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1.
J Dairy Sci ; 98(2): 765-80, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25497798

RESUMEN

Increasing the temperature of microfiltration (MF) to >50°C may allow for operation at higher fluxes and reduce the bacterial growth during MF. However, there is a concern that operating at higher temperatures could cause calcium phosphate precipitation that would lead to membrane fouling. Our objective was to determine the effect of operating a 0.1-µm ceramic uniform transmembrane pressure MF unit at temperatures of 50, 55, 60, and 65°C on membrane fouling and serum protein (SP) removal from skim milk with and without removal of low-molecular-weight soluble milk components by ultrafiltration (UF) before MF at a flux of 54kg/m(2) per hour. For each replicate, 1,000kg of pasteurized skim milk was split into 2 batches. One batch was ultrafiltered (with diafiltration) to remove an average of 89±2% of the lactose and a percentage of the soluble calcium and phosphorus. The retentate from UF was diluted back to the protein concentration of skim milk, creating the diluted UF retentate (DUR). On subsequent days, both the DUR and skim milk were run on the MF unit with the flux maintained at 54kg/m(2) per hour and a concentration factor of 3× and the system run in recycle mode. The temperature of MF was increased in 5°C steps from 50 to 65°C, with a 1-h stabilization period after each increase. During the run, transmembrane pressure was monitored and permeate and retentate samples were taken and analyzed to determine if any changes in SP, calcium, or phosphorus passage through the membrane occurred. Increasing temperature of MF from 50 to 65°C at a flux of 54kg/m(2) per hour did not produce a large increase in membrane fouling when using either skim milk or a DUR as the MF feed type as measured by changes in transmembrane pressure. Increasing the temperature to 65°C only caused a slight reduction in calcium concentration in the permeate (11±3%) that was similar between the 2MF feed types. Increasing processing temperature reduced the percentage of SP removal by the process, but the increased temperature also caused a decrease in casein contamination in the permeate with no evidence of membrane fouling.


Asunto(s)
Manipulación de Alimentos , Calor , Leche/química , Ultrafiltración/métodos , Análisis de Varianza , Animales , Proteínas Sanguíneas/análisis , Calcio/análisis , Caseínas/análisis , Cerámica , Femenino , Membranas Artificiales , Filtros Microporos/normas , Modelos Biológicos , Nitrógeno/análisis , Pasteurización , Permeabilidad , Fósforo/análisis , Presión , Ultrafiltración/instrumentación , Ultrafiltración/normas
2.
Bioorg Med Chem ; 19(16): 4876-81, 2011 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-21775156

RESUMEN

Phytochemical investigations of the n-hexane extract from the roots of Peltodon longipes (Lamiaceae) resulted in the isolation of 12 known abietane diterpenes (1-12). Structures were established on the basis of one and two dimensional nuclear magnetic resonance spectroscopic data ((1)H and (13)C, COSY, HSQC and HMBC), electron ionization mass spectrometric analysis (EIMS) as well as comparison with data from literature. These compounds, as well as eight known diterpenes (13-19) from Salvia miltiorrhiza, and two from Salvia sahendica (20 and 21) were evaluated for their cytotoxic effects in human pancreatic (MIAPaCa-2) and melanoma (MV-3) tumor cell lines using the MTT assay. Tanshinone IIa (13), 7α-acetoxyroyleanone (1), 1,2-dihydrotanshinone (16) and cryptotanshinone (14) had the highest cytotoxic effects in MIAPaCa-2, displaying IC(50) of 1.9, 4.7, 5.6, and 5.8 µM, respectively. Structure-activity relationships of abietane diterpenoid quinones are discussed.


Asunto(s)
Abietanos/farmacología , Antineoplásicos Fitogénicos/farmacología , Citotoxinas/farmacología , Lamiaceae , Extractos Vegetales/farmacología , Salvia , Abietanos/análisis , Abietanos/química , Abietanos/aislamiento & purificación , Antineoplásicos Fitogénicos/análisis , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Fitoterapia , Extractos Vegetales/análisis , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Relación Estructura-Actividad
3.
Benef Microbes ; 1(1): 53-60, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21831750

RESUMEN

The effects of the probiotic, Propionibacterium jensenii 702 (PJ 702), supplementation on egg productivity, egg shell thickness, fatty acid profile of eggs, and body weight in early layer hens were investigated. Twenty eight twenty-week-old starter pullets were evenly divided into a treatment and a control group for an eight week experiment. Each bird in the treatment group received 107 cfu PJ 702 daily in a total volume of 1 ml by oral administration. No adverse effect was observed due to administration of PJ 702, and successful gastrointestinal transit in the bird was demonstrated by recovery of PJ 702 from faeces of the treatment group. Layer production was significantly improved by the supplementation of PJ 702. Total egg weight in the treatment group was significantly higher than the control (P<0.001). Average egg weight for the treatment group was 55.26 g, 4.2% higher than the control which averaged 53.02 g. Moreover, the fatty acid profile was significantly altered by the supplementation of PJ 702. Myristic acid (P<0.001), palmitoleic acid (P=0.001) and all-cis-11,14-eicosadienoic acid (P=0.02) were significantly lower in the treatment group compared to the control group. No difference in egg shell thickness was observed between the treatment and control group (P=0.23). In conclusion, the application of novel probiotic PJ 702 in the early layer hen is safe and effective to promote production and the quality of products in layer husbandry.


Asunto(s)
Pollos/fisiología , Oviparidad , Probióticos/metabolismo , Propionibacterium/fisiología , Animales , Pollos/microbiología , Suplementos Dietéticos , Huevos/análisis , Femenino , Tracto Gastrointestinal/microbiología , Probióticos/administración & dosificación
4.
QJM ; 103(1): 33-40, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19864348

RESUMEN

BACKGROUND: A past history of low trauma fracture is a strong risk factor for future fractures in postmenopausal women and national guidance recommends treatment in the majority of such women AIM: To establish the prevalence of bone protective therapy use in postmenopausal women with a history of low trauma fracture Design and METHODS: Clinical audit of 1641 postmenopausal women presenting with a low trauma fracture to the Fracture Liaison Service at Addenbrooke's Hospital, Cambridge between January 2006 and December 2007. RESULTS: A total of 526 (31%) women presenting with a fracture had a past history of fracture, defined as a low trauma fracture after the age of 45 years. The wrist was the most common site of previous fracture, followed by hip, hand or foot, lower leg and humerus. Of these women, only 27.6% were receiving bone protective therapy with a bisphosphonate (89%) or other medication. Calcium and vitamin D supplements were received by 35.6%. The highest rates of treatment were seen for spine and hip fracture (61.9 and 49.3%, respectively). Only 45.1% of women aged 75 years and over with a previous history of fracture were receiving bone protective therapy. CONCLUSION: The results of our audit demonstrate low rates of treatment in postmenopausal women with a history of low trauma fracture. Better education of healthcare professionals, more consistent recording of fractures in primary care and the use of clearly defined care pathways that involve patients and their carers provide rational approaches to reducing this care gap.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Fracturas Óseas/prevención & control , Osteoporosis Posmenopáusica/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Densidad Ósea , Calcio/uso terapéutico , Suplementos Dietéticos , Inglaterra/epidemiología , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Vitamina D/uso terapéutico
6.
Arch Environ Contam Toxicol ; 53(3): 365-70, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17571202

RESUMEN

The purpose of the current study was to evaluate the role of visible light during trophic transfer of the essential metalloid, selenium (Se) from sediments by way of the microalgae Phaeodactylum tricornutum to bivalves. Initial experiments compared uptake of Se with algal cell number after deposit-feeding (Tellina deltoidalis) and filter-feeding (Soletellina alba) bivalves were exposed for 12 days under 16:8 h light:dark and 24-hour dark regimes to sediments amended with Se (17 mg/kg dry weight). Comparisons of filter-feeding with deposit-feeding organisms indicated >2-fold higher body burdens in the deposit-feeding organisms after 12 days. Darkness failed to significantly and consistently diminish algal cell densities. However, general trends indicated a decrease of pelagic algal numbers in +Se/dark treatments during the 12-day exposure. To determine whether time-dependent patterns were present in the uptake of Se by the deposit-feeding species, a second experiment was conducted using Se-laden sediments under light and dark conditions. Algal cell counts were measured and Se concentrations determined in animals sampled at days 0, 3, 6, 9, and 12. Deposit-feeding animals maintained in the dark accumulated, Se more rapidly than animals on light to dark cycles until 12 days at which time no significant differences were observed between treatments. Concentrations of Se in tissues of deposit-feeding bivalves were not directly related to algal cell density in lighted or dark chambers. These results indicate that pelagic microalgae may only play a key role in Se uptake during early hours of exposure, and feeding behavior may be a more important factor in deposite-feeding bivalves.


Asunto(s)
Bivalvos/metabolismo , Sedimentos Geológicos/química , Luz , Selenio/farmacocinética , Animales , Eucariontes/metabolismo , Conducta Alimentaria
7.
J Dairy Sci ; 90(6): 2705-9, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17517709

RESUMEN

Low methoxyl (LM) pectin was combined with 3-kDa molecular weight cut-off permeates from milk subjected to pH 6.7 to 5 and 7 degrees C or 40 degrees C with the objective of studying the effect of solubilized micellar calcium on viscoelastic properties of LM-pectin-milk mixes. Lowering the pH of skim milk with hydrochloric acid during ultrafiltration gradually promoted permeates to exhibit gel-like behavior when combined with LM-pectin. The onset of the gel-like behavior (G' > 1) occurred at a higher pH when permeates were obtained from milk filtered at 7 degrees C compared with 40 degrees C. As pH value during ultrafiltration approached 5 and regardless of temperature, G' for permeate-pectin mixes approached the same values (approximately 70 Pa) as G' for skim milk-pectin mixes. In all cases G' was highly correlated with free calcium concentration (r > 0.95). The gradual acidification of skim milk-LM-pectin using glucono-delta-lactone, promoted a sharp increase in storage modulus as pH approached 5.2 and a maximum G' increment (DeltaG') at pH approximately 4.9. From pH 4.9 to 4, G' continued to increase but at smaller increments. It was concluded that LM-pectin-casein micelle interaction in milk is a 2-step process: 1) solubilized micellar calcium dependent pectin-pectin interaction as pH approaches 5.0 to 4.9, and 2) pectin-casein micelle interaction in the 5.0-4.9 to 4.0 pH range.


Asunto(s)
Calcio/química , Manipulación de Alimentos/métodos , Concentración de Iones de Hidrógeno , Leche/química , Pectinas/química , Animales , Tecnología de Alimentos , Geles , Calor , Micelas , Peso Molecular , Tamaño de la Partícula , Solubilidad , Viscosidad
8.
Int J Obstet Anesth ; 16(1): 17-21, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17125997

RESUMEN

BACKGROUND: This double-blind randomised controlled trial investigated the most appropriate dose of intrathecal diamorphine to use with high-dose diclofenac as part of a multimodal analgesic regimen for caesarean section under subarachnoid block. We also wished to establish whether it was possible to satisfy the Royal College of Anaesthetists postoperative pain audit recommendation for this patient group. METHODS: One hundred and twenty patients presenting for elective caesarean section under subarachnoid block were recruited and divided into four groups. Treatment was standard except that patients were given either placebo or one of three different doses of intrathecal diamorphine (100 microg, 200 microg or 300 microg). All patients were given regular paracetamol, high-dose diclofenac and an hourly subcutaneous diamorphine regimen for breakthrough pain. RESULTS: There was a dose-dependent improvement in analgesia with intrathecal diamorphine. Only 37.9% of patients given 300 microg of intrathecal diamorphine had a visual analogue pain score of 3/10 or less throughout the study. There was a dose-dependent increase in the incidence of itching with intrathecal diamorphine although the incidence of nausea and vomiting was similar between groups. CONCLUSIONS: We found that for elective caesarean section under subarachnoid block with high dose diclofenac, analgesia was optimal with 300 microg of intrathecal diamorphine. Even the highest dose of intrathecal diamorphine did not achieve the Royal College of Anaesthetists postoperative audit target that 90% of patients should have a pain score of no more than 3/10. We believe that this target is too arduous.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Anestesia Raquidea/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificación , Cesárea , Diclofenaco/administración & dosificación , Heroína/administración & dosificación , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Interacciones Farmacológicas , Femenino , Humanos , Irlanda , Auditoría Médica/normas , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Náusea y Vómito Posoperatorios/etiología , Náusea y Vómito Posoperatorios/prevención & control , Embarazo , Prurito/etiología , Prurito/prevención & control
9.
J Urol ; 176(4 Pt 2): 1816-20; discussion 1820, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16945657

RESUMEN

PURPOSE: We reviewed our experience with continent catheterizable channels with interest in the timing of conduit related complications. MATERIALS AND METHODS: A retrospective review was performed of the outcome of continent catheterizable channels in all patients between 1998 and 2003 who had undergone construction of an antegrade continence enema and/or a Mitrofanoff procedure using appendix, small bowel or continent cutaneous vesicostomy. We performed a total of 117 such stomas in 37 male and 41 female patients 2.5 to 20 years old (mean age 8.9). For the antegrade continence enema we used appendix in 92% of cases, an ileal Yang-Monti tube in 6% and a cecal tube in 2%. For the continent catheterizable channel we used appendix in 43% of cases, a Yang-Monti tube in 38% and continent cutaneous vesicostomy in 19%. RESULTS: Continence was achieved in 98% of patients. Followup was 6 to 71 months (mean 28.4). There were 27 channel related complications (23%). Stomal stenosis occurred in 7 antegrade continence enema procedures (14%) within 1 to 10 months (mean 6.2) and in 9 continent bladder channels (13%), including 5 continent cutaneous vesicostomies, within 1 to 24 months (mean 9.4) after surgery. False passages occurred in 5 antegrade continence enema procedures (10%) within 1 to 13 months (mean 3.6) and in 4 continent catheterizable channels (6%) within 1 to 13 months (mean 6.5) after surgery. Of patients with stomal stenosis 50% were treated with surgical revision, while the remainder was successfully treated with dilation. Most false passages were managed by catheter drainage alone. Reasons for revision were contained perforation, colovesical fistula and inability to catheterize. Patient noncompliance appeared to have a role in stomal stenosis. CONCLUSIONS: Continent catheterizable stomas help patients achieve bowel and bladder continence. Stomal incontinence after reconstruction is rare. In our experience most stoma related complications occurred in the first year after reconstruction. Experience with more patients and longer followup will help determine whether such problems continue to accumulate with time or whether continent stomas function well with time, particularly after the initial period of healing.


Asunto(s)
Cateterismo Urinario , Reservorios Urinarios Continentes , Adolescente , Adulto , Niño , Preescolar , Constricción Patológica , Femenino , Humanos , Masculino , Reoperación , Análisis de Supervivencia , Reservorios Urinarios Continentes/efectos adversos , Reservorios Urinarios Continentes/patología
10.
Phytomedicine ; 13(6): 452-6, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16716917

RESUMEN

Inhibition of leukotriene formation is one of the approaches to the treatment of asthma and other inflammatory diseases. We have investigated knipholone, isolated from the roots of Kniphofia foliosa, Hochst (Asphodelaceae), for inhibition of leukotriene biosynthesis in an ex vivo bioassay using activated human neutrophile granulocytes. Moreover, activities on 12-lipoxygenase from human platelets and cycloxygenase (COX)-1 and -2 from sheep cotyledons and seminal vesicles, respectively, have been evaluated. Knipholone was found to be a selective inhibitor of leukotriene metabolism in a human blood assay with an IC(50) value of 4.2microM. However, at a concentration of 10microg/ml, the compound showed weak inhibition of 12(S)-HETE production in human platelets and at a concentration of 50microM it produced no inhibition of COX-1 and -2. In our attempt to explain the mechanism of inhibition, we examined the antioxidant activity of knipholone using various in vitro assay systems including free radical scavenging, non-enzymatic lipid peroxidation, and metal chelation. Knipholone was found to be a weak dose-independent free radical scavenger and lipid peroxidation inhibitor, but not a metal chelator. Therefore, the leukotriene biosynthesis inhibitory effect of knipholone was evident by its ability either to inhibit the 5-lipoxygenase activating protein (FLAP) or as a competitive (non-redox) inhibitor of the enzyme. Cytotoxicity results also provided evidence that knipholone exhibits less toxicity for a mammalian host cell.


Asunto(s)
Antraquinonas/farmacología , Leucotrienos/biosíntesis , Magnoliopsida , Fitoterapia , Extractos Vegetales/farmacología , Animales , Artemia/efectos de los fármacos , Compuestos de Bifenilo , Depuradores de Radicales Libres/farmacología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Picratos/química , Placenta/efectos de los fármacos , Raíces de Plantas , Vesículas Seminales/efectos de los fármacos , Ovinos
11.
Spinal Cord ; 44(3): 143-51, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16130018

RESUMEN

OBJECTIVE: To determine the clinical efficacy of functional electrical therapy in the rehabilitation of grasping function for quadriplegics. STUDY DESIGN: Randomized intervention-versus-control trial. SETTING: Rehabilitation hospital for spinal cord injury in Toronto, Canada. METHODS: A total of 21 people with new spinal cord injuries ranging from C3 to C7 were randomly assigned to two groups: Control (N=9) and Intervention (N=12). The intervention was functional electrical therapy, which consisted of repetitive grasping exercises using a neuroprosthesis that applied surface electrical stimulation to the arm to generate and/or assist grasping movements. It was applied by registered Occupational Therapists in a clinical setting. Main outcome measures were: Functional Independence Measure (FIM), Spinal Cord Independence Measure (SCIM), and the Rehabilitation Engineering Laboratory Hand Function Test. Consumer perceptions of functional electrical therapy were assessed via qualitative interviews. RESULTS: Differences between the Control and Intervention groups could be observed although they are not significant due to an insufficient number of participants. Consumer perceptions were positive, including improved Activities of Daily Living and self-satisfaction. CONCLUSION: Functional electrical therapy has the potential to be an effective treatment modality to restore grasping function in quadriplegia. It can be implemented by occupational therapists in a clinical setting. Further research is required to establish suitable indications for participant selection. In addition, a larger number of participants is needed to demonstrate statistical significance of the Functional Electrical Therapy.


Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Fuerza de la Mano/fisiología , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Adolescente , Adulto , Anciano , Evaluación de la Discapacidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Ocupacional/métodos , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento
12.
Arch Virol ; 150(1): 125-35, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15449140

RESUMEN

Degenerate primers were used to detect and amplify 3'-terminal genome fragments of potyviruses from medicinal aroid plants growing at 16 sites in China. Virus was detected in 7 samples of which six, all of Pinellia ternata, contained a strain of soybean mosaic virus (SMV) similar to that previously reported from this host in China. The complete sequence of one isolate and the P1 protein coding region of the other isolates were also sequenced. In all cases, the P1 proteins resembled isolates of Dasheen mosaic virus (DsMV) more closely than SMV, confirming earlier suggestions of recombination in this region. In a phylogenetic analysis of SMV, DsMV and related sequences, the aroid sequences of SMV formed a distinct group which also included a sequence published as Zantedeschia symptomless virus (AF469171). One of the P. ternata samples was also infected with a second potyvirus, the 3'-terminal sequence of which was similar to DsMV and to some sequences published as Vanilla mosaic virus. The seventh infected sample was Typhonium flagelliforme and the virus from it was identified from its sequence as zantedeschia mosaic virus (ZaMV), providing the first report of this virus from mainland China.


Asunto(s)
Plantas Medicinales/virología , Potyvirus/clasificación , Potyvirus/genética , China , Filogenia , Enfermedades de las Plantas/virología , Potyvirus/aislamiento & purificación , Potyvirus/metabolismo
13.
Arch Virol ; 149(3): 435-45, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14991435

RESUMEN

Degenerate primers for RT-PCR were designed and used to amplify genome fragments ( c. 750 nt in the coat protein-ORF6 region) of allexiviruses from a total of 28 garlic samples from 24 provinces in China. Many samples contained more than one distinct sequence. A total of 60 different sequences were obtained. Phylogenetic analysis and two-way comparisons were used to assess the status of the sequences and to re-examine the criteria for distinguishing species within the genus. Most of the sequences could be allocated to either Garlic virus D or Garlic virus X on the basis of sequence similarity but some appeared to be intermediate between existing species. There were no sequences of Garlic virus C or Shallot virus X. A comparison with the related genera Carlavirus, Foveavirus and Potexvirus suggests that the published allexivirus species demarcation criteria may have been drawn too tightly and should be re-examined.


Asunto(s)
Ajo/virología , Virus de Plantas/clasificación , Virus de Plantas/aislamiento & purificación , Virus ARN/clasificación , Virus ARN/aislamiento & purificación , China , Cartilla de ADN , ADN Complementario/genética , Datos de Secuencia Molecular , Filogenia , Enfermedades de las Plantas/virología , Virus de Plantas/genética , Virus ARN/genética , Análisis de Secuencia de ADN
14.
Arch Virol ; 148(6): 1165-73, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12756621

RESUMEN

The complete sequence of an isolate of Onion yellow dwarf virus (OYDV) from Yuhang, Zhejiang province, China, was determined. It was 10538 nts in length and was predicted to encode a polyprotein 3403 amino acids (aa) long with a calculated M(r) of 385.1 kDa. The predicted P3 protein (530 aa) was larger than that of any of the potyviruses sequenced to date (344-378 aa). The additional sequence occurs at the N-terminus of the protein, does not represent a duplication from elsewhere in the OYDV genome and could not be matched to any other sequences in the databases. Similar sequences were found in 4 other Chinese OYDV isolates. Phylogenetic analysis of the amino acid sequences of the polyprotein showed that OYDV is distantly related to Pea seed-borne mosaic virus and the potyviruses of grasses and cereals.


Asunto(s)
Cebollas/virología , Potyviridae/clasificación , Potyviridae/genética , Secuencia de Aminoácidos , China , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Análisis de Secuencia de ADN , Proteínas Virales/química , Proteínas Virales/genética
15.
Am J Physiol Heart Circ Physiol ; 283(2): H540-8, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12124199

RESUMEN

We used spontaneously hypertensive rats to study remodeling of cardiac bioenergetics associated with changes in blood pressure. Blood pressure was manipulated with aggressive antihypertensive treatment combining low dietary salt and the angiotensin-converting enzyme inhibitor enalapril. Successive cycles of 2 wk on, 2 wk off treatment led to rapid, reversible changes in left ventricular (LV) mass (30% change in <10 days). Despite changes in LV mass, specific activities of bioenergetic (cytochrome-c oxidase, citrate synthase, lactate dehydrogenase) and reactive oxygen species (ROS) (total cellular superoxide dismutase) enzymes were actively maintained within relatively narrow ranges regardless of treatment duration, organismal age, or transmural region. Although enalapril led to parallel declines in mitochondrial enzyme content and ventricular mass, total ventricular mtDNA content was unaffected. Altered enzymatic content occurred without significant changes in relevant mRNA and protein levels. Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2alpha) were also unchanged. In contrast, enalapril-mediated ventricular and mitochondrial remodeling was accompanied by a twofold increase in specific activity of catalase, an indicator of oxidative stress, suggesting that rapid cardiac adaptation is accompanied by tight regulation of mitochondrial enzyme activities and increased ROS production.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enalapril/uso terapéutico , Metabolismo Energético/fisiología , Hipertensión/tratamiento farmacológico , Ratas Endogámicas SHR/fisiología , Remodelación Ventricular , Animales , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Miocardio/enzimología , Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
16.
J Natl Cancer Inst ; 93(24): 1879-85, 2001 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-11752013

RESUMEN

BACKGROUND: Hypoxia in tumors is associated with malignant progression, metastatic spread, and increased resistance to radiotherapy and chemotherapy. Molecular O(2) is required for the cellular production of nitric oxide (NO) by the enzyme NO synthase (NOS), and NO may block components of the adaptive response to hypoxia. Hence, we hypothesized that hypoxia increases drug resistance in tumor cells by inhibiting endogenous NO production. METHODS: Human breast carcinoma (MDA-MB-231) and mouse melanoma (B16F10) cells were pre-exposed to 20% O(2), 5% O(2), or 1% O(2), incubated with a pharmacologic inhibitor of endogenous NO production, and then treated with chemotherapeutic agents. Resistance was assessed by colony-formation assays, and western blot analysis was used to measure NOS protein levels. All P values were two-sided. RESULTS: Incubation of MDA-MB-231 tumor cells in 1% O(2) maximally increased their resistance to doxorubicin and 5-fluorouracil by 8.5-fold (P =.002) and 2.3-fold (P =.002), respectively, compared with incubation in 20% O(2). B16F10 mouse melanoma cells preincubated in 1% O(2) (versus 20% O(2)) for 12 hours exhibited a twofold increase in resistance to doxorubicin (P<.001). The rapid acquisition of drug resistance after exposure to 1% O(2) could be mimicked by incubating the MDA-MB-231 cells for 12 hours with the NOS inhibitor N(G)-monomethyl-Larginine (fivefold increase; P<.001). Conversely, replacement of NO activity by use of the NO-mimetic glyceryl trinitrate (GTN) and diethylenetriamine NO adduct produced statistically significant attenuations in the development of resistance of 59% (P<.001) and 40% (P<.001), respectively, in MDA-MB-231 cells. Treatment of B16F10 cells with GTN produced a 58% reduction in resistance (P<.001). MDA-MB-231 cells expressed all three isoforms of the NOS enzyme at levels that were not altered by exposure to hypoxia. CONCLUSIONS: NO mediates chemosensitivity in tumor cells, and hypoxia-induced drug resistance appears to result, in part, from downstream suppression of endogenous NO production. These results raise the possibility that administration of small doses of NO mimetics could be used as an adjuvant in chemotherapy.


Asunto(s)
Hipoxia , Neoplasias/tratamiento farmacológico , Óxido Nítrico/metabolismo , Oxígeno/metabolismo , Animales , Antimetabolitos Antineoplásicos/farmacología , Antineoplásicos/farmacología , Western Blotting , Ciclo Celular , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Citometría de Flujo , Fluorouracilo/farmacología , Humanos , Melanoma Experimental , Ratones , Óxido Nítrico Sintasa/metabolismo , Fenotipo , Factores de Tiempo , Células Tumorales Cultivadas , omega-N-Metilarginina/farmacología
17.
Arch Virol ; 146(10): 1841-53, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11722009

RESUMEN

Degenerate primers were used to detect and amplify cDNA of viruses of the genera Carlavirus, Allexivirus and Potyvirus from garlic plants with mosaic symptoms growing in Zhejiang province, China. Plants contained a complex mixture of viruses and strains. Three distinct stains of Garlic latent virus were detected; the most frequent one was completely sequenced and partial sequences were obtained for the other two. The complete sequence (8363 nt) was 76.4% identical to a Korean isolate. Two allexiviruses were detected and completely sequenced. One (8319 nt) was identified as Garlic virus X and comparisons showed that a published Korean isolate (which had 90.2% identical nucleotides) had an N-terminal deletion in the serine-rich ORF4. The other isolate (8451 nt), tentatively named Garlic virus E, appeared to be a new member of the genus. Phylogenetic analyses of the different viral proteins and distinctive conserved sequence motifs within the genus are discussed. This is the first report of allexiviruses from China. Using potyvirus primers, three distinct isolates of Onion yellow dwarf virus and one of Leek yellow stripe virus were detected and the 3'-terminal sequences of their genomes were determined. In a coat protein phylogenetic analysis, the new isolates were most closely related to other published isolates from Japan and China.


Asunto(s)
Carlavirus/genética , ADN Complementario/química , Ajo/virología , Potyvirus/genética , Secuencia de Aminoácidos , Secuencia de Bases , Sistemas de Lectura Abierta , Filogenia
18.
Invest Radiol ; 36(7): 401-12, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11496095

RESUMEN

RATIONALE AND OBJECTIVES: A series of preclinical tests were undertaken during the developmental process to determine the safety profile of gadoversetamide injection (OptiMARK). METHODS: Acute intravenous, acute intracisternal, and repeated-dose toxicities; cardiovascular effects; and genetic and reproductive toxicology characteristics were assessed in several animal species. RESULTS: Gadoversetamide injection demonstrated an acute intravenous median lethal dose of 25 to 28 mmol/kg and a maximum nonlethal dose of 14 mmol/kg in mice. In the dog, acute administration of gadoversetamide injection showed a no observable effect level at 3 mmol/kg. Dosed daily for 4 weeks, gadoversetamide injection (0.1 mmol x kg(-1) x d(-1)) caused no serious irreversible changes in any organs in rats and dogs. At a dose of 0.1 mmol/kg, gadoversetamide injection caused no significant (P < 0.05) changes in cardiovascular function in anesthetized dogs. Gadoversetamide injection showed no mutagenic activity. Fertility, reproductive performance, and postnatal fetal development were not affected at doses up to 0.5 mmol x kg(-1) x d(-1) in the rat. No teratogenicity was observed at doses up to 4.2 mmol x kg(-1) x d(-1) in the rat and up to 1.6 mmol x kg(-1) x d(-1) in the rabbit. CONCLUSIONS: Data from our toxicological assessment demonstrate the safety of gadoversetamide injection in a number of animal species at doses exceeding the intended human clinical dose.


Asunto(s)
Medios de Contraste/toxicidad , Compuestos Organometálicos/toxicidad , Anomalías Inducidas por Medicamentos , Animales , Células Sanguíneas , Sistema Cardiovascular/efectos de los fármacos , Medios de Contraste/administración & dosificación , Perros , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Fertilidad/efectos de los fármacos , Feto/efectos de los fármacos , Inyecciones Intravenosas , Dosificación Letal Mediana , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos ICR , Mutagénesis/efectos de los fármacos , Mutagénesis/genética , Compuestos Organometálicos/administración & dosificación , Embarazo , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad
19.
Reproduction ; 122(2): 195-204, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11467970

RESUMEN

A range of pathophysiological factors can result in a perturbation or restriction of fetal growth, and the cardiovascular, neuroendocrine and metabolic adaptations of the fetus to these stimuli will depend on their nature, timing and intensity. The critical importance of these physiological adaptations for both immediate survival and long-term health outcomes has provided an impetus for experimental studies of the nature and consequences of specific fetal adaptations to a poor intrauterine environment. This review summarizes data from recent studies that have focused on the responses of the fetal cardiovascular, sympathoadrenal, hypothalamo-pituitary-adrenal and renin-angiotensin systems to experimental restriction of placental function in the sheep and discusses the consequences of these adaptations for fetal, neonatal and adult health.


Asunto(s)
Adaptación Fisiológica , Retardo del Crecimiento Fetal/fisiopatología , Glándulas Suprarrenales/embriología , Animales , Sistema Cardiovascular/embriología , Femenino , Retardo del Crecimiento Fetal/complicaciones , Glucocorticoides/fisiología , Humanos , Hipotálamo/embriología , Hipófisis/embriología , Placenta/fisiopatología , Embarazo , Sistema Renina-Angiotensina/fisiología , Sistema Nervioso Simpático/embriología
20.
Arch Virol ; 146(4): 757-66, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11402861

RESUMEN

A universal primer (Sprimer: 5'-GGX AAY AAY AGY GGX CAZ CC-3', X = A, G, C or T; Y = T or C; Z = A or G), designed from the consensus sequences that code for the conserved sequence GNNSGQP in the NIb region of members of the family Potyviridae, was used to amplify by RT-PCR the 3'-terminal genome regions from infected plant samples representing 21 different viruses in the family. Sequencing of some of the fragments (c. 1.7 kb) showed that the type strain (ATTC PV-107) of Oat necrotic mottle virus is not a distinct species in the genus Rymovirus, but is synonymous with Brome streak mosaic virus (genus Tritimovirus) and that Celery mosaic virus is a distinct member of the genus Potyvirus not closely related to any other sequenced species. Potyviruses infecting crops in China were also investigated, showing that viruses on cowpea and maize in Hangzhou, Zhejiang province were respectively Bean common mosaic virus and Sugarcane mosaic virus and that one on garlic in Nanjing, Jiangsu province was Onion yellow dwarf virus. Fragments were also sequenced from Chinese isolates of Lettuce mosaic virus and Soybean mosaic virus (from Hangzhou), Turnip mosaic virus (2 different isolates from Zhejiang province) and RNA1 of Wheat yellow mosaic virus (from Rongcheng, Shandong province).


Asunto(s)
Enfermedades de las Plantas/virología , Potyviridae/clasificación , Potyviridae/genética , ARN Viral/genética , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Apiaceae/virología , Avena/virología , China , Secuencia de Consenso , Ajo/virología , Virus del Mosaico/genética , Virus del Mosaico/aislamiento & purificación , Filogenia , Plantas Medicinales , Potyviridae/aislamiento & purificación , Potyvirus/genética , Potyvirus/aislamiento & purificación , Zea mays/virología
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