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1.
Clin Neurophysiol ; 154: 116-125, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37595481

RESUMEN

OBJECTIVE: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. METHODS: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. RESULTS: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400 ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. CONCLUSIONS: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. SIGNIFICANCE: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.


Asunto(s)
Epilepsias Parciales , Epilepsia , Neocórtex , Niño , Humanos , Preescolar , Adolescente , Adulto Joven , Adulto , Epilepsias Parciales/diagnóstico , Epilepsia/diagnóstico , Convulsiones , Tálamo , Electroencefalografía
2.
JDS Commun ; 3(1): 49-54, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36340684

RESUMEN

White willow bark (WWB) is commonly used in combination with other medicinal herbs and analgesics to alleviate inflammatory pain in disbudded calves under organic management, but there is no evidence to confirm an effect of WWB on inflammatory biomarkers in calves. The objective of this study was to determine whether WWB affects the inflammatory biomarker prostaglandin E2 (PGE2) in healthy dairy calves. A randomized crossover trial with 2 periods and 5 treatments was used for this experiment. A 7-d washout period was used to minimize carryover effects. The treatments were (1) 57.6 mg/kg oral WWB (low dose; L-WWB), (2) 115.1 mg/kg oral WWB (medium dose; M-WWB), (3) 230.3 mg/kg oral WWB (high dose; H-WWB), (4) 2.2 mg/kg i.v. flunixin meglumine (FM), or (5) no treatment (NT). Calves (n = 25) were randomly assigned to receive 1 of the 25 treatment sequences. Blood samples were collected at 1, 2, and 4 h after administration to determine PGE2 and salicylic acid plasma concentrations. The WWB had 2,171 µg/g (± 4.3% relative standard error) salicin (0.22%). On average, calves in the FM (721 ± 274 pg/mL) treatment had lower PGE2 than calves in all other treatments. Calves in the NT (2,606 ± 271 pg/mL), L-WWB (2,509 ± 276 pg/mL), M-WWB (2,343 ± 270 pg/mL), and H-WWB (3,039 ± 270 pg/mL) treatments had similar PGE2 averaged across sampling times. Calves in the L-WWB (23.4 ± 1.9 ng/mL), M-WWB (21.5 ± 1.9 ng/mL), and H-WWB (23.3 ± 1.9 ng/mL) treatments had similar maximum salicylic acid plasma concentrations. Results from this study indicate that the WWB doses used in this experiment were ineffective at achieving dose-dependent PGE2 and salicylic acid plasma concentration responses.

3.
J Dairy Sci ; 104(3): 2966-2978, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33358799

RESUMEN

Choline is usually supplemented as ruminally protected choline chloride to prevent its degradation in the rumen, but the effects of unprotected choline on ruminal fermentation are unclear. Some research indicates a possible role of dietary fiber on microbial degradation of choline; therefore we aimed to evaluate the effects of unprotected choline chloride on ruminal fermentation and to investigate whether those effects depend on dietary neutral detergent fiber (NDF) concentration. Our hypothesis was that dietary NDF concentration would influence choline chloride effects on microbial ruminal fermentation. We used 8 fermentors in a duplicated 4 × 4 Latin square with a 2 × 2 factorial arrangement, combining 2 factors: (1) dietary NDF concentration and (2) unprotected choline chloride supplementation. Resulting treatments are (1) 30%NDF/Ctrl [30% NDF control diet without supplemental choline (Cho)]; (2) 30%NDF/Cho [30% NDF diet plus 1.9 g of choline ion per kg of dry matter (DM)]; (3) 40%NDF/Ctrl (40% NDF control diet without supplemental choline); and (4) 40%NDF/Cho (40% NDF diet plus 1.9 g of choline ion per kg of DM). Four 10-d periods were completed, each consisting of 7 d for adaptation and 3 d for collection of samples for estimation of nutrient disappearance and daily average concentrations of volatile fatty acids and NH3-N. In addition, kinetics of pH, acetate, and propionate were evaluated at 0, 1, 2, 4, 6, and 8 h after morning feeding. On the last day of each period, bacteria pellets were harvested for 15N analysis and N metabolism. Fixed effects of dietary NDF concentration, unprotected choline chloride supplementation, and their interaction (NDF × Cho) were tested using the MIXED procedure of SAS version 9.4 (SAS Institute Inc., Cary, NC). Choline tended to increase total volatile fatty acid concentrations and decreased acetate molar proportion regardless of dietary NDF concentration, but it increased propionate molar proportion and decreased acetate to propionate ratio only with the 30% NDF diet. Supplementing choline decreased NDF disappearance regardless of dietary NDF; however, organic matter disappearance tended to be reduced only when choline was added to 40% NDF. Our data indicate that unprotected choline chloride effects on ruminal fermentation depend on dietary NDF concentration, allowing for a greater propionate synthesis without decreasing organic matter disappearance when fed with a 30% NDF diet.


Asunto(s)
Detergentes , Rumen , Alimentación Animal/análisis , Animales , Colina/metabolismo , Detergentes/metabolismo , Dieta/veterinaria , Fibras de la Dieta/metabolismo , Digestión , Fermentación , Rumen/metabolismo
4.
Animal ; 9(7): 1113-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25743337

RESUMEN

Channel catfish raised in the southern United States require two growing seasons to reach market size. Growing seasons are separated by a cool period of about 3 months when feed intake and growth are greatly reduced. A cool-weather feeding strategy to improve feed intake, growth or health of catfish might improve survival and reduce the time needed to achieve market size. We conducted a feeding trial with channel catfish at a suboptimal temperature (15°C) to determine the effects of supplementing diets with either a dairy/yeast prebiotic or flaxseed oil (high in 18:3n-3) compared with a control with soybean oil (high in 18:2n-6). The trial was conducted in recirculating systems with 1140-l tanks containing 100 fish each (mean initial weight 61.4 g±0.43 s.e.m.). A 28%-protein basal diet was supplemented with 20 g/kg cellulose and 20 g/kg soybean oil (SBO, control), 20 g/kg cellulose and 20 g/kg flaxseed oil (FLAX) or 20 g/kg of a dairy/yeast prebiotic and 20 g/kg soybean oil (PREB). Fish were fed once daily to satiation and weighed every 3 weeks to track growth. Hematology, non-specific immune responses, proximate and fatty acid composition of muscle were determined to assess diet effects. Catfish-fed FLAX or PREB had higher weight gain, feed consumption and lysozyme activity than fish fed SBO. Total n-3 fatty acids in muscle were higher in fish fed SBO or FLAX than those fed PREB. Total n-6 long-chain polyunsaturated acids were higher in muscle of fish fed PREB than those fed SBO. Fatty acids in the PREB and SBO diets were similar, so the PREB appeared to increase elongation and desaturation of n-6 fatty acids in muscle. Flaxseed oil and the dairy/yeast prebiotic both have potential to increase catfish performance at a low temperature.


Asunto(s)
Acuicultura/métodos , Suplementos Dietéticos , Ictaluridae/crecimiento & desarrollo , Ictaluridae/inmunología , Aceite de Linaza/farmacología , Prebióticos/administración & dosificación , Temperatura , Animales , Peso Corporal , Ácidos Grasos/análisis , Aceite de Linaza/administración & dosificación , Muramidasa/metabolismo , Músculo Esquelético/química , Aceite de Soja/administración & dosificación , Aceite de Soja/farmacología
5.
Ann Oncol ; 21(8): 1657-1661, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20089559

RESUMEN

BACKGROUND: There is speculation that peripheral neuropathy (PN) with capecitabine and oxaliplatin (CapOx; 130 mg/m(2), day 1, every 21 days) may be more common than with FOLFOX4 (5-fluorouracil and oxaliplatin 85 mg/m(2), day 1, every 14 days). We aimed to determine PN incidence and associations during CapOx, and 6 and 12 months after CapOx. PATIENTS AND METHODS: Retrospective audit of 188 oxaliplatin-naive colorectal cancer patients (87 adjuvant, 101 palliative) who received at least one cycle of CapOx. Neurosensory Common Toxicity Criteria Adverse Events version 3 were applied. RESULTS: Overall, 94% experienced acute PN. Worst severities for adjuvant and palliative patients, respectively, were grade 1, 44% and 54%; grade 2, 35% and 32%; grade 3, 16% and 3%; grade 4, 0% and 1% and grade unclear 1% and 1%. Two patients developed PN after CapOx completion despite no symptoms during treatment. Chronic PN at 6 months affected 57% and 18% of adjuvant and palliative patients, respectively. At 12 months, 35% and 16% were affected. Chronic PN at 12 months was associated with cumulative oxaliplatin dose but not age, gender, acute myotonia, pseudolaryngospasm or grade 2 or more PN during treatment. CONCLUSION: Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Incidencia , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico/epidemiología , Estudios Retrospectivos , Escocia/epidemiología
6.
Clin Neuropsychol ; 15(3): 289-304, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11778766

RESUMEN

There is considerable controversy regarding whether persistent postconcussive symptoms (PCS) are injury-specific, in a subgroup of individuals after mild traumatic brain injury (TBI). The following findings have contributed to this controversy: (1) The base rate of PCS in mild TBI is comparable to uninjured controls; and (2) The severity of PCS covary with daily stress levels (Gouvier, Cubic, Jones, Brantley, & Cutlip, 1992). We examined this relationship further by evaluating the effects of experimental conditions of stress or relaxation on individuals with TBI and uninjured control subjects, with low and high PCS endorsement. We evaluated psychophysiological parameters, neuropsychological performance, and changes in PCS and stress perception. In our study, subjects with TBI increased PCS after engaging in cognitively challenging tasks, and demonstrated significant autonomic changes in the stress condition. Symptomatic TBI subjects exposed to high stress had increases in PCS complaints, decreased speed of information processing, and subtle memory deficits. Our results suggest that PCS are injury-specific and that individuals with a history of TBI are susceptible to the effects of stress. Relaxation training including breathing retraining may be an effective means of decreasing PCS and cognitive complaints in subjects with mild TBI.


Asunto(s)
Conmoción Encefálica/diagnóstico , Conmoción Encefálica/psicología , Lesiones Encefálicas/psicología , Estrés Psicológico/diagnóstico , Estrés Psicológico/psicología , Adulto , Conmoción Encefálica/etiología , Lesiones Encefálicas/complicaciones , Femenino , Respuesta Galvánica de la Piel/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Pruebas Neuropsicológicas , Relajación , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
7.
Br J Cancer ; 76(2): 260-3, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9231929

RESUMEN

Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia-modifying agents during radical radiotherapy for bladder cancer using a standard daily 20-fraction schedule. Three groups of patients have received (a) nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in 20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4 weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4 weeks. Ten patients were treated in each group. All patients completed carbogen and radiotherapy as prescribed, but only 45% completed daily nicotinamide over the 4-week treatment period. The end points of this study were acute bowel and bladder morbidity and local control at cystoscopy 6 months after treatment. An expected level of acute bowel and bladder morbidity was seen that reverted to normal in most patients by 12 weeks with no difference between the three treatment groups. Complete response rates at 6 months were seven out of ten (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It is concluded that carbogen and nicotinamide may improve the results of daily fractionated radiotherapy in bladder cancer and that further evaluation is required.


Asunto(s)
Dióxido de Carbono/uso terapéutico , Carcinoma/terapia , Niacinamida/uso terapéutico , Oxígeno/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Carcinoma/mortalidad , Carcinoma/patología , Quimioterapia Adyuvante , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/sangre , Radioterapia Adyuvante , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Micción
8.
J Biol Chem ; 270(24): 14523-32, 1995 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-7782315

RESUMEN

The heregulin family of polypeptides arise as splice variants from a single gene and share a conserved epidermal growth factor (EGF)-like domain thought to be the major determinant of their biological activities. We report here the cloning of a novel member of this family, termed sensory and motor neuron-derived factor or SMDF, which is highly expressed in sensory and motor neurons in human and rodent species. It contains a C-terminal beta-type EGF-like domain and an unique N-terminal sequence which lacks an Ig-like domain and is distinct from all known heregulin variants. Mammalian cell-expressed SMDF activates tyrosine phosphorylation of a 185-kDa protein in cell lines expressing p185erbB2, indicating that it is biologically active. Analyses of expression patterns suggest that, unlike other heregulin variants, SMDF is expressed mainly in the nervous system. In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF-like domain are comparable, suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons. Expression of SMDF is maintained in both adult motor neurons and dorsal root ganglion neurons. These findings suggest that SMDF may mediate biological responses such as Schwann cell proliferation and acetylcholine receptor induction in the peripheral nervous system.


Asunto(s)
Neuronas Motoras/química , Proteínas del Tejido Nervioso/genética , Neuronas Aferentes/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Línea Celular , Clonación Molecular , ADN Complementario , Factor de Crecimiento Epidérmico/genética , Humanos , Hibridación in Situ , Datos de Secuencia Molecular , Neurregulina-1 , Fosforilación , ARN Mensajero/genética , Ratas , Receptor ErbB-2/genética , Homología de Secuencia de Aminoácido , Tirosina/metabolismo
9.
Appl Microbiol Biotechnol ; 42(5): 797-806, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7765919

RESUMEN

Abundant and common yeast biomass has been examined for its capacity to sequester heavy metals from dilute aqueous solutions. Live and non-living biomass of Saccharomyces cerevisiae differs in the uptake of uranium, zinc and copper at the optimum pH 4-5. Culture growth conditions can influence the biosorbent metal uptake capacity which normally was: living and non-living brewer's yeast: U > Zn > Cd > Cu; non-living baker's yeast: Zn > (Cd) > U > Cu; living baker's yeast: Zn > Cu approximately (Cd) > U. Non-living brewer's yeast biomass accumulated 0.58 mmol U/g. The best biosorbent of zinc was non-living baker's yeast (approximately 0.56 mmol Zn/g). Dead cells of S. cerevisiae removed approximately 40% more uranium or zinc than the corresponding live cultures. Biosorption of uranium by S. cerevisiae was a rapid process reaching 60% of the final uptake value within the first 15 min of contact. Its deposition differing from that of other heavy metals more associated with the cell wall, uranium was deposited as fine needle-like crystals both on the inside and outside of the S. cerevisiae cells.


Asunto(s)
Metales/farmacocinética , Saccharomyces cerevisiae/metabolismo , Adsorción , Transporte Biológico Activo , Biomasa , Biotecnología , Tampones (Química) , Cinética , Microscopía Electrónica , Saccharomyces cerevisiae/ultraestructura , Soluciones , Uranio/farmacocinética
10.
Genes Dev ; 8(4): 399-413, 1994 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-8125255

RESUMEN

Mice harboring the waved-1 (wa-1) and waved-2 (wa-2) mutations exhibit skin and eye abnormalities that are strikingly similar to those of TGF-alpha-deficient mice, and wa-1 and TGF-alpha were recently shown to be allelic. Because the wa-2 mutation was mapped previously to the vicinity of the EGF/TGF-alpha receptor (EGFR) gene on mouse chromosome 11, we hypothesized that the wa-2 phenotype might result from a defect in either the expression or activity of EGFR, or both. In the present report, we show that EGFR mRNA and protein of normal size are expressed in wa-2 liver and skin at levels that are comparable to those in the corresponding normal tissues, and that the ability of wa-2 EGFR to bind ligand is unaltered. However, ligand-dependent autophosphorylation of wa-2 EGFR is diminished 5- to 10-fold in vitro, and the ability of wa-2 EGFR to phosphorylate an exogenous substrate is reduced by > 90% compared with that of the control receptor. EGF-induced tyrosine phosphorylation, including that of EGFR itself, is also diminished in skin, particularly at lower dose of exogenous EGF. To establish the nature of the wa-2 mutation, we determined the nucleotide sequence of the coding region of normal and wa-2 murine EGFR cDNAs. A comparison of these sequences revealed a single-nucleotide transversion resulting in the substitution of a glycine for a conserved valine residue near the amino terminus of the tyrosine kinase domain. The importance of this mutation was confirmed by showing that its introduction into an otherwise normal EGFR markedly reduced the receptor's tyrosine kinase activity in transfected Chinese hamster ovary cells. Finally, in situ hybridization analysis demonstrated expression of EGFR predominantly in the outer root sheath of active hair follicles in neonatal mice. As we previously localized TGF-alpha mRNA to the inner root sheath, this pattern of EGFR expression is consistent with the effect of the wa-2 mutation on hair structure, and together with our previous characterization of TGF-alpha-deficient mice, reveals a critical role for signaling by this ligand/receptor system in skin.


Asunto(s)
Receptores ErbB/genética , Mutación Puntual , Anomalías Múltiples/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario/genética , Anomalías del Ojo/genética , Cabello/metabolismo , Hibridación in Situ , Hígado/metabolismo , Masculino , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Homología de Secuencia de Aminoácido , Anomalías Cutáneas , Factor de Crecimiento Transformador alfa/genética
11.
Chest ; 104(5): 1387-92, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8222793

RESUMEN

In this multicenter, observer-blinded study, 301 patients with signs and symptoms of acute bacterial exacerbation of COPD were randomized (2:1) to receive either cefpodoxime proxetil (200 mg, bid) or cefaclor (250 mg, tid) for 10 days. Clinical and microbiologic evaluations were performed before treatment, during therapy (study days 3 to 5), at the end of therapy (3 to 7 days posttreatment), and at long-term follow-up (4 weeks posttreatment). The most common pretreatment isolates were Haemophilus influenzae, Haemophilus parainfluenzae, and Streptococcus pneumoniae. Significantly (p < 0.001) more bacterial isolates were susceptible in vitro to cefpodoxime (233 of 256, 91 percent) than to cefaclor (215 of 255, 84 percent). There were no statistically significant differences between the two drug regimens in eradication of the initial pathogen (cefpodoxime, 116 of 128, 91 percent; cefaclor, 59 of 64, 92 percent) or end-of-therapy clinical response (cure + proved; cefpodoxime, 99 of 100, 99 percent; cefaclor, 45 of 49, 92 percent) rates for evaluable patients. Both drug treatments were well-tolerated, with a similar incidence of drug-related adverse events (cefpodoxime 11 percent, cefaclor 12 percent). Cefpodoxime (bid) was as safe and effective as cefaclor (tid) in the treatment of acute exacerbation of COPD. The less frequent dosing regimen of cefpodoxime may improve patient compliance compared to those antibiotics that require three or four daily doses.


Asunto(s)
Cefaclor/uso terapéutico , Ceftizoxima/análogos & derivados , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Profármacos/uso terapéutico , Enfermedad Aguda , Adulto , Anciano , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Cefaclor/efectos adversos , Cefaclor/farmacología , Ceftizoxima/efectos adversos , Ceftizoxima/farmacología , Ceftizoxima/uso terapéutico , Tolerancia a Medicamentos , Femenino , Humanos , Enfermedades Pulmonares Obstructivas/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Profármacos/efectos adversos , Profármacos/farmacología , Estados Unidos , Cefpodoxima , Cefpodoxima Proxetilo
12.
Ala Med ; 58(10): 28-32, 1989 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2729030

RESUMEN

The efficacy and safety of ciprofloxacin (500 mg administered every 12 hours) were evaluated in 62 patients enrolled in a prospective, open study. Fifty-three courses in the treatment of 56 infection sites suitable for evaluation were assessed. The infection sites involved were skin and skin structure (28), respiratory tract (21), urinary tract (5), and gastrointestinal tract (2). Bacterial isolates included 16 Pseudomonas aeruginosa, 13 Staphylococcus aureus, and 8 Escherichia coli. Signs and symptoms of infection completely resolved in 46 (82%) of the infection sites. Nine (16%) improved, and one (2%) failed to respond. Ciprofloxacin was well tolerated.


Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Ciprofloxacina/farmacología , Ciprofloxacina/administración & dosificación , Ciprofloxacina/uso terapéutico , Humanos
13.
Cancer Res ; 45(3): 1058-65, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3155990

RESUMEN

In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Carboximetilcelulosa de Sodio/farmacología , Inductores de Interferón/farmacología , Metilcelulosa/análogos & derivados , Péptidos/farmacología , Poli I-C/farmacología , Polilisina/farmacología , Animales , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Prueba de Cultivo Mixto de Linfocitos , Activación de Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Linfocitos T/efectos de los fármacos
14.
Cancer Res ; 45(3): 1066-72, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3971361

RESUMEN

The systemic administration of multiple, nontoxic doses of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose [poly(I,C)-LC] eradicated established experimental and spontaneous pulmonary metastases. Optimal immunotherapy was schedule dependent, requiring three to five injections of poly(I,C)-LC per week for a minimum of 4 weeks; in addition, therapeutic efficiency was partially dosage independent. Immunotherapy by poly(I,C)-LC was found to be limited by tumor burden, although when combined with chemotherapy as a debulking regimen it resulted in increased survival with protocols in which poly(I,C)-LC alone was insufficient. These data suggest that the systemic administration of poly(I,C)-LC may provide a successful adjuvant therapeutic modality against cancer metastasis.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Carboximetilcelulosa de Sodio/uso terapéutico , Inductores de Interferón/uso terapéutico , Metilcelulosa/análogos & derivados , Neoplasias Experimentales/tratamiento farmacológico , Péptidos/uso terapéutico , Poli I-C/uso terapéutico , Polilisina/uso terapéutico , Animales , Carboximetilcelulosa de Sodio/administración & dosificación , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Inmunoterapia , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Poli I-C/administración & dosificación , Polilisina/administración & dosificación
15.
Chest ; 83(4): 704-6, 1983 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-6682029

RESUMEN

A 62-year-old man with obstructive hypertrophic cardiomyopathy was given sublingual nifedipine, 10 mg, during invasive hemodynamic monitoring. After 15 minutes, his left ventricular outflow gradient increased from 22 to 80 mm Hg while arterial pressure fell from 152/70 to 122/64 mm Hg. Left ventricular end-diastolic pressure increased from 15 to 22 mm Hg. These adverse hemodynamic responses may have been a result of vasodilation of the peripheral circulation induced by nifedipine. Thus, some patients with hypertrophic obstructive cardiomyopathy may develop serious hemodynamic compromise when treated with nifedipine.


Asunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Nifedipino/efectos adversos , Piridinas/efectos adversos , Fibrilación Atrial/inducido químicamente , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Cardiomiopatía Hipertrófica/fisiopatología , Humanos , Masculino , Persona de Mediana Edad
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