Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119
Filtrar
2.
Sci Rep ; 13(1): 10195, 2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37353683

RESUMEN

Plastics are an important new component of the global sedimentary system, and much concern exists about their transport, fate and impact. This study presents the first system-scale assessment of sedimentary storage of microplastic for an estuary, Narragansett Bay, RI (USA), and the measurements of shoreline and seabed sediments add to the growing body of literature demonstrating high coastal concentrations. Microplastic concentrations in sediments ranged from 396 to over 13,000 MP particles kg-1 dry sediment (DW), comparable to other shoreline and seafloor sites located near urban centers. As previously reported for fine sediment and other pollutants, estuarine plastic storage is extensive in Narragansett Bay, especially within the upper urbanized reaches. Over 16 trillion pieces of plastic weighing near 1000 tonnes is calculated to be stored in surface sediments of the Bay based on a power-law fit. This work highlights that estuaries may serve as a significant filter for plastic pollution, and this trapping may have negative consequences for these valuable, productive ecosystems but offer potential for efficient removal.


Asunto(s)
Plásticos , Contaminantes Químicos del Agua , Microplásticos , Contaminantes Químicos del Agua/análisis , Bahías , Rhode Island , Ecosistema , Monitoreo del Ambiente , Estuarios , Sedimentos Geológicos
3.
Osteoporos Int ; 34(9): 1601-1611, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37233793

RESUMEN

There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD). In 3671 participants aged 46-70 years at baseline, ∆lean mass was a stronger determinant than ∆fat mass of ∆BMD over 6 years. Maintained or increased lean mass may slow down age-related bone loss. PURPOSE: There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD) with ageing. We examined these in the Busselton Healthy Ageing Study. METHODS: We studied 3671 participants (2019 females) aged 46-70 years at baseline with body composition and BMD assessments by dual-energy x-ray absorptiometry at baseline and after ~6 years. Relationships between changes in total body mass (∆TM), lean mass (∆LM) and fat mass (∆FM) with ∆BMD at total hip, femoral neck and lumbar spine were evaluated using restricted cubic spline modelling (accounting for baseline covariates) and mid-quartile least square means were compared. RESULTS: ∆TM was positively associated with ∆BMD of total hip and femoral neck in both sexes, and spine in females; in females but not males, associations plateaued at ∆TM above ~5kg for all sites. In females, ∆LM was positively associated with ∆BMD of all three sites with plateauing of the relationship at ∆LM above ~1kg. Women in the highest quartile of ∆LM (Q4, mid-quartile value +1.6 kg) had 0.019-0.028 g/cm2 less reduction in BMD than those in the lowest quartile (Q1, -2.1 kg). In males, ∆LM was positively associated with ∆BMD of total hip and femoral neck; men in Q4 (+1.6 kg) had 0.015 and 0.011 g/cm2 less bone loss, respectively, compared with Q1 (-2.7 kg). ∆FM was positively associated with ∆BMD of total hip only in both sexes. CONCLUSION: ∆LM is a stronger determinant than ∆FM of ∆BMD. Maintained or increased LM is associated with less age-related bone loss.


Asunto(s)
Densidad Ósea , Osteoporosis , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Australia/epidemiología , Composición Corporal , Osteoporosis/epidemiología , Absorciometría de Fotón , Vértebras Lumbares
4.
Osteoporos Int ; 31(12): 2439-2448, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32719992

RESUMEN

Adiposity has a complex relationship with bone health. In 4865 Australian baby boomers (2642 females) aged 45-70 years, we found that higher visceral adipose tissue mass is associated with reduced bone density adjusting for body mass and lifestyle factors, suggesting that excess visceral fat may be deleterious to bone. INTRODUCTION: Increased body mass is associated with higher bone mineral density (BMD), but higher visceral adipose tissue (VAT) may have a negative impact on bone health. In the Busselton Healthy Ageing Study, we examined associations between VAT mass and BMD in 4865 participants (2642 females) aged 45-70 years. METHODS: VAT mass and BMD of whole body, total hip, femoral neck and lumbar spine were measured using DXA. VAT mass was examined as a continuous variable and in quartiles using sex-specific cut-offs. RESULTS: The mean age was 58.0 ± 5.8 years. Males had significantly higher BMI (28.3 ± 3.7 vs 27.5 ± 4.9 kg/m2) and VAT mass (1675 ± 878 vs 882 ± 600 g) than females (both P < 0.001). In males, after adjustment for age, body mass, height and lifestyle factors, VAT mass negatively associated with total body, total hip and femoral neck BMD (ß = - 0.153 to - 0.293, all P < 0.001). Males in the highest quartile of VAT mass (> 2200 g) had significantly lower BMD at all three sites than those in lower quartiles, with estimated BMD differences of 2.3-5.7% (all P < 0.05). In females, VAT mass negatively associated with total body, femoral neck and lumbar spine BMD (ß = - 0.067 to - 0.178, all P < 0.05) and those in the highest quartile (> 1250 g) had significantly lower total body BMD than other quartiles (by 1.7-3.7%, all P < 0.05). CONCLUSION: In middle-aged Australians, after covariate adjustment, higher DXA-derived VAT mass is associated with reduced bone density, suggesting that excess visceral fat may be deleterious to bone, especially in males.


Asunto(s)
Densidad Ósea , Grasa Intraabdominal , Absorciometría de Fotón , Tejido Adiposo , Adiposidad , Anciano , Australia/epidemiología , Femenino , Cuello Femoral , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Masculino , Persona de Mediana Edad
5.
Can Assoc Radiol J ; 71(3): 266-280, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32157894

RESUMEN

Although acute ischemic stroke remains one of the most common causes of death and disability worldwide, it is a potentially treatable condition if appropriately managed in a timely manner. The goals of acute stroke imaging include establishing a diagnosis as fast as possible with (1) accurate infarct quantification, (2) intracranial and cervical vasculature assessment, and (3) brain perfusion analysis for detection of infarct core and potentially salvageable penumbra allowing optimal patient selection for appropriate therapy. Given the extensive number of images generated from acute stroke imaging studies and as "time is brain," this article aims to highlight a logical approach for the radiologist in acute stroke computed tomography imaging in order to accurately interpret and communicate results in a timely manner.


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada/métodos , Humanos , Interpretación de Imagen Radiográfica Asistida por Computador
6.
AJNR Am J Neuroradiol ; 41(1): 64-70, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31896566

RESUMEN

BACKGROUND AND PURPOSE: Brain parenchymal hyperdensity on postthrombectomy CT in patients with acute stroke can be due to hemorrhage and/or contrast staining. We aimed to determine whether iodine concentration within contrast-stained parenchyma compared with an internal reference in the superior sagittal sinus on dual-energy CT could predict subsequent intracerebral hemorrhage. MATERIALS AND METHODS: Seventy-one patients with small infarct cores (ASPECTS ≥ 7) and good endovascular recanalization (modified TICI 2b or 3) for anterior circulation large-vessel occlusion were included. Brain parenchymal iodine concentration as per dual-energy CT and the percentage of contrast staining relative to the superior sagittal sinus were recorded and correlated with the development of intracerebral hemorrhage using Mann-Whitney U and Fisher exact tests. RESULTS: Forty-three of 71 patients had parenchymal hyperdensity on initial dual-energy CT. The median relative iodine concentration compared with the superior sagittal sinus was significantly higher in those with subsequent intracerebral hemorrhage (137.9% versus 109.2%, P = .007). By means of receiver operating characteristic analysis, a cutoff value of 100% (iodine concentration relative to the superior sagittal sinus) enabled identification of patients going on to develop intracerebral hemorrhage with 94.75% sensitivity, 43.4% specificity, and a likelihood ratio of 1.71. CONCLUSIONS: Within our cohort of patients, the relative percentage of iodine concentration at dual-energy CT compared with the superior sagittal sinus was a reliable predictor of intracerebral hemorrhage development and may be a useful imaging biomarker for risk stratification after endovascular treatment.


Asunto(s)
Hemorragia Cerebral/diagnóstico por imagen , Yodo/análisis , Neuroimagen/métodos , Accidente Cerebrovascular/cirugía , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/cirugía , Hemorragia Cerebral/etiología , Estudios de Cohortes , Procedimientos Endovasculares , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Accidente Cerebrovascular/complicaciones , Seno Sagital Superior/diagnóstico por imagen , Trombectomía
7.
JAMA ; 322(7): 632-641, 2019 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-31429897

RESUMEN

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.


Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Yoduro Peroxidasa/inmunología , Complicaciones del Embarazo/diagnóstico , Nacimiento Prematuro/etiología , Enfermedades de la Tiroides/diagnóstico , Pruebas de Función de la Tiroides , Adulto , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/complicaciones , Femenino , Edad Gestacional , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico , Recién Nacido , Embarazo , Complicaciones del Embarazo/sangre , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/complicaciones , Tirotropina/sangre , Tiroxina/sangre
8.
Bone Rep ; 10: 100198, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30886882

RESUMEN

Paget's disease of bone (PDB) has a strong genetic component. Variants in SQSTM1 are found in up to 40% of patients with a family history of the disease, where a pattern of autosomal dominance with incomplete penetrance is apparent. By contrast, SQSTM1 variants are only found in up to 10% of patients with sporadic disease. It has been hypothesised that the remaining genetic susceptibility to PDB, particularly in familial cases, could be explained by rare genetic variants in loci previously identified by Genome Wide Association Studies. It is likely that polygenic factors are involved in many individuals. In this study we utilised whole exome sequencing to investigate predisposing genetic factors in an unsolved PDB kindred and identified a c.1189C > T p.L397F variant in DC-STAMP, also known as TM7SF4, that co-segregated with disease. DCSTAMP was identified as a gene of interest in PDB following Genome Wide Association Studies and has been previously shown to play critical roles in osteoclast fusion. The variant we identified has also been reported in association with PDB in a French-Canadian cohort however the significance of this variant was inconclusive. Targeted screening of DCSTAMP in our familial cohort of PDB patients revealed an additional 8 variants; however we did not find a significant association between any of these, including p.L397F, with PDB. Osteoclastogenesis assays from the affected proband and his unaffected brother demonstrated an increase in osteoclast number and nucleation, consistent with the pagetic phenotype. In converse to other established Paget's associated genetic variations such as SQSTM1, TNFRSF11A and OPTN, expression of the mutant DC-STAMP protein attenuated the activation of transcription factors NFκB and AP-1 when exogenously expressed. We found that the p.L397F variant did not influence the subcellular localization of the protein. Based on these findings we conclude that genetic variation in DCSTAMP is not a significant predisposing factor in our specific cohort of PDB patients and the p.L397F variant is unlikely to be a contributing factor in PDB pathogenesis.

10.
AJNR Am J Neuroradiol ; 39(4): E48, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29301778
11.
AJNR Am J Neuroradiol ; 38(10): 1911-1916, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28798219

RESUMEN

BACKGROUND AND PURPOSE: Multiphase CTA, a technique to dynamically assess the vasculature in acute ischemic stroke, was primarily developed to evaluate collateral filling. We have observed that it is also useful in identifying distal anterior circulation occlusions due to delayed anterior circulation opacification on multiphase CTA, an observation we term the "delayed vessel sign." We aimed to determine the usefulness of this sign by comparing multiphase CTA with single-phase CTA. MATERIALS AND METHODS: All 23 distal anterior circulation occlusions during a 2-year period were included. Ten M1-segment occlusions and 10 cases without a vessel occlusion were also included. All patients had follow-up imaging confirming the diagnosis. Initially, the noncontrast CT and first phase of the multiphase CTA study for each patient were blindly evaluated (2 neuroradiologists, 2 radiology trainees) for an anterior circulation occlusion. Readers' confidence, speed, and sensitivity of detection were recorded. Readers were then educated on the "delayed vessel sign," and each multiphase CTA study was re-examined for a vessel occlusion after at least 14 days. RESULTS: There was significant improvement in the sensitivity of detection of distal anterior circulation vessel occlusions (P < .001), overall confidence (P < .001), and time taken to interpret (P < .001) with multiphase CTA compared with single-phase CTA. Readers preferred MIP images compared with source images in >90% of cases. CONCLUSIONS: The delayed vessel sign is a reliable indicator of anterior circulation vessel occlusion, particularly in cases involving distal branches. Assessment of the later phases of multiphase CTA for the delayed vessel sign leads to a significant improvement in the speed and confidence of interpretation, compared with single-phase CTA.


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Int J Obes (Lond) ; 41(4): 576-581, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27881857

RESUMEN

BACKGROUND: An association between depression and obesity is well recognised, but longitudinal studies of depressive symptoms in adolescents as a predictor of body composition are lacking. OBJECTIVE: We examined depressive symptoms at age 14, 17 and 20 years as predictors of lean, fat and bone mass at age 20 years in a birth cohort. SUBJECTS/METHODS: In 1161 participants (569 females) in the Western Australia Pregnancy Cohort (Raine) Study, depressive symptoms were assessed using the Beck Depression Inventory for Youth at age 14 and 17 years, and the Depression, Anxiety and Stress Scale 21 at age 20 years. Participants were further classified into two trajectories using latent class analysis: no/transient and persistent/recurrent depression. At age 20 years, lean body mass (LBM), fat body mass (FBM) and total body bone mass were measured by dual-energy X-ray absorptiometry. RESULTS: In females, accounting for age and lifestyle factors, depression scores at age 14 and 20 years were positively associated with body weight, body mass index (BMI), FBM and % FBM (r=0.110-0.184, P<0.05) but negatively correlated with % LBM (r=-0.120, P<0.05) at age 20 years. Females in the persistent/recurrent depression trajectory (n=99) had significantly higher body weight (+5.1 kg), BMI (+1.8 kg m-2), FBM (+3.9 kg) and % FBM (+2.2%) and significantly lower % LBM (-2.2%) at age 20 years than those with no/transient depression (n=470; all P<0.05). In males, depression scores at age 17 and 20 years were negatively associated with LBM but not weight or BMI, and depression trajectory was not a predictor of body composition at age 20 years. Depression scores and trajectories did not predict bone mass in either males or females. CONCLUSIONS: Depressive symptoms and persistent/recurrent depression in adolescence are predictors of greater adiposity at age 20 years in females, but not males, but do not predict bone mass in either gender.


Asunto(s)
Composición Corporal , Depresión/epidemiología , Obesidad/epidemiología , Tamaño de los Órganos , Absorciometría de Fotón , Adiposidad , Adolescente , Imagen Corporal/psicología , Índice de Masa Corporal , Densidad Ósea , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Estilo de Vida , Estudios Longitudinales , Masculino , Encuestas Nutricionales , Obesidad/complicaciones , Obesidad/psicología , Embarazo , Estudios Prospectivos , Factores Sexuales , Medio Social , Factores Socioeconómicos , Australia Occidental/epidemiología , Adulto Joven
13.
Osteoporos Int ; 28(1): 259-268, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27468902

RESUMEN

The obesity-BMD relationship is complex. In 3045 middle-aged adults, we found that in women (but not men) with discordant fat mass index (FMI)/BMI categories, higher body fat for BMI was associated with lower BMD, suggesting that increased fat mass without an accompanying increase in lean mass may be deleterious to bone. INTRODUCTION: The relationship between obesity and BMD is complex. FMI (fat mass (kg) / height (m)2) is a more accurate measure of fatness than BMI, and depending on body composition, some individuals have discordant BMI/FMI categories. We examined associations between FMI, BMI and BMD in participants in the Busselton Healthy Ageing Study. METHODS: Body composition and BMD of the hip, spine and total body were measured using DXA in 3045 participants (1644 females) aged 45-67 years. Using standard BMI/FMI categories, the participants were classified as underweight/fat deficit, normal, overweight/excess fat, obese I and obese II-III. RESULTS: BMI and FMI categories were concordant in 77.3 % of females and 71.2 % of males. There were 12.9 % females and 13.2 % males in a higher FMI than BMI category (high body fat for BMI), whereas 9.8 % females and 15.6 % males were in a lower category (low body fat for BMI). Females with high body fat for BMI had significantly lower covariate-adjusted BMD at the femoral neck, total hip and total body (differences of 3.8, 5.1 and 2.6 %, respectively, all P < 0.05) than females with low body fat for BMI and lower total body BMD than women with concordant FMI/BMI (by 1.4 %, P = 0.04). In males, BMD did not differ significantly between those who were concordant or discordant for FMI/BMI categories. CONCLUSION: In women (but not men) with discordant FMI/BMI categories, higher body fat for BMI was associated with lower BMD, suggesting that increased fat mass without an accompanying increase in lean mass may be deleterious to bone.


Asunto(s)
Tejido Adiposo/anatomía & histología , Índice de Masa Corporal , Densidad Ósea/fisiología , Caracteres Sexuales , Absorciometría de Fotón/métodos , Tejido Adiposo/fisiología , Anciano , Antropometría/métodos , Composición Corporal/fisiología , Femenino , Envejecimiento Saludable/fisiología , Articulación de la Cadera/fisiología , Humanos , Vértebras Lumbares/fisiología , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Sobrepeso/fisiopatología
14.
Osteoporos Int ; 25(5): 1563-70, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24647886

RESUMEN

UNLABELLED: The relationships between fat mass and bone mass in young adults are unclear. In 1,183 young Australians, lean body mass had a strong positive relationship with total body bone mass in both genders. Fat mass was a positive predictor of total body bone mass in females, with weaker association in males. INTRODUCTION: Body weight and lean body mass are established as major determinants of bone mass, but the relationships between fat mass (including visceral fat) and peak bone mass in young adults are unclear. The aim of this study was to evaluate the associations between bone mass in young adults and three body composition measurements: lean body mass, fat mass and trunk-to-limb fat mass ratio (a surrogate measure of visceral fat). METHODS: Study participants were 574 women and 609 men aged 19-22 years from the Raine study. Body composition, total body bone mineral content (TBBMC), bone area and areal bone mineral density (TBBMD) were measured using DXA. RESULTS: In multivariate linear regression models with height, lean body mass, fat mass and trunk-to-limb fat mass ratio as predictor variables, lean mass was uniquely associated with the largest proportion of variance of TBBMC and TBBMD in males (semi-partial R(2) 0.275 and 0.345, respectively) and TBBMC in females (semi-partial R(2) 0.183). Fat mass was a more important predictor of TBBMC and TBBMD in females (semi-partial R(2) 0.126 and 0.039, respectively) than males (semi-partial R(2) 0.006 and 0.018, respectively). Trunk-to-limb fat mass ratio had a weak, negative association with TBBMC and bone area in both genders (semi-partial R(2) 0.004 to 0.034). CONCLUSIONS: Lean body mass has strong positive relationship with total body bone mass in both genders. Fat mass may play a positive role in peak bone mass attainment in women but the association was weaker in men; different fat compartments may have different effects.


Asunto(s)
Tejido Adiposo/anatomía & histología , Composición Corporal/fisiología , Densidad Ósea/fisiología , Caracteres Sexuales , Absorciometría de Fotón/métodos , Antropometría/métodos , Estatura/fisiología , Índice de Masa Corporal , Femenino , Humanos , Masculino , Delgadez/patología , Adulto Joven
16.
J Neurosci Res ; 91(11): 1492-507, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23918451

RESUMEN

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid-type glutamate receptor (AMPAR) plays a critical role in modulating experience-dependent neuroplasticity, and alterations in AMPAR expression may underlie synaptic dysfunction and disease pathophysiology. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of dopamine (DA) depletion, our previous work showed exercise increases total GluA2 subunit expression and the contribution of GluA2-containing channels in MPTP mice. The purpose of this study was to determine whether exercise-dependent changes in AMPAR expression after MPTP are specific to the striatopallidal (D2 R) or striatonigral (D1 R) medium spiny neuron (MSN) striatal projection pathways. Drd2 -eGFP-BAC transgenic mice were used to delineate differences in AMPAR expression between striatal D2 R-MSNs and D1 R-MSNs. Striatal AMPAR expression was assessed by immunohistochemical (IHC) staining, Western immunoblotting (WB) of preparations enriched for postsynaptic density (PSD), and alterations in the current-voltage relationship of MSNs. We found DA depletion results in the emergence of GluA2-lacking AMPARs selectively in striatopallidal D2 R-MSNs and that exercise reverses this effect in MPTP mice. Exercise-induced changes in AMPAR channels observed after DA depletion were associated with alterations in GluA1 and GluA2 subunit expression in postsynaptic protein, D2 R-MSN cell surface expression, and restoration of corticostriatal plasticity. Mechanisms regulating experience-dependent changes in AMPAR expression may provide innovative therapeutic targets to increase the efficacy of treatments for basal ganglia disorders, including Parkinson's disease.


Asunto(s)
Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Trastornos Parkinsonianos/metabolismo , Condicionamiento Físico Animal/fisiología , Receptores AMPA/biosíntesis , Animales , Western Blotting , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Técnicas de Placa-Clamp
17.
Neuroscience ; 215: 149-59, 2012 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-22554779

RESUMEN

The striatum is particularly vulnerable to mitochondrial dysfunction and this problem is linked to pathology created by environmental neurotoxins, stimulants like amphetamine, and metabolic disease and ischemia. We studied the course of recovery following a single systemic injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP) and found 3-NP caused lasting changes in motor behavior that were associated with altered activity-dependent plasticity at corticostriatal synapses in Fischer 344 rats. The changes in synapse behavior varied with the time after exposure to the 3-NP injection. The earliest time point studied, 24h after 3-NP, revealed 3-NP-induced an exaggeration of D1 Dopamine (DA) receptor dependent long-term potentiation (LTP) that reversed to normal by 48 h post-3-NP exposure. Thereafter, the likelihood and degree of inducing D2 DA receptor dependent long-term depression (LTD) gradually increased, relative to saline controls, peaking at 1 month after the 3-NP exposure. NMDA receptor binding did not change over the same post 3-NP time points. These data indicate even brief exposure to 3-NP can have lasting behavioral effects mediated by changes in the way DA and glutamate synapses interact.


Asunto(s)
Corteza Cerebral/citología , Cuerpo Estriado/citología , Inhibidores Enzimáticos/farmacología , Movimiento/efectos de los fármacos , Nitrocompuestos/farmacología , Propionatos/farmacología , Sinapsis/efectos de los fármacos , Adrenérgicos/toxicidad , Análisis de Varianza , Animales , Benzazepinas/farmacología , Biofisica , Maleato de Dizocilpina/farmacocinética , Antagonistas de Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Antagonistas de Aminoácidos Excitadores/farmacocinética , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Lateralidad Funcional , Técnicas In Vitro , Oxidopamina/toxicidad , Unión Proteica/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Sustancia Negra/lesiones , Sustancia Negra/fisiología , Sulpirida/farmacología , Factores de Tiempo , Tritio/farmacocinética , Tirosina 3-Monooxigenasa/metabolismo
18.
Clin Endocrinol (Oxf) ; 74(5): 631-5, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21470286

RESUMEN

BACKGROUND: Postpartum thyroid dysfunction (PPTD) is characterized by an early hyperthyroid phase followed, with peak prevalence at 6 months, by a hypothyroid phase which carries a risk of long-term hypothyroidism. Iodine has a major effect on thyroid function. Western Australia has previously been shown to be iodine replete. OBJECTIVE: To examine the iodine status of women with and without PPTD and the relationship of iodine status postpartum with long-term hypothyroidism. DESIGN: Case-control with follow-up. PATIENTS: A total of 149 women at 6 months postpartum (74 PPTD, 75 controls) with 98 (46 PPTD, 52 controls) followed up at 12 years. MEASUREMENTS: Urinary iodine concentration (UIC) and thyroid function at 6 months postpartum; thyroid function at 12-year follow-up. RESULTS: At 6 months postpartum, median UIC (quartiles) for observed TSH ranges were: for TSH < 0·4 mU/l 130·0 µg/l (82·0, 170·0); for TSH 0·4-4·0 mU/l 123·0 µg/l (80·5, 168·0); for TSH > 4·0 mU/l 85·0 µg/l (40·0, 141·5), P = 0·018. The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2·54, (95%CI: 1·47, 4·35), and with UIC < 50 µg/l, OR 4·22, (95%CI: 1·54, 11·55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12-year follow-up (P = 0·002); as did UIC < 100 µg/l (P = 0·03) and UIC < 50 µg/l (P = 0·02). The association was independent of antibody status. CONCLUSION: Low UIC measured at 6 months postpartum is associated with hypothyroid PPTD and independently predicts long-term hypothyroidism. We believe that it results from more severe preceding destructive thyroiditis, with discharge of thyroidal iodine, and thereby predicts a greater risk of long-term hypothyroidism.


Asunto(s)
Hipotiroidismo/orina , Yodo/orina , Periodo Posparto , Valor Predictivo de las Pruebas , Trastornos Puerperales , Estudios de Casos y Controles , Femenino , Humanos , Hipotiroidismo/epidemiología , Yodo/metabolismo , Estudios Longitudinales , Trastornos Puerperales/epidemiología , Enfermedades de la Tiroides , Australia Occidental
19.
Clin Endocrinol (Oxf) ; 73(3): 389-95, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20184598

RESUMEN

BACKGROUND: The long-term risk of hypothyroidism following postpartum thyroid dysfunction (PPTD) is uncertain. Most previous studies have been small, short-term or have lacked a control group. OBJECTIVE: To ascertain the long-term risk of hypothyroidism in women following PPTD. Design and participants A 12-year longitudinal study of 409 women (including 71 with PPTD) who previously participated in a PPTD prevalence study. MEASUREMENTS: The primary outcome measure was hypothyroidism (defined as TSH greater than 4 mU/l or on thyroxine replacement) at follow-up. Outcomes in women with and without PPTD were compared by logistic regression. Receiver operating characteristic analysis was used to determine the optimal cut-off for baseline TSH as a predictor of hypothyroidism in the cohort. RESULTS: At follow-up, hypothyroidism was present in 27 of 71 women who had PPTD at baseline (38%) and 14 of 338 women without PPTD (4%). From multivariate analysis, odds ratios (with 95% confidence intervals) for hypothyroidism were - 4.8 (1.6, 14.1) for PPTD; 8.2 (2.8, 24.6) for positive thyroid peroxidase antibodies (TPOAb); 9.7 (2.6, 37.0) for the hypothyroid phase of PPTD and 51.4 (19.2, 137.5) for hypothyroid PPTD with positive TPOAb. A baseline TSH above 2.6 mU/l was the optimal cut-off for predicting hypothyroidism (sensitivity 76%, specificity 86%). CONCLUSIONS: PPTD is a strong predictor of hypothyroidism in the long-term. Women who present with postpartum hypothyroidism or have positive TPOAb are at particularly high risk, suggesting that close long-term follow-up is advisable if thyroxine replacement is not instituted at an early stage.


Asunto(s)
Hipotiroidismo/sangre , Enfermedades de la Tiroides/sangre , Tirotropina/sangre , Adulto , Autoanticuerpos/sangre , Femenino , Estudios de Seguimiento , Humanos , Hipotiroidismo/etiología , Yoduro Peroxidasa/inmunología , Modelos Logísticos , Estudios Longitudinales , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Periodo Posparto , Medición de Riesgo , Factores de Riesgo , Enfermedades de la Tiroides/complicaciones , Factores de Tiempo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA