infants. Insulin use, patent ductus arteriosus (PDA), inltraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), sepsis and duration of ventilator/oxygen use weresimilar among the groups. CONCLUSION: Infants < or = 27 weeks' gestation who had Aquaphor applied to their skin from birth required less fluids and had better urine output. These infants had lower serum potassium and bilirubin values during their first two weeks of life. Therefore, we conclude that topical Aquaphor application to thee skin is beneficial for fluid and electrolyte balance in extreme preterm infants.


Asunto(s)
Emolientes/uso terapéutico , Recien Nacido Prematuro , Equilibrio Hidroelectrolítico , Administración Tópica , Bilirrubina/análisis , Estudios de Casos y Controles , Emolientes/administración & dosificación , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Estudios Retrospectivos
18.
Proc (Bayl Univ Med Cent) ; 29(2): 128-30, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27034542

RESUMEN

This double-blinded, randomized, crossover study evaluated the safety and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC) transfusions versus 15 mL/kg aliquot transfusions in very low birth weight (VLBW) infants with anemia. The study enrolled 22 hemodynamically stable VLBW infants requiring PRBC transfusions, with a mean gestational age of 25.7 ± 2.2 weeks and birth weight of 804 ± 261 g. Each infant was randomized to receive one of two treatment sequences: 15 mL/kg followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants were monitored during and after transfusions, and the efficacy and safety of the treatments were evaluated. Infants had higher posttransfusion hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels (38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions when compared to 15 mL/kg transfusions. There were no differences in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign instability between groups. In conclusion, high-volume PRBC transfusions (20 mL/kg) were associated with higher posttransfusion hemoglobin and hematocrit levels but no adverse effects. Higher-volume transfusions may reduce the need for multiple transfusions and therefore the number of donors the infant is exposed to.

19.
Proc (Bayl Univ Med Cent) ; 29(4): 387-388, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27695169

RESUMEN

Bilateral congenital pseudoarthrosis of the clavicles is extremely rare. We report a case of this entity presenting in the neonatal period. We highlight the importance of the differential diagnosis when clavicular fracture shows no evidence of healing or occurs bilaterally.

20.
AJP Rep ; 6(1): e42-7, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26929869

RESUMEN

Introduction Preeclampsia (preE) is pregnancy-induced hypertension affecting a significant proportion of pregnant women worldwide and can cause detrimental effects in the mother and newborn. Some of the effects in the newborn include neonatal thrombocytopenia. Pertaining specifically to neonatal thrombocytopenia, several questions remain unanswered. Discussion According to the current literature, neonatal thrombocytopenia due to maternal preE is highly prevalent in the general population and the incidence is reported to be around 30% worldwide. This review gives an insight into the syndrome and summarizes the possible pathological mechanisms, the diagnostic approach, complications, and therapeutic interventions of neonatal thrombocytopenia. It also identifies the involvement of other cell lines, apart from platelets in the newborns. Furthermore, we suggest a future prospective study to investigate the pathogenesis of preE and plan a study involving animal models to come up with a possible therapeutic intervention to prevent preE and its various consequences in neonates.

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