RESUMEN
BACKGROUND: Addressing childhood obesity in Latin America requires a package of multisectoral, evidence-based policies that enable environments conducive to healthy lifestyles. OBJECTIVE: Identify and examine key elements to translating research into effective obesity policies in Latin America. METHODS: We examined obesity prevention policies through case studies developed with an expert in the specific policy. Policies were selected based on their level of implementation, visibility and potential impact to reduce childhood obesity. They include: (i) excise taxes on sugar sweetened beverages and energy-dense foods; (ii) front-of-package food label legislation; (iii) trans fatty acids removal from processed foods; and (iv) Ciclovías recreativas or 'open streets'. Case studies were coded to identify components that explained successful implementation and sustainability using the Complex Adaptive Health Systems framework. RESULTS: The analysis identified key elements for effective and sustainable policy, including evidence justifying policy; evidence-based advocacy by civil society; political will; and legislation and skillful negotiations across government, academia, the private sector and civil society. Scientific evidence and evaluation played an important role in achieving tipping points for policies' launch and sustain effective implementation. CONCLUSIONS: Well-coordinated, intersectoral partnerships are needed to successfully implement evidence-based anti-obesity policies. Prospective policy research may be useful for advancing knowledge translation.
Asunto(s)
Etiquetado de Alimentos , Programas de Gobierno , Política Nutricional , Obesidad Infantil/prevención & control , Bebidas , Niño , Humanos , América Latina , Estudios Prospectivos , Edulcorantes , ImpuestosRESUMEN
Childhood obesity rates in Latin America are among the highest in the world. This paper examines and evaluates the many efforts underway in the region to reduce and prevent further increases in obesity, identifies and discusses unique research challenges and opportunities in Latin America, and proposes a research agenda in Latin America for the prevention of childhood obesity and concomitant non-communicable diseases. Identified research gaps include biological challenges to healthy growth across the life cycle, diet and physical activity dynamics, community interventions promoting healthy child growth, and rigorous evaluation of national food and activity programs and regulatory actions. Addressing these research gaps is critical to advance the evidence-based policy and practice in childhood obesity tailored to the Latin American context that will be effective in addressing obesity.
Asunto(s)
Ejercicio Físico , Promoción de la Salud , Obesidad Infantil/prevención & control , Investigación , Niño , Humanos , América LatinaRESUMEN
Progesterone (P) has an inhibitory effect on the contractility of gastrointestinal smooth muscle, including the gallbladder. Since P levels are elevated during pregnancy, a biliary stasis may develop during pregnancy that is characterized by an increase in the fasting and residual volumes and by a decrease in emptying capacity. This study investigates the effect of P and two metabolites on contraction in guinea pig gallbladder strips. P induced a concentration-dependent relaxation in guinea pig gallbladder strips precontracted with cholecystokinin octapeptide (CCK). Pretreatment of gallbladder strips with P (50 microM) also reduced the amount of CCK-induced tension. Nifedipine (1 microM) produced a similar effect. Pretreatment of the strips with PKA inhibitor 14--22 amide myristolated (180 nM) or the PKG inhibitor KT5823 (1.2 microM) either separately or in combination significantly reduced the amount of P-induced relaxation. Rp-cAMPs (0.1mM) or H-89 (10 microM) separately or in combination significantly reduced the P-effect; however, the combination of agents produced the largest reduction. Genistein (1 microM), an inhibitor of protein tyrosine kinases, significantly (p<0.01) reduced the amount of P-induced relaxation. The use of strontium in the Kreb's solution as a substitute for Ca(2+) significantly (p<0.01) reduced the amount of CCK-induced tension. Pretreatment of the strips with 2-APB (26 microM), an inhibitor of IP(3,) induced Ca(2+) release, produced a significant (p<0.01) reduction in P-induced relaxation. We conclude that P inhibits gallbladder motility rapidly by nongenomic actions of the hormone. Several pathways that include tyrosine kinase and PKA/cAMP activity may mediate this effect.
Asunto(s)
Vaciamiento Vesicular/fisiología , Músculo Liso/fisiología , Progesterona/farmacología , Transducción de Señal/fisiología , 17-alfa-Hidroxiprogesterona/farmacología , 20-alfa-Dihidroprogesterona/farmacología , Animales , Compuestos de Boro/farmacología , Calcio/deficiencia , Carbazoles/farmacología , Proteínas Portadoras/farmacología , Colecistoquinina/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de GMP Cíclico/antagonistas & inhibidores , Vesícula Biliar/efectos de los fármacos , Vesícula Biliar/fisiología , Vaciamiento Vesicular/efectos de los fármacos , Genisteína/farmacología , Cobayas , Técnicas In Vitro , Indoles/farmacología , Isoquinolinas/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Nifedipino/farmacología , Fragmentos de Péptidos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Estroncio/farmacología , Sulfonamidas/farmacologíaRESUMEN
Obstructive sleep apnea (OSA) is a disease with significant morbidity, increased risk of accidents attributed to daytime somnolence, and has been associated with cardiovascular complications. The treatment of choice for OSA is nasal continuous positive airway pressure (nCPAP). Some OSA patients, however, are unable to benefit from this therapy as they find nCPAP intolerable due to the related nasal inflammation. It is hypothesized that nCPAP may cause nasal inflammation in these patients by inducing changes in the expression of genes that encode interleukins (IL-3, IL-4, IL-6, IL-8, IL-13) or adhesion molecules (i.e., ICAM-1) in T-helper lymphocytes. An understanding of the underlying inflammatory mechanism could lead to specific interventions that render nCPAP therapy tolerable for these individuals.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Citocinas/inmunología , Regulación de la Expresión Génica/inmunología , Rinitis/etiología , Rinitis/inmunología , Apnea Obstructiva del Sueño/inmunología , Apnea Obstructiva del Sueño/terapia , Linfocitos T Colaboradores-Inductores/inmunología , Ensayos Clínicos como Asunto , Presión de las Vías Aéreas Positiva Contínua/métodos , Medicina Basada en la Evidencia , Humanos , Modelos Biológicos , Apnea Obstructiva del Sueño/patología , Resultado del TratamientoAsunto(s)
Síndrome de Tolosa-Hunt/diagnóstico , Antiinflamatorios/uso terapéutico , Arterias Carótidas/patología , Seno Cavernoso/patología , Diagnóstico Diferencial , Fibroblastos/patología , Humanos , Imagen por Resonancia Magnética , Necrosis , Seudotumor Orbitario/patología , Esteroides , Síndrome de Tolosa-Hunt/tratamiento farmacológicoRESUMEN
The effects of rat parathyroid hormone-related protein (rPTHrP) and bovine and rat parathyroid hormone (bPTH and rPTH) on L-type Ca2+ channels in UMR 106 cells were investigated using the patch clamp technique. rPTHrP increased the whole cell L-type Ca2+ channel currents and the increase was concentration dependent. rPTHrP, at a concentration of 62.5 nM, increased the L-type Ca2+ channel current by 122+/-25%. bPTH was less potent. A concentration of 7.5 microM bPTH increased the current by 99+/-24%. Results obtained with rPTH were similar to those obtained using bPTH. Single channel measurements, using the cell-attached version of the patch clamp technique, showed an increase in both the number of channel openings and the mean open time when the cells were exposed to rPTHrP. This suggested that rPTHrP affected the gating of L-type Ca2+ channels in UMR 106 cells. This study demonstrates that the actions of bPTH and rPTHrP in UMR cells are mediated in part by extracellular Ca2+ entry. PTHrP, a paracrine agent important in development, is more potent in regulating Ca2+ entry than PTH.
Asunto(s)
Canales de Calcio Tipo L/metabolismo , Hormona Paratiroidea/farmacología , Proteínas/farmacología , Animales , Bovinos , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Activación del Canal Iónico/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Proteína Relacionada con la Hormona Paratiroidea , Técnicas de Placa-Clamp , Ratas , Proteínas Recombinantes , Especificidad de la Especie , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismoRESUMEN
Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) have been shown to relax various types of smooth muscle, e.g. vascular, uterine and gastric. This study demonstrates that PTH and PTHrP both relaxed cholecystokinin octapeptide (CCK)-induced tension in guinea pig gallbladder strips. This relaxation was concentration-dependent. The use of PTHrP (7-34) blocked the relaxant effect of both agents. This suggested PTH and PTHrP were acting through the same receptor. The use of Rp-cAMPs, an inhibitor of cAMP activation of protein kinase A, and H-89, a selective inhibitor of protein kinase A, suggested that cAMP mediated the relaxant action of PTH and PTHrP. The use of iberiotoxin indicated that the high conductance Ca(2+)-activated potassium channels also mediated the actions of PTH/PTHrP. The use of KT5823, a selective blocker of protein kinase G, also decreased the amount of relaxation induced by PTH/PTHrP. This suggested that crosstalk between the two second messenger (cAMP and cGMP) systems occurred.
Asunto(s)
Carbazoles , Colecistoquinina/metabolismo , Vesícula Biliar/efectos de los fármacos , Indoles , Hormona Paratiroidea/farmacología , Proteínas/farmacología , Alcaloides/farmacología , Animales , Canales de Calcio/efectos de los fármacos , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Cobayas , Técnicas In Vitro , Masculino , Óxido Nítrico/metabolismo , Hormona Paratiroidea/metabolismo , Proteína Relacionada con la Hormona Paratiroidea , Péptidos/farmacología , Proteínas/metabolismo , Transducción de SeñalRESUMEN
The p38 family of mitogen-activated protein kinases is believed to mediate a variety of leukocyte responses to pro-inflammatory stimuli. There are four members of the p38 family, and although activation of the different members has been studied in transiently transfected cells much less is known about activation of the endogenous p38s, particularly in myeloid lineage cells. To investigate activation of endogenous p38s, we have made monoclonal antibodies specific for each p38 and have used these antibodies to study p38 activation by pro-inflammatory stimuli in several human monocytic cell lines. Without stimulation endogenous p38alpha kinase activity was readily detectable, whereas that of p38beta, gamma, and delta was barely measurable. In response to inflammatory stimuli, we observed a time- and dose-dependent activation of all four p38s. The kinetics of activation of each of the p38s were similar for each stimulus used, suggesting a common upstream activation pathway. Simultaneous activation of the p38s suggests that all four may be important in inflammation.
Asunto(s)
Proteínas Quinasas Activadas por Mitógenos/metabolismo , Anticuerpos Monoclonales/farmacología , Astrocitoma , Línea Celular , Activación Enzimática , Escherichia coli , Humanos , Inflamación , Interferón gamma/farmacología , Cinética , Lipopolisacáridos/farmacología , Proteína Quinasa 12 Activada por Mitógenos , Proteínas Recombinantes/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Transfección , Células Tumorales Cultivadas , Células U937 , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
OBJECTIVE: To report a patient with agenesis of the right internal carotid artery associated with ipsilateral, congenital Homer's syndrome. DESIGN: Case report. METHODS: A 30-year-old woman, with a past history of migraine headaches, underwent neuro-ophthalmologic and neuroradiologic evaluation for transient visual obscurations and congenital Horner's syndrome. RESULTS: A right, third-order neuron Horner's syndrome was confirmed with 1% hydroxyamphetamine topical drops. Cranial magnetic resonance imaging revealed an absent right internal carotid artery flow void, computed tomography demonstrated absence of the right carotid canal, and cerebral angiography confirmed absence of the right internal carotid artery. No atheromatous lesions were found and the results of coagulation studies were normal. CONCLUSIONS: Agenesis of the internal carotid artery is a rare cause of congenital Horner's syndrome. The cause of transient visual blurring in the current patient remains unproven.
Asunto(s)
Enfermedades de las Arterias Carótidas/congénito , Arteria Carótida Interna/anomalías , Síndrome de Horner/congénito , Adulto , Enfermedades de las Arterias Carótidas/diagnóstico , Arteria Carótida Interna/diagnóstico por imagen , Angiografía Cerebral , Femenino , Síndrome de Horner/diagnóstico , Humanos , Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos XRESUMEN
Mammalian Toll-like receptors (TLRs) are expressed on innate immune cells and respond to the membrane components of Gram-positive or Gram-negative bacteria. When activated, they convey signals to transcription factors that orchestrate the inflammatory response. However, the intracellular signaling events following TLR activation are largely unknown. Here we show that TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2. Dominant-negative Rac1N17, but not dominant-negative Cdc42N17, block nuclear factor-kappa B (NF-kappa B) transactivation. S. aureus stimulation causes the recruitment of active Rac1 and phosphatidylinositol-3 kinase (PI3K) to the TLR2 cytosolic domain. Tyrosine phosphorylation of TLR2 is required for assembly of a multiprotein complex that is necessary for subsequent NF-kappa B transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of I kappa B alpha degradation. Thus Rac1 controls a second, I kappa B-independent, pathway to NF-kappa B activation and is essential in innate immune cell signaling via TLR2.
Asunto(s)
Proteínas de Drosophila , Glicoproteínas de Membrana/metabolismo , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas , Receptores de Superficie Celular/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Línea Celular , Expresión Génica , Humanos , Glicoproteínas de Membrana/genética , Modelos Biológicos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfotirosina/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Receptores de Superficie Celular/genética , Transducción de Señal , Staphylococcus aureus/inmunología , Receptor Toll-Like 2 , Receptores Toll-Like , Transfección , Proteína de Unión al GTP cdc42/metabolismoRESUMEN
This is a report of the use of endoscopic sinus surgery in the management of three patients diagnosed with rhino-orbital or rhino-orbito-cerebral mucormycosis. A retrospective review was performed of the clinical examinations and imaging studies of three patients who underwent endoscopic sinus surgery as part of their therapy for mucormycosis. In addition to endoscopic surgery, all patients had aggressive control of underlying risk factors (diabetes mellitus, immunosuppression) and prolonged intravenous amphotericin B therapy. All three patients survived and avoided orbital exenteration. In selected patients with rhino-orbito-cerebral mucormycosis, endoscopic techniques can play a valuable role in diagnosis and management.
Asunto(s)
Encefalopatías/cirugía , Endoscopía , Mucormicosis/cirugía , Enfermedades Orbitales/cirugía , Senos Paranasales/cirugía , Sinusitis/cirugía , Adulto , Anfotericina B/uso terapéutico , Encefalopatías/diagnóstico , Encefalopatías/microbiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/microbiología , Sinusitis/diagnóstico , Sinusitis/microbiologíaRESUMEN
Pituitary adenylate cyclase activating polypeptide (PACAP) was shown to relax guinea pig gallbladder strips contracted with cholecystokinin. This relaxation was mediated by PACAP interacting with VIP/PACAP receptors. PACAP was also shown to cause contraction in guinea pig gallbladder strips. The present study demonstrated that calphostin C and bisindolylmaleimide IV, both blockers of protein kinase C, significantly reduced tension, Rp-adenosine 3', 5'-cyclic monophosphatase triethylamine, a blocker of protein kinase A, had no effect on PACAP-induced tension. Nifedipine also significantly reduced the PACAP effect. The contractile effects of PACAP are mediated by protein kinase C.
Asunto(s)
Vesícula Biliar/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Neuropéptidos/farmacología , Proteína Quinasa C/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/farmacología , Colecistoquinina/farmacología , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacología , Cobayas , Indoles/farmacología , Masculino , Maleimidas/farmacología , Naftalenos/farmacología , Nifedipino/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Proteína Quinasa C/antagonistas & inhibidores , Receptores de Péptido Intestinal Vasoactivo/metabolismoRESUMEN
The acoustic startle reflex (ASR) is inhibited by low intensity acoustic stimuli (prepulse inhibition; PPI) delivered prior to the startle stimulus. PPI may reflect underlying sensorimotor processes involved in the filtering of exteroceptive stimuli for their cognitive or physiological relevance. Latent inhibition (LI) is a cognitive process in which pre-exposure to the conditioned stimulus (CS) produces pro-active interference with the acquisition of an associative learning task. LI is thought to reflect a selective attention mechanism that contributes to an organism's ability to adjust its behavior to changing contingencies of reinforcement. In the present series of experiments, the ASR, PPI at three prepulse intensities (56, 68, and 80 dB), locomotor activity, and LI using an active avoidance paradigm were assessed in mice bidirectionally selected from a heterogeneous stock for response (NR line) or nonresponse (NNR line) to neuroleptic-induced catalepsy. A randomly selected line was used as the control. Mice from the NNR line displayed weak startle responses and a complete absence of PPI. In contrast, the NR line displayed the largest ASR and the greatest PPI. The control line displayed ASRs and PPI values intermediate to the selected lines. Locomotor activity which is known to affect LI was lowest in the NR line but was similar in the NNR and control lines. In the LI paradigm, acquisition of the avoidance response was impaired in mice from the NR and control lines that were pre-exposed to the auditory CS (normal response). In contrast, the acquisition of the avoidance response in the NNR line was similar in CS pre-exposed and CS non-pre-exposed animals. Overall, the results demonstrate that some of the same genetic factors which regulate neuroleptic response also play a significant role in PPI and LI.
Asunto(s)
Actividad Motora , Reflejo de Sobresalto , Estimulación Acústica , Análisis de Varianza , Animales , Reacción de Prevención , Catalepsia/fisiopatología , Catalepsia/psicología , Masculino , Ratones , Ratones Endogámicos , Psicología del EsquizofrénicoRESUMEN
CD14 is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein which functions as a receptor on myeloid cells for ligands derived from microbial pathogens such as lipopolysaccharide (LPS). We have studied the importance of the GPI tail of CD14 in signalling with the promonocytic cell line THP-1 expressing recombinant CD14 in a GPI-anchored form (THP1-wtCD14 cells) or in a transmembrane form (THP1-tmCD14). We found that, like other GPI-anchored molecules, GPI-anchored CD14 was recovered mainly from a Triton X-100-insoluble fraction, whereas transmembrane CD14 was fully soluble in Triton X-100. LPS induced cell activation of THP1-wtCD14 and of THP1-tmCD14 (protein tyrosine kinase phosphorylation, NF-kappaB activation, and cytokine production) in a very similar manner. However, anti-CD14 antibody-induced cross-linking caused a rapid calcium mobilization signal only in GPI-anchored CD14 cells. Studies with pharmacologic inhibitors of intracellular signalling events implicate phospholipase C and protein tyrosine kinases in the genesis of this antibody-induced calcium signal. Our results suggest that GPI anchoring and CD14 targeting to glycolipid-rich membrane microdomains are not required for LPS-mediated myeloid cell activation. GPI anchoring may however be important for other signalling functions, such as those events reflected by antibody cross-linking.
Asunto(s)
Glicosilfosfatidilinositoles/fisiología , Receptores de Lipopolisacáridos/fisiología , Línea Celular , Humanos , Lipopolisacáridos/farmacología , Fosforilación , Tirosina/metabolismoRESUMEN
For 11 years, a 50-year-old woman with euthyroid Graves' disease experienced intermittent exacerbations of her orbitopathy associated with a decline in visual acuity. On each occasion, treatment with systemic corticosteroids led to prompt recovery of vision. Upon referral for consideration for orbital decompressive surgery, computed tomography and magnetic resonance imaging scanning detected bilateral optic-nerve sheath meningiomas, as well as typical findings of Graves' disease. Orbital radiation therapy led to stabilization of visual function and orbital findings, eliminating the need for systemic steroids. To our knowledge, this is the first reported case of Graves' disease associated with bilateral optic nerve sheath meningiomas.
Asunto(s)
Enfermedad de Graves/complicaciones , Neoplasias Meníngeas/complicaciones , Meningioma/complicaciones , Músculos Oculomotores/patología , Neoplasias del Nervio Óptico/complicaciones , Nervio Óptico/patología , Femenino , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/radioterapia , Humanos , Imagen por Resonancia Magnética , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/radioterapia , Meningioma/diagnóstico , Meningioma/radioterapia , Persona de Mediana Edad , Músculos Oculomotores/efectos de la radiación , Nervio Óptico/efectos de la radiación , Neoplasias del Nervio Óptico/diagnóstico , Neoplasias del Nervio Óptico/radioterapia , Tomografía Computarizada por Rayos X , Agudeza Visual , Campos VisualesRESUMEN
Calcitonin gene-related peptide (CGRP) has been shown to relax cholecystokinin-induced tension in guinea pig gallbladder strips. This relaxation is dependent on the concentration of CGRP, and is primarily due to the opening of ATP sensitive K+ channels; however, other mechanisms may also be involved. Studies using forskolin, 8-bromoadenosine 3', 5' cyclic monophosphate, dibutyryl cAMP, cholera toxin, and Rp-adenosine 3', 5'-cyclic monophosphothioate triethylamine, which measured changes in tension suggest that cAMP may be involved in mediating the actions of CGRP. Radioimmunoassay of strips precontracted with cholecystokinin octapeptide (CCK) and either treated with CGRP or its solvent demonstrated that cAMP concentrations increased with CGRP treatment. The results of these studies demonstrate that CGRP acts through multiple mechanisms to induce relaxation of guinea pig gallbladder strips precontracted with CCK.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/farmacología , AMP Cíclico/metabolismo , Relajación Muscular/efectos de los fármacos , Músculo Liso/fisiología , 8-Bromo Monofosfato de Adenosina Cíclica/farmacología , Inhibidores de Adenilato Ciclasa , Animales , Bucladesina/farmacología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Colecistoquinina/antagonistas & inhibidores , Colecistoquinina/farmacología , Toxina del Cólera/farmacología , Colforsina/farmacología , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacología , Inhibidores Enzimáticos/farmacología , Ensayo de Inmunoadsorción Enzimática , Vesícula Biliar , Cobayas , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Ratas , Tionucleótidos/farmacologíaRESUMEN
THP-1-derived cell lines were stably transfected with constructs encoding glycophosphatidylinositol (GPI)-anchored or transmembrane forms of human CD14. CD14 expression was associated with enhanced phagocytosis of serum (heat-inactivated)-opsonized Escherichia coli (opEc). Both the GPI-anchored and transmembrane forms of CD14 supported phagocytosis of opEc equally well. Lipopolysaccharide-binding protein (LBP) played a role in CD14-dependent phagocytosis as evidenced by inhibition of CD14-dependent phagocytosis of opEc with anti-LBP monoclonal antibody (mAb) and by enhanced phagocytosis of E. coli opsonized with purified LBP. CD14-dependent phagocytosis was inhibited by a phosphatidylinositol (PI) 3-kinase inhibitor (wortmannin) and a protein tyrosine kinase inhibitor (tyrphostin 23) but not a protein kinase C inhibitor (bisindolyl-maleimide) or a divalent cation chelator (ethylenediaminetetraacetate). Anti-LBP mAb 18G4 and anti-CD14 mAb 18E12 were used to differentiate between the pathways involved in CD14-dependent phagocytosis and CD14-dependent cell activation. F(ab')2 fragments of 18G4, a mAb to LBP that does not block cell activation, inhibited ingestion of opEc by THP1-wtCD14 cells. 18E12 (an anti-CD14 mAb that does not block LPS binding to CD14 but does inhibit CD14-dependent cell activation) did not inhibit phagocytosis of LBP-opEc by THP1-wtCD14 cells. Furthermore, CD14-dependent phagocytosis was not inhibited by anti-CD18 (CR3 and CR4 beta-chain) or anti-Fcgamma receptor mAb.
Asunto(s)
Escherichia coli/fisiología , Receptores de Lipopolisacáridos/fisiología , Monocitos/microbiología , Monocitos/fisiología , Fagocitosis/fisiología , Línea Celular , Humanos , Lipopolisacáridos/farmacologíaRESUMEN
Cholecystokinin octapeptide (CCK), acetylcholine (ACh) and ceruletide have been shown to produce contraction in bullfrog (Rana catesbeiana) gallbladder strips. Agents capable of relaxing the bullfrog gallbladder are less numerous. Calcitonin gene-related peptide reduced the amount of both CCK- and ACh-induced tension in bullfrog gallbladder strips. The purpose of this study was to determine whether vasoactive intestinal peptide (VIP), nitric oxide (NO) and the second messengers cyclic GMP or cyclic AMP had any effect on gallbladder motility in the bullfrog. In vitro tension studies using l-NG-nitro-arginine methyl ester, Methylene Blue, sodium nitroprusside and N2,2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate suggested that nitric oxide did not modulate gallbladder motility in the bullfrog gallbladder. Histochemical staining for NADPH diaphorase (nitric oxide synthase) failed to demonstrate nerve fibers containing nitric oxide synthase in the bullfrog gallbladder. In vitro studies demonstrated that VIP had no effect on CCK-induced tension. However, in vitro studies using either 8-bromoadenosine 3',5'-cyclic monophosphate or forskolin demonstrated that both agents relaxed strips precontracted with CCK. The results of this study suggested that, while neither NO nor VIP had a role in modulating bullfrog gallbladder motility, cyclic AMP was capable of modulating bullfrog gallbladder motility.
Asunto(s)
AMP Cíclico/farmacología , Vesícula Biliar/fisiología , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiología , Óxido Nítrico/farmacología , Rana catesbeiana , AnimalesRESUMEN
PURPOSE: The purpose of the study is to report the occurrence of optic neuropathy after stereotactic radiosurgery for perichiasmal tumors. METHODS: Records of four patients with visual deterioration after stereotactic radiosurgery were reviewed, including clinical findings, neuroimaging results, and treatment methods. RESULTS: Optic neuropathy developed 7 to 30 months after gamma knife radiosurgery. All patients experienced an abrupt change in visual function. Clinical findings indicated anterior visual pathway involvement. Patterns of field loss included nerve fiber bundle and homonymous hemianopic defects. Gadolinium-enhanced magnetic resonance imaging (MRI) showed swelling and enhancement of the affected portion of the visual apparatus in three patients. Systemic corticosteroids were administered in all patients and one partially recovered. One patient also received hyperbaric oxygen without improvement. CONCLUSIONS: Although rare, optic neuropathy may follow radiosurgery to lesions near the visual pathways. Careful dose planning guided by MRI with restriction of the maximal dose to the visual pathways to less than 8 Gy will likely reduce the incidence of this complication.