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Biomedical subjects

D B Allison

Publications and source records attributed to D B Allison.

At least 19 recordsLinked to original sources
PubMed2007

No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs.

RATIONALE: Atypical antipsychotic drugs (AAD) induce significant weight gain in female C57BL/6J mice. The effect of dietary fat on weight gain and serum lipids in this model is unknown. OBJECTIVES: Test the hypothesis that the obesigenic effects of these drugs are greater in the presence of a high-fat diet. METHODS: Female C57BL/6J mice were treated with atypical antipsychotics for 3 weeks and fed either a low-fat or high-fat diet (4.6 vs 15.6% fat by wt). Food intake (FI), body weight (BW), body composition, and serum lipids were measured during treatment with optimized doses of olanzapine, quetiapine, and risperidone. Energy intake (EI) and feed efficiency (FE) were calculated. Group differences in change were analyzed via repeated measures analysis of variance (ANOVA). Serum lipid concentrations, EI and FE were compared using two-way ANOVA. RESULTS: AAD-treated mice gained significantly more weight than controls after 3 weeks (P<0.001). Treatment and diet had significant effects on FI and EI over time (P<0.001). AAD-treated mice had significantly higher FE than controls (P<0.05); however, there was no significant drug by diet interaction (P=0.65). Risperidone low-fat mice gained significantly more absolute fat mass than placebo low-fat mice (P<0.05). All treatment groups, except quetiapine low-fat and olanzapine high-fat, gained significantly more absolute lean mass than placebo controls (P<0.05). Cholesterol levels were significantly lower in quetiapine and risperidone than placebo (P<0.05). Risperidone low-fat mice had significantly higher triglyceride levels than placebo and risperidone high-fat mice (P<0.05). CONCLUSIONS: A high-fat diet does not increase AAD-induced BW gain in female mice during a 3-week treatment period.

Adipose Tissue↗
PubMed2006

Racial differences in the prevalence of Factor V Leiden mutation among patients on chronic warfarin therapy.

We report the prevalence of Factor V Leiden (FVL) in European American and African American patients on warfarin therapy residing in Alabama. METHODS.: Detailed history was obtained and FVL genotype was determined for 288 patients enrolled in a prospective cohort: Pharmacogenetic Optimization of Anticoagulation Therapy. Racial differences in genotype frequency were assessed by the Chi-square statistics and HWE assumptions by G-statistics. Race-specific analysis for the association between site of thromboembolism and the presence of FVL mutation was assessed using logistic regression. RESULTS.: The overall heterozygote (GA genotype) frequency was 4.9%. No patient was found to be homozygous (AA) for the variant allele. The prevalence of GA was higher in European American (8.6%) compared to African American (1.4%) patients (p=0.004). The FVL genotype frequency was significantly different across race for venous thromboembolic events (p=0.014) but not for arterial thromboembolic events (p=0.20). Multivariable race-specific analysis highlights the contribution of FVL mutation to the risk of venous thromboembolic events in European American (p=0.03) but not in African American patients (p=0.95). European American patients with the GA mutation were approximately 6.3 times more likely to have experienced a venous, rather than arterial thromboembolic event. CONCLUSION.: In Alabama, among patients on warfarin, the GA genotype is more prevalent in European Americans compared to African Americans. In European Americans, but not in African Americans, the GA genotype was more prevalent in patients with venous compared to arterial thromboembolic events.

Black or African American↗
PubMed2006

Putative contributors to the secular increase in obesity: exploring the roads less traveled.

OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices. DESIGN: A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity. DATA: Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available. RESULTS: For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations. CONCLUSION: Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Age Factors↗
PubMed2006

Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial.

BACKGROUND AND OBJECTIVE: Atomoxetine is a potent central norepinephrine uptake inhibitor, currently marketed for treatment of attention-deficit/hyperactivity disorder (ADHD). With the understanding that noradrenergic agents could be useful in assisting obese individuals to lose weight, we conducted this preliminary study to evaluate short-term efficacy and safety of atomoxetine in obese adults. DESIGN: At 12-week randomised, double-blind, placebo-controlled trial, conducted at Duke University Medical Centre, USA, from May 2004 to December 2004. PARTICIPANTS: A total of 30 obese women (mean (s.e.) body mass index of 36.1 (0.6) kg/m2). INTERVENTIONS: Participants were randomly assigned to receive atomoxetine (n=15) or placebo (n=15). All participants were advised to follow a balanced hypocaloric diet (500 kcal/day deficit). Atomoxetine therapy was started at 25 mg/day orally, with gradual increase to 100 mg/day over 1 week. Placebo dosing was identical. MEASUREMENTS: Body weight in kilograms was the primary outcome measure. Other measurements included waist circumference, blood pressure and heart rate, fasting plasma glucose and lipids, and depressive symptoms. RESULTS: Last-observation-carried-forward analysis of the available data for participants who had completed at least one post-randomisation assessment, demonstrated that the atomoxetine group (n=12) lost more body weight over the 12-week period than the placebo (n=14) group (mean (s.e.) -3.6 (1.0) kg (-3.7% loss) vs 0.1 (0.4) kg (0.2% gain); F (4,96)=11.9; P<0.0001). Three participants in the atomoxetine group and none in the placebo group lost >or=5% weight. Side effects were minimal. CONCLUSION: Atomoxetine demonstrated modest short-term weight loss efficacy relative to placebo in this preliminary study of obese women.

Adolescent↗
PubMed2006

Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults.

OBJECTIVE: To test for association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q polymorphism with body mass index (BMI) and diabetes in a large sample of Caucasians and African-Americans by selectively genotyping individuals at the extremes of the phenotypic distribution. SUBJECTS: Subsets comprising the extremes of the BMI distribution (10th-20th and above the 90th BMI percentile for Caucasians and between the 10th-30th and above the 80th percentile for African-Americans) from a group of 10,260 Caucasian and 2268 African-American adults participating in New York Cancer Project were studied. METHODS: Subjects were genotyped for the ENPP1 K121Q polymorphism by pyrosequencing and tested for association with BMI and diabetes by regression analysis. RESULTS: Regression analysis with BMI as the dependent variable demonstrated a significant association (P = 0.02) of genotype at K121Q with BMI, with no significant race-by-genotype interaction (P = 0.30). Compared with Q/Q or Q/K individuals, the K/K individuals had a BMI approximately 1.3 kg/m2 higher, without effects of age, gender or race. By logistic regression analysis, the K121Q alleles had no significant effect on diabetes status (P = 0.37) in obese subjects. CONCLUSION: In both Caucasians and African-Americans, the K121 polymorphism in ENPP1 was associated with increased BMI, but not with diabetes.

Adult↗
PubMed2006

Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update.

Obesity is a major health problem facing the developed and developing world. Efforts by individuals, health professionals, educators, and policy makers to combat the escalating trend of growing obesity prevalence have been multifaceted and mixed in outcome. Various dietary supplements have been marketed to reduce obesity. These products have been suggested to accomplish this by decreasing energy intake and energy absorption, and/or increasing metabolic rate. Ephedra, one such supplement, was banned from sale in the US market because of concerns about adverse events. Another substance, Citrus aurantium, which contains several compounds including synephrine alkaloids, has been suggested as a safe alternative. This review examines the evidence for safety and efficacy of C. aurantium and synephrine alkaloids as examined in animal studies, clinical weight loss trials, acute physiologic studies and case reports. Although at least three reviews of C. aurantium have been published, our review expands upon these by: (i) distinguishing and evaluating the efficacy of C. aurantium and related compounds; (ii) including results from previously unreviewed research; (iii) incorporating recent case reports that serve to highlight, in an anecdotal way, potential adverse events related to the use of C. aurantium and related compounds; and (iv) offering recommendations to guide the design of future trials to evaluate the safety and efficacy of C. aurantium. While some evidence is promising, we conclude that larger and more rigorous clinical trials are necessary to draw adequate conclusions regarding the safety and efficacy of C. aurantium and synephrine alkaloids for promoting weight loss.

Alkaloids↗
PubMed2005

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes.

AIMS/HYPOTHESIS: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. METHODS: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25+/-3 kg/m2) and 19 obese (BMI 55+/-8 kg/m2) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. RESULTS: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1alpha. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. CONCLUSIONS/INTERPRETATION: This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity.

Abdomen↗
PubMed2005

Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level.

To investigate whether functional polymorphisms exist in the C-reactive protein (CRP) gene, i.e., ones that contribute directly to differences in baseline CRP among individuals, we sequenced a 1,156-nucleotide-long stretch of the CRP gene promoter in 287 ostensibly healthy people. We identified two single-nucleotide polymorphisms (SNPs), a bi-allelic one at nucleotide -409 (G-->A), and a tri-allelic one at -390 (C-->T-->A), both resident within the hexameric core of transcription factor binding E-box elements. Electrophoretic mobility shift assays confirmed that the SNP within the sequence (-412)CACGTG(-407) (E-box 1) modulates transcription factor binding, and that the one within (-394)CACTTG(-389) (E-box 2) supports transcription factor binding only when the -390 T allele is present. The commonest of four E-box 1/E-box 2 haplotypes (-409G/-390T) identified in the population supported highest promoter activity in luciferase reporter assays, and the rarest one (-409A/-390T) supported the least. Importantly, serum CRP in people with these haplotypes reproduced this rank order, i.e., people with the -409G/-390T haplotype had the highest baseline serum CRP (mean +/- SEM 10.9 +/- 2.25 microg/ml) and people with the -409A/-390T haplotype had the lowest (5.01 +/- 1.56 microg/ml). Furthermore, haplotype-associated differences in baseline CRP were not due to differences in age, sex, or race, and were still apparent in people with no history of smoking. At least two other SNPs in the CRP promoter lie within E-box elements (-198 C-->T, E-box 4, and -861 T-->C, E-box 3), indicating that not only is the quality of E-box sites in CRP a major determinant of baseline CRP level, but also that the number of E-boxes may be important. These data confirm that the CRP promoter does encode functional polymorphisms, which should be considered when baseline CRP is being used as an indicator of clinical outcome. Ultimately, development of genetic tests to screen for CRP expression variants could allow categorization of healthy people into groups at high versus low future risk of inflammatory disease.

Adult↗
PubMed2005

Obesity and prostate cancer screening in the USA.

OBJECTIVE: To estimate the association between body mass index (BMI: kg/m2) and prostate-specific antigen (PSA) cancer screening in a nationally representative sample of US men aged 50 years and older using data from the 2001 Behavioral Risk Factor Surveillance Survey. RESPONDENTS: Men aged 50 years or older classified by BMI as healthy weight range (18.5-24.9), overweight (25-29.9), obese class I (30-34.9), obese class II (35-39.9), and obese class III (> or =40). OUTCOME MEASURES: Interval since most recent screening for PSA. RESULTS: Adjusting for age, race, smoking, education, employment, income and health insurance status, we found that, compared with men in the healthy weight range, men in the overweight [odds ratio (OR)=1.13; 95% confidence interval (95% CI)=1.04-1.35], obese class I (OR=1.26; 95% CI=1.06-1.36) and obese class II (OR=1.14, 95% CI=1.02-1.26) categories were significantly more likely to have obtained a PSA test within the previous year. A similar pattern was observed when we examined other screening intervals (e.g. within past 2 years, within past 3 years, etc.). CONCLUSIONS: Among men aged 50 years and older, overweight and obesity is associated with obtaining a PSA test.

Body Mass Index↗
PubMed2005

Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids.

BACKGROUND: Human adenovirus-36 (Ad-36) increases adiposity and paradoxically lowers serum cholesterol and triglycerides in chickens, mice, and non-human primates. The role of Ad-36 in human obesity is unknown. OBJECTIVES: To determine the prevalence of Ad-36 antibodies in obese and nonobese humans. To evaluate the association of Ad-36 antibodies with body mass index (BMI) and serum lipids. DESIGN: Cohort study. Volunteers from obesity treatment programs, communities, and a research study. SUBJECTS: Obese and nonobese volunteers at the University of Wisconsin, Madison, WI, and the Bowen Center, Naples, Florida. Obese and thin volunteer research subjects and 89 twin pairs at Columbia University, New York. INTERVENTIONS: Study 1: 502 subjects; serum neutralization assay for antibodies to Ad-2, Ad-31, Ad-36, and Ad-37; serum cholesterol and triglycerides assays. Study 2: BMI and %body fat in 28 twin pairs discordant for Ad-36 antibodies. MAIN OUTCOME MEASURES: Presence of antibodies to adenoviruses, BMI, serum cholesterol and triglycerides levels. RESULTS: Significant (P < 0.001) association of obesity and positive Ad-36 antibody status, independent of age, sex, and collection site. Ad-36 antibodies in 30% of obese, 11% of nonobese. Lower serum cholesterol and triglycerides (P < 0.003) in Ad-36 antibody-positive vs -negative subjects. Twin pairs: antibody-positive twins had higher BMIs (24.5+/-5.2 vs 23.1+/-4.5 kg/m2, P < 0.03) and %body fat (29.6+/-9.5% vs 27.5+/-9.9%, P < 0.04). No association of Ad-2, Ad-31, or Ad-37 antibodies with BMI or serum lipids. CONCLUSIONS: Ad-36 is associated with increased body weight and lower serum lipids in humans. Prospective studies are indicated to determine if Ad-36 plays a role in the etiology of human obesity.

Adenovirus Infections, Human↗
PubMed2005

Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?

Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers.

Alkaloids↗
PubMed2005

Antipsychotic drug-induced weight gain: development of an animal model.

OBJECTIVE: Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition. METHODS: Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment. RESULTS: After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased. CONCLUSIONS: Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

Animals↗
PubMed2005

Lack of association between polymorphism of the human cyclic GMP-dependent protein kinase gene and obesity.

OBJECTIVE: To investigate whether genetic variation in the cyclic GMP-dependent protein kinase gene (PRKG1) is associated with obesity. METHODS: The study included 143 individuals from New York City area, NY, USA. The subjects were sampled on the basis of body mass index (BMI): obese (BMI ranging from 33.8 to 89.5 kg/m(2)), and nonobese (BMI ranging from 16.0 to 29.4 kg/m(2)). The association between C2276T polymorphism in PRKG1 gene and obesity was tested using linear regression analysis. RESULTS: BMI levels were predicted by linear regression models adjusted for demographic factors. An analysis was performed twice: in individuals of all ethnic backgrounds and in European-Americans only. In both cases, genotype did not have a significant effect. CONCLUSION: We found no evidence that the C2276T polymorphism in the PKRG1 gene is associated with obesity.

Adolescent↗
PubMed2005

Prevalence of obesity in the United States.

Obesity is a major public health problem in the United States. Data on measured heights and weights indicates that the prevalence of obesity has significantly increased among the US population over the past 30 years. Data collected from 1999 to 2002 estimates that nearly 1/3 of adults are obese (27.6% of men and 33.2% of women) and one in six children and adolescents is overweight. Increased prevalence of excessive weight is noted among all age, gender and racial/ethnic groups; however, disparities exist. There is a need for further research to better understand why these increases have occurred, why the observed disparities exist and how to reverse these trends.

Adolescent↗
PubMed2005

PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Animals↗
PubMed2004

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

Animals↗
PubMed2004

Caloric restriction and body weight independently affect longevity in Wistar rats.

OBJECTIVE: To evaluate the independent effects of caloric restriction (CR) and body weight (BW) on mortality rate (MR) and the extent to which BW may mediate the effect of CR on MR. DESIGN AND SUBJECTS: Data were from the Biosure Study, a randomized, controlled, prospective intervention study of diet regimens in 1200 Wistar rats. Animals were followed until they died spontaneously, were euthanized because of illness, or reached age 30 months. STATISTICAL ANALYSIS: Cox regression was performed to evaluate the effects of CR and BW on MR. Bootstrap procedures were used to test the contribution of BW to the effect of CR on MR. RESULTS: CR initiated after age 13 weeks decreased the rate of subsequent mortality. The MR increased with higher BW in early adulthood (21 weeks) and this effect persisted even after adjustment for CR. After adjustment for BW in early adulthood, we did not find a similar relation between mortality and BW in late adulthood (105 weeks). Mediation analysis indicated that low BW associated with CR appeared to mediate some of the mortality-reducing effects of CR, but CR clearly had effects independent of BW. The reductions in BW appeared to account for approximately 11% of the effect of CR. CONCLUSION: CR and BW have independent effects on MR in Wistar rats. BW may mediate a small part of the CR effects on MR.

Aging↗