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Atopic dermatitis (AD) is a chronic skin disease that significantly impacts patient quality of life (QoL). It is unknown whether patients and physicians have the same interpretation of AD burden. Unmet needs and AD disease burden were evaluated by comparing terminology used in social media with terminology used in scientific literature. AD terminology in social media was identified using the NetBase platform, and natural language processing was performed. Topics and words driving negative sentiment were evaluated overall and in relation to specific symptoms. The systematic review of scientific literature identified publications that included AD and QoL terms was identified from PubMed. Term analysis of titles and abstracts was conducted via natural language processing. The occurrence of topics and co-occurrence of words associated with QoL terms were evaluated. More than 3 million social media mentions (2018-2020) and 1519 scientific publications (2000-2020) were evaluated. There were more negative than positive social media mentions, and flare and pain were common symptoms driving negative sentiment. Face and hands were major drivers of negative sentiment in relation to AD symptoms in social media. Sleep and pain were often mentioned together. In scientific literature, pruritus and depression were the most frequently occurring symptoms. Similarly, pruritus was the most common AD symptom co-occurring with QoL terms in the assessed scientific literature. Social media analyses provide a unique view into the patient experience of AD. Symptoms driving negative sentiment in social media appear to be discordantly represented in scientific literature. Incorporating patient perspectives may improve disease understanding and management.
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Dermatite Atópica , Mídias Sociais , Humanos , Dor , Prurido/etiologia , Qualidade de VidaRESUMO
BACKGROUND: Fusionless techniques for the treatment of neuromuscular early-onset scoliosis (EOS) are increasingly used to preserve spinal and thoracic growth and to postpone posterior spinal fusion (PSF). These techniques have greatly improved thanks to magnetically controlled growing rods, which allow the avoidance of repeated surgery. However, the surgery-related complication rate remains high. The objective of the current study was to report the preliminary outcomes of 21 patients with neuromuscular EOS who were treated with a 1-way self-expanding rod (OWSER). This device was designed to avoid repeated surgery and preserve spinal and thoracic growth thanks to its free rod sliding. METHODS: Patients with neuromuscular EOS who underwent OWSER fixation were prospectively reviewed; follow-up was a minimum of 3 years. The instrumentation relies on a bipolar construct from T1 to the sacrum, with proximal fixation by double thoracic hook-claws and distal fixation by iliosacral screws. The device comprises a rod with a notched part sliding in 1 direction inside a domino. Changes in Cobb angle, pelvic obliquity, thoracic kyphosis, lumbar lordosis, T1-S1 and T1-T12 length, space available for the lung, and chest width were assessed. Complications were reviewed. RESULTS: The mean age at surgery was 10.5 years. The mean follow-up was 3.9 years. The mean pelvic obliquity improved from 20° preoperatively to 8° postoperatively and to 6° at the latest follow-up. The mean Cobb angle improved from 66° preoperatively to 38° postoperatively and to 32° at the latest follow-up. The mean preoperative kyphosis was reduced from 41° to 26° at the latest follow-up (p = 0.14). The mean lordosis was 34° preoperatively and 38° at the latest follow-up. The mean growth per month was 0.8 mm for the T1-T12 segment and 1.5 mm for T1-S1. The global complication rate was 38% (2 surgical site infections, 3 cases of lack of rod expansion, 1 case of pyelonephritis, and 2 central venous catheter-related infections). No PSF had been performed at the latest follow-up. CONCLUSIONS: Use of the OWSER with a minimally invasive bipolar technique for neuromuscular EOS provided satisfactory correction of spinal and pelvic deformities at 3 years of follow-up. A longer follow-up is required. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Intravenous drug use and sexual practices account for 60% of hepatitis C (HCV) and B (HBV) infection. Disclosing these activities can be embarrassing and reduce risk reporting, blood testing and diagnosis. In diagnosed patients, linkage to care remains a challenge. Audio-computer-assisted survey interview (Audio-CASI) was used to guide HCV and HBV infection testing in urban clinics. Risk reporting, blood testing and serology results were compared to historical controls. A patient navigator (PN) followed up blood test results and provided patients with positive serology linkage to care (LTC). Of 1932 patients surveyed, 574 (30%) were at risk for chronic viral hepatitis. A total of 254 (44.3%) patients were tested, 34 (13.5%) had serology warranting treatment evaluation, and 64% required HBV vaccination. Of 16 patients with infection, seven HCV and three HBV patients started treatment following patient LTC. Of 146 HBV-naïve patients, 70 completed vaccination. About 75% and 49% of HCV antibody and HBV surface antigen-positive patients were born between 1945 and 1965. Subsequently, automated HCV testing of patients born between 1945 and 1965 was built into our hospital electronic medical records. Average monthly HCV antibody testing increased from 245 (January-June) to 1187 (July-October). Patient navigator directed LTC for HCV antibody-positive patients was 61.6%. In conclusion, audio-CASI can identify patients at risk for HCV or HBV infection and those in need of HBV vaccination in urban medical clinics. Although blood testing once a patient is identified at risk for infection needs to increase, a PN is useful to provide LTC of newly diagnosed patients.
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Gerenciamento Clínico , Hepatite B Crônica/diagnóstico , Hepatite C Crônica/diagnóstico , Navegação de Pacientes/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite B Crônica/terapia , Hepatite C Crônica/terapia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Saúde da População Urbana , Adulto JovemRESUMO
Congenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into ß-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents. This analysis identified a de novo mutation, p.G403D, in the proband's CACNA1D gene. CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic ß-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia. Sequence analysis of the CACNA1D gene in 60 further cases with HH did not identify a pathogenic mutation. Identification of an activating CACNA1D mutation in a second patient with congenital HH confirms the aetiological role of CACNA1D mutations in this disorder. A genetic diagnosis is important as treatment with a calcium channel blocker may be an option for the medical management of this patient.
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Canais de Cálcio Tipo L/genética , Cardiopatias Congênitas/genética , Hiperinsulinismo/genética , Hipoglicemia/genética , Mutação , Doenças Neuromusculares/genética , Substituição de Aminoácidos , Insuficiência da Valva Aórtica/etiologia , Canais de Cálcio Tipo L/química , Canais de Cálcio Tipo L/metabolismo , Análise Mutacional de DNA , Deficiências do Desenvolvimento/etiologia , Feminino , Macrossomia Fetal/etiologia , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/fisiopatologia , Humanos , Hiperinsulinismo/metabolismo , Hiperinsulinismo/fisiopatologia , Hipoglicemia/metabolismo , Hipoglicemia/fisiopatologia , Recém-Nascido , Hipotonia Muscular/etiologia , Doenças Neuromusculares/metabolismo , Doenças Neuromusculares/fisiopatologiaRESUMO
The potential of particle therapy due to focused dose deposition in the Bragg peak has not yet been fully realized due to inaccuracies in range verification. The purpose of this work was to correlate the Bragg peak location with target structure, by overlaying the location of the Bragg peak onto a standard ultrasound image. Pulsed delivery of 50 MeV protons was accomplished by a fast chopper installed between the ion source and the cyclotron inflector. The chopper limited the train of bunches so that 2 Gy were delivered in [Formula: see text]. The ion pulse generated thermoacoustic pulses that were detected by a cardiac ultrasound array, which also produced a grayscale ultrasound image. A filtered backprojection algorithm focused the received signal to the Bragg peak location with perfect co-registration to the ultrasound images. Data was collected in a room temperature water bath and gelatin phantom with a cavity designed to mimic the intestine, in which gas pockets can displace the Bragg peak. Phantom experiments performed with the cavity both empty and filled with olive oil confirmed that displacement of the Bragg peak due to anatomical change could be detected. Thermoacoustic range measurements in the waterbath agreed with Monte Carlo simulation within 1.2 mm. In the phantom, thermoacoustic range estimates and first-order range estimates from CT images agreed to within 1.5 mm.
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Acústica , Processamento de Imagem Assistida por Computador/métodos , Temperatura , Ultrassonografia/instrumentação , Algoritmos , Método de Monte Carlo , Imagens de Fantasmas , Prótons , ÁguaRESUMO
BACKGROUND: D-Penicillamine is the most commonly used copper-chelating agent in the treatment of copper-associated hepatitis in dogs. Response to therapy can be variable, and there is a lack of pharmacokinetic information available for dogs. Coadministering the drug with food to alleviate vomiting has been recommended for dogs, which contradicts recommendations for drug administration to humans. HYPOTHESIS: Coadministration of d-penicillamine with food decreases relative bioavailability and maximum plasma drug concentrations (C(max)) in dogs. ANIMALS: Nine purpose-bred dogs with a median body weight of 17.0 kg. METHODS: Dogs received D-penicillamine (12.5 mg/kg PO) fasted and with food in a randomized, crossover design. Blood samples were collected before and 0.25, 0.5, 1, 2, 3, 4, 8, 12, and 24 hours after dosing. Total d-penicillamine concentrations were measured using liquid chromatography coupled with tandem quadrupole mass spectrometry. Pharmacokinetic parameters were calculated for each dog. RESULTS: Two fasted dogs (22%) vomited after receiving d-penicillamine. Mean C(max) ± standard deviation (SD) was 8.7 ± 3.1 µg/mL (fasted) and 1.9 ± 1.6 µg/mL (fed). Mean area under the plasma concentration curve ± SD was 16.9 ± 5.9 µg/mL·h (fasted) and 4.9 ± 3.4 µg/mL·h (fed). There were significant reductions in relative bioavailability and C(max) in fed dogs (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Coadministration of d-penicillamine with food significantly decreases plasma drug concentrations in dogs. Decreased drug exposure could result in decreased copper chelation efficacy, prolonged therapy, additional cost, and greater disease morbidity. Administration of d-penicillamine with food cannot be categorically recommended without additional studies.
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Quelantes/farmacocinética , Cães/sangue , Privação de Alimentos/fisiologia , Penicilamina/farmacocinética , Animais , Área Sob a Curva , Feminino , Meia-Vida , Masculino , Penicilamina/sangueRESUMO
The aim of this work is to develop a physical model to describe the evolution of the apparent contact angle for four different liquids on nanotextured alumina surfaces with different pore radius. The nanoporous alumina templates were fabricated by anodization of Al foil in a 0.3 M oxalic acid solution. Scanning electron microscopy was used to characterize the morphology of the surfaces. The templates are approximately 400 nm in thickness and consist of a well-ordered hexagonal array of uniform radius pores spaced 105 nm apart with pore radii from 12 to 42 nm. The wettability of nanoporous alumina templates was investigated using contact-angle measurements. We measured the contact angles using four liquids: water, ethylene glycol, aniline, and a mixture of ethylene glycol and aniline. We developed a new theoretical model for the contact angle on nanoporous surfaces as a function of the pore radius. This model is based on energy considerations and involves liquid penetration into the nanopores driven by the capillarity (Laplace's law). Because the air is compressed inside the pores, this model also includes the effect of the line tension. This is important because the three-phase line length is greatly enhanced in our nanoporous structures. For example: for a millimeter-sized droplet, the three-phase line around the perimeter of the droplet is a few millimeters long, whereas the total three-phase line within the pores can reach several tens of meters. Using our model, the line-tension value for our nanopore samples is positive and ranges from 4 to 13 × 10(-9) N, which falls within the wide interval from 10(-11) to 10(-5) N quoted in the literature. Nanoporous surfaces may allow the effect of line tension to be visible for micro- to macrodroplets.
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Óxido de Alumínio/química , Nanoporos , Propriedades de Superfície , MolhabilidadeRESUMO
People with multiple sclerosis (MS) often report problems with balance, which may be most apparent during challenging postural tasks such as leaning or reaching, and when relying on non-visual sensory systems. An additional obstacle facing people with MS is a high incidence of symptomatic fatigue (>70%). The purpose of this study was to investigate the changes in balance during upright stance in individuals with mild-to-moderate disability due to MS under normal and restricted vision and different levels of self-reported fatigue. Limb loading asymmetry, sway and magnitude of postural shift in center of pressure, and time-to-contact the stability boundary of the center of mass and center of pressure were assessed during quiet standing and maximal lean and reach tasks. Compared to controls, people with MS displayed greater postural sway, greater loading asymmetry, and shorter time-to-contact during quiet standing. In the postural perturbation tasks the MS group had smaller postural shifts and reduced stability compared to controls in the direction perpendicular to the lean and reach. Limiting vision increased loading asymmetry during quiet standing and postural instability during backward lean in the MS group. Inducing additional fatigue in the MS group did affect postural control in the more challenging balance conditions but had no impact during quiet upright standing. The results of this study indicate subtle changes in postural control during standing in people with mild-to-moderate impairments due to MS.
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Fadiga/fisiopatologia , Marcha/fisiologia , Esclerose Múltipla/fisiopatologia , Equilíbrio Postural/fisiologia , Adolescente , Adulto , Criança , Pré-Escolar , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Análise e Desempenho de Tarefas , Baixa Visão/epidemiologia , Baixa Visão/fisiopatologia , Adulto JovemRESUMO
PURPOSE: This study's purpose was to compare pediatric dental services provided for Medicaid and military dependent children to determine if differences in dental treatment choices exist based on site and payment method. METHODS: Subjects included 120 Medicaid patients at the University of Texas Health Science Center at San Antonio and 120 military dependents at Lackland Air Force Base, Texas. Demographic data and treatment information were abstracted for children younger than 6 years old receiving dental treatment under general anesthesia between 2002 and 2006. Data was analyzed using Wilcoxon rank sum, Kruskal-Wallis, and Fisher's exact tests. RESULTS: The Medicaid recipients were younger (40.2 vs 49.8 months, P<.001) and more likely to be Hispanic (78% vs 30%, P<.001). The means of decayed teeth, fillings, and stainless steel crowns did not differ between sites. Medicaid children received more composite fillings (P<.001), fewer amalgam fillings (P<.001), fewer pulp therapies (P<.001), more extractions (P=.01), and fewer sealants (P<.001). Age and gender did not affect decay rates, but those of Hispanic ethnicity did experience more decay than non-Hispanics (9.5 vs 8.6, P=.02). CONCLUSION: This study found no difference in the number of less conservative, albeit more costly, procedures performed with Medicaid children at a university compared to military dependents at a military base.
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Anestesia Dentária , Anestesia Geral , Assistência Odontológica para Crianças , Acessibilidade aos Serviços de Saúde , Medicaid , Militares , Fatores Etários , Anestesia Dentária/estatística & dados numéricos , Anestesia Geral/estatística & dados numéricos , Pré-Escolar , Resinas Compostas/química , Coroas/estatística & dados numéricos , Índice CPO , Ligas Dentárias/química , Amálgama Dentário/química , Assistência Odontológica para Crianças/economia , Assistência Odontológica para Crianças/estatística & dados numéricos , Clínicas Odontológicas/estatística & dados numéricos , Materiais Dentários/química , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Lactente , Masculino , Selantes de Fossas e Fissuras/química , Pulpectomia/estatística & dados numéricos , Aço Inoxidável/química , Texas , Extração Dentária/estatística & dados numéricos , Estados UnidosRESUMO
Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations.In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30-50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization-Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na(+) and K(+) ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 microg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed.There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI(+) MS/MS in samples originating from veterinary dosage forms.
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Ivermectina/análise , Ivermectina/toxicidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Antiparasitários/análise , Antiparasitários/toxicidade , Técnicas de Química Analítica/métodos , Cães , Feminino , Masculino , Ombro/patologia , Tela Subcutânea/química , Fatores de TempoRESUMO
We report detailed measurements of the low temperature magnetic phase diagram of Er2Ti2O7. Heat capacity and time-of-flight neutron scattering studies of single crystals reveal unconventional low-energy states. Er3+ magnetic ions reside on a pyrochlore lattice in Er2Ti2O7, where local XY anisotropy and antiferromagnetic interactions give rise to a unique frustrated system. In zero field, the ground state exhibits coexisting short and long-range order, accompanied by soft collective spin excitations previously believed to be absent. The application of finite magnetic fields tunes the ground state continuously through a landscape of noncollinear phases, divided by a zero temperature phase transition at micro{0}H{c} approximately 1.5 T. The characteristic energy scale for spin fluctuations is seen to vanish at the critical point, as expected for a second order quantum phase transition driven by quantum fluctuations.
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INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour with a propensity for local recurrence and nodal metastasis. About 300 cases have been reported, thus further clarification regarding the course and outcome of the disease is required. METHODS: Patients with a histopathologic diagnosis of CCS were identified from prospective histopathology and sarcoma databases and supplemented with a retrospective analysis of the patients' hospital records. RESULTS: Between 1990 and 2005, a total of 72 patients with a diagnosis of CCS were identified, 35 having been referred for management and 37 having been referred for histopathologic opinion. The median age was 39 years (range 5-90 years). Of the 35 patients referred to the Royal Marsden Hospital for management, 23% developed local recurrence or in-transit metastases at a median of 9 months (2-79 months) after resection of the primary, and nodal or distant metastatic disease was seen in 63% after 14 months (range 0-177 months). Five- and 10-year survival were 52% and 25%, respectively. CONCLUSIONS: CCS has a number of similarities with melanoma, particularly in its peripheral distribution and propensity for nodal disease. Wide excision with clear margins offers the best chance of cure. Local recurrence and regional metastases are common, and are almost always followed by distant metastases and death.
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Sarcoma de Células Claras , Neoplasias de Tecidos Moles , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Sarcoma de Células Claras/epidemiologia , Sarcoma de Células Claras/mortalidade , Sarcoma de Células Claras/patologia , Sarcoma de Células Claras/terapia , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Taxa de Sobrevida , Reino Unido/epidemiologia , Extremidade SuperiorRESUMO
Nanomechanical properties of a Ni nanodot-patterned surface (NDPS) on a Si substrate were investigated using nanoindentation. The Ni NDPS was fabricated by thermal evaporation of Ni through a porous anodized aluminum oxide template onto a Si substrate. Plan-view transmission electron microscopy and nanobeam diffraction were used to characterize the Ni nanodot crystal structure. Scanning electron microscopy and atomic force microscopy were used to characterize the morphology and deformation of the Ni nanodots before and after nanoindentation. The elastic modulus and hardness of the Ni nanodots were found to be 159 ± 22 and 7.7 ± 1.0 GPa, respectively. The critical shear stress for initiating plastic deformation in the Ni nanodot was estimated to be 8.3 ± 1.0 GPa, which is close to the theoretical shear strength of 7.6 GPa in dislocation-free single crystal Ni.
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The spin dynamics of high-aspect-ratio nickel nanorings in a longitudinal magnetic field have been investigated by Brillouin spectroscopy and the results are compared with a macroscopic theory and three-dimensional micromagnetic simulations. Good agreement is found between the measured and calculated magnetic field dependence of the spin wave frequency. Simulations show that as the field decreases from saturation, the rings switch from a "bamboo" to a novel "twisted bamboo" state at a certain critical field, and predict a corresponding dip in the dependence of the spin wave frequency on the magnetic field.
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Uniform arrays of nano-scale electrolyte-molecule-silicon capacitors have been successfully fabricated. This was done by a combination of reactive ion etch and a selective wet etch through an anodic aluminium oxide mask to form nano-holes in silicon oxide/silicon nitride insulator layers on silicon. Self-assembled monolayers of 4-ferrocenylbenzyl alcohol were then attached to the exposed silicon surfaces at the bottom of the nano-holes. Characterization by conventional capacitance and conductance techniques showed very high capacitance and conductance peaks near -0.6 V, that were attributed to the charging and discharging of electrons into and from discrete levels in the monolayer owing to the presence of the redox-active ferrocenes.
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Traumatic hepatic arterioportal fistulae (APF) are described infrequently as sequelae of hepatic trauma. These anomalies are usually associated with blunt hepatic trauma or iatrogenic injury. The majority of APF present within weeks to months of injury with gastrointestinal hemorrhage, hemobilia, abdominal pain, and diarrhea. When presenting remotely APFs are associated with portal hypertension, heart failure, gastrointestinal hemorrhage, ascites, and splenomegaly. We report an unusual case of mesenteric ischemia due to an APF that resulted from a penetrating liver injury 20 years before presentation. Successful treatment of the APF was achieved by intravascular catheter occlusion resulting in resolution of symptoms.
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Fístula Arteriovenosa/complicações , Artéria Hepática , Isquemia/etiologia , Fígado/lesões , Mesentério/irrigação sanguínea , Veia Porta , Ferimentos Perfurantes/complicações , Adulto , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/terapia , Embolização Terapêutica , Artéria Hepática/diagnóstico por imagem , Humanos , Isquemia/diagnóstico por imagem , Masculino , Mesentério/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , RadiografiaRESUMO
Acid-sensing ion channels (ASICs) are ligand-gated cation channels that respond to acidic stimuli. They are expressed throughout the mammalian nervous system. In the peripheral nervous system, ASICs act as nociceptors, responding to the tissue acidosis that accompanies ischemic and inflammatory conditions. The function of ASICs in the central nervous system is not known. In this article, the authors present evidence that transient global ischemia induces ASIC 2a protein expression in neurons that survive ischemia. Western blot analysis with an anti-ASIC 2a antibody revealed up-regulation of an 80 kD protein in ischemic rat brain. Immunohistochemical analysis showed that ASIC 2a protein expression increased in neurons of the hippocampus and cortex. Klenow fragment-mediated labeling of DNA strand breaks determined that ASIC 2a induction did not occur in cells with detectable DNA damage. The current results suggest a possible role for ASICs in mediating a cellular response to ischemia.
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Encéfalo/metabolismo , Expressão Gênica , Isquemia/metabolismo , Proteínas de Membrana , Proteínas do Tecido Nervoso , Canais de Sódio/genética , Canais Iônicos Sensíveis a Ácido , Animais , Astrócitos/metabolismo , Northern Blotting , Western Blotting , Isquemia Encefálica/metabolismo , Artéria Carótida Primitiva , Córtex Cerebral/metabolismo , Constrição , Dano ao DNA , Corantes Fluorescentes , Hipocampo/metabolismo , Ligadura , Masculino , Neurônios/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Isquemia do Cordão Espinal/metabolismo , Artéria VertebralRESUMO
We report an analysis of the nuclear dependence of the yield of Drell-Yan dimuons from the 800 GeV/c proton bombardment of 2H, C, Ca, Fe, and W targets. Employing a new formulation of the Drell-Yan process in the rest frame of the nucleus, this analysis examines the effect of initial-state energy loss and shadowing on the nuclear-dependence ratios versus the incident proton's momentum fraction and dimuon effective mass. The resulting energy loss per unit path length is -dE/dz = 2.32+/-0.52+/-0.5 GeV/fm. This is the first observation of a nonzero energy loss of partons traveling in a nuclear environment.
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IGF-II is a growth factor implicated in human cancers and animal tumor models. While the mitogenic properties of IGF-II are well documented, its ability to suppress apoptosis in vivo has never been proven. We generated independent MMTV-IGF-II transgenic mice to examine the control of epithelial apoptosis at the morphological, cellular and molecular levels during the physiological event of postlactation mammary involution. Transgenic IGF-II expression was achieved in mammary epithelium and increased IGF-II bioactivity was confirmed by phosphorylation of the insulin receptor substrate-1, a signaling molecule downstream of the type I IGF receptor. IGF-II overexpression induced a delay in mammary involution, as evident by increased mammary gland to body weight ratios and persistence of both functionally intact lobulo-alveoli and mammary epithelial cellularity. The delayed mammary involution resulted from a significant reduction in mammary epithelial apoptosis, and not from increased epithelial proliferation. Recombinant IGF-II pellets implanted into involuting mammary glands of wild-type mice provided further evidence that IGF-II protein inhibited local epithelial apoptosis. At the molecular level, phosphorylated Akt/PKB, but not Erk1 or Erk2, persisted in IGF-II overexpressors and temporally correlated with reduced epithelial apoptosis. Levels of the phosphatase PTEN were unaltered in the transgenic tissue suggesting that the maintenance of Akt/PKB phosphorylation resulted from sustained phosphorylation rather than altered dephosphorylation of PIP-3. Together, this data reveal that IGF-II inhibits apoptosis in vivo and this effect correlates with prolonged phosphorylation of Akt/PKB