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1.
Theriogenology ; 172: 307-314, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34311222

RESUMEN

Two studies were conducted to evaluate the effects of trace mineral supplementation on traditional and novel measures of bull fertility. In Experiment 1, 37 mature bulls received one of three dietary supplements daily for 71 d: 1) Supplement without Cu, Zn, and Mn (CON); 2) Supplement with Cu, Zn, and Mn sulfate (SULF); and 3) Supplement with basic Cu chloride, and Zn and Mn hydroxychloride (CHLR). In Experiment 2, 128 Angus or Angus-Hereford bull calves were maintained on a growing diet for 75 d (year 1) or 119 d (year 2) in Calan gate equipped pens without mineral supplementation. Bulls (n = 32 head/treatment) received one of four trace mineral supplements daily for 84 d: 1) Zn with no Cu (ZN), 2) Cu with no Zn (CU), 3) Cu and Zn (ZNCU), or 4) no Cu or Zn (CON). Bull fertility measures included a breeding soundness evaluation (BSE) and novel fertility measures conducted using flow cytometry. In mature bulls, final liver Zn concentration was positively correlated (P = 0.02) with sperm concentration (r = 0.31) and tended (P = 0.06) to be negatively correlated with acrosome damage (r = -0.39). Peripubertal bulls receiving ZNCU had greater ADG than bulls in the CU group (P = 0.05). Each BSE and novel fertility component improved from Day 0-84 in peripubertal bulls and were not affected (P > 0.10) by mineral supplementation. Bulls that received no supplement (CON) had greater (P < 0.01) percentage of sperm with distal midpiece reflex (6.9 vs 4.0% for CON and TM supplement, respectively) and Dag or Dag-like defect (2.6 vs 1.4% for CON and TM supplement, respectively) in their ejaculates. Sperm viability after 30 min of incubation were not affected by trace mineral supplementation, but after 3 h incubation, sperm viability tended to differ (P = 0.06) between treatments and tended to be less for CON bulls (48.5%) compared to ZNCU bulls (55.1%). Among contrast comparisons, trace mineral supplemented bulls had greater (P < 0.05) percentage of viable sperm at 3 h post collection and reactive oxygen resistant sperm than CON bulls. Addition of Zn to trace mineral containing Cu (ZNCU) improved (P < 0.05) percentage of sperm in the ejaculate with high mitochondrial energy potential and viable sperm with intact acrosome membrane. In summary, it appears the homeostasis mechanisms for bull trace mineral maintenance are extremely efficient and mineral supplementation of mature and peripubertal bulls did not have major improvements in any laboratory or chute-side measures of bull fertility, however bulls exposed to breeding or in environments with diet antagonists might respond differently.


Asunto(s)
Oligoelementos , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bovinos , Suplementos Dietéticos , Fertilidad , Masculino , Oligoelementos/farmacología , Zinc/farmacología
2.
Diabet Med ; 31(9): 1069-77, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24867069

RESUMEN

AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.


Asunto(s)
Arginina/administración & dosificación , Pie Diabético/fisiopatología , Suplementos Dietéticos , Glutamina/administración & dosificación , Valeratos/administración & dosificación , Cicatrización de Heridas , Adulto , Anciano , Anciano de 80 o más Años , Índice Tobillo Braquial , Pie Diabético/dietoterapia , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
3.
Mol Vis ; 19: 1433-45, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23825923

RESUMEN

PURPOSE: Zinc oxide effectively reduces visual cell loss in rats exposed to intense visible light and is known to slow the rate of disease progression in advanced stages of age-related macular degeneration. Our goal was to determine the efficacy of zinc oxide in combination with novel and well-established antioxidants in an animal model of light-induced oxidative retinal damage. METHODS: One group of male Sprague-Dawley rats was pretreated with zinc oxide with or without a detergent extract of rosemary powder and then exposed to intense visible light for 4-24 h. Another group of animals received zinc oxide combined with rosemary oil diluted with a mixture of polyunsaturated fatty acids (ROPUFA) and a third group was given an antioxidant mineral mix containing zinc oxide, as recommended by the Age Related Eye Disease Study group's first clinical trial (AREDS1). Visual cell survival was determined 2 weeks after intense light treatment by measuring rhodopsin and photoreceptor cell DNA levels and confirmed by retinal histology and agarose gel electrophoresis of DNA. Western analysis was used to determine the effects of zinc and antioxidants on the oxidative stress markers, glial fibrillary acidic protein (GFAP), heme-oxygenase-1 (HO-1), and carboxyethylpyrrole (CEP). Rod and cone opsin and arrestin levels were used as markers of photoreceptor cell function. RESULTS: Dark-reared rats treated with 1.3 mg/kg zinc oxide and 17 mg/kg rosemary extract, or with one-half those doses, and exposed to moderate intensity green light retained 75%-85% of the rhodopsin and retinal DNA measured in unexposed rats. These levels were significantly higher than found for zinc oxide or rosemary treatment alone. Rosemary oil was also effective when combined with zinc oxide, but ROPUFA alone was no more effective than the detergent vehicle. Prolonged intense green light led to increases in retinal GFAP and HO-1 levels and to decreases in cone cell opsin and rod and cone arrestins. Rosemary plus zinc treatment reduced the expression of oxidative stress protein markers and enhanced visual cell survival, as shown by improved photoreceptor cell morphology and by decreased retinal DNA degradation. Using higher intensity white light for exposures in cyclic light-reared rats, treatment with an AREDS antioxidant/mineral mixture was found to be ineffective, whereas rosemary extract plus an equivalent dose of zinc oxide was significantly more effective in preserving visual cells. CEP protein adduct formation was reduced by all antioxidant treatments, but rosemary plus zinc oxide also prevented the loss of cone cell opsin and arrestin more effectively than AREDS. CONCLUSIONS: In the rat model of acute retinal light damage, zinc oxide combined with a detergent extract of rosemary powder or rosemary oil is more effective than treatment with either component alone and significantly more effective than an AREDS mixture containing a comparable dose of zinc oxide. Light-induced oxidative stress in animal models of retinal degeneration can be a useful preclinical paradigm for screening novel antioxidants and for testing potential therapeutics designed to slow the progression of age-related ocular disease.


Asunto(s)
Extractos Vegetales/farmacología , Retina/efectos de los fármacos , Retina/patología , Rosmarinus/química , Óxido de Zinc/farmacología , Animales , Western Blotting , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Electroforesis en Gel de Poliacrilamida , Ácidos Grasos Insaturados/farmacología , Masculino , Aceites Volátiles/farmacología , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-Dawley , Retina/efectos de la radiación
4.
Zoo Biol ; 30(5): 523-31, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20954252

RESUMEN

In response to new recommendations for feeding giraffe in zoos, giraffe (n = 6) were transitioned from a typical hoofstock diet to diets containing reduced starch, protein, Ca and P and added n3 fatty acids. This diet was fed as a 50:50 mix with alfalfa and grass hay. Over the next 4 years, serum Ca, P, and fatty acids were measured every 6 months (summer and winter). Serum Ca was not affected by season (P = 0.67) or by diet (P = 0.12). Serum P was not affected season (P = 0.14), but was reduced by diet (P<0.01), and serum Ca:P was also increased by diet (P<0.01). The ratio of serum Ca:P tended to be affected by season (P = 0.07), in which animals tended to have greater Ca:P during the summer vs. the winter. The diet transition resulted in reduced serum saturated fatty acids (including lauric, myristic, palmitic, arachidic, and behenic acids), and increases in n6 fatty acids (including linolenic and arachidonic acids) and n3 fatty acids (docosahexaenoic acid) (P<0.05 for each). Overall, this diet transition resulted in blood nutrient profiles that more closely match that of values found in free-ranging giraffe.


Asunto(s)
Antílopes/sangre , Calcio/sangre , Dieta/veterinaria , Ácidos Grasos/sangre , Fósforo/sangre , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Animales de Zoológico , Femenino , Masculino
5.
Regul Toxicol Pharmacol ; 53(2): 107-20, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19027814

RESUMEN

In response to a Hazard Notice by the Medical Devices Agency of the UK in 2000 regarding the Trilucent breast implant (TBI), an expert panel was convened to implement a research program to determine whether genotoxic compounds were formed in the soybean oil filler (SOF) of TBIs and whether these could be released to produce local or systemic genotoxicity. The panel established a research program involving six laboratories. The program recruited 47 patients who had received TBIs (9 patients had received silicone implants previously). A reference group (REBI) of 34 patients who had exchanged either silicone (17 patients) implants (REBI-E) or patients (17) who were to receive primary implantation augmentation with silicone (REBI-PIA), and who were included as needed to increase either the pre- or post-explantation sample number. Of the 17 REBI-E patients, 5 had silicone implants and 12 had saline implants previously (prior to the last exchange). Investigation was undertaken before and after replacement surgery in the TBI patients and before and after replacement or augmentation surgery in the REBI patients. The pre- to post-operative sample interval was 8-12 weeks. Pre-operative samples were collected within 7 days prior to the operation. Information on a variety of demographic and behavioral features was collected. Biochemical and biological endpoints relating to genotoxic lipid peroxidation (LPO) products potentially formed in the SOF, and released locally or distributed systemically, were measured. The SOF of explanted TBIs was found to have substantial levels of LPO products, particularly malondialdehyde (MDA), and low levels of trans-4-hydroxy-2-nonenal (HNE) not found in unused implants. Mutagenicity of the SOF was related to the levels of MDA. Capsules that formed around TBIs were microscopically similar to those of reference implants, but MDA-DNA adducts were observed in capsular macrophages and fibroblasts of only TBI capsules. These cell types are not progenitors of breast carcinoma (BCa) and the location of the implants precludes LPO products reaching the mammary epithelial cells which are progenitors of BCa. Blood levels of LPO products were not increased in TBI patients compared to REBI patients and did not change with explantation. In TBI patients, white blood cells did not show evidence of increased levels of LPO-related aldehyde DNA adducts. In conclusion, based on a number of measured parameters, there was no evident effect that would contribute to breast or systemic cancer risk in the TBI patients, and the recommended treatment of TBI patients involving explantation was judged appropriate.


Asunto(s)
Implantes de Mama/efectos adversos , Peroxidación de Lípido , Pruebas de Mutagenicidad , Aceite de Soja/efectos adversos , Adulto , Aldehídos/metabolismo , Remoción de Dispositivos , Femenino , Fibroblastos/metabolismo , Humanos , Macrófagos/metabolismo , Malondialdehído/metabolismo , Persona de Mediana Edad , Falla de Prótesis , Geles de Silicona , Cloruro de Sodio/química
6.
Diabetes Metab Res Rev ; 24 Suppl 1: S119-44, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18442185

RESUMEN

The outcome of management of diabetic foot ulcers is poor and there is uncertainty concerning optimal approaches to management. We have undertaken a systematic review to identify interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection; hyperbaric oxygen (HBO); reduction of tissue oedema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic (HBO) therapy may be effective. Topical negative pressure (TNP) may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. More information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. Further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.


Asunto(s)
Pie Diabético/terapia , Úlcera del Pie/terapia , Cicatrización de Heridas , Antiinfecciosos/uso terapéutico , Vendajes , Enfermedad Crónica , Desbridamiento , Pie Diabético/tratamiento farmacológico , Pie Diabético/cirugía , Edema/prevención & control , Úlcera del Pie/tratamiento farmacológico , Úlcera del Pie/cirugía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica , Trasplante de Piel , Resultado del Tratamiento
7.
J Paediatr Child Health ; 41(12): 663-8, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16398871

RESUMEN

OBJECTIVES: Vitamin A and E deficiency is common in cystic fibrosis (CF). These vitamins have immunomodulating properties and we determined whether decreased serum vitamin A and E levels in young infants are associated with early CF lung disease and lower airway inflammation. METHODS: A post-hoc analysis was undertaken on previous data collected prospectively in 39 newly diagnosed infants identified by a newborn CF screening programme. Assessment of CF genotype, nutrition, pancreatic status, serum retinol and alpha-tocopherol levels was performed at diagnosis. Pulmonary status was determined clinically, by Brasfield chest radiographic scores and analysis of bacterial counts and inflammatory indices in bronchial lavage (BL) fluid. These assessments were repeated 12 months later. RESULTS: At diagnosis, 20 out of 39 (51%) CF infants had low serum retinol (mean (SD) 0.7 (0.3) micromol/L) and 9/38 (24%) had low alpha-tocopherol (mean (SD) 13.4 (8.4) micromol/L) levels. Dietary energy intake was related to serum retinol concentrations at diagnosis (r(2) = 0.27; P = 0.001). At 1 year, serum retinol and alpha-tocopherol levels had normalized following vitamin A and E supplementation. Respiratory symptoms, radiographic scores and BL inflammatory indices systematically deteriorated during infancy, reaching significance for free neutrophil elastase activity (9 out of 29 vs 21 out of 33; P = 0.01) and IL-8 levels (79 vs 416; P = 0.046) in BL fluid. No association was seen between serum vitamin levels at diagnosis and airway inflammatory indices at either diagnosis or 12 months later. CONCLUSION: We found in this CF birth cohort no evidence to implicate vitamin A or E deficiency in the development of lung disease or airway inflammation during infancy.


Asunto(s)
Fibrosis Quística/complicaciones , Enfermedades Pulmonares/etiología , Deficiencia de Vitamina A/complicaciones , Deficiencia de Vitamina E/complicaciones , Estudios Transversales , Fibrosis Quística/diagnóstico , Ingestión de Energía , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades Pulmonares/diagnóstico , Masculino , Tamizaje Neonatal , Vitamina A/sangre , alfa-Tocoferol/sangre
8.
Arch Phys Med Rehabil ; 82(6): 721-5, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11387573

RESUMEN

OBJECTIVE: To evaluate high-voltage, pulse-galvanic electric stimulation as an adjunct to healing diabetic foot ulcers. DESIGN: Randomized, double-blind, placebo-controlled pilot trial. SETTING: University medical center. PATIENTS: Forty patients with diabetic foot ulcers, consecutively sampled. Twenty patients each assigned to treatment and placebo groups. Five patients (2 treated, 3 placebo) withdrew because of severe infection. INTERVENTIONS: Electric stimulation through a microcomputer every night for 8 hours. The placebo group used identical functioning units that delivered no current. Additional wound care consisted of weekly débridements, topical hydrogel, and off-loading with removable cast walkers. Patients were followed for 12 weeks or until healing, whichever occurred first. MAIN OUTCOME MEASURES: Proportion of wounds that healed during the study period. Compliance with use of device (in hr/wk), rate of wound healing, and time until healing. RESULTS: Sixty-five percent of the patients healed in the group treated with stimulation, whereas 35% healed with placebo (p = .058). After stratification by compliance, a significant difference was identified among compliant patients in the treatment group (71% healed), noncompliant patients in the treatment group (50% healed), compliant patients in the placebo group (39% healed), and noncompliant patients in the placebo group (29% healed, linear-by-linear association = 4.32, p = .038). There was no significant difference in compliance between the 2 groups. CONCLUSION: Electric simulation enhances wound healing when used in conjunction with appropriate off-loading and local wound care.


Asunto(s)
Pie Diabético/terapia , Terapia por Estimulación Eléctrica , Método Doble Ciego , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Proyectos Piloto , Análisis de Supervivencia , Factores de Tiempo , Cicatrización de Heridas
9.
Antimicrob Agents Chemother ; 45(7): 2129-33, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11408236

RESUMEN

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of Candida spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349 Candida isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS. Candida albicans was the predominant species (67.3%); among 114 non-albicans Candida spp., C. glabrata (45.6%) was the most frequent, followed by C. tropicalis (18.4%), C. parapsilosis (16.6%), and C. krusei (9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of C. albicans strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of C. glabrata strains were resistant to fluconazole (MIC > or = 64 microg/ml) and itraconazole (MIC > or = 1 microg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant C. albicans (P = 0.005, OR 36), although this relationship was not seen in C. glabrata isolates (P = 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Neoplasias/microbiología , Candida/clasificación , Candida/aislamiento & purificación , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos
10.
J Dairy Sci ; 84(4): 917-28, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11352168

RESUMEN

In this study, we evaluated the effects of dietary supplementation at two stages of lactation with various levels of Mepron85 (M85) and M85 plus DL-methionine (DL-Met) on milk production and composition of Holstein and Brown Swiss cows fed an alfalfa-hay and corn grain-based diet. In experiment 1, control diets were formulated to supplement, in early lactation [days in milk (DIM) = 73.2], concentrations of metabolizable methionine at 104% of the estimated requirements based on the Cornell Net Carbohydrate and Protein System. Treatment groups were fed the control diet plus 10, 20, or 30 g/d of M85 at 116, 128, or 139% of the estimated requirements for metabolizable methionine. The supplementation with 10 g/d in Brown Swiss and 30 g/d of M85 in Holstein cows increased milk yields and fat percentage, but had no effects on protein percentage. These data suggested that the estimated postruminal supply of metabolizable methionine in the control ration was limiting for maximum milk fat synthesis. Conversely, in experiment 2, the cosupplementation with M85 (15 g/d) plus DL-Met (15 g/d) to cows in midlactation (DIM = 140.5) did not influence fat percentage, but increased protein yield and percentage (+0.1%) in both Holstein and Brown Swiss, and lactose percentage (+0.18%) in Holstein cows. The supplementation with 15 g/d of M85 reduced milk and protein yields, whereas 15 g/d of DL-Met reduced protein percentage in four of the five experimental weeks for Holstein cows. We conclude that supplementation with M85, alone or in combination with DL-Met, may be used to influence milk composition, but these effects are influenced by dosage and type of supplemental methionine, breed, and stage of lactation.


Asunto(s)
Bovinos/fisiología , Lactancia/efectos de los fármacos , Metionina/farmacología , Leche/química , Animales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Lactancia/fisiología , Lactosa/análisis , Medicago sativa , Metionina/análisis , Proteínas de la Leche/análisis , Factores de Tiempo
11.
FEMS Microbiol Lett ; 194(1): 33-7, 2001 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-11150662

RESUMEN

Recent advances in high efficiency separation methods of bacteria allow their rapid identification and quantitation in some cases. A specific capillary electrophoresis (CE) technique is used to identify and quantitate Lactobacillus acidophilus in both pill and syrup health products as well as Bifidobacterium infantis in a powdered formula supplement. Cell viability can be evaluated as well. In some cases, both the living and dead bacterial cells as well as the molecular excipients can be evaluated in a single run.


Asunto(s)
Bifidobacterium/aislamiento & purificación , Suplementos Dietéticos/microbiología , Electroforesis Capilar , Alimentos Infantiles/microbiología , Lactobacillus acidophilus/aislamiento & purificación , Técnicas Bacteriológicas/métodos , Bifidobacterium/clasificación , Bifidobacterium/crecimiento & desarrollo , Microbiología de Alimentos , Humanos , Recién Nacido , Lactobacillus acidophilus/clasificación , Lactobacillus acidophilus/crecimiento & desarrollo , Polvos , Comprimidos
12.
Biol Blood Marrow Transplant ; 6(3A): 335-43, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10905771

RESUMEN

We conducted the first phase 2 and pharmacologic study to evaluate the combination of novobiocin (a coumeromycin antibiotic that has been shown to augment alkylating agent cytotoxicity in experimental models) and high-dose cyclophosphamide and thiotepa followed by autologous marrow support in women with chemosensitive advanced breast cancer. Its aims were (1) to determine progression-free survival (PFS) and overall survival (OS), (2) to evaluate the pharmacokinetics of cyclophosphamide and thiotepa, and (3) to measure the ability of novobiocin to reverse alkylator drug resistance in vitro. Forty-one women with chemotherapy-responsive advanced breast cancer received cyclophosphamide (4 g/m2) for peripheral blood stem cell mobilization (treatment 1) followed by high-dose cyclophosphamide (1.5 g/m2 per day for 4 days), thiotepa (200 mg/m2 per day for 4 days), and novobiocin (4 g/day orally for 7 days) (treatment 2) and autologous marrow support. The median PFS was 10 months (range, 0.2-70.6 months) and OS, 21.5 months (range, 0.2-70.6 months). There was no statistically significant relationship between PFS or OS and area-under-the-curve values of cyclophosphamide, thiotepa, or 4-hydroxycyclophosphamide. Patient plasma samples (n = 12) obtained during novobiocin therapy were able to reverse alkylator drug resistance in an in vitro colony-forming assay. Correlative laboratory studies in an in vitro model system demonstrated that patient plasma after novobiocin treatment resulted in the magnitude of resistance reversal that had been predicted by prior preclinical experiments. Clinically, however, this activity of novobiocin did not translate into a substantial increase in PFS or OS compared with historical controls treated with high-dose alkylator therapy alone.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Novobiocina/administración & dosificación , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/farmacología , Área Bajo la Curva , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/análogos & derivados , Ciclofosfamida/metabolismo , Ciclofosfamida/farmacocinética , Ciclofosfamida/farmacología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Sinergismo Farmacológico , Femenino , Humanos , Persona de Mediana Edad , Novobiocina/farmacología , Análisis de Supervivencia , Tiotepa/administración & dosificación , Tiotepa/farmacocinética , Tiotepa/farmacología , Insuficiencia del Tratamiento , Células Tumorales Cultivadas , Ensayo de Tumor de Célula Madre
13.
Pediatr Neurol ; 22(4): 259-66, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10788742

RESUMEN

Severe autonomic dysfunction occurs in Rett syndrome (RS). Substance P, a tachykinin peptide that localizes to several brain regions, including the autonomic nervous system, is reduced in the cerebrospinal fluid of patients with RS. The anatomic localization and intensity of substance P immunoreactivity and glial fibrillary acidic protein-positive astrocytes in the brains of 14 patients with RS were compared with those in the brains of 10 age-matched normal patients. Substance P immunoreactivity expression was significantly decreased in RS tissue compared with control tissue in the following regions: dorsal horns, intermediolateral column of the spinal cord, spinal trigeminal tract, solitary tract and nucleus, parvocellular and pontine reticular nuclei, and locus ceruleus. A less significant decrease of substance P immunoreactivity occurred in the substantia nigra, central gray of the midbrain, frontal cortex, caudate, putamen, globus pallidus, and thalamus. Antiglial fibrillary acidic protein-positive astrocytes were increased in the areas in which substance P immunoreactivity was decreased and in other brain regions. Because many of the brain regions with the greatest decrease in substance P immunoreactivity are involved in the control of the autonomic nervous system, especially the solitary tracts and reticular formation, reduced substance P may contribute to the autonomic dysfunction in RS.


Asunto(s)
Química Encefálica , Encéfalo/patología , Síndrome de Rett/patología , Sustancia P/análisis , Adolescente , Adulto , Factores de Edad , Anticuerpos , Astrocitos/química , Astrocitos/patología , Ganglios Basales/química , Ganglios Basales/patología , Tronco Encefálico/química , Tronco Encefálico/patología , Niño , Femenino , Lóbulo Frontal/química , Lóbulo Frontal/patología , Proteína Ácida Fibrilar de la Glía/análisis , Proteína Ácida Fibrilar de la Glía/inmunología , Hipocampo/química , Hipocampo/patología , Humanos , Mesencéfalo/química , Mesencéfalo/patología , Neuronas/química , Neuronas/patología , Sustancia P/inmunología , Tálamo/química , Tálamo/patología
14.
Arch Environ Contam Toxicol ; 37(4): 434-9, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10508890

RESUMEN

The toxicities and oxidative stress-inducing actions of (-)-nicotine and smokeless tobacco extract (STE), containing equivalent amounts of nicotine, were studied. Toxicities were determined by colony formation assays using Chinese hamster ovary (CHO) cells. Results indicated that nicotine is less toxic than smokeless tobacco extract that contained the same amount of nicotine. The generation of reactive oxygen species, following treatment with smokeless tobacco extract and nicotine, was assessed by measurement of changes in glutathione (GSH) and malondialdehyde (MDA) levels. CHO cells (5 x 10(5) cells/5 ml media) were incubated with 4, 0.8, and 0.08 mg of nicotine and STE containing the same amounts of nicotine. All preparations of smokeless tobacco extract significantly decreased GSH levels and increased MDA generation. However, 0.08 mg of nicotine treatment did not result in a significant change in GSH level, and only 4 mg of nicotine were sufficient to increase MDA generation. Addition of free radical scavenging enzymes, superoxide dismutase (SOD) and catalase (CAT), and an intracellular GSH precursor, N-acetyl-L-cysteine (NAC), replenished the GSH levels in nicotine-treated cells. GSH levels in cells exposed to smokeless tobacco extract containing 4 and 0.8 mg nicotine remained significantly lower than the control with the addition of SOD and CAT. However, co-addition of NAC with smokeless tobacco extract preparations returned the GSH levels to the control level. Lactate dehydrogenase (LDH) activities were measured in the media to establish the membrane damage following exposure to smokeless tobacco extract and nicotine. Treatment of cells with 4 mg nicotine caused a significant increase in LDH activity, which was returned to control level in the presence of the antioxidant enzymes and NAC. Smokeless tobacco extract did not change the LDH activity. http://link.springer-ny. com/link/service/journals/00244/bibs/37n4p434.html

Asunto(s)
Nicotina/toxicidad , Estrés Oxidativo/efectos de los fármacos , Plantas Tóxicas , Tabaco sin Humo/toxicidad , 3,4-Metilenodioxianfetamina/metabolismo , Acetilcisteína/metabolismo , Animales , Células CHO , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Cricetinae , Glutatión/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Extractos Vegetales/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
15.
Chirality ; 11(4): 330-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10224660

RESUMEN

The biodegradation of the chiral phenoxyalkanoic herbicides 2-(2,4-dichlorophenoxy)propionic aid (2,4-DP) and 2-(4-chloro-2-methylphenoxy)propionic acid (MCPP) was investigated using enantioselective HPLC and chiroptical detection. Racemic mixtures of 2,4-DP and MCPP were applied to three species of turf grass, four species of broadleaf weeds, and soil. Preferential degradation of the S-(-) enantiomer of each herbicide was observed in most species of broadleaf weeds and soil, while the degradation in all species of grass occurred without enantioselectivity. The biodegradation in all systems appeared to follow pseudo first-order kinetics with the fastest degradation occurring in broadleaf weeds, followed by the grasses. The slowest degradation was observed in soil. The results of this work illustrate the need to characterize both enantiomers of chiral agrochemicals in order to have an accurate understanding of their distribution and fate in the environment.


Asunto(s)
Ácido 2,4-Diclorofenoxiacético/análogos & derivados , Ácido 2-Metil-4-clorofenoxiacético/análogos & derivados , Herbicidas/farmacocinética , Plantago/metabolismo , Plantas Medicinales , Poaceae/metabolismo , Suelo , Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/farmacocinética , Ácido 2-Metil-4-clorofenoxiacético/química , Ácido 2-Metil-4-clorofenoxiacético/farmacocinética , Biodegradación Ambiental , Cromatografía Líquida de Alta Presión/métodos , Herbicidas/química , Estructura Molecular , Estereoisomerismo
17.
Am J Infect Control ; 26(6): 584-7, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9836843

RESUMEN

BACKGROUND: Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. METHODS: The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. RESULTS: Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. CONCLUSION: Our policy to control the spread of nosocomial C difficile required interdisciplinary cooperation between infection control and the admitting department. By identifying patients who were positive for toxin through admitting, we were able to place all potentially infected patients into isolation. Our positivity rate of 15% on readmission demonstrates the importance of this policy. The cost of controlling C difficile can be significantly lowered by clearing patients who were previously positive for toxin before hospital readmission.


Asunto(s)
Clostridioides difficile , Infección Hospitalaria/prevención & control , Enterocolitis Seudomembranosa/prevención & control , Política Organizacional , Aislamiento de Pacientes/organización & administración , Readmisión del Paciente , Instituciones Oncológicas , Ahorro de Costo , Infección Hospitalaria/economía , Enterocolitis Seudomembranosa/economía , Humanos , Ciudad de Nueva York , Grupo de Atención al Paciente , Evaluación de Programas y Proyectos de Salud , Recurrencia
18.
J Foot Ankle Surg ; 37(5): 396-400; discussion 447-8, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9798171

RESUMEN

The purpose of this study was to evaluate the effect of galvanic electrical stimulation on vascular perfusion in diabetic patients. Nineteen subjects with diabetes were enrolled. Eleven subjects (57.9%) were diagnosed with impaired peripheral perfusion based upon their initial transcutaneous oximetry values (< 40 mm Hg). The subjects were studied over a 2-day period. On the 1st day, one foot was electrically stimulated for four 60-minute periods by an external electrical stimulation device. Vascular perfusion of both feet was assessed before and after the sessions of electrical stimulation. On the 2nd day, no electrical stimulation was applied and noninvasive vascular measurements were repeated. For the 1st hour, transcutaneous oxygen pressure was measured continuously during stimulation at the lateral aspect of the leg. Subsequently, perfusion between the periods of stimulation was measured on the dorsum of the foot with both transcutaneous oximetry and laser Doppler flowmetry after each stimulation period. In the group with impaired peripheral perfusion, a significant rise in tissue oxygenation as compared to the control measurements was measured during the first 5 minutes of stimulation (p < .040). For those without vascular disease (TcpO2 > 40 mm Hg) however, there was not a significant increase compared to baseline (p = .280). After the periods of stimulation, the stimulated feet did not show any higher perfusion levels than the control feet. Patterns in perfusion during the day, as measured by laser Doppler flowmetry, were similar in the tested feet and in the controls. These data suggest that external subsensory electrical stimulation induces a transient rise in skin perfusion in persons with diabetes and impaired peripheral perfusion.


Asunto(s)
Pie Diabético/fisiopatología , Pie Diabético/terapia , Terapia por Estimulación Eléctrica , Pie/irrigación sanguínea , Adulto , Anciano , Circulación Sanguínea , Monitoreo de Gas Sanguíneo Transcutáneo , Pie Diabético/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
South Med J ; 91(10): 894-8, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9786282

RESUMEN

BACKGROUND: Symptomatic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of Americans with diabetes. METHODS: We reviewed the literature using the National Library of Medicine's MEDLINE search service. In total, we reviewed 54 articles. RESULTS: Hyperglycemia leads to increased activity in the polyol pathway in nerve cells; this ultimately results in abnormal nerve function. Numerous pharmacologic agents have been used to treat symptomatic peripheral neuropathy, but all of these drugs can be associated with adverse side effects. Recent work has indicated that subsensory electrical stimulation may be preferred to pharmacotherapy, since it is equally effective and has a more favorable safety profile. CONCLUSION: Although the pathophysiology of diabetic neuropathy is well understood, treatment of the symptoms associated with this condition can be challenging. Additional research is needed to reveal a safe and effective treatment for this debilitating sequela of diabetes mellitus.


Asunto(s)
Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/terapia , Humanos , Dolor/fisiopatología , Manejo del Dolor , Estimulación Eléctrica Transcutánea del Nervio
20.
J Environ Sci Health B ; 33(1): 99-121, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9491570

RESUMEN

Pinto beans (Phaselous vulgaris), sweet corn (Zea mays), and zucchini squash (Cucurbita pepo) were grown in a field pot study using alluvial floodplain soils contaminated with various radionuclides within Los Alamos Canyon (LAC) at Los Alamos National Laboratory, New Mexico. Soils as well as washed edible (fruit) and nonedible (stems and leaves) crop tissues were analyzed for tritium (3H), cesium (137Cs), strontium (90Sr), plutonium (238Pu and 239,240Pu), americium (241Am), and total uranium (totU). Most radionuclides, with the exception of 3H and totU, in soil and crop tissues from LAC were detected in significantly higher concentrations (p < 0.05) than in soil or crop tissues collected from regional background locations. Significant differences in radionuclide concentrations among crop species (squash were generally higher than beans or corn) and plant parts (nonedible tissue were generally higher than edible tissue) were observed. Most soil-to-plant concentration ratios for radionuclides in edible and nonedible crop tissues grown in soils from LAC were within default values in the literature commonly used in dose and risk assessment models. Overall, the maximum net positive committed effective dose equivalent (CEDE)--the CEDE plus two sigma for each radioisotope minus background and then all positive doses summed--to a hypothetical 50-year resident that ingested 352 lb ([160 kg]; the maxiumum ingestion rate per person per year) of beans, corn, and squash in equal proportions was 74 mrem y-1 (740 microS y-1). This upper bound dose was below the International Commission on Radiological Protection permissible dose limit of 100 mrem y-1 (1000 microS y-1) from all pathways and corresponds to a risk of an excess cancer fatality of 3.7 x 10(-5) (37 in a million), which is also below the U.S. Environmental Protection Agency's guideline of 10(-4).


Asunto(s)
Salud Ambiental , Fabaceae/metabolismo , Guerra Nuclear , Plantas Medicinales , Contaminantes Radiactivos del Suelo/metabolismo , Verduras/metabolismo , Zea mays/metabolismo , Fabaceae/crecimiento & desarrollo , Humanos , Laboratorios , Neoplasias Inducidas por Radiación/epidemiología , New Mexico , Factores de Riesgo , Especificidad de la Especie , Verduras/crecimiento & desarrollo , Zea mays/crecimiento & desarrollo
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