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1.
Glob Chang Biol ; 29(2): 324-340, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36229037

RESUMO

Understanding the environmental mechanisms that govern population change is a fundamental objective in ecology. Although the determination of how top-down and bottom-up drivers affect demography is important, it is often equally critical to understand the extent to which, environmental conditions that underpin these drivers fluctuate across time. For example, associations between climate and both food availability and predation risk may suggest the presence of trophic interactions that may influence inferences made from patterns in ecological data. Analytical tools have been developed to account for these correlations, while providing opportunities to ask novel questions regarding how populations change across space and time. Here, we combine two modeling disciplines-path analysis and mark-recapture-recovery models-to explore whether shifts in sea-surface temperatures (SSTs) influenced top-down (entanglement in fishing equipment) or bottom-up (forage fish production) population constraints over 60 years, and the extent to which these covarying processes shaped the survival of a long-lived seabird, the Royal tern. We found that hemispheric trends in SST were associated with variation in the amount of fish harvested along the Atlantic coast of North America and in the Caribbean, whereas reductions in forage fish production were mostly driven by shifts in the amount of fish harvested by commercial fisheries throughout the North Atlantic the year prior. Although the indirect (i.e., stock depletion) and direct (i.e., entanglement) impacts of commercial fishing on Royal tern mortality has declined over the last 60 years, increased SSTs during this time period has resulted in a comparable increase in mortality risk, which disproportionately impacted the survival of the youngest age-classes of Royal terns. Given climate projections for the North Atlantic, our results indicate that threats to Royal tern population persistence in the Mid-Atlantic will most likely be driven by failures to recruit juveniles into the breeding population.


Assuntos
Charadriiformes , Mudança Climática , Animais , Ecossistema , Pesqueiros , Comportamento Predatório , Dinâmica Populacional
2.
Stud Hist Philos Sci ; 89: 114-128, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34450421

RESUMO

This paper traces the origin of renormalization group concepts back to two strands of 1950s high energy physics: the causal perturbation theory programme, which gave rise to the Stueckelberg-Petermann renormalization group, and the debate about the consistency of quantum electrodynamics, which gave rise to the Gell-Mann-Low renormalization group. Recognising the different motivations that shaped these early approaches sheds light on the formal and interpretive diversity we find in contemporary renormalization group methods.


Assuntos
Física , Gravidez de Gêmeos , Humanos
3.
J Card Surg ; 35(3): 692-695, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945233

RESUMO

BACKGROUND: We present a case of a 83-year-old man with a prior history of coronary artery bypass who presented to his family physician with progressive symptoms that raised concern for heart failure exacerbation. A chest X-ray was performed, which showed a fractured topmost sternal wire in the lateral projection and indicated that the sternal wire had migrated into the anterior mediastinum. An emergent electrocardiogram-gated flash computed tomography angiography confirmed the location of the fractured wire to be in close proximity to the main pulmonary artery. A discussion of migrated sternal wires with a literature review of cases is provided as well. AIMS: To present a case of a migrated sternal wire and a literature review. METHODS: An extensive literature review using pubmed and medline with relevant keywords was preformed. RESULTS: 11 known cases of migrated sternal wires with various complications, as detailed in the review table. The mortality rate is low but can be associated with significant morbidity. DISCUSSION: Fractured wires are quite common and are usually a benign radiographic finding. However, migration of sternal wires is an extremely rare phenomenon. Only a few reported cases in the literature were sternal wires have migrated beyond the sternum, leading to catastrophic clinical consequences, as detailed in the review table. CONCLUSION: Sternal wire complications secondary to migration beyond the sternum are rare but potentially fatal. Precise wire location and risk assessment with CT are more appropriate when wire location cannot be clearly delineated by plain film radiography.


Assuntos
Fios Ortopédicos/efeitos adversos , Migração de Corpo Estranho/etiologia , Idoso de 80 Anos ou mais , Migração de Corpo Estranho/diagnóstico por imagem , Humanos , Masculino , Artéria Pulmonar , Radiografia Torácica , Esterno , Tomografia Computadorizada por Raios X
5.
Parasit Vectors ; 17(1): 248, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844973

RESUMO

BACKGROUND: Sarcoptic mange is a skin disease caused by the contagious ectoparasite Sarcoptes scabiei, capable of suppressing and extirpating wild canid populations. Starting in 2015, we observed a multi-year epizootic of sarcoptic mange affecting a red fox (Vulpes vulpes) population on Fire Island, NY, USA. We explored the ecological factors that contributed to the spread of sarcoptic mange and characterized the epizootic in a landscape where red foxes are geographically constrained. METHODS: We tested for the presence of S. scabiei DNA in skin samples collected from deceased red foxes with lesions visibly consistent with sarcoptic mange disease. We deployed 96-100 remote trail camera stations each year to capture red fox occurrences and used generalized linear mixed-effects models to assess the affects of red fox ecology, human and other wildlife activity, and island geography on the frequency of detecting diseased red foxes. We rated the extent of visual lesions in diseased individuals and mapped the severity and variability of the sarcoptic mange disease. RESULTS: Skin samples that we analyzed demonstrated 99.8% similarity to S. scabiei sequences in GenBank. Our top-ranked model (weight = 0.94) showed that diseased red foxes were detected more frequently close to roadways, close to territories of other diseased red foxes, away from human shelters, and in areas with more mammal activity. There was no evidence that detection rates in humans and their dogs or distance to the nearest red fox den explained the detection rates of diseased red foxes. Although detected infrequently, we observed the most severe signs of sarcoptic mange at the periphery of residential villages. The spread of visual signs of the disease was approximately 7.3 ha/week in 2015 and 12.1 ha/week in 2017. CONCLUSIONS: We quantified two separate outbreaks of sarcoptic mange disease that occurred > 40 km apart and were separated by a year. Sarcoptic mange revealed an unfettered spread across the red fox population. The transmission of S. scabiei mites in this system was likely driven by red fox behaviors and contact between individuals, in line with previous studies. Sarcoptic mange is likely an important contributor to red fox population dynamics within barrier island systems.


Assuntos
Raposas , Sarcoptes scabiei , Escabiose , Animais , Raposas/parasitologia , Escabiose/veterinária , Escabiose/epidemiologia , Escabiose/parasitologia , Sarcoptes scabiei/genética , Pele/parasitologia , Pele/patologia , New York/epidemiologia , Animais Selvagens/parasitologia , Geografia , Humanos
6.
J Urol ; 187(6): 2228-35, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22503050

RESUMO

PURPOSE: Proper induction of the T-helper type 1 immune response is required for effective bacillus Calmette-Guérin immunotherapy for bladder cancer. Interleukin-10 down-regulates the T-helper 1 response and is associated with bacillus Calmette-Guérin failure. We investigated whether blocking interleukin-10 receptor 1 would enhance the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity in a mouse model. MATERIALS AND METHODS: Splenocytes were incubated with bacillus Calmette-Guérin or bacillus Calmette-Guérin plus control IgG1, anti-interleukin-10 receptor 1 mAb or anti-interleukin-10 neutralizing mAb, followed by enzyme-linked immunosorbent assay of interferon-γ production. Bladder RNA was extracted after intravesical bacillus Calmette-Guérin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb and analyzed by reverse transcriptase and/or quantitative polymerase chain reaction. Urine was collected and analyzed by enzyme-linked immunosorbent assay. Mice bearing a luciferase expressing MB49 orthotopic tumor were treated with intravesical bacillus Calmette-Guérin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb. Tumor response was assessed by bioluminescent imaging and bladder weight measurement. RESULTS: Bacillus Calmette-Guérin plus anti-interleukin-10R1 mAb induced significantly higher interferon-γ production by splenocytes than bacillus Calmette-Guérin plus anti-interleukin-10 mAb. Bacillus Calmette-Guérin plus anti-interleukin-10 receptor 1 mAb also induced significantly higher interferon-γ mRNA and protein in bladder and urine, respectively, in a dose dependent manner. Treatment with phosphate buffered saline, bacillus Calmette-Guérin plus control IgG1 and bacillus Calmette-Guérin plus anti-interleukin-10 receptor 1 mAb showed a 0% tumor-free rate with a 20% death rate, a 20% tumor-free rate with a 20% death rate and a 40% tumor-free rate with a 0% death rate, respectively. Bladder weight also revealed the effect of anti-interleukin-10 receptor 1 mAb on the bacillus Calmette-Guérin induced bladder tumor response. CONCLUSIONS: Anti-interleukin-10 receptor 1 mAb enhanced the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity. A humanized form of this mAb warrants future investigation for bacillus Calmette-Guérin treatment of bladder cancer.


Assuntos
Anticorpos Monoclonais/imunologia , Carcinoma de Células de Transição/imunologia , Imunoterapia , Subunidade alfa de Receptor de Interleucina-10/imunologia , Mycobacterium bovis/imunologia , Células Th1/imunologia , Neoplasias da Bexiga Urinária/imunologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL
7.
PLoS One ; 17(7): e0270224, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35776754

RESUMO

Understanding factors that influence a species' distribution and abundance across the annual cycle is required for range-wide conservation. Thousands of imperiled red knots (Calidris cantus rufa) stop on Virginia's barrier islands each year to replenish fat during spring migration. We investigated the variation in red knot presence and flock size, the effects of prey on this variation, and factors influencing prey abundance on Virginia's barrier islands. We counted red knots and collected potential prey samples at randomly selected sites from 2007-2018 during a two-week period during early and peak migration. Core samples contained crustaceans (Orders Amphipoda and Calanoida), blue mussels (Mytilus edulis), coquina clams (Donax variabilis), and miscellaneous prey (horseshoe crab eggs (Limulus polyphemus), angel wing clams (Cyrtopleura costata), and other organisms (e.g., insect larvae, snails, worms)). Estimated red knot peak counts in Virginia during 21-27 May were highest in 2012 (11,959) and lowest in 2014 (2,857; 12-year peak migration [Formula: see text] = 7,175, SD = 2,869). Red knot and prey numbers varied across sampling periods and substrates (i.e., peat and sand). Red knots generally used sites with more prey. Miscellaneous prey ([Formula: see text] = 2401.00/m2, SE = 169.16) influenced red knot presence at a site early in migration, when we only sampled on peat banks. Coquina clams ([Formula: see text] = 1383.54/m2, SE = 125.32) and blue mussels ([Formula: see text] = 777.91/m2, SE = 259.31) affected red knot presence at a site during peak migration, when we sampled both substrates. Few relationships between prey and red knot flock size existed, suggesting that other unmeasured factors determined red knot numbers at occupied sites. Tide and mean daily water temperature affected prey abundance. Maximizing the diversity, availability, and abundance of prey for red knots on barrier islands requires management that encourages the presence of both sand and peat bank intertidal habitats.


Assuntos
Bivalves , Charadriiformes , Animais , Ecossistema , Areia , Estações do Ano , Virginia
9.
Ecol Evol ; 10(20): 11055-11068, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33144948

RESUMO

Many waterbird populations have become increasingly dependent on agricultural habitats for feeding. While habitat destruction has been proposed as a key reason forcing waterbirds to move from natural habitats to agricultural habitats, few have used long-term data to test this hypothesis. The Siberian crane (Leucogeranus leucogeranus) is an IUCN Critically Endangered species. About 98% of its global population winters at Poyang Lake, China. Recently, many cranes shifted from feeding in natural wetlands to agricultural habitats. Here, we integrate bird surveys, Vallisneria tuber (the traditional food of cranes in natural wetlands) surveys, water level data, and remotely sensed images from 1999 to 2016 to explore the drivers of this habitat shift. Changes in Siberian crane numbers in natural wetlands and agricultural fields indicated that the habitat shift occurred in the winters of 2015-2016. Analyses using generalized linear mixed models suggested that crane numbers in natural wetlands were positively related to tuber density and the interaction between dry season (October-March) water level and tuber density. The changes in tuber density and dry season water level in 2015-2016 indicated that tuber disappearance may have been the primary driver of the habitat shift, with a smaller effect of high water level. Submerged plants at Poyang Lake have degraded seriously in the past two decades. The plant degradation at Shahu Lake, a sublake of Poyang Lake, may have been caused by high spring water, high winter temperature, and low summer temperature. However, the drivers of tuber disappearance at Poyang Lake may not be restricted to these variables. Because Poyang Lake is an important refuge for many waterbirds in the Yangtze River floodplain, it is urgent to take effective measures to restore its submerged plants and ecosystem health. Agricultural fields can be important refuges for Siberian cranes, mitigating the negative impacts of wetland deterioration.

10.
J Wildl Dis ; 45(3): 817-22, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19617494

RESUMO

We documented the antibody prevalence to three arboviruses, St. Louis encephalitis virus (SLEV), eastern equine encephalitis virus (EEEV), and West Nile virus (WNV), in Crested Caracaras (Caracara cheriway; n = 80) in Florida from 2007 to 2008. Antibody prevalence to WNV was higher (9%) than for the other viruses. Most seropositive birds were adults (< or =3 yr of age), with 55% of adults testing positive for antibodies to at least one virus. Adults were significantly more likely to have antibodies to WNV than nonadults (P<0.001). Prevalence of SLEV and EEEV antibodies among Crested Caracaras was 3% for each virus, and three adult caracaras had indistinguishable anti-flavivirus antibodies. The susceptibility of Crested Caracaras to adverse effects of WNV, SLEV, or EEEV infection remains unknown; however, we observed that some free-ranging individuals survived infection and successfully fledged young. Knowledge of arboviral infection among Florida's Crested Caracara, which is both state and federally threatened, is valuable considering increasing pressure on this population from rapid and extensive habitat alterations.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Arbovirus/veterinária , Arbovírus/imunologia , Doenças das Aves/epidemiologia , Vírus do Nilo Ocidental/imunologia , Fatores Etários , Animais , Infecções por Arbovirus/epidemiologia , Aves , Conservação dos Recursos Naturais , Vírus da Encefalite Equina do Leste/imunologia , Vírus da Encefalite de St. Louis/imunologia , Feminino , Florida/epidemiologia , Masculino , Estudos Soroepidemiológicos
11.
Ecol Evol ; 9(24): 13966-13978, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31938495

RESUMO

Habitat selection and its relationship to fitness is a fundamental concept in ecology, but the mechanisms driving this connection are complex and difficult to detect. Despite the difficulties in understanding such intricate relationships, it is imperative that we study habitat selection and its relationship with fitness. We compared habitat selection of least terns (Sternula antillarum) and piping plovers (Charadrius melodus) on the Missouri River (2012-2014) to examine the consequences of those choices on nest and chick survival. We hypothesized that plovers and terns would select habitat that minimized the chance of flooding and predation of eggs, chicks, and adults, but that plovers would also select habitat that would provide foraging habitat for their chicks. We developed an integrated habitat selection model that assessed selection across multiple scales (sandbar and nest scales) and directly modeled the effect of selection on nest and chick survival. In general, the species selected habitat in keeping with our hypotheses, such that predation and flooding, in particular, may have been reduced. Sandbar selection had either a negative or no appreciable effect on nest survival for both species across years. Nest-site selection in 2012 had a generally positive effect on nest survival and chick survival for both terns and plovers, and this trended toward a negative effect by 2014. This result suggested that early selection decisions appeared to be adaptive, but we speculate that relatively high site fidelity and habitat degradation led to reduced benefit over time. Our results highlight the complex nature of habitat selection and its relationship to fitness.

12.
PLoS One ; 14(7): e0209986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31344034

RESUMO

Coastal storms have consequences for human lives and infrastructure but also create important early successional habitats for myriad species. For example, storm-induced overwash creates nesting habitat for shorebirds like piping plovers (Charadrius melodus). We examined how piping plover habitat extent and location changed on barrier islands in New York, New Jersey, and Virginia after Hurricane Sandy made landfall following the 2012 breeding season. We modeled nesting habitat using a nest presence/absence dataset that included characterizations of coastal morphology and vegetation. Using a Bayesian network, we predicted nesting habitat for each study site for the years 2010/2011, 2012, and 2014/2015 based on remotely sensed spatial datasets (e.g., lidar, orthophotos). We found that Hurricane Sandy increased piping plover habitat by 9 to 300% at 4 of 5 study sites but that one site saw a decrease in habitat by 27%. The amount, location, and longevity of new habitat appeared to be influenced by the level of human development at each site. At three of the five sites, the amount of habitat created and the time new habitat persisted were inversely related to the amount of development. Furthermore, the proportion of new habitat created in high-quality overwash was inversely related to the level of development on study areas, from 17% of all new habitat in overwash at one of the most densely developed sites to 80% of all new habitat at an undeveloped site. We also show that piping plovers exploited new habitat after the storm, with 14-57% of all nests located in newly created habitat in the 2013 breeding season. Our results quantify the importance of storms in creating and maintaining coastal habitats for beach-nesting species like piping plovers, and these results suggest a negative correlation between human development and beneficial ecological impacts of these natural disturbances.


Assuntos
Charadriiformes/fisiologia , Tempestades Ciclônicas , Ecossistema , Modelos Biológicos , Comportamento de Nidação/fisiologia , Animais , Teorema de Bayes , Conservação dos Recursos Naturais , Mid-Atlantic Region , Dinâmica Populacional
13.
J Comp Neurol ; 503(6): 790-802, 2007 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-17570500

RESUMO

The expression of estrogen receptors (ERs) in the developing and adult human brain has not been clearly established, although estrogens are crucial for neuronal differentiation, synapse formation, and cognitive functions. By using immunohistochemistry, we have studied the distribution of ER alpha and ER beta in human cerebral cortex and hippocampus from early prenatal stages to adult life. ER alpha was detected in the cortex at 9 gestational weeks (GW), with a high expression in proliferating zones and the cortical plate. The staining intensity decreased gradually during prenatal development but increased again from birth to adulthood. In contrast, ER beta was first detected at 15 GW in proliferating zones, and at 16/17 GW, numerous ER beta immunopositive cells were also observed in the cortical plate. ER beta expression persisted in the adult cortex, being widely distributed throughout cortical layers II-VI. In addition, from around 15 GW to adulthood, ER alpha and ER beta were expressed in human hippocampus mainly in pyramidal cells of Ammon's horn and in the dentate gyrus. Western blotting and immunohistochemistry in the adult cerebral cortex and hippocampus revealed lower protein expression of ER alpha compared with ER beta. Double immunostaining showed that during fetal life both ERs are expressed in neurons as well as in radial glia, although only ER alpha is expressed in the Cajal-Retzius neurons of the marginal zone. These observations demonstrate that the expression of ER alpha and ER beta displays different spatial-temporal patterns during human cortical and hippocampal development and suggest that both ERs may play distinct roles in several processes related to prenatal brain development.


Assuntos
Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Adolescente , Adulto , Western Blotting , Feminino , Feto , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neurônios/citologia , Neurônios/metabolismo
14.
Immun Inflamm Dis ; 4(2): 135-147, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27957325

RESUMO

The anti-human immunoglobulin E (IgE) monoclonal antibody, omalizumab (Xolair®, Genentech, South San Fransisco, CA), is effective in the treatment of poorly controlled moderate to severe allergic asthma and chronic idiopathic urticaria. It acts by specifically binding to the constant domain (Cϵ3) of free human IgE in the blood and interstitial fluid. Although efficacious, use of omalizumab is limited due to restrictions on patient weight and pre-existing IgE levels, and frequent dosing (q2-4 weeks). A vaccine inducing anti-IgE antibodies has the potential for similar clinical benefits with less frequent dosing and relatively lower cost of goods. We developed a vaccine containing two IgE peptide-conjugates targeting the Cϵ3 domain of human IgE. As part of preclinical evaluation of the vaccine to optimize formulation and dose prior to initiating clinical studies, we evaluated the vaccine in non-human primates, and demonstrate the induction of anti-peptide antibodies that can bind to conformationally intact human IgE and are capable, at least in some animals, of substantial lowering circulating IgE levels.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais Humanizados , Vacinas Conjugadas/imunologia , Animais , Anticorpos Monoclonais , Asma/terapia , Humanos , Omalizumab , Primatas , Urticária/terapia
15.
Mov Ecol ; 4: 6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26981249

RESUMO

BACKGROUND: Many species are distributed as metapopulations in dynamic landscapes, where habitats change through space and time. Individuals locate habitat through dispersal, and the relationship between a species and landscape characteristics can have profound effects on population persistence. Despite the importance of connectivity in dynamic environments, few empirical studies have examined temporal variability in dispersal or its effect on metapopulation dynamics. In response to this knowledge gap, we studied the dispersal, demography, and viability of a metapopulation of an endangered, disturbance-dependent shorebird. We examined three subpopulations of piping plovers (Charadrius melodus) on the lower Platte and Missouri rivers from 2008-2013. High flow events from an upstream dam on the Missouri River in 2010 and 2011 allowed us to assess the effect of total habitat loss and the subsequent creation of new habitat associated with a large disturbance at one 'natural' study location. The other two sites within the metapopulation, which were maintained by anthropogenic activities (e.g., mining, development, habitat restoration), were largely unaffected by this disturbance, resulting in a controlled natural experiment. RESULTS: High flow events were associated with increased emigration, decreased immigration, and decreased survival in the subpopulation that experienced high flows. Following the high flow event, immigration into that subpopulation increased. Dispersal rates among subpopulations were negatively correlated with distance. The metapopulation had a low probability of extinction over 100 years (0 %) under the current disturbance interval and associated dispersal and survival rates. However, persistence depended on relatively stable, human-created habitats, not the dynamic, natural habitat (47.7 % extinction probability for this subpopulation). CONCLUSIONS: We found that functional connectivity, as measured by the rate of dispersal among subpopulations, increased as a result of the high flow event in our study metapopulation. Plovers also increased reproductive output following this event. Although the study metapopulation had a low overall probability of extinction, metapopulation persistence depended on anthropogenically created habitats that provided a small but stable source of nesting habitat and dispersers through time. However, all subpopulations remained small, even if persistent, making them individually vulnerable to extinction through stochastic events. Given the highly dynamic nature of habitat availability in this system, maintaining several subpopulations within the metapopulation and stable sources of habitat will be critical, and this species will likely remain conservation-reliant.

16.
Radiol Clin North Am ; 42(2): 279-96, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15136017

RESUMO

Deep venous thrombosis and pulmonary embolism are common problems and frequently included in the differential diagnosis of patients presenting to the emergency department and in the acute care setting. Clinical signs and symptoms of these entities are nonspecific and it is important to perform objective testing to confirm the diagnosis and initiate proper therapy. Compression ultrasonography is the diagnostic procedure of choice for the investigation of patients with suspected deep venous thrombosis. This article reviews the clinical indications, diagnostic techniques, and interpretation of compression ultrasound to assess deep venous thrombosis in the upper and lower extremities and to evaluate the role of compression ultrasonography in the assessment of patients with suspected pulmonary embolism.


Assuntos
Diagnóstico por Imagem/métodos , Trombose Venosa/diagnóstico por imagem , Feminino , Humanos , Extremidade Inferior/diagnóstico por imagem , Masculino , Flebografia/métodos , Embolia Pulmonar/diagnóstico por imagem , Medição de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Doppler , Extremidade Superior/diagnóstico por imagem
17.
Fertil Steril ; 86(6): 1736-43, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17011556

RESUMO

OBJECTIVE: Cellular and subcellular localization of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) in uterine leiomyomas. DESIGN: Retrospective study. SETTING: University of La Laguna (ULL) and Canary University Hospital (HUC). PATIENT(S): Premenopausal and postmenopausal women with uterine leiomyomas. INTERVENTION(S): Hysterectomy and myomectomy. RESULT(S): Estrogen receptor alpha was only present in smooth muscle cells with variation in the subcellular location in different leiomyomas. Estrogen receptor beta was widely distributed in smooth muscle, endothelial, and connective tissue cells with nuclear location in all cases studied; variations were only found in the muscle cells for this receptor. CONCLUSION(S): Estrogens operate in leiomyoma smooth muscle cells through different receptors, alpha and beta. However they only act through the ERbeta in endothelial and connective cells.


Assuntos
Envelhecimento/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Leiomioma/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição Tecidual
18.
Bioorg Med Chem Lett ; 16(23): 6116-9, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16979341

RESUMO

A series of novel pyridine-2-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compound (S)-13 was selected for further profiling.


Assuntos
Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , PPAR alfa/agonistas , PPAR gama/agonistas , Piridinas/química , Piridinas/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/patologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Masculino , Camundongos , Estrutura Molecular , PPAR alfa/metabolismo , PPAR gama/metabolismo , Piridinas/síntese química , Piridinas/uso terapêutico , Relação Estrutura-Atividade
19.
Bioorg Med Chem Lett ; 16(23): 6120-3, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16973358

RESUMO

A series of novel pyridine-3-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compounds (S)-14 and (S)-19 were selected for further profiling.


Assuntos
Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , PPAR alfa/agonistas , PPAR gama/agonistas , Piridinas/sangue , Piridinas/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/patologia , Éter/química , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Camundongos , Estrutura Molecular , PPAR alfa/metabolismo , PPAR gama/metabolismo , Piridinas/síntese química , Piridinas/uso terapêutico , Relação Estrutura-Atividade , Tiazolidinedionas/química
20.
Bioorg Med Chem Lett ; 15(1): 51-5, 2005 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-15582409

RESUMO

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.


Assuntos
Cinamatos/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Animais , Glicemia/metabolismo , Cinamatos/administração & dosagem , Cinamatos/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ratos , Ratos Zucker , Relação Estrutura-Atividade , Triglicerídeos/sangue
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