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1.
J Fish Biol ; 96(1): 194-201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729024

RESUMO

We explored the macroevolutionary dynamics of miniaturisation in New World anchovies by integrating a time-calibrated phylogeny, geometric morphometrics and phylogenetic comparative methods. We found that the paedomorphic species Amazonsprattus scintilla occupies a novel region of shape space, while the dwarf species Anchoviella manamensis has an overall shape consistent with other anchovies. We found that miniaturisation did not increase overall clade disparity in size or shape beyond the expectations of Brownian motion, nor were there differences in rates of size or shape evolution among clades. Overall, our study shows that while the mode of miniaturisation influences shape evolution, the phenotypic novelty produced by the evolution of miniaturisation did not seem to alter macroevolutionary dynamics.

2.
J R Soc Interface ; 16(156): 20190239, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31362613

RESUMO

Dry adhesives using surface microstructures inspired by climbing animals have been recognized for their potentially novel capabilities, with relevance to a range of applications including pick-and-place handling. Past work has suggested that performance may be strongly dependent on variability in the critical defect size among fibrillar sub-contacts. However, it has not been directly verified that the resulting adhesive strength distribution is well described by the statistical theory of fracture used. Using in situ contact visualization, we characterize adhesive strength on a fibril-by-fibril basis for a synthetic fibrillar adhesive. Two distinct detachment mechanisms are observed. The fundamental, design-dependent mechanism involves defect propagation from within the contact. The secondary mechanism involves defect propagation from fabrication imperfections at the perimeter. The existence of two defect populations complicates characterization of the statistical properties. This is addressed by using the mean order ranking method to isolate the fundamental mechanism. The statistical properties obtained are subsequently used within a bimodal framework, allowing description of the secondary mechanism. Implications for performance are discussed, including the improvement of strength associated with elimination of fabrication imperfections. This statistical analysis of defect-dependent detachment represents a more complete approach to the characterization of fibrillar adhesives, offering new insight for design and fabrication.

3.
Pharmacol Res Perspect ; 7(3): e00488, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31149343

RESUMO

In this study, we describe a novel approach for collecting bile from dogs and cynomolgus monkeys for metabolite profiling, ultrasound-guided cholecystocentesis (UCC). Sampling bile by UCC twice within 24 hours was well tolerated by dogs and monkeys. In studies with atorvastatin (ATV) the metabolite profiles were similar in bile obtained through UCC and from bile duct-cannulated (BDC) dogs. Similar results were observed in UCC and BDC monkeys as well. In both monkey and dog, the primary metabolic pathway observed for ATV was oxidative metabolism. The 2-hydroxy- and 4-hydroxyatorvastatin metabolites were the major oxidation products, which is consistent with previously published metabolite profiles. S-cysteine and glucuronide conjugates were also observed. UCC offers a viable alternative to bile duct cannulation for collection of bile for metabolite profiling of compounds that undergo biliary excretion, given the similar metabolite profiles in bile obtained via each method. Use of UCC for metabolite profiling may reduce the need for studies using BDC animals, a resource-intensive model.

4.
Interv Neuroradiol ; 25(3): 322-329, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31138039

RESUMO

We present a case of a novel restrictive cerebral venopathy in a child, consisting of a bilateral network of small to medium cortical veins without evidence of arteriovenous shunting, absence of the deep venous system, venous ischemia, elevated intracranial pressure, and intracranial calcifications. The condition is unlike other diseases characterized by networks of small veins, including cerebral proliferative angiopathy, Sturge-Weber syndrome, or developmental venous anomaly. While this case may be the result of an anatomic variation leading to the congenital absence of or early occlusion of the deep venous system, the insidious nature over many years argues against this. The absence of large cortical veins suggests a congenital abnormality of the venous structure. The child's presentation with a seizure-like event followed by protracted hemiparesis is consistent with venous ischemia. We propose that this is likely to represent a new clinicopathological entity.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Adolescente , Isquemia Encefálica/etiologia , Córtex Cerebral/irrigação sanguínea , Paralisia Cerebral/complicações , Transtornos Cerebrovasculares/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Exame Neurológico , Paresia/etiologia , Convulsões/etiologia , Tomografia Computadorizada por Raios X , Derivação Ventriculoperitoneal
5.
J Pediatr Hematol Oncol ; 41(1): e34-e37, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29432310

RESUMO

Congenital brain tumors are rare, representing <2% of all childhood brain tumors. Of these, ependymoblastoma is a profoundly aggressive embryonal brain tumor that is included in the diagnostic entity known as an embryonal tumor with multilayered rosettes. This report of a congenital ependymoblastoma diagnosed at birth aims to highlight how much remains unknown about embryonal tumor with multilayered rosettes and the devastating prognosis of this condition. Despite recent advancements made in identifying molecular targets for therapy, this tumor continues to have a high rate of recurrence with few successful treatment options, especially when diagnosed in the newborn period.


Assuntos
Neoplasias Encefálicas/congênito , Neoplasias Encefálicas/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos/congênito , Tumores Neuroectodérmicos Primitivos/diagnóstico por imagem , Adulto , Neoplasias Encefálicas/patologia , Feminino , Humanos , Recém-Nascido , Tumores Neuroectodérmicos Primitivos/patologia , Gravidez
6.
Pediatr Dermatol ; 35(6): e389-e390, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30178566

RESUMO

Melanotic neuroectodermal tumors of infancy are rare tumors arising from the neural crest and typically present during the first 12 months of life. The majority involve the facial bones, although melanotic neuroectodermal tumors of infancy of the skull and extremities have been observed with less frequency, as in the present case. This entity may initially be presented to the dermatologist as a scalp mass and should be considered in the differential diagnosis of infants with rapidly growing head and neck lesions.


Assuntos
Tumor Neuroectodérmico Melanótico/diagnóstico , Neoplasias Cranianas/diagnóstico , Diagnóstico Diferencial , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Tumor Neuroectodérmico Melanótico/cirurgia , Crânio/patologia , Neoplasias Cranianas/patologia
7.
BMC Evol Biol ; 18(1): 116, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021522

RESUMO

BACKGROUND: One of the most perplexing questions in evolutionary biology is why some lineages diversify into many species, and others do not. In many cases, ecological opportunity has played an important role, leading to diversification along trophic or habitat-based axes. The Goodeidae (Teleostomi: Cyprinodontiformes) are a family of freshwater fishes with two subfamilies: Goodeinae (42 species, viviparous, heterogeneous habitats, Mesa Central of Mexico) and Empetrichthyinae (4 species, oviparous, homogeneous habitats, Great Basin of the United States). These discrepant sets of characteristics and their sister-group relationship make the goodeids amenable to a comparative study of diversification. We gathered lateral body images from more than 1600 specimens of all extant species in the family. Geometric morphometric, and phylogenetic comparative analyses were used to address whether higher species diversity correlates with higher rates of morphological shape evolution and whether there are differences in functional/habitat modules between the two subfamilies. RESULTS: This study recovered a higher rate of overall body shape evolution in the Goodeinae that is nearly double in magnitude compared to the Empetrichthyinae. A modularity test indicated that the Goodeinae displayed elevated rates of morphological evolution in comparison to the Empetrichthyinae when only trunk (locomotor) regions were compared between subfamilies. No significant differences in evolutionary shape rates were recovered when the trophic (head) regions were compared between subfamilies. DISCUSSION: These results support the hypothesis that Mexican goodeids radiated via an ecological opportunity scenario into a wide-array of novel habitats in the island-like Mesa Central as evidenced by their high rate of shape evolution, relative to the Empetrichthyinae. This study quantitatively unraveled the drivers of evolution and eliminated trophic specialization as a driving force within the Goodeidae. CONCLUSIONS: A combination of phylogenetic and morphometric data, and phylogenetic comparative analyses were used to examine body shape rate evolution within the Goodeidae. Results support the hypothesis that species in the subfamily Goodeinae on the central Mexican plateau had a higher rate of body shape evolution relative to its sister subfamily Empetrichthyinae in the Great Basin suggesting that the Goodeinae diversified via an ecological opportunity scenario along habitat, rather than trophic axes.


Assuntos
Biodiversidade , Ciprinodontiformes/classificação , Espécies em Perigo de Extinção , Água Doce , Animais , Calibragem , Ciprinodontiformes/anatomia & histologia , Geografia , México , Filogenia , Especificidade da Espécie , Fatores de Tempo
8.
J Med Chem ; 61(3): 681-694, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29316397

RESUMO

G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.


Assuntos
Descoberta de Drogas , Pirazóis/farmacologia , Pirazóis/farmacocinética , Receptores Acoplados a Proteínas-G/agonistas , Administração Oral , Animais , Disponibilidade Biológica , Humanos , Masculino , Camundongos , Modelos Moleculares , Conformação Molecular , Pirazóis/administração & dosagem , Pirazóis/química , Pirrolidinas/química
9.
Pediatr Neurosurg ; 53(2): 100-107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29316543

RESUMO

INTRODUCTION: Myelomeningocele (MMC) is an open neural tube defect routinely surgically closed within 48 h of birth to prevent secondary infection. Up to 18% of patients experience wound complications, and 85% require shunting for hydrocephalus. We hypothesized that wound complications could be reduced by cerebrospinal fluid (CSF) diversion at the time of closure. METHODS: Institutional review board approval was obtained to review records of the 88 patients who underwent MMC closure between January 2005 and June 2016 at the Children's Hospital of Pittsburgh. Twenty-three patients (26%) had an external ventricular drain (EVD) placed at the time of MMC closure and underwent 7-11 days of CSF drainage. Fourteen patients (16%) had a shunt placed at the time of MMC closure, and 51 (58%) had no form of CSF diversion at the time of MMC closure. RESULTS: Patients with an EVD or shunt placed at the time of closure had no wound complications. In contrast, 8 patients (16%) without CSF diversion at closure developed wound complications (p = 0.048). Seven of the 8 wound complications occurred in the 71 patients with evidence of hydrocephalus at birth (p = 0.98). Of patients with evidence of hydrocephalus at the time of MMC closure, wound complications had a higher rate of occurrence among patients who did not receive a shunt or EVD at closure (p = 0.01). When comparing only patients with evidence of hydrocephalus at birth, the EVD group alone had a lower rate of wound complications than patients who did not receive CSF diversion at the time of closure (p = 0.031). CONCLUSIONS: These results suggest that addressing hydrocephalus at the time of MMC closure significantly reduces the likelihood of wound complications and may justify temporary CSF diversion at birth, at least in those patients manifesting hydrocephalus.


Assuntos
Drenagem , Hidrocefalia/cirurgia , Meningomielocele/complicações , Derivação Ventriculoperitoneal/métodos , Feminino , Humanos , Hidrocefalia/complicações , Recém-Nascido , Masculino , Meningomielocele/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Estudos Retrospectivos
10.
Blood ; 131(1): 108-120, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29051183

RESUMO

Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell transplantation (HCT) failure, and the prognosis for patients with post-HCT relapse is poor. There is compelling evidence that potent selective antileukemic effects can be delivered by donor T cells specific for particular minor histocompatibility (H) antigens. Thus, T-cell receptors (TCRs) isolated from minor H antigen-specific T cells represent an untapped resource for developing targeted T-cell immunotherapy to manage post-HCT leukemic relapse. Recognizing that several elements may be crucial to the efficacy and safety of engineered T-cell immunotherapy, we developed a therapeutic transgene with 4 components: (1) a TCR specific for the hematopoietic-restricted, leukemia-associated minor H antigen, HA-1; (2) a CD8 coreceptor to promote function of the class I-restricted TCR in CD4+ T cells; (3) an inducible caspase 9 safety switch to enable elimination of the HA-1 TCR T cells in case of toxicity; and (4) a CD34-CD20 epitope to facilitate selection of the engineered cell product and tracking of transferred HA-1 TCR T cells. The T-cell product includes HA-1 TCR CD4+ T cells to augment the persistence and function of the HA-1 TCR CD8+ T cells and includes only memory T cells; naive T cells are excluded to limit the potential for alloreactivity mediated by native TCR coexpressed by HA-1 TCR T cells. We describe the development of this unique immunotherapy and demonstrate functional responses to primary leukemia by CD4+ and CD8+ T cells transduced with a lentiviral vector incorporating the HA-1 TCR transgene construct.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoterapia , Leucemia/terapia , Linfócitos T/imunologia , Células Cultivadas , Humanos , Leucemia/imunologia , Antígenos de Histocompatibilidade Menor/metabolismo , Oligopeptídeos/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo
11.
J Pharm Sci ; 107(1): 317-326, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29107047

RESUMO

Amorphous phase separation (APS) is commonly observed in amorphous solid dispersions (ASD) when exposed to moisture. The objective of this study was to investigate: (1) the phase behavior of amorphous solid dispersions composed of a poorly water-soluble drug with extremely low crystallization propensity, BMS-817399, and PVP, following exposure to different relative humidity (RH), and (2) the impact of phase separation on the intrinsic dissolution rate of amorphous solid dispersion. Drug-polymer interaction was confirmed in ASDs at different drug loading using infrared (IR) spectroscopy and water vapor sorption analysis. It was found that the drug-polymer interaction could persist at low RH (≤75% RH) but was disrupted after exposure to high RH, with the advent of phase separation. Surface morphology and composition of 40/60 ASD at micro-/nano-scale before and after exposure to 95% RH were also compared. It was found that hydrophobic drug enriched on the surface of ASD after APS. However, for the 40/60 ASD system, the intrinsic dissolution rate of amorphous drug was hardly affected by the phase behavior of ASD, which may be partially attributed to the low crystallization tendency of amorphous BMS-817399 and enriched drug amount on the surface of ASD. Intrinsic dissolution rate of PVP decreased resulting from APS, leading to a lower concentration in the dissolution medium, but supersaturation maintenance was not anticipated to be altered after phase separation due to the limited ability of PVP to inhibit drug precipitation and prolong the supersaturation of drug in solution. This study indicated that for compounds with low crystallization propensity and high hydrophobicity, the risk of moisture-induced APS is high but such phase separation may not have profound impact on the drug dissolution performance of ASDs. Therefore, application of ASD technology on slow crystallizers could incur low risks not only in physical stability but also in dissolution performance.


Assuntos
Liberação Controlada de Fármacos/efeitos dos fármacos , Polímeros/química , Cristalização/métodos , Estabilidade de Medicamentos , Umidade , Interações Hidrofóbicas e Hidrofílicas , Polivinil/química , Pirrolidinas/química , Solubilidade , Ureia/análogos & derivados , Ureia/química , Valina/análogos & derivados , Valina/química , Água/química
12.
J Neurosurg Pediatr ; 20(3): 247-255, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28686121

RESUMO

OBJECTIVE Thalamopeduncular tumors are a group of pediatric low-grade gliomas that arise at the interface of the thalamus and brainstem peduncle. They typically occur within the first 2 decades of life, presenting with progressive spastic hemiparesis. Treatment strategies, including surgical intervention, have varied significantly. The authors present their experience in the treatment of 13 children, ages 2-15 years, with non-neurofibromatosis-related pilocytic astrocytomas located in the thalamopeduncular region. METHODS Between 2003 and 2016, 13 children presenting with progressive spastic hemiparesis due to a pilocytic astrocytoma at the interface of the thalamus and cerebral peduncles were identified. Medical records were reviewed retrospectively for clinical, radiological, pathological, and surgical data. Formalin-fixed, paraffin-embedded tissue was obtained for 12 cases and tested for KIAA1549-BRAF fusion and BRAF V600E point mutation. RESULTS On preoperative diffusion tensor imaging tractography (performed in 12 patients), the ipsilateral corticospinal tract was displaced laterally in 1 case (8.3%), medially in 1 case (8.3%), anterolaterally in 10 cases (83%), and posteriorly in no cases. Ten patients underwent resection via a transtemporal, transchoroidal approach, which was chosen to avoid further damage to motor function in cases of tumors that caused anterolateral or medial corticospinal tract displacement. With this approach, complications included hemianopia, oculomotor palsy, and tremor at a rate of 50%. Among the 12 patients with obtainable follow-up (mean 50.9 months), none received adjuvant therapy, and only 2 (17%) experienced recurrence or progression. KIAA1549-BRAF fusions were present in 10 cases (83%), while BRAF V600E was absent (0%). The 2 fusion-negative tumors had clinical features atypical for the series, including multi-focality and infiltration. CONCLUSIONS Transcortical, transchoroidal resection of thalamopeduncular tumors through the middle temporal gyrus allows for a high rate of gross-total resection and cure. Diffuse tensor tractography is a critical component of the preoperative planning process to determine the location of white matter tracts in proximity. Molecular status may correlate with clinical features, and the presence of BRAF lesions offers an additional target for future novel therapeutics.


Assuntos
Astrocitoma/genética , Astrocitoma/cirurgia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Tronco Encefálico/cirurgia , Tálamo/cirurgia , Adolescente , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Tronco Encefálico/metabolismo , Criança , Pré-Escolar , Análise Mutacional de DNA , Imagem de Tensor de Difusão , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Procedimentos Neurocirúrgicos/métodos , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Tálamo/metabolismo
13.
Front Microbiol ; 8: 1148, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28713335

RESUMO

In Escherichia coli, OmpF is an important outer membrane protein, which serves as a passive diffusion pore for small compounds including nutrients, antibiotics, and toxic compounds. OmpF expression responds to environmental changes such as temperature, osmolarity, nutrients availability, and toxic compounds via complex regulatory pathways involving transcriptional and post-transcriptional regulation. Our study identified a new regulatory cascade that controls the expression of OmpF porin. This pathway involves BluR, a transcriptional regulator repressing the expression of the ycgZ-ymgABC operon. We showed that BluR was responsible for the temperature-dependent regulation of the ycgZ-ymgABC operon. Furthermore, our results showed that independent expression of YcgZ led to a decreased activity of the ompF promoter, while YmgA, YmgB, and YmgC expression had no effect. We also determined that YcgZ accumulates in the absence of the Lon protease. Thus, mutation in bluR leads to de-repression of ycgZ-ymgABC transcription. With a second mutation in lon, YcgZ protein accumulates to reach levels that do not allow increased expression of OmpF under growth conditions that usually would, i.e., low temperature. With BluR responding to blue-light and temperature, this study sheds a new light on novel signals able to regulate OmpF porin.

14.
J Med Chem ; 60(14): 6166-6190, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28635286

RESUMO

Agonism of the 5-HT2C receptor represents one of the most well-studied and clinically proven mechanisms for pharmacological weight reduction. Selectivity over the closely related 5-HT2A and 5-HT2B receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT2C receptor to identify atypical agonist structures. We additionally report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT2C. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT2C with high selectivity over the related 5-HT2A and 5-HT2B receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT2C antagonist.


Assuntos
Arginina/análogos & derivados , Flavonas/química , Receptor 5-HT2C de Serotonina/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Arginina/síntese química , Arginina/química , Arginina/farmacologia , Encéfalo/metabolismo , Células CACO-2 , Permeabilidade da Membrana Celular , Comportamento Alimentar/efeitos dos fármacos , Flavonas/síntese química , Flavonas/farmacologia , Células HEK293 , Humanos , Masculino , Membranas Artificiais , Camundongos Knockout , Microssomos Hepáticos/metabolismo , Mutação , Ratos Sprague-Dawley , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2B de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/genética , Agonistas do Receptor 5-HT2 de Serotonina/síntese química , Agonistas do Receptor 5-HT2 de Serotonina/farmacocinética , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Relação Estrutura-Atividade
15.
Artigo em Inglês | MEDLINE | ID: mdl-28320655

RESUMO

Through the use of a laser Doppler vibrometer, it is shown that a 31% variation in quality factor can occur due to the effect of undercutting of the device layers outside of the anchors of a 220-MHz aluminum nitride contour-mode resonator. This undercutting is a result of the isotropic etch process used to release the device from the substrate. This paper shows that the variation in Q is a function of the release distance, L , between the active region of the resonator and the edge of this released region. This paper also determined a design modification that eliminated this issue and achieved a Q of 3048, which is independent of L .

16.
J Med Chem ; 60(4): 1417-1431, 2017 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-28112924

RESUMO

A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding Ki and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both Gq-coupled intracellular Ca2+ flux and Gs-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.


Assuntos
Hipoglicemiantes/farmacologia , Pirrolidinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Animais , Glicemia/análise , Glicemia/metabolismo , Linhagem Celular , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Moleculares , Pirrolidinas/química , Pirrolidinas/farmacocinética , Pirrolidinas/uso terapêutico , Ratos , Receptores Acoplados a Proteínas-G/metabolismo
17.
Pediatr Neurosurg ; 52(1): 36-40, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27595482

RESUMO

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare lesion that typically manifests in the first year of life, most commonly involving the facial bones. We present 2 infants with MNTI involving the posterior skull with associated compression of the superior sagittal sinus (SSS). A review of the anatomical locations of MNTI is offered, and the implications of SSS involvement are described. This represents the first known description of MNTI with involvement of the posterior SSS.


Assuntos
Tumor Neuroectodérmico Melanótico/diagnóstico por imagem , Tumor Neuroectodérmico Melanótico/cirurgia , Seio Sagital Superior/diagnóstico por imagem , Seio Sagital Superior/cirurgia , Feminino , Humanos , Lactente , Masculino
18.
Childs Nerv Syst ; 32(8): 1463-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27125518

RESUMO

INTRODUCTION: PHACE syndrome is a neurocutaneous disorder involving large facial hemangiomas in association with posterior fossa abnormalities, cerebral arterial anomalies, cardiac defects, and eye abnormalities. A recent consensus statement has delineated criteria necessary for the diagnosis of PHACE syndrome. Extracutaneous manifestations of PHACE syndrome predominately affect the cerebrovascular system. To date, there are no reports of cerebral cavernous malformations (CCMs) in children with PHACE syndrome. METHODS: We reviewed the charts of children admitted to the Children''s Hospital of Pittsburgh who met criteria for PHACE syndrome, and evaluated neuroimaging for cerebrovascular abnormalities, including the finding of CCMs. RESULTS: Six children met criteria for PHACE syndrome at our institution over a 10-year period. All children were female. All children had cerebrovascular abnormalities sufficient to meet major criteria for diagnosis. Four children (66.7 %) were found incidentally to have CCMs; all lesions measured less than 5 mm at the time of diagnosis and were asymptomatic. CONCLUSION: At present, CCMs are not listed among the diagnostic criteria for PHACE syndrome, and they have not previously been reported in association with PHACE syndrome. Hypoxic injury in utero may be the common denominator in the pathogenesis of many of the abnormalities already accepted in the criteria for PHACE syndrome and the formation of CCMs. In the setting of PHACE syndrome, we encourage clinicians to evaluate children for CCMs, which are readily apparent on the already-recommended screening MRIs.


Assuntos
Coartação Aórtica/complicações , Anormalidades do Olho/complicações , Malformações Arteriovenosas Intracranianas/complicações , Síndromes Neurocutâneas/complicações , Coartação Aórtica/diagnóstico por imagem , Pré-Escolar , Anormalidades do Olho/diagnóstico por imagem , Feminino , Humanos , Imagem Tridimensional , Lactente , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Angiografia por Ressonância Magnética , Imagem por Ressonância Magnética , Masculino , Síndromes Neurocutâneas/diagnóstico por imagem
19.
Surg Neurol Int ; 7: 26, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27069743

RESUMO

BACKGROUND: Treatment of low-pressure hydrocephalus (LPH) may require prolonged external ventricular drainage (EVD) at sub-zero pressures to reverse ventriculomegaly. Endoscopic third ventriculostomy (ETV) has been used in the treatment of noncommunicating hydrocephalus; however, indications for ETV are expanding. METHODS: Patients with the diagnosis of LPH as defined by the Pang and Altschuler criteria who underwent sub-zero drainage treatment over an 8-year period were included. Patients were divided into two cohorts based on whether or not ETV was employed during their treatment. Time from EVD placement to internalization of shunt was recorded for both groups; time from ETV to placement of shunt was recorded for the patients undergoing ETV. RESULTS: Sixteen adult patients with LPH were managed with sub-zero drainage method. Ten (62.5%) patients did not undergo ETV and the average time from first ventriculostomy to shunting was 73 days (range 14-257 days). Six (37.5%) patients underwent ETV during the course of their treatment; average time from initial ventriculostomy to shunt was 114 days (range 0-236 days) (P = 0.16). Time from development of LPH to ETV ranged from 28 days to 6.5 months. In the ETV group, of the 4 patients who underwent shunting, the average time to shunting following ETV was 15.25 days. CONCLUSIONS: ETV can be used successfully in the management of refractory LPH to decrease the duration of EVD.

20.
World Neurosurg ; 95: 414-418, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26921704

RESUMO

OBJECTIVE: A variety of biomaterials have been developed for cranial reconstruction after craniectomy, including polyethylene titanium mesh and calcium phosphate cement. This study sought to compare complication rates of calcium phosphate cement and titanium mesh cranioplasty in patients undergoing retromastoid craniectomy. METHODS: The authors retrospectively reviewed clinical data from 672 consecutive patients who underwent retromastoid craniectomy at a single institution for microvascular decompression or tumor resection from July 2009 to July 2014. Of these, 336 patients received calcium phosphate cement cranioplasty and 336 underwent (polyethylene) mesh cranioplasty. Charts were abstracted for occurrence of cerebrospinal fluid (CSF) leak, wound infection and/or other wound complication, and the groups were compared. RESULTS: In the mesh cranioplasty group, there were 38 complications related to the surgical site, including 18 infections (5.4%), 20 patients (6%) with CSF leak or pseudomeningocele, and no (0%) other wound complications. In the cement cranioplasty cohort, 2 patients (0.6%) experienced wound infection, no patients (0%) had CSF leak, and 2 patients (0.6%) had other wound complications (including one sterile wound dehiscence and one reoperation for removal of excess cement). There was a statistically significant decrease in the rate of wound infection and CSF leak in the patients who underwent cement cranioplasty (P <0.001 for both). CONCLUSIONS: Calcium phosphate cement cranioplasty offers an alternative to titanium cranioplasty and may reduce the risk of surgical site complication. Randomized, prospective comparisons of cement cranioplasty to traditional techniques are warranted.


Assuntos
Cimentos para Ossos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Telas Cirúrgicas , Infecção da Ferida Cirúrgica/epidemiologia , Titânio , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , Craniectomia Descompressiva , Feminino , Doenças do Nervo Glossofaríngeo/cirurgia , Espasmo Hemifacial/cirurgia , Herpes Zoster da Orelha Externa/cirurgia , Humanos , Masculino , Cirurgia de Descompressão Microvascular , Pessoa de Meia-Idade , Polietileno , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Crânio/cirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto Jovem
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