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1.
Lett Appl Microbiol ; 66(2): 118-123, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29168197

RESUMEN

The total direct count (TDC) microbial enumeration method is rapid and suitable for analysing environmental samples containing numerous un-culturable micro-organisms. Conventional TDC methods require the addition of a fluorescent stain and are thus unsuitable for automatic monitoring. We unexpectedly found that heated micro-organisms emit strong autofluorescence. This study was conducted to determine how heating enhances the autofluorescence of bacteria and fungi and to evaluate whether the phenomenon could be exploited to develop a new TDC method. Bacterial autofluorescence was augmented by heating cells at 200°C. ELISA results indicated that levels of advanced glycation end products (AGEs) increased in heated microbes. Catechin, an inhibitor of the Maillard reaction, disrupted the intensification of autofluorescence. These results suggest that the enhanced autofluorescence is associated with the formation of AGEs and that the reaction could be utilized as alternative probe in TDC methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Autofluorescence of bacteria and fungi was prominently intensified by heat treatment at 200°C. This phenomenon was associated with advanced glycation end products formed in micro-organisms via the Maillard reaction. The fluorescence signal was strong enough to be utilized as an alternative probe for fluorescent dye in the total direct count method. This phenomenon could be incorporated in an automatic apparatus for microbial enumeration, as it does not require staining.


Asunto(s)
Bacterias/aislamiento & purificación , Hongos/aislamiento & purificación , Bacterias/metabolismo , Recuento de Colonia Microbiana/métodos , Colorantes Fluorescentes , Hongos/metabolismo , Calor , Microscopía Fluorescente/métodos
2.
Int J Obes (Lond) ; 40(9): 1369-75, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27328752

RESUMEN

BACKGROUND/OBJECTIVES: Weight management medications increase the likelihood that patients will achieve clinically meaningful improvements in cardiovascular, metabolic and other weight-related measures of health. However, the weight loss achieved with any weight management intervention can vary widely among individuals, and patients who do not respond to pharmacotherapy by achieving clinically meaningful weight loss should discontinue therapy. We characterized 1-year weight loss in the phase 3 clinical trial program of the weight management medication, naltrexone/bupropion 32/360 mg (NB), as well as the relationship between early weight loss and long-term weight loss, particularly with respect to participants who achieved the clinically recommended threshold of ⩾5% weight loss by Week 16. PARTICIPANTS/METHODS: Data from participants from each of the four phase 3, randomized, placebo-controlled, 56-week clinical trials with NB were pooled (modified intent-to-treat population; NB N=2043, Placebo N=1319). This exploratory analysis examined the relationship between participant achievement of various weight loss thresholds early in treatment (at Week 8, 12 or 16) and the associated weight loss at Week 56 (Completers population; NB N=1310, Placebo N=763). RESULTS: In the NB participants who completed 1 year of treatment, weight loss of at least 5% at Week 16 (n=873) was associated with least-squares mean weight loss of 11.7% at Week 56 and 85% of these participants had Week 56 weight loss of ⩾5%. Eighty percent (95% confidence interval: 78-82%) of the participants who would, and would not, achieve ⩾5% weight loss at Week 56 were correctly identified using the clinically recommended threshold of ⩾5% at Week 16. Safety and tolerability of NB was similar to previously published reports. CONCLUSIONS: Participants who meet the Week 16 threshold of ⩾5% weight loss are likely to maintain clinically significant weight loss after 1 year of treatment. Further evaluations are required to evaluate improvements in measures of cardiovascular and metabolic risk.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Bupropión/uso terapéutico , Naltrexona/uso terapéutico , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Adolescente , Adulto , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/prevención & control , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
3.
Diabetes Obes Metab ; 18(6): 558-70, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26936802

RESUMEN

Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs.


Asunto(s)
Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Obesidad/tratamiento farmacológico , Aprobación de Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Obesidad/epidemiología , Estados Unidos , United States Food and Drug Administration , Pérdida de Peso/efectos de los fármacos
4.
Diabetes Obes Metab ; 17(11): 1021-32, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26040215

RESUMEN

Recently, the recognition of obesity as a complex disease that requires chronic management has become more widespread. There has also been a movement away from a focus on body mass index alone, and toward the management of obesity-related comorbidities as well as excess weight. This article examines the current and emerging pharmacological options for weight management in people with overweight or obesity who have, or are at a high risk of, weight-related comorbidities. In the USA, the current options for pharmacological weight management are phentermine (indicated for short-term use only), orlistat, combined phentermine/topiramate extended release, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg. Currently, orlistat, naltrexone/bupropion and liraglutide 3.0 mg are approved in Europe. All of the above-mentioned medications have shown weight-loss efficacy versus placebo. Those approved for long-term weight management have also been associated with improvements in weight-related comorbidities, such as hypertension, prediabetes, diabetes or dyslipidaemia, or related biomarkers. As with all drugs, the safety and tolerability profiles of medications for weight management should be considered alongside their efficacy to ensure correct use. Additional medications for weight management that are in clinical development include bupropion/zonisamide and beloranib. The field of obesity treatment is advancing with a number of medications being recently approved, and with other pharmacological options emerging.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Bupropión/uso terapéutico , Cinamatos/uso terapéutico , Comorbilidad , Ciclohexanos/uso terapéutico , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Compuestos Epoxi/uso terapéutico , Humanos , Hipertensión/epidemiología , Isoxazoles/uso terapéutico , Obesidad/epidemiología , Sobrepeso/epidemiología , Estado Prediabético/epidemiología , Sesquiterpenos/uso terapéutico , Pérdida de Peso/efectos de los fármacos , Zonisamida
5.
Diabetes Obes Metab ; 15(9): 863-6, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23489381

RESUMEN

The effects of combination naltrexone/bupropion therapy on body composition and visceral adipose tissue (VAT) mass were examined in a subset (n = 107) of obese subjects from a Phase 2 trial that compared the efficacy and safety of placebo, naltrexone monotherapy, bupropion monotherapy or one of three naltrexone/bupropion dose combinations for 24 weeks. Body composition data were obtained using dual-energy X-ray absorptiometry and computed tomography. Eighty subjects completed the substudy. Naltrexone/bupropion resulted in weight loss and a greater reduction in body fat (-14.0 ± 1.3%) than placebo (-4.0 ± 2.0%), naltrexone monotherapy (-3.2 ± 2.5%) and bupropion monotherapy (-4.1 ± 2.9%; all p < 0.01). Reduction in VAT mass was also greater with naltrexone/bupropion (-15.0 ± 1.8%) than placebo (-4.6 ± 2.7%), naltrexone monotherapy (-0.1 ± 3.5%) and bupropion monotherapy (-2.3 ± 4.2%; all p < 0.01). Reductions in body fat and VAT mass with naltrexone/bupropion were proportional with weight loss. Weight loss with naltrexone/bupropion was not associated with a greater relative reduction in lean mass than placebo or the monotherapies.


Asunto(s)
Adiposidad/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Bupropión/uso terapéutico , Inhibidores de Captación de Dopamina/uso terapéutico , Grasa Intraabdominal/efectos de los fármacos , Naltrexona/uso terapéutico , Obesidad/tratamiento farmacológico , Absorciometría de Fotón , Análisis de Varianza , Bupropión/administración & dosificación , Inhibidores de Captación de Dopamina/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Naltrexona/administración & dosificación , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos
7.
Diabetes Obes Metab ; 13(3): 204-6, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21205108

RESUMEN

Obesity in the USA continues to be a medical problem of epidemic proportions, affecting one-third of American adults. This increase in body weight and body mass index (BMI) is a risk factor for insulin resistance; individuals with insulin resistance are at increased risk for the development of type 2 diabetes and cardiovascular disease. The identification of effective dietary treatments (e.g. low-carbohydrate diet, low-fat diet) for patient populations with insulin resistance remains controversial. While a variety of dietary approaches will result in weight and cardiac risk factor reduction, individuals who have been identified as insulin-resistant may derive additional short-term weight loss results from a low-carbohydrate diet compared to a low-fat diet.


Asunto(s)
Diabetes Mellitus Tipo 2/dietoterapia , Dieta Baja en Carbohidratos/métodos , Resistencia a la Insulina/fisiología , Obesidad/dietoterapia , Adulto , Femenino , Humanos , Masculino , Conducta de Reducción del Riesgo
8.
Diabetes Obes Metab ; 12(6): 517-31, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20518807

RESUMEN

AIM: To evaluate the efficacy and safety of taranabant in overweight and obese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a multicenter, double-blind, randomized, placebo-controlled study in overweight and obese patients with T2DM (ages > or = 18 and < or = 75 years) with a BMI > or = 27 kg/m(2) and < or = 43 kg/m(2) and HbA1c > or =7.0 and < or = 10.0%, who were either not on an antihyperglycaemic agent or on a stable dose of metformin (> or = 1500 mg/day). After a 2-week placebo run-in, patients were randomized to placebo (N = 156) or taranabant 0.5-mg (N = 155), 1-mg (N = 157), or 2-mg (N = 155) once daily for 52 weeks. Primary efficacy endpoints were changes from baseline in body weight (BW) and HbA1c at Week 36, with results at Week 52 being key secondary endpoints. RESULTS: In the all-patients-treated population, using a last-observation-carried-forward analysis, reductions in BW were -2.5, -3.7, -4.5 and -5.1 kg at Week 36 and -2.4, -4.0, -4.6 and -5.3 kg at Week 52 in the placebo, 0.5-, 1- and 2-mg groups, respectively (all doses significant vs. placebo at both time points). The proportion of patients who lost > or = 5 and > or = 10% of their baseline BW was significantly greater in the 1- and 2-mg groups vs. placebo at Week 36 and all taranabant groups vs. placebo at Week 52. Reductions in HbA1c were -0.40, -0.47, -0.68 and -0.71% at Week 36 and -0.30, -0.43, -0.65 and -0.64% at Week 52, in the placebo, 0.5-, 1- and 2-mg groups, respectively (1- and 2-mg doses significant vs. placebo at both time points). After 52 weeks, the incidences of adverse experiences classified in the gastrointestinal (diarrhoea, nausea, vomiting), nervous system-related (dizziness, sensory-related), and psychiatric (irritability, depression-related) organ systems were numerically higher or statistically significantly higher in all taranabant groups compared with the placebo group. CONCLUSIONS: After 36 and 52 weeks, treatment with taranabant at the 1- and 2-mg doses led to clinically significant weight loss and improvement in glycaemic parameters in overweight and obese patients with T2DM that was associated with dose-related increases in adverse experiences. Based on these data and data from other Phase III clinical studies, it was determined that the overall safety and efficacy profile of taranabant did not support further development for the treatment of obesity.


Asunto(s)
Amidas/administración & dosificación , Fármacos Antiobesidad/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Piridinas/administración & dosificación , Receptor Cannabinoide CB1/agonistas , Adolescente , Adulto , Anciano , Amidas/efectos adversos , Fármacos Antiobesidad/efectos adversos , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Dieta Reductora , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Piridinas/efectos adversos , Pérdida de Peso/efectos de los fármacos , Adulto Joven
9.
Opt Express ; 17(10): 7744-9, 2009 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-19434105

RESUMEN

Using a partially deuterated KDP crystal for an optical parametric amplifier, we demonstrated ultrabroadband optical parametric chirped-pulse amplification of more than 250 nm bandwidth at a center wavelength of 1050 nm. We numerically show how to control the broadband phase matching conditions at different wavelengths to match center wavelengths of suitable broadband seed sources by adjusting the deuteration level in partially deuterated KDP.

10.
Science ; 248(4960): 1214-7, 1990 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-17809906

RESUMEN

Eruption of 1-million-year-old tholeiitic basalt >1800 meters below sea level (>18 megapascals) in a backarc rift behind the Bonin arc produced a scoriaceous breccia similar in some respects to that formed during subaerial eruptions. Explosion of the magma is thought to have produced frothy agglutinate which welded either on the sea floor or in a submarine eruption column. The resulting 135-meter-thick pyroclastic deposit has paleomagnetic inclinations that are random at a scale of <2.5 meters. High magmatic water content, which is about 1.3 percent by weight after vesiculation, contributed to the explosivity.

11.
Obes Sci Pract ; 5(3): 238-245, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31275597

RESUMEN

STUDY OBJECTIVES: To evaluate weight loss with lorcaserin in persons with obstructive sleep apnea (OSA). METHODS: This retrospective analysis evaluated weight loss of lorcaserin (10 mg twice daily) versus placebo in persons with obesity or overweight persons with OSA from a pooled database of three randomized, controlled trials. Primary end points were reductions in the baseline body weight of ≥5% and ≥10% at year 1 and overall weight change at year 1. Changes in heart rate and blood pressure were also evaluated. RESULTS: A total of 336 persons with OSA were identified in the overall pooled population (N = 6,636). At year 1, more patients receiving lorcaserin lost ≥5% (47.2% lorcaserin vs. 25.6% placebo; p < 0.0001) and 10% (22.2% lorcaserin vs. 13.1% placebo; p < 0.0354) of their baseline body weight. Weight loss at year 1 was 6.4 kg versus 3.5 kg in the lorcaserin and placebo groups, respectively (p < 0.0001). Similar results were observed for change in blood pressure and heart rate, with responders having larger benefits. Weight loss was similar between persons with and without OSA. CONCLUSIONS: In this retrospective analysis, persons with OSA showed significant and meaningful weight loss, blood pressure and heart rate reductions in patients treated with lorcaserin versus placebo. Persons with OSA lost just as much weight as those without OSA. Health care providers can expect persons with OSA to lose weight by diet, exercise and the weight loss medication lorcaserin comparable with persons without OSA. Further prospective research is warranted to evaluate impact of weight loss on OSA and overall outcomes for patients.

12.
Obes Sci Pract ; 5(2): 120-129, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31019729

RESUMEN

INTRODUCTION: The elderly population is projected to be the fastest growing group of individuals with obesity group in the United States. As such, there is merit in examining factors that contribute to healthy aging and weight management. The effects of newer weight loss medications approved after 2013 have been studied but are not often assessed specifically in older persons. METHODS: This post hoc analysis evaluated the magnitude of weight loss in adults across age quartiles with lorcaserin, a serotonin (5-HT) 2C receptor agonist indicated as an adjunct to a reduced-caloric diet and increased physical activity for chronic weight management. Data from three lorcaserin pivotal phase 3 studies were used in this analysis. Data for patients with overweight/obesity without type 2 diabetes (T2D; BLOOM/BLOSSOM; body mass index [BMI] 27.0-29.9 kg/m2 and ≥1 comorbidity or BMI 30.0-45.0 kg/m2) and patients with overweight/obesity with T2D (BLOOM-DM; BMI 27.0-45.0 kg/m2) were used. Patients were randomized to receive lorcaserin 10 mg twice daily or placebo in addition to diet and exercise for 52 weeks. Age quartiles between the studies differed as the T2D population was on average, 9 years older. RESULTS: This analysis shows that lorcaserin was associated with improved weight loss relative to placebo regardless of age. Importantly, these results were consistent for patients with and without T2D. Interestingly, the magnitude of weight loss for lorcaserin appeared to increase with increasing age. In patients without T2D, odds of achieving ≥5% and ≥10% reduction in body weight at 52 weeks were significantly higher for patients >36 years. Lorcaserin was well tolerated in all patients across all quartiles including the oldest quartile. CONCLUSIONS: In summary, this post hoc analysis demonstrates that lorcaserin treatment in patients with and without T2D was safe and effective at reducing weight across all age groups analysed. Weight loss appeared to be greater for older patients; additional analyses are warranted to confirm these findings and to better understand the factors for improved weight loss.

13.
Int J Obes (Lond) ; 32(10): 1559-65, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18698316

RESUMEN

OBJECTIVE: To determine the magnitude and determinants of weight loss in humans exposed to betahistine, a centrally acting histamine-1 (H-1) agonist and partial histamine-3 (H-3) antagonist. DESIGN: A multicenter randomized, placebo-controlled dose-ranging weight loss trial with a 12-week treatment period. SUBJECTS: Two hundred and eighty-one obese but otherwise healthy participants. MEASUREMENTS: Weight and obesity-related comorbidities at baseline and at the end of the intervention. RESULTS: Betahistine, at the doses tested, did not induce significant weight loss. With the exception of headache, no difference in adverse effect profile was noted between placebo and treatment groups. Subgroup analysis revealed that age below 50 years, ethnicity (non-Hispanics) and gender (women) were the strongest predictors of weight loss in this population. When these three factors were combined together, the betahistine 48 mg group (n=23) lost -4.24+/-3.87 kg, whereas the placebo group (n=25) lost -1.65+/-2.96 kg during this time period (P=0.005). CONCLUSION: Betahistine, at the doses tested, induced significant weight loss with minimal adverse events only in women below 50 years.


Asunto(s)
Betahistina/administración & dosificación , Agonistas de los Receptores Histamínicos/administración & dosificación , Obesidad/tratamiento farmacológico , Adolescente , Adulto , Anciano , Betahistina/efectos adversos , Método Doble Ciego , Erupciones por Medicamentos , Femenino , Trastornos de Cefalalgia/inducido químicamente , Agonistas de los Receptores Histamínicos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos , Adulto Joven
14.
Clin Obes ; 8(1): 1-10, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29045079

RESUMEN

Previously in the SCALE Obesity and Prediabetes trial, at 1 year, participants with obesity (or overweight with comorbidities) and prediabetes receiving liraglutide 3.0 mg experienced greater improvements in health-related quality of life (HRQoL) than those receiving placebo. The current study extends these findings by examining 3-year changes in HRQoL. HRQoL was assessed using the obesity-specific Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, as well as the Short-Form 36 v2 (SF-36) health survey. At 3 years, mean change (±standard deviation) in IWQOL-Lite total score from baseline for liraglutide (n = 1472) was 11.0 ± 14.2, vs. 8.1 ± 14.7 for placebo (n = 738) (estimated treatment difference [ETD] 3.4 [95% confidence interval (CI): 2.0, 4.7], P < 0.0001). Mean change in SF-36 physical component summary (PCS) score from baseline for liraglutide was 3.1 ± 7.3, vs. 2.6 ± 7.6 for placebo (ETD 0.87 [95% CI: 0.17, 1.6], P = 0.0156). Mean change in SF-36 mental component summary score did not significantly differ between groups. Both IWQOL-Lite total score and PCS score demonstrated an association between greater HRQoL improvement with higher weight loss. Liraglutide 3.0 mg was also associated with improved health utility (Short-Form-6D and EuroQol-5D, mapped from IWQOL-Lite and/or SF-36) vs. placebo. Liraglutide 3.0 mg, plus diet and exercise, is associated with long-term improvements in HRQoL with obesity or overweight with comorbidity vs. placebo.


Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Incretinas/administración & dosificación , Liraglutida/administración & dosificación , Obesidad/tratamiento farmacológico , Calidad de Vida , Pérdida de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Fármacos Antiobesidad/efectos adversos , Costo de Enfermedad , Método Doble Ciego , Femenino , Estado de Salud , Humanos , Incretinas/efectos adversos , Liraglutida/efectos adversos , Masculino , Salud Mental , Persona de Mediana Edad , Obesidad/diagnóstico , Obesidad/fisiopatología , Obesidad/psicología , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
15.
Obes Sci Pract ; 4(2): 141-152, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29670752

RESUMEN

Objective: This multicenter, randomized, controlled, open-label trial examined weight-related quality of life, control over eating behaviour and sexual function after 26 weeks of treatment with either 32 mg naltrexone sustained release (SR)/360 mg bupropion SR plus a comprehensive lifestyle intervention program (NB + CLI, N = 153) or usual care (UC, N = 89), which included minimal lifestyle intervention. Methods: Impact of Weight on Quality of Life-Lite, Binge Eating Scale and Arizona Sexual Experiences Scale were assessed at baseline (BL) and weeks 16 and 26. Results: NB + CLI and UC participants lost 9.46 and 0.94% respectively of initial body weight at week 26 (P < 0.0001). NB + CLI participants had greater improvements in Impact of Weight on Quality of Life-Lite total score than UC participants (P < 0.0001). In participants with moderate/severe Binge Eating Scale scores at BL, 91% of NB + CLI and 18% of UC participants experienced categorical improvements. In participants with Arizona Sexual Experiences Scale-defined sexual dysfunction at BL, 58% of NB + CLI and 19% of UC participants no longer met dysfunction criteria at week 26. The most frequent adverse events leading to discontinuation before week 26 in NB + CLI included nausea (10.5%); anxiety (3.3%); and headache, hypertension, insomnia and palpitations (1.3% each). Conclusion: Compared with UC, participants treated with NB + CLI experienced greater improvements in weight-related quality of life, control over eating behaviour, and sexual function.

16.
Mol Cell Biol ; 14(12): 8085-95, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7969146

RESUMEN

The receptor for the macrophage colony-stimulating factor (or colony-stimulating factor 1 [CSF-1]) is expressed from different promoters in monocytic cells and placental trophoblasts. We have demonstrated that the monocyte-specific expression of the CSF-1 receptor is regulated at the level of transcription by a tissue-specific promoter whose activity is stimulated by the monocyte/B-cell-specific transcription factor PU.1 (D.-E. Zhang, C.J. Hetherington, H.-M. Chen, and D.G. Tenen, Mol. Cell. Biol. 14:373-381, 1994). Here we report that the tissue specificity of this promoter is also mediated by sequences in a region II (bp -88 to -59), which lies 10 bp upstream from the PU.1-binding site. When analyzed by DNase footprinting, region II was protected preferentially in monocytic cells. Electrophoretic mobility shift assays confirmed that region II interacts specifically with nuclear proteins from monocytic cells. Two gel shift complexes (Mono A and Mono B) were formed with separate sequence elements within this region. Competition and supershift experiments indicate that Mono B contains a member of the polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) family, which includes the AML1 gene product, while Mono A is a distinct complex preferentially expressed in monocytic cells. Promoter constructs with mutations in these sequence elements were no longer expressed specifically in monocytes. Furthermore, multimerized region II sequence elements enhanced the activity of a heterologous thymidine kinase promoter in monocytic cells but not other cell types tested. These results indicate that the monocyte/B-cell-specific transcription factor PU.1 and the Mono A and Mono B protein complexes act in concert to regulate monocyte-specific transcription of the CSF-1 receptor.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Monocitos/fisiología , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogénicas , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Factores de Transcripción/metabolismo , Animales , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Factores de Unión al Sitio Principal , Cartilla de ADN/química , Elementos de Facilitación Genéticos , Expresión Génica , Humanos , Técnicas In Vitro , Ratones , Mutagénesis Sitio-Dirigida , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/genética , Eliminación de Secuencia , Relación Estructura-Actividad , Factor de Transcripción AP-2
17.
Food Chem Toxicol ; 44(8): 1372-6, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16624473

RESUMEN

Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.


Asunto(s)
ADN/metabolismo , Grasas de la Dieta/toxicidad , Guanina/análogos & derivados , Hígado/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina/análogos & derivados , Animales , Peso Corporal/efectos de los fármacos , Daño del ADN , ADN Glicosilasas/biosíntesis , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , Enzimas Reparadoras del ADN/biosíntesis , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Dieta , Grasas de la Dieta/administración & dosificación , Aceites de Pescado/administración & dosificación , Aceites de Pescado/toxicidad , Guanina/biosíntesis , Guanina/metabolismo , Hígado/enzimología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/etiología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Monoéster Fosfórico Hidrolasas/biosíntesis , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Aceite de Soja/administración & dosificación , Aceite de Soja/toxicidad
18.
Cancer Res ; 50(21): 7003-7, 1990 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-2208166

RESUMEN

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 minipellet, using a murine hepatic metastasis model. The IL-2 minipellet consists of atelocollagen derived from natural bovine skin together with 1 x 10(6) units of recombinant IL-2. Administration of the IL-2 minipellet was performed into the spleens of BALB/c mice after translocation of the spleens to the s.c. position. Administration produced detectable serum IL-2 levels for 72 h. The IL-2 minipellet was evaluated for its efficacy against hepatic metastases from colon 26 adenocarcinoma in the BALB/c mice. Both the administration of the IL-2 minipellet alone and its combination with the injection of 5 x 10(7) lymphokine-activated killer cells resulted in significant reductions of the number of metastatic nodules. Moreover, increased survival of mice bearing colon 26 adenocarcinoma was noted in these two treatment groups. To investigate the mechanism of the IL-2 minipellet activity, we tested the lytic potential of splenocytes obtained after administration of the IL-2 minipellet in a 51Cr release assay. Cytotoxicity against YAC-1 cells and colon 26 cells was significantly augmented on Day 2 after minipellet administration. These results demonstrated that local administration of the IL-2 minipellet into the hepatic circulation was extremely effective against metastatic liver cancer.


Asunto(s)
Adenocarcinoma/terapia , Neoplasias del Colon/terapia , Inmunoterapia , Interleucina-2/administración & dosificación , Neoplasias Hepáticas/secundario , Animales , Preparaciones de Acción Retardada , Interleucina-2/sangre , Interleucina-2/farmacología , Interleucina-2/uso terapéutico , Circulación Hepática/fisiología , Neoplasias Hepáticas/terapia , Masculino , Ratones , Ratones Endogámicos BALB C , Bazo/citología , Bazo/fisiología
19.
Obes Sci Pract ; 2(4): 477-482, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28090354

RESUMEN

INTRODUCTION: Since the 1990s, a number of weight loss medications have been removed from the USA and or European market because of adverse events associated with these medications. These medications include fenfluramine (heart valve thickening), sibutramine (cardiovascular risk) and rimonabant (depression). This history may affect a patient's desire to consider weight loss medications as an option for weight management. OBJECTIVE: This descriptive study was designed to observe what treatment options the geriatric patient (age 65 or higher) seeking weight loss would like to consider, as well as the reasons they felt they struggled with overweight or obesity. METHODS: A questionnaire was given to 102 geriatric patients with overweight or obesity before starting a weight loss programme at a weight management centre. The questionnaire asked the patient why they felt they were overweight or obese and what treatment options they wished to consider. The geriatric patients were matched with younger patients in body mass index and sex. RESULTS: The three most common perceptions that geriatric patients felt were causes of their increased weight were 'lack of exercise' (76.2%), 'poor food choices' (59.4%) and 'cravings' (47.5%). When geriatric patients were asked what treatment options they would like to discuss, the four most common options requested were 'diet and healthy eating' (67.3%), weight loss medications (57.4%), a request for a 'metabolic work up' (55.4%) and 'exercise' (53.5%). These responses were no different from their younger cohorts. When geriatric patients with a body mass index of 35 or higher were given bariatric surgery as a treatment option, 21.9% marked it as a treatment option they would like to consider. CONCLUSIONS: Over half of geriatric patients desired to discuss weight loss medications as a treatment option. Diet and exercise were also of strong interest, which is in line with current weight management guidelines.

20.
Clin Obes ; 6(4): 233-42, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27198973

RESUMEN

Obesity has a negative impact on health-related quality of life (HRQoL). The SCALE Obesity and Prediabetes study investigated the effect of liraglutide 3.0 mg, as adjunct to diet and exercise, on HRQoL in patients with obesity [body mass index (BMI) ≥ 30 kg m(-2) ] or overweight (BMI ≥ 27 kg m(-2) ) with comorbidity. Participants were advised on a 500 kcal d(-1) deficit diet and a 150-min week(-1) exercise programme and were randomised 2:1 to once-daily subcutaneous liraglutide 3.0 mg or placebo. HRQoL was assessed using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Short-Form 36 (SF-36) v2 health questionnaires. Individuals on liraglutide 3.0 mg (n = 2046) had significantly greater improvements in IWQOL-Lite total score (10.6 ± 13.3) vs. placebo (n = 1020) (7.7 ± 12.8) and SF-36 physical (PCS) and mental (MCS) component summary scores (PCS, 3.6 ± 6.8; MCS, 0.2 ± 8.1) vs. placebo (PCS, 2.2 ± 7.7; MCS, -0.9 ± 9.1). The estimated treatment differences were IWQOL-Lite total score 3.1 (95% CI: 2.2; 4.0), P < 0.0001; SF-36 PCS 1.7 (95% CI: 1.2; 2.2), P < 0.0001 and MCS 0.9 (95% CI: 0.3; 1.5), P = 0.003. All subscales of the IWQOL-Lite and SF-36 were significantly improved with liraglutide 3.0 mg vs. placebo. More patients on liraglutide 3.0 mg experienced meaningful improvement on the IWQOL-Lite total (P < 0.0001) and the SF-36 PCS (P < 0.0001) scores.


Asunto(s)
Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Sobrepeso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Masculino , Persona de Mediana Edad , Calidad de Vida , Adulto Joven
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