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1.
Nature ; 497(7449): 357-60, 2013 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-23676753

RESUMEN

Fluids trapped as inclusions within minerals can be billions of years old and preserve a record of the fluid chemistry and environment at the time of mineralization. Aqueous fluids that have had a similar residence time at mineral interfaces and in fractures (fracture fluids) have not been previously identified. Expulsion of fracture fluids from basement systems with low connectivity occurs through deformation and fracturing of the brittle crust. The fractal nature of this process must, at some scale, preserve pockets of interconnected fluid from the earliest crustal history. In one such system, 2.8 kilometres below the surface in a South African gold mine, extant chemoautotrophic microbes have been identified in fluids isolated from the photosphere on timescales of tens of millions of years. Deep fracture fluids with similar chemistry have been found in a mine in the Timmins, Ontario, area of the Canadian Precambrian Shield. Here we show that excesses of (124)Xe, (126)Xe and (128)Xe in the Timmins mine fluids can be linked to xenon isotope changes in the ancient atmosphere and used to calculate a minimum mean residence time for this fluid of about 1.5 billion years. Further evidence of an ancient fluid system is found in (129)Xe excesses that, owing to the absence of any identifiable mantle input, are probably sourced in sediments and extracted by fluid migration processes operating during or shortly after mineralization at around 2.64 billion years ago. We also provide closed-system radiogenic noble-gas ((4)He, (21)Ne, (40)Ar, (136)Xe) residence times. Together, the different noble gases show that ancient pockets of water can survive the crustal fracturing process and remain in the crust for billions of years.


Asunto(s)
Gases Nobles/análisis , Agua/análisis , Agua/química , Argón/análisis , Argón/química , Atmósfera/química , Canadá , Sedimentos Geológicos/química , Helio/análisis , Helio/química , Historia Antigua , Vida , Minería , Neón/análisis , Neón/química , Gases Nobles/química , Ontario , Xenón/análisis , Xenón/química
2.
Eur J Dent Educ ; 18(2): e25-33, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24750223

RESUMEN

On March 20th 2013, a one-hour session for Editors, Associate Editors, Publishers and others with an interest in scientific publishing was held at the IADR International Session in Seattle. Organised by Kenneth Eaton and Chris Lynch (Chair and Secretary, respectively, of the British Dental Editors Forum), the meeting sought to bring together leading international experts in dental publishing, as well as authors, reviewers and students engaged in research. The meeting was an overwhelming success, with more than 100 attendees. A panel involving four leading dental editors led a discussion on anticipated developments in publishing dental research with much involvement and contribution from audience members. This was the third such meeting held at the IADR for Editors, Associate Editors, Publishers and others with an interest in scientific publishing. A follow up session will take place in Cape Town on 25 June 2014 as part of the annual IADR meeting. The transcript of the meeting is reproduced in this article. Where possible speakers are identified by name. At the first time of mention their role/ position is also stated, thereafter only their name appears. We are grateful to Stephen Hancocks Ltd for their generous sponsorship of this event. For those who were not able to attend the authors hope this article gives a flavour of the discussions and will encourage colleagues to attend future events. Involvement is open to Editors, Associate Editors, Publishers and others with an interest in scientific publishing. It is a very open group and all those with an interest will be welcome to join in.


Asunto(s)
Investigación Dental/tendencias , Edición/tendencias , Congresos como Asunto , Europa (Continente) , Predicción , Humanos
3.
Sci Adv ; 9(46): eadg3256, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37967182

RESUMEN

Games have a long history as benchmarks for progress in artificial intelligence. Approaches using search and learning produced strong performance across many perfect information games, and approaches using game-theoretic reasoning and learning demonstrated strong performance for specific imperfect information poker variants. We introduce Student of Games, a general-purpose algorithm that unifies previous approaches, combining guided search, self-play learning, and game-theoretic reasoning. Student of Games achieves strong empirical performance in large perfect and imperfect information games-an important step toward truly general algorithms for arbitrary environments. We prove that Student of Games is sound, converging to perfect play as available computation and approximation capacity increases. Student of Games reaches strong performance in chess and Go, beats the strongest openly available agent in heads-up no-limit Texas hold'em poker, and defeats the state-of-the-art agent in Scotland Yard, an imperfect information game that illustrates the value of guided search, learning, and game-theoretic reasoning.

4.
Immunother Adv ; 2(1): ltac002, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35919496

RESUMEN

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

6.
Dis Esophagus ; 24(7): 476-80, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21385285

RESUMEN

Symptomatic dysphagia is believed to be more common in the older population; however, the factors that predict age-related dysphagia are less well-understood. Here, we describe a questionnaire-based survey of swallowing dysfunction in a large, otherwise 'healthy' community dwelling older population in the UK in whom additional cognitive and depression related scores were evaluated. A postal survey using Sydney oropharyngeal dysphagia questionnaire was sent to 800 residences in the North of England that formed part of the University of Manchester Age and Cognitive Performance Longitudinal Study. This cohort was composed of older individuals (mean age 81 [range 69-98 years]) who are otherwise healthy with no history of previous neurological disease. The postal questionnaire is a validated self-report inventory measuring symptoms of oropharyngeal dysphagia covering a total of 17 domains of swallowing function. The maximal score obtainable is 1700, with a score of ≥200 arbitrarily considered to indicate swallowing difficulty. Cognitive performance and depression scores utilized the telephone interview cognitive screen and the Geriatric Depression Scale. All data were analyzed in SPSS. Of the 800 questionnaires sent out, 637 where returned. Three were later discarded as unusable after follow-up telephone interviews of incomplete forms, giving a completed response rate of 79%. Females made up 77% of the total respondents. Of the population, 11.4% reported symptoms indicative of significant dysphagia. Unsurprisingly, dysphagia severity was directly correlated with subject age (r= 0.11, P= 0.007). When cognitive factors were taken into account, there was no correlation between memory, recall, and mental performance and dysphagia; however, depression was strongly and independently associated (P= 0.002) with dysphagia symptoms. Dysphagia symptoms are prevalent in older people, affecting nearly one in nine people who are otherwise living independently in the community. While cognitive factors such as memory recall do not seem to influence dysphagia symptoms, depression is associated with dysphagia, suggesting a potential interaction. This could relate to associations with quality of life or psychological factors.


Asunto(s)
Trastornos de Deglución/diagnóstico , Trastornos de Deglución/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Prevalencia , Características de la Residencia , Autoinforme , Encuestas y Cuestionarios
7.
Appl Environ Microbiol ; 75(13): 4506-15, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19411431

RESUMEN

Legionella pneumophila, the causative agent of Legionnaires' disease, is an intracellular parasite of eukaryotic cells. In the environment, it colonizes amoebae. After being inhaled into the human lung, the bacteria infect and damage alveolar cells in a way that is mechanistically similar to the amoeba infection. Several L. pneumophila traits, among those the Dot/Icm type IVB protein secretion machinery, are essential for exploiting host cells. In our search for novel Legionella virulence factors, we developed an agar plate assay, designated the scatter screen, which allowed screening for mutants deficient in infecting Acanthamoeba castellanii amoebae. Likewise, an L. pneumophila clone bank consisting of 23,000 transposon mutants was investigated here, and 19 different established Legionella virulence genes, for example, dot/icm genes, were identified. Importantly, 70 novel virulence-associated genes were found. One of those is L. pneumophila bdhA, coding for a protein with homology to established 3-hydroxybutyrate dehydrogenases involved in poly-3-hydroxybutyrate metabolism. Our study revealed that bdhA is cotranscribed with patD, encoding a patatin-like protein of L. pneumophila showing phospholipase A and lysophospholipase A activities. In addition to strongly reduced lipolytic activities and increased poly-3-hydroxybutyrate levels, the L. pneumophila bdhA-patD mutant showed a severe replication defect in amoebae and U937 macrophages. Our data suggest that the operon is involved in poly-3-hydroxybutyrate utilization and phospholipolysis and show that the bdhA-patD operon is a virulence determinant of L. pneumophila. In summary, the screen for amoeba-sensitive Legionella clones efficiently isolated mutants that do not grow in amoebae and, in the case of the bdhA-patD mutant, also human cells.


Asunto(s)
Acanthamoeba castellanii/microbiología , Proteínas Bacterianas/genética , Hidroxibutirato Deshidrogenasa/genética , Legionella pneumophila/patogenicidad , Macrófagos/microbiología , Fosfolipasas/genética , Factores de Virulencia/genética , Animales , Línea Celular , Elementos Transponibles de ADN , Humanos , Mutagénesis Insercional , Operón , Virulencia
8.
J Cell Biol ; 150(3): 499-512, 2000 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-10931863

RESUMEN

We have investigated the intracellular roles of an Xklp2-related kinesin motor, KRP(180), in positioning spindle poles during early sea urchin embryonic cell division using quantitative, real-time analysis. Immunolocalization reveals that KRP(180) concentrates on microtubules in the central spindle, but is absent from centrosomes. Microinjection of inhibitory antibodies and dominant negative constructs suggest that KRP(180) is not required for the initial separation of spindle poles, but instead functions to transiently position spindle poles specifically during prometaphase.


Asunto(s)
Proteínas de Unión al Calcio/aislamiento & purificación , Embrión no Mamífero/ultraestructura , Metafase , Proteínas Motoras Moleculares , Proteínas Musculares/aislamiento & purificación , Huso Acromático/ultraestructura , Proteínas de Xenopus , Secuencia de Aminoácidos , Animales , Proteínas de Unión al Calcio/genética , Proteínas de Ciclo Celular/genética , Dimerización , Técnica del Anticuerpo Fluorescente , Cinesinas/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/aislamiento & purificación , Modelos Biológicos , Datos de Secuencia Molecular , Proteínas Musculares/genética , Erizos de Mar , Homología de Secuencia de Aminoácido
9.
Emerg Med J ; 26(7): 479-83, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19546266

RESUMEN

BACKGROUND: Pathways to guide clinical care are well accepted and used in many emergency departments. We wanted to introduce a number ("bundle") over a short space of time and involve the whole patient stay in the pathway. It was hypothesised that a more efficient process would result with an overall reduction in length of stay (LoS). METHODS: A "bundle" of 14 evidence-based pathways of care was introduced into a medium-sized district general hospital (DGH) in late 2006/early 2007. These pathways covered emergency department care and acute medical care for a period of up to 48 h. A total of 8184 acute emergency admission episodes were audited, 3852 in the 8 months before introduction of the new pathways and 4332 in the 8 months after their introduction. RESULTS: The overall effect of introducing the pathway bundle had a trend towards reduction in LoS by 0.2 days (95% CI -0.2 to 0.5), but this was not statistically significant (p>0.1). However, in those patients with

Asunto(s)
Vías Clínicas/organización & administración , Servicio de Urgencia en Hospital/organización & administración , Tiempo de Internación/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Inglaterra , Femenino , Hospitales de Distrito/organización & administración , Hospitales Generales/organización & administración , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad
10.
Genes Immun ; 9(3): 249-58, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18340360

RESUMEN

Birdshot chorioretinopathy (BCR), a chronic ocular inflammatory disease with characteristic choroidal lymphocytic infiltrates, has been strongly associated with human leukocyte antigen (HLA)-A29. Although HLA-A29 occurs frequently in all populations, BCR affects only a small percentage of HLA-A29-positive Caucasians, indicating additional susceptibility factors for BCR. Discovery of HLA class I-specific killer cell immunoglobulin-like receptors (KIR) led to a series of epidemiological studies implicating KIR-HLA gene combinations in disease. Here, we characterized KIR-HLA pairs in BCR patients and controls carrying HLA-A*29 as well as controls lacking HLA-A*29. KIR-HLA pairs implicated for weak inhibition (KIR2DL2/3+HLA-C1 and KIR3DL1+HLA-Bw4(T80)) in combination with activating KIR genes associated with autoimmunity (KIR2DS2, 2DS3 and 2DS4) augment the risk of developing BCR in HLA-A*29-positive individuals. The reciprocal association of strong inhibitory pairs (KIR3DL1+HLA-Bw4(I80) and KIR2DL1+HLA-C2) in combination with those implicated in protection from infection (KIR3DS1+HLA-Bw4(I80) and KIR2DS1+HLA-C2) was observed in HLA-A*29-negative controls. These results suggest that a profound effect of KIR2DS2/S3/S4 in the absence of strong inhibition may enhance the activation of natural killer cells and T-cell subsets against intraocular self-antigens, thereby contributing to pathogenesis of BCR.


Asunto(s)
Autoinmunidad/genética , Coriorretinitis/genética , Regulación de la Expresión Génica/inmunología , Predisposición Genética a la Enfermedad/genética , Antígenos HLA-A/genética , Células Asesinas Naturales/inmunología , Receptores KIR/genética , Autoinmunidad/inmunología , Secuencia de Bases , Coriorretinitis/inmunología , Francia , Regulación de la Expresión Génica/genética , Genotipo , Antígenos HLA-A/inmunología , Humanos , Células Asesinas Naturales/metabolismo , Datos de Secuencia Molecular , Receptores KIR/inmunología , Receptores KIR3DL1/genética , Análisis de Secuencia de ADN , Población Blanca/genética
11.
Chem Commun (Camb) ; 54(76): 10746-10749, 2018 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-30191228

RESUMEN

Solid-State NMR results on 13C-Ala/Ser and 13C-Val enriched Argiope argentata prey-wrapping silk show that native, freshly spun aciniform silk nanofibers are dominated by α-helical (∼50% total) and random-coil (∼35% total) secondary structures, with minor ß-sheet nanocrystalline domains (∼15% total). This is the most in-depth study to date characterizing the protein structural conformation of the toughest natural biopolymer: aciniform prey-wrapping silks.


Asunto(s)
Fibroínas/química , Nanofibras/química , Seda/química , Alanina/química , Secuencia de Aminoácidos , Animales , Isótopos de Carbono , Espectroscopía de Resonancia Magnética con Carbono-13 , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Serina/química , Arañas/química , Valina/química
12.
J Clin Invest ; 98(4): 1010-20, 1996 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-8770874

RESUMEN

We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption in the IL-10 gene (IL-10-/-). Our longitudinal studies showed that inflammatory changes first appear in the cecum, ascending and transverse colon of 3-wk-old mutants. As the disease progressed, lesions appeared in the remainder of the colon and in the rectum. Some aged IL-10-/- mice also developed inflammation in the small intestine. Prolonged disease with transmural lesions and a high incidence of colorectal adenocarcinomas (60%) was observed in 6-mo-old mutants. Mechanistic studies have associated uncontrolled cytokine production by activated macrophages and CD4+ Th1-like T cells with the enterocolitis exhibited by IL-10-/- mice. A major role for a pathogenic Th1 response was further suggested by showing that anti-IFNgamma antibody (Ab) treatment significantly attenuated intestinal inflammation in young IL-10-/- mice. When weanlings were treated with IL-10, they failed to develop any signs of intestinal inflammation. Interestingly, IL-10 treatment of adults was not curative but did ameliorate disease progression. Our studies have also shown that inheritable factors strongly influence the disease susceptibility of IL-10-/- mice. In 3-mo-old mutants, intestinal lesions were most severe in IL-10-/- 129/SvEv and IL-10-/- BALB/c strains, of intermediate severity in the IL-10-/- 129 x C57BL/6J outbreds, and least severe in the IL-10-/- C57BL/6J strain.


Asunto(s)
Neoplasias del Colon/etiología , Citocinas/biosíntesis , Enterocolitis/etiología , Enfermedades Inflamatorias del Intestino/etiología , Interleucina-10/fisiología , Células TH1/inmunología , Envejecimiento , Animales , Neoplasias del Colon/patología , Enterocolitis/patología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Directa , Enfermedades Inflamatorias del Intestino/patología , Interferón gamma/fisiología , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados
13.
Mol Biol Cell ; 11(1): 241-53, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10637305

RESUMEN

It is well established that multiple microtubule-based motors contribute to the formation and function of the mitotic spindle, but how the activities of these motors interrelate remains unclear. Here we visualize spindle formation in living Drosophila embryos to show that spindle pole movements are directed by a temporally coordinated balance of forces generated by three mitotic motors, cytoplasmic dynein, KLP61F, and Ncd. Specifically, our findings suggest that dynein acts to move the poles apart throughout mitosis and that this activity is augmented by KLP61F after the fenestration of the nuclear envelope, a process analogous to nuclear envelope breakdown, which occurs at the onset of prometaphase. Conversely, we find that Ncd generates forces that pull the poles together between interphase and metaphase, antagonizing the activity of both dynein and KLP61F and serving as a brake for spindle assembly. During anaphase, however, Ncd appears to have no effect on spindle pole movements, suggesting that its activity is down-regulated at this time, allowing dynein and KLP61F to drive spindle elongation during anaphase B.


Asunto(s)
Drosophila melanogaster/embriología , Mitosis/fisiología , Proteínas Motoras Moleculares , Huso Acromático/fisiología , Anafase/fisiología , Animales , Blastodermo/ultraestructura , Femenino , Humanos , Interfase/fisiología , Masculino , Metafase/fisiología , Microtúbulos/ultraestructura , Profase/fisiología , Huso Acromático/ultraestructura
14.
J Endod ; 43(9S): S75-S81, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28844307

RESUMEN

Clinicians face many challenges when treating immature permanent teeth in young patients. Immediate blood clot induction can be a successful option as described by some case reports. No experimental studies or clinical trials have addressed this question. We have designed a clinical trial in which we hypothesized that there is no difference in success between immediate or delayed induction protocols. After confirmation of pulpal necrosis, patients were randomized. In the delayed group, 15 teeth were treated following the American Association of Endodontists guidelines, and calcium hydroxide was used as the intracanal medication. In the immediate group, 13 teeth had a blood clot inducted at the first appointment. The teeth were evaluated after 1, 3, and 12 months. Three independent evaluators assessed the periapical healing. The Pearson chi-square test or the Fisher exact test was used to compare the success rates between the 2 groups. Currently, of the 25 recruited patients (28 teeth), 19 have completed their 12-month follow-up. The group with delayed induction had a 71% success rate, and the group with immediate induction had a 33% success rate. In most cases (79%), trauma was the etiology. All successful cases started at stage 9 of root development (Nolla), and the majority showed healing type 2. Determination of the stage of root formation and etiology are possible critical factors for any therapeutic decision. In summary, it is early to conclude or suggest any of the protocols. Clearly, much more data are needed before sample size requirements can be met.


Asunto(s)
Necrosis de la Pulpa Dental/cirugía , Pulpa Dental/fisiología , Regeneración , Niño , Femenino , Humanos , Masculino , Factores de Tiempo , Cicatrización de Heridas
15.
J Magn Reson ; 180(2): 210-21, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16563820

RESUMEN

Two-dimensional (1)H-(13)C INEPT MAS NMR experiments utilizing a (1)H-(1)H magnetization exchange mixing period are presented for characterization of lipid systems. The introduction of the exchange period allows for structural information to be obtained via (1)H-(1)H dipolar couplings but with (13)C chemical shift resolution. It is shown that utilizing a RFDR recoupling sequence with short mixing times in place of the more standard NOE cross-relaxation for magnetization exchange during the mixing period allowed for the identification and separation of close (1)H-(1)H dipolar contacts versus longer-range inter-molecular (1)H-(1)H dipolar cross-relaxation. These 2D INEPT experiments were used to address both intra- and inter-molecular contacts in lipid and lipid/cholesterol mixtures.


Asunto(s)
Membrana Dobles de Lípidos/química , Resonancia Magnética Nuclear Biomolecular/métodos , Isótopos de Carbono , Colesterol/química , Lípidos/química , Modelos Teóricos
16.
J Endod ; 32(10): 951-5, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16982271

RESUMEN

Lipopolysaccharide (LPS) from gram-negative bacteria cell walls such as Prevotella intermedia and Escherichia coli induce vascular endothelial growth factor (VEGF) expression in odontoblasts, but not in undifferentiated dental pulp cells. CD14 and TLR4 are responsible for LPS signaling in macrophages, but their expression levels and function in dental pulp cells are unknown. We showed here that murine odontoblast-like cells (MDPC-23) express CD14 and TLR4 by immunohistochemistry and flow cytometry. In contrast, undifferentiated dental pulp cells (OD-21) presented low or no expression of these two receptors. MDPC-23 cells showed CD14 and TLR4 up-regulation upon exposure to LPS, as determined by real time PCR. Dominant negative murine TLR4 (DN-mTLR4) transfected MDPC-23 cells did not show upregulated VEGF expression in response to LPS stimulation. These results demonstrate that odontoblast-like cells express CD14 and TLR4, and that LPS-induced VEGF expression is mediated, at least in part, by TLR4 signaling.


Asunto(s)
Lipopolisacáridos/farmacología , Odontoblastos/fisiología , Receptor Toll-Like 4/fisiología , Factor A de Crecimiento Endotelial Vascular/fisiología , Animales , Western Blotting , Línea Celular , Pulpa Dental/citología , Escherichia coli , Fibroblastos/fisiología , Citometría de Flujo , Encía/citología , Humanos , Inmunohistoquímica , Riñón/citología , Receptores de Lipopolisacáridos/análisis , Receptores de Lipopolisacáridos/fisiología , Macrófagos/fisiología , Ratones , Transducción de Señal/fisiología , Receptor Toll-Like 4/análisis , Transfección , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/análisis
17.
Diabetes ; 39(10): 1218-27, 1990 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-2210074

RESUMEN

The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non-insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM.


Asunto(s)
Benzopiranos/farmacología , Glucemia/metabolismo , Hiperglucemia/sangre , Hiperinsulinismo/sangre , Hipoglucemiantes/farmacología , Insulina/sangre , Tiazoles/farmacología , Tiazolidinedionas , Ácido 3-Hidroxibutírico , Animales , Colesterol/sangre , Ácidos Grasos no Esterificados/sangre , Glucagón/sangre , Glicerol/sangre , Hidroxibutiratos/sangre , Insulina/farmacología , Cinética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Valores de Referencia , Triglicéridos/sangre
18.
J Am Coll Cardiol ; 37(4): 1120-8, 2001 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-11263618

RESUMEN

OBJECTIVES: The purpose of our study was to evaluate patients with suspected anomalous pulmonary veins (APVs) and atrial septal defects (ASDs) using fast cine magnetic resonance imaging (MRI) and ultrafast three-dimensional magnetic resonance angiography (MRA). BACKGROUND: Precise anatomic definition of anomalous pulmonary and systemic veins, and the atrial septum are prerequisites for surgical correction of ASDs. Cardiac catheterization and transesophageal echocardiography (TEE) are currently used to diagnose APVs, but did not provide complete information in our patients. METHODS: Twenty consecutive patients with suspected APVs were studied by MRA after inconclusive assessment by catheterization, TEE or both. The MRI images were acquired with a fast cine sequence and a novel ultrafast three-dimensional sequence before and after contrast injection. RESULTS: Partial anomalous pulmonary venous drainage was demonstrated in 16 of 20 patients and was excluded in four patients. Magnetic resonance imaging correctly diagnosed APVs and ASDs in all patients (100%) who underwent surgery. For the diagnosis of APVs, the MRI and catheterization results agreed in 74% of patients and the MRI and TEE agreed in 75% of patients. For ASDs, MRI agreed with catheterization and TEE in 53% and 83% of patients, respectively. CONCLUSIONS: Fast cine MRI with three-dimensional contrast-enhanced MRA provides rapid and comprehensive anatomic definition of APVs and ASDs in patients with adult congenital heart disease in a single examination.


Asunto(s)
Medios de Contraste , Defectos del Tabique Interatrial/diagnóstico , Imagenología Tridimensional , Angiografía por Resonancia Magnética , Venas Pulmonares/anomalías , Adulto , Anciano , Cateterismo Cardíaco , Ecocardiografía Transesofágica , Femenino , Defectos del Tabique Interatrial/cirugía , Humanos , Imagen por Resonancia Magnética , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Venas Pulmonares/cirugía , Sensibilidad y Especificidad
19.
HIV Clin Trials ; 6(3): 136-46, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16192248

RESUMEN

BACKGROUND: Reconstitution of immune function during potent antiretroviral therapy can prompt discontinuation of maintenance cytomegalovirus (CMV) therapy but has also been associated with sight-threatening inflammatory conditions including immune recovery uveitis (IRU). METHOD: Patients with inactive CMV retinitis and a CD4+ cell count above 100/mm3, receiving CMV therapy and stable combination antiretroviral therapy, were assigned to one of two groups based on willingness to discontinue CMV therapy. RESULTS: Thirty-eight participants were enrolled: 28 discontinued anti-CMV therapy (Group 1) and 10 continued CMV treatment (Group 2). Median on-study follow-up was 16 months. One Group 1 participant who experienced an increase in plasma HIV viral load and a decline in CD4+ cell count developed confirmed progression of CMV retinitis. Progression or reactivation CMV retinitis was not observed among Group 2. IRU was present at study entry in 3 participants. Six participants in Group 1 and 3 participants in Group 2 developed IRU on-study. CMV viremia was not detected in any participants, and urinary shedding of CMV was intermittent. CONCLUSION: Recurrence of CMV retinitis following discontinuation of anti-CMV therapy among patients with antiretroviral-induced increases in CD4+ cell count was rare. However, IRU was common in both those who maintained and discontinued anti-CMV therapy.


Asunto(s)
Antivirales/uso terapéutico , Retinitis por Citomegalovirus/tratamiento farmacológico , Retinitis por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Infecciones por VIH/complicaciones , VIH-1/inmunología , Uveítis/inmunología , Adulto , Recuento de Linfocito CD4 , Retinitis por Citomegalovirus/complicaciones , Retinitis por Citomegalovirus/virología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/sangre , Recurrencia , Síndrome de Abstinencia a Sustancias/inmunología , Uveítis/complicaciones , Uveítis/virología
20.
Arch Intern Med ; 146(10): 1973-7, 1986 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-3767542

RESUMEN

We evaluated the long-term effects of indapamide, a non-thiazide diuretic, on blood pressure, glucoregulation, free insulin and C-peptide levels, and lipoprotein and apoprotein metabolism in 13 hypertensive diabetic patients for 24 weeks. Indapamide significantly reduced both systolic and diastolic blood pressure by 15% and 17%, respectively. Both mean fasting serum glucose and integrated glucose responses after oral glucose load (75 g) were significantly higher during indapamide therapy than at week 0. The mean fasting and stimulated C-peptide responses were significantly increased despite worsening glucose control. At the end of 24 weeks, mean glycosylated hemoglobin level had increased significantly. Indapamide caused a slight but insignificant rise in the total triglyceride, cholesterol, and low-density lipoprotein cholesterol levels, while the high-density lipoprotein cholesterol level decreased. In addition, the apoprotein A-1 concentrations remained unchanged while the apoprotein B-100 level decreased. Apart from hypokalemia (less than 3.5 mEq/L [less than 3.5 mmol/L]) in three patients that required oral potassium supplementation, biochemical changes were of no clinical consequence.


Asunto(s)
Apoproteínas/sangre , Glucemia/metabolismo , Angiopatías Diabéticas/tratamiento farmacológico , Diuréticos/uso terapéutico , Hipertensión/tratamiento farmacológico , Indapamida/uso terapéutico , Lipoproteínas/sangre , Adulto , Anciano , Péptido C/sangre , Angiopatías Diabéticas/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Factores de Tiempo
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