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1.
J Public Health (Oxf) ; 45(4): 935-946, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-37496202

ABSTRACT

BACKGROUND: The prevalence of childhood obesity has been increasing for several decades. Active video games (AVG) may be an effective intervention to help manage this rising health crisis. The aim of this review is to evaluate whether AVG are effective at reducing weight or improving body composition in overweight youths. METHOD: Medline, Embase, SportDiscus, ASSIA, CINAHL Plus, CENTRAL, CDSR and PsychINFO databases were searched for studies assessing quantitative or qualitative impact of AVG in overweight adolescents published in English. Three authors screened the results using inclusion/exclusion criteria. RESULTS: A total of 12 studies met the inclusion criteria; 11 reported a significant decrease in at least one weight outcome. Results from seven randomized controlled trials were pooled by meta-analysis, which compared with controls subjects in AVG groups demonstrated greater body mass index (BMI) Z-score reduction (mean difference: -0.09 (-0.12, -0.05) I2 = 34%, P < 0.0001). The mean weight reduction (-2.66 Kg (-5.67, +0.35) I2 = 0%, P = 0.08) and BMI (-2.29 (-4.81, +0.22) I2 = 49%, P = 0.07) were greater in AVG groups but results did not reach statistical significance. CONCLUSIONS: BMI Z-score was significantly reduced in the AVG group and the majority of included studies reported significant results in at least one weight outcome, suggesting AVG can be used to reduce weight or improve body composition in overweight youths. Further studies investigating the long-term sustainability of this change in body composition are needed.


Subject(s)
Pediatric Obesity , Video Games , Child , Humans , Adolescent , Pediatric Obesity/prevention & control , Overweight/prevention & control , Body Mass Index
2.
Herz ; 45(6): 564-571, 2020 Sep.
Article in English | MEDLINE | ID: mdl-30209519

ABSTRACT

BACKGROUND: Emerging evidence indicates combination therapy with anticoagulants and antiplatelet agents for atrial fibrillation (AF) will be increasingly required. Numerous studies compare the efficacy and cost-effectiveness of anticoagulation alone in AF, i. e., non-vitamin K oral anticoagulants (NOACs) vs. warfarin. However, the addition of antiplatelet agents with their potential for decreasing thromboembolic stroke counter-balanced by an increased bleeding risk has received less attention. Thus, we evaluated the cost-utility of this combination therapy. METHOD AND RESULTS: We obtained event estimates from our recent meta-analysis of four randomized clinical trials designed to compare NOACs with warfarin in patients with AF. We examined patient subgroups within each trial that received antiplatelet therapy in addition to anticoagulation. Utilities were derived from the literature and cost estimates from the German health-care system. A decision tree was constructed and populated with these parameters. We used a 1-year time horizon because combination therapy is not recommended beyond this time. We calculated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). The derived ICER was 13,168.50 € per QALY. NOAC prices exerted considerable influence on the calculation. Nevertheless, there is potential for ICER shifts in favor of warfarin, e.g., if warfarin-mediated anticoagulation control is improved and thereby adverse events decrease. Conversely, if NOAC adherence decreases, adverse events could increase. CONCLUSION: The derived ICER was 13,168.50 € per QALY, consistent with NOACs being cost-effective vs. warfarin when anticoagulation is used with antiplatelet agents. Nevertheless, country-, practice-, and patient-related factors influence the ICER. Our cost-utility calculation should be used a starting point for decision-making.


Subject(s)
Atrial Fibrillation , Stroke , Administration, Oral , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Humans , Platelet Aggregation Inhibitors/therapeutic use , Stroke/drug therapy , Stroke/prevention & control , Vitamin K , Warfarin/therapeutic use
3.
Theriogenology ; 118: 90-95, 2018 Sep 15.
Article in English | MEDLINE | ID: mdl-29885645

ABSTRACT

The main objective was to compare pregnancy per AI (P/AI) between sex-selected and conventional semen in cyclic beef heifers subjected to a 5-day Co-synch plus CIDR protocol and evaluated the usefulness of an estrus detection (ED) aid to identify heifers that were most likely to conceive. This study also determined if the expression of estrus before timed-AI (TAI) would be associated with increased P/AI in acyclic heifers inseminated with conventional semen. Heifers (n = 1690; 320-523 kg of body weight, and 13-15 mo of age) at three locations over 2 years were scanned by ultrasonography to determine cyclicity (presence of luteal tissue) and reproductive tract normalcy. Cyclic heifers (n = 1331) received a progesterone releasing device (CIDR) on Day 0, CIDR removal and 500 µg of cloprostenol (PGF) on Day 5, and 100 µg of GnRH along with TAI on Day 8. Acyclic heifers (n = 275) received the same treatment with the addition of GnRH on Day 0. On Day 5, all heifers received ED patches (Estrotect™) that were scored from 0 to 3, based on color change between initial application and Day 8; 0 = unchanged, 1 = ≤ 50% color change, 2 = > 50% color change, 3 = missing. Estrus was defined to have occurred when an ED patch was scored 2 or 3. Cyclic heifers were inseminated with either frozen-thawed sex-selected or conventional semen from either of three sires available commercially (two per year). Acyclic heifers were inseminated with conventional semen. Pregnancy diagnosis was performed by transrectal ultrasonography 28 or 48 d after TAI, depending on management. The percentage of cyclic heifers was 83.9% and the average estrus response was 63.8%. P/AI was greater (P < 0.01) in cyclic compared to acyclic heifers (53.3 vs. 36.0%) and tended to be greater (P = 0.07) for conventional semen (52.3 vs. 47.6%), despite all acyclic heifers being inseminated with conventional semen. Heifers with an ED patch scored 2 (61.1%) or 3 (58.6%) had greater (P < 0.01) P/AI than those scored 0 (31.8%) or 1 (33.1%), regardless of semen type. Pregnancy per AI was greater (P < 0.01) for heifers detected in estrus (60.6 vs. 32.3%). In cyclic heifers that did not exhibit estrus, P/AI was lower (P < 0.01) in those inseminated with sex-selected semen (27.8 vs. 45.9%), while in heifers that exhibited estrus, P/AI only tended to be lower (P = 0.08; 56.7 vs. 65.5%). In summary, P/AI was greater in cyclic heifers, in those inseminated with conventional semen and in those exhibiting estrus before TAI. The ED patches were considered useful to identify animals for TAI with sex-selected semen and could be used to increase the adoption of this technology in beef herds.


Subject(s)
Cattle , Estrus Detection , Gonadotropin-Releasing Hormone/administration & dosage , Insemination, Artificial/veterinary , Semen , Sex Preselection/veterinary , Animal Husbandry/methods , Animals , Cryopreservation/veterinary , Estrus/physiology , Female , Insemination, Artificial/methods , Pregnancy , Red Meat , Semen Preservation/veterinary , Time Factors
4.
Theriogenology ; 106: 39-45, 2018 Jan 15.
Article in English | MEDLINE | ID: mdl-29035836

ABSTRACT

This study evaluated the effect of initial GnRH and timing of AI in a 5-d Co-synch plus CIDR (device containing 1.38 g of progesterone) protocol on pregnancy per AI (P/AI) and pregnancy loss in beef heifers. A secondary objective was to determine if the effect of initial GnRH on reproductive performance was influenced by cyclicity. Crossbred beef heifers (n = 1068; 301-514 kg of body weight, and 13-15 mo of age) at three locations were assigned to either a 5-d Co-synch plus CIDR protocol with (CIDR5G) or without (CIDR5NG) an initial injection of 100 µg of GnRH at CIDR insertion (Day 0). All heifers received a single dose of 500 µg of cloprostenol at CIDR removal (Day 5) and were divided into two groups to receive GnRH and TAI at either 66 or 72 h (Day 8) after CIDR removal. All heifers were inseminated by one technician with frozen-thawed semen from 1 of 4 sires available commercially. Transrectal ultrasonography was performed on Day 0 to determine cyclicity (presence of CL) and normalcy of the reproductive track, and 27 d after TAI to determine pregnancy status. Non-pregnant heifers (n = 470) were assigned to either a CIDR5G or a CIDR5NG protocol with TAI at 72 h after CIDR removal. Twelve days after second AI, heifers were exposure to bulls for 20 d and pregnancy diagnoses were performed approximately 30 d after second TAI and 60 d after bulls were removed to diagnose bull pregnancies and determine pregnancy loss rate. The percentage of acyclic heifers was 20.3%. Overall P/AI after first TAI was 55.6% (594/1068) and did not differ between CIDR5G and CIDR5NG (56.1 vs. 55.1%), or between TAI66 and TAI72 (55.8 vs. 55.4%). However, cyclic heifers were more likely to become pregnant than acyclic ones (59.3 vs. 41.2%; P < 0.01). Moreover, acyclic heifers subjected to the CIDR5NG had fewer P/AI than those subjected to CIDR5G (P < 0.01). Overall P/AI after resynchronization was 55.1% and did not differ between CIDR5G and CIDR5NG (51.3 vs. 59.0%). Overall pregnancy loss after first and second TAI were 3.0% (18/594) and 3.9% (8/205), respectively. When pregnancy loss data were combined, synchronization protocol (4.1 vs. 2.3% for CIDR5NG and CIDR5G; P = 0.01), cyclicity (5.8 vs. 2.9% for acyclic and cyclic; P = 0.03) and the interaction between synchronization protocol and cyclicity (P = 0.04) were significant. The overall cumulative pregnancy at the end of the breeding season was 94.2% (1006/1068); acyclic heifers were less likely to be pregnant at the end of the breeding season (88.4 vs. 95.8%; P < 0.01). In summary, the initial GnRH administration in a 5-d Co-synch plus CIDR protocol that includes a single PGF treatment is necessary in acyclic beef heifers to optimize P/AI, but not in cyclic heifers. Moreover, omission of initial GnRH was associated to greater pregnancy losses, particularly in acyclic heifers. Timing of AI did not affect P/AI.


Subject(s)
Cattle , Estrus Synchronization/methods , Gonadotropin-Releasing Hormone/pharmacology , Insemination, Artificial/veterinary , Progesterone/pharmacology , Abortion, Veterinary , Animals , Corpus Luteum/drug effects , Corpus Luteum/physiology , Female , Fertility Agents, Female , Gonadotropin-Releasing Hormone/administration & dosage , Pregnancy , Pregnancy Rate , Progesterone/administration & dosage , Progestins/administration & dosage , Progestins/pharmacology
5.
Public Health ; 148: 140-148, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28482322

ABSTRACT

OBJECTIVES: This study aims to review the current literature to assess the effectiveness of E-health interventions in increasing physical activity (PA) in young people. STUDY DESIGN: This study is a systematic review of the literature. METHODS: A search of the literature databases Embase, MEDLINE and the Cochrane Library using key words 'Adolescents'; 'Young people'; 'Students'; 'Young Adults'; 'Teenagers'; 'E-health'; 'Internet-based'; 'Web-based'; 'Exercise'; 'Activity'; 'Sport' and 'Intervention' yielded 10 articles which fit the criteria for inclusion. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used, and papers were excluded if they were disease focused, not specific to young people (those attending school, college or university) or did not measure PA as an outcome. RESULTS: Eight of the 10 studies had significant increases in PA as a result of an E-health intervention. Studies that did not use a theoretical principle to underpin their intervention did not achieve successful results. Interventions based on social cognitive theory were very successful in achieving an increase in PA. The theory of planned behaviour had mixed results, with studies having contrasting results. Specific, measurable, achievable, relevant and time-bound (SMART) goal principle was not effective in increasing PA but had positive findings in supplementary outcomes such as goal setting. CONCLUSIONS: E-health interventions are a very successful way to increase PA. More research is required to look at what theoretical principles are best to underpin interventions and also to assess the length of intervention required for optimal results after intervention. Ideas surrounding implementation and the mediums used require more studies to evidence base these interventions for schools, colleges and university via intracurriculum or extracurriculum.


Subject(s)
Exercise , Health Promotion/methods , Internet , Telemedicine , Adolescent , Humans , Program Evaluation , Randomized Controlled Trials as Topic
6.
J Public Health (Oxf) ; 36(1): 156-60, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23596195

ABSTRACT

BACKGROUND: Infant male circumcision is practised by many groups for religious and cultural reasons. Prompted by a desire to minimize the complication rate and to help parents identify good quality providers, a quality assurance (QA) process for infant male circumcision providers has been developed in Greater Manchester. METHODS: Local stakeholders agreed a set of minimum standards, and providers were invited to submit evidence of their practice in relation to these standards. In participation with parents, community groups, faith groups, healthcare staff and safeguarding partners, an information leaflet for parents was produced. Engagement work with local community groups, faith groups, providers and healthcare staff was vital to ensure that the resources are accessible to parents and that providers continue to engage in the process. RESULTS: Providers that met the QA standards have been listed on a local website. Details of the website are included in the information leaflet distributed by maternity services, health visitors, primary care and community and faith groups. The leaflet is available in seven languages. CONCLUSIONS: Local QA processes can be used to encourage and identify good practice and to support parents who need to access services outside the remit of the National Health Service.


Subject(s)
Circumcision, Male/standards , Quality Assurance, Health Care/methods , England , Health Education/methods , Humans , Infant , Male , Quality Assurance, Health Care/organization & administration
7.
J Thromb Haemost ; 8(2): 331-40, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19922435

ABSTRACT

BACKGROUND: Release of serotonin and activation of serotonin 5HT2A receptors on platelet surfaces is a potent augmentative stimulus for platelet aggregation. However, earlier-generation serotonin receptor antagonists were not successfully exploited as antiplatelet agents, possibly owing to their lack of specificity for the 5HT2A receptor subtype. OBJECTIVE: To assess whether targeted inhibition of the serotonin 5HT2A receptor attenuates recurrent thrombosis and improves coronary patency in an in vivo canine model mimicking unstable angina. METHODS: In protocol 1, anesthetized dogs were pretreated with a novel, selective inverse agonist of the 5HT2A receptor (APD791) or saline. Recurrent coronary thrombosis was then initiated by coronary artery injury+stenosis, and coronary patency was monitored for 3 h. Protocol 2 was similar, except that: (i) treatment with APD791 or saline was begun 1 h after the onset of recurrent thrombosis; (ii) template bleeding time was measured; and (iii) blood samples were obtained for in vitro flow cytometric assessment of platelet responsiveness to serotonin. RESULTS: APD791 attenuated recurrent thrombosis, irrespective of the time of treatment: in both protocols, flow-time area (index of coronary patency; normalized to baseline coronary flow) averaged 58-59% (P<0.01) following administration of APD791 vs. 21-28% in saline controls. Moreover, the in vivo antithrombotic effect of APD791 was not accompanied by increased bleeding, but was associated with significant and selective inhibition of serotonin-mediated platelet activation. CONCLUSION: 5HT2A receptor inhibition with APD791, even when initiated after the onset of recurrent thrombosis, improves coronary patency in the in vivo canine model.


Subject(s)
Benzamides/pharmacology , Blood Platelets/drug effects , Coronary Thrombosis/drug therapy , Fibrinolytic Agents/pharmacology , Morpholines/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Pyrazoles/pharmacology , Serotonin 5-HT2 Receptor Antagonists , Serotonin Antagonists/pharmacology , Vascular Patency/drug effects , Animals , Benzamides/blood , Benzamides/toxicity , Blood Platelets/metabolism , Coronary Circulation/drug effects , Coronary Thrombosis/blood , Coronary Thrombosis/pathology , Coronary Thrombosis/physiopathology , Disease Models, Animal , Dogs , Drug Inverse Agonism , Fibrinolytic Agents/blood , Fibrinolytic Agents/toxicity , Hemodynamics/drug effects , Hemorrhage/chemically induced , Morpholines/blood , Morpholines/toxicity , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/blood , Platelet Aggregation Inhibitors/toxicity , Pyrazoles/blood , Pyrazoles/toxicity , Receptor, Serotonin, 5-HT2A/blood , Recurrence , Serotonin Antagonists/blood , Serotonin Antagonists/toxicity , Time Factors
8.
Diabetes Obes Metab ; 11 Suppl 1: 8-16, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19143810

ABSTRACT

AIM: The aim of this study was to test chromosomes carrying the same DRB1-DQA1-DQB1 haplotype for single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) that might mark subgroups of the haplotype with different risks for type 1 diabetes (T1D). METHODS: Chromosomes from T1D children, their parents and non-diabetic siblings in families of the Type 1 Diabetes Genetics Consortium (T1DGC) were analysed by two haplotype-based methods: (i) logistic regression analysis restricted to phased chromosomes carrying the same DRB1-DQA1-DQB1 haplotype but differentiated by the two alleles at MHC SNPs, which were individually tested for association with T1D and (ii) homozygous parent transmission disequilibrium test (TDT) for biased transmission of a SNP allele to diabetic children from parents who are heterozygous at the SNP but homozygous for the specific DRB1-DQA1-DQB1 haplotype being evaluated. RESULTS: A number of SNPs gave nominally significant (p < 0.05) evidence of marking two subsets of the 301-501-201 haplotype that might differ with respect to their diabetogenic potency. However, none of the SNPs achieved experiment-wide significance and hence may be false-positive associations. CONCLUSIONS: We discuss limitations and possible deficiencies of our study suggesting further work that might yield more robust SNP associations marking two subgroups of a DRB1-DQA1-DQB1 haplotype with different T1D risks.


Subject(s)
Diabetes Mellitus, Type 1/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Major Histocompatibility Complex/genetics , Polymorphism, Single Nucleotide/genetics , Genetic Predisposition to Disease/genetics , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , HLA-DRB1 Chains , Haplotypes , Heterozygote , Homozygote , Humans , Pedigree , Regression Analysis , Risk Factors
9.
Epidemiol Infect ; 137(3): 375-82, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19102799

ABSTRACT

A national outbreak of verotoxin-producing Escherichia coli O157 infection affected five English regions and Wales. Twelve cases were associated with lemon-and-coriander chicken wrap from a single supermarket chain consumed over a 5-day period. An outbreak investigation aimed to identify the source of infection. Descriptive epidemiology and phenotypic and genotypic tests on human isolates indicated a point-source outbreak; a case-control study showed a very strong association between consumption of lemon-and-coriander chicken wrap from the single supermarket chain and being a case (OR 46.40, 95% CI 5.39-infinity, P=0.0002). Testing of raw ingredients, products and faecal samples from staff in the food production unit did not yield any positive results. The outbreak was probably caused by one contaminated batch of an ingredient in the chicken wrap. Even when current best practice is in place, ready-to-eat foods can still be a risk for widespread infection.


Subject(s)
Chickens/microbiology , Citrus/microbiology , Coriandrum/microbiology , Disease Outbreaks , Escherichia coli Infections/epidemiology , Food Microbiology , Foodborne Diseases/epidemiology , Foodborne Diseases/microbiology , Shiga-Toxigenic Escherichia coli/isolation & purification , Adolescent , Adult , Animals , Case-Control Studies , Chi-Square Distribution , Electrophoresis, Gel, Pulsed-Field , Female , Food Contamination , Food Handling , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology
10.
Diabetologia ; 51(11): 1998-2002, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18773191

ABSTRACT

AIMS/HYPOTHESIS: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. METHODS: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A chi (2) test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. RESULTS: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups. CONCLUSIONS/INTERPRETATION: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.


Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetic Nephropathies/genetics , Polymorphism, Single Nucleotide , Adult , Diabetes Mellitus, Type 1/drug therapy , Genetic Predisposition to Disease , Humans , Insulin/therapeutic use , Ireland , Kidney Failure, Chronic/genetics , United Kingdom
11.
Lancet ; 371(9623): 1505-12, 2008 May 03.
Article in English | MEDLINE | ID: mdl-18455228

ABSTRACT

BACKGROUND: Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density. METHODS: In this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies. FINDINGS: We identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density. INTERPRETATION: Two gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.


Subject(s)
Bone Density/genetics , Fractures, Bone/etiology , LDL-Receptor Related Proteins/genetics , Osteoporosis/genetics , Osteoprotegerin/genetics , Polymorphism, Single Nucleotide/genetics , Alleles , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 8 , Female , Gene Expression , Genetic Markers , Genome, Human , Genotype , Humans , Low Density Lipoprotein Receptor-Related Protein-5 , Lumbar Vertebrae , Male , Middle Aged , Osteoporosis/complications
12.
Inhal Toxicol ; 19(11): 915-23, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17849276

ABSTRACT

Although small airway remodeling (SAR) leading to airflow obstruction is a common consequence of human cigarette smoking, the airways have been largely ignored in animal models of chronic obstructive pulmonary disease (COPD). We examined lung structure in a guinea pig model of chronic cigarette smoke exposure to ascertain whether smoke induced SAR, and to evaluate how these anatomic lesions correlate with physiologic changes. We used tissue from guinea pigs exposed to cigarette smoke or air for 6 mo. Pulmonary function tests were performed, and histologic sections were prepared. Airspace size (Lm) and changes in the structure of the small airways were evaluated by morphometric analysis. Chronic smoke exposure was associated with increased airway wall thickness and increased amounts of thick collagen fibers in the walls of the small airways, as well as with increased Lm. The increase in thick collagen fibers related negatively to peak expiratory volume (PEF) and the ratio of forced expiratory volume in 1 s to forced ventilatory capacity (FEV(0.1)/FVC), and positively to airway resistance. Physiologic lung volumes were predicted by airspace size, but residual volume (RV) and total lung capacity (TLC) also were related to airway wall thickness. Amounts of smooth muscle were not changed and did not predict any physiologic abnormalities. We conclude that cigarette smoke exposure results in SAR in the guinea pig, alterations that are reflected in increased airways resistance with diminished airflow and air trapping, mimicking human disease. This model should prove useful in further investigations into the mechanisms of airway remodeling.


Subject(s)
Disease Models, Animal , Pulmonary Disease, Chronic Obstructive/pathology , Respiratory Mucosa/pathology , Smoking/pathology , Animals , Female , Guinea Pigs , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests/methods , Respiratory Mucosa/physiopathology , Smoking/adverse effects , Smoking/physiopathology
13.
J Thromb Haemost ; 4(12): 2670-7, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16995902

ABSTRACT

BACKGROUND: Previous studies have shown that ischemic preconditioning (PC) not only limits infarct size, but also improves arterial patency in models of recurrent thrombosis. We hypothesize that this enhanced patency is presumably because of a PC-induced attenuation of platelet-mediated thrombosis. However, there is, at present, no direct evidence that PC acts on the platelets per se and favorably down-regulates platelet reactivity. OBJECTIVES: Our goal was to test the concept that PC ischemia attenuates molecular indices of platelet activation-aggregation. METHODS: Anesthetized dogs were randomly assigned to receive 10 min of PC ischemia followed by 10 min of reperfusion or a time-matched control period. Spontaneous recurrent coronary thrombosis was then initiated in all dogs by injury + stenosis of the left anterior descending coronary artery. Coronary flow was monitored for 3 h poststenosis, and molecular indices of platelet activation-aggregation were quantified by whole blood flow cytometry. RESULTS: Coronary patency was, as expected, better-maintained following injury + stenosis in the PC group vs. controls (53% +/- 5%* vs. 23% +/- 5% of baseline flow, respectively; *P < 0.05). Moreover, PC was accompanied by: (i) a significant down-regulation of platelet-fibrinogen binding and formation of neutrophil-platelet aggregates (112% +/- 14%* vs. 177% +/- 21% and 107% +/- 8%* vs. 155% +/- 19% of baseline values in PC vs. control groups); and (ii) a trend towards a reduction in platelet P-selectin expression (148% +/- 12% vs. 190% +/- 21% of baseline; *P < 0.05 and P = 0.09 vs. control). CONCLUSION: These data provide novel, direct evidence in support of the concept that ischemic PC attenuates molecular indices of platelet activation-aggregation.


Subject(s)
Coronary Thrombosis/blood , Ischemic Preconditioning, Myocardial , Myocardial Reperfusion Injury/blood , Platelet Activation , Animals , Blood Flow Velocity , Blood Platelets/metabolism , Coronary Circulation , Coronary Thrombosis/pathology , Coronary Thrombosis/physiopathology , Coronary Thrombosis/prevention & control , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Disease Models, Animal , Dogs , Fibrinogen/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/prevention & control , P-Selectin/metabolism , Platelet Adhesiveness , Platelet Aggregation , Random Allocation , Vascular Patency
14.
Theriogenology ; 65(3): 557-72, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16039702

ABSTRACT

The objective was to determine the efficacy of a previously used CIDR or melengestrol acetate (MGA; 0.5mg/head/day) for resynchronization of estrus in beef heifers not pregnant to timed-AI (TAI). In three experiments and a field trial, heifers were reinseminated 6-12 h after first detection of estrus. Pregnancy diagnosis was done from approximately 25-43 days after either TAI or reinsemination. In Experiment 1, 79 heifers received a once-used CIDR from 13 to 20 days after TAI and 80 heifers were untreated controls. For these two groups, there were 34 and 35 heifers, respectively, not pregnant to TAI; median +/- S.E. intervals from TAI to onset of estrus were 22 +/- 0.2 days versus 20 +/- 0.6 days (P < 0.001); estrus rates were 70.6% versus 85.7% (P = 0.1); conception rates were 62.5% versus 76.7% (P < 0.3); and pregnancy rates were 44.1% versus 65.7% (P = 0.07), for CIDR and untreated (control) groups, respectively. In Experiment 2, heifers (n = 651) were TAI (Day 0) and 13 days later randomly assigned to one of seven groups (n = 93 per group) to receive a once-used CIDR (three groups; Days 13-20), MGA (three groups; Days 13-19), or no treatment (control group). Groups given a CIDR or MGA also received: no further treatment (CIDR or MGA alone); 1.5mg estradiol-17beta (E-17beta) and 50 mg progesterone (P4) in 2 mL canola oil on Day 13; or E-17beta and P4 on Day 13 and 0.5 mg E-17beta on Day 21 (24 h after CIDR removal or 48 h after the last feeding of MGA). Pregnancy rate to TAI was lowest (P < 0.05) for the group given a CIDR plus E-17beta and P4 on Day 13 and E-17beta on Day 21. Variability in return to estrus was greater (P < 0.001) in the control and MGA groups than in CIDR groups. Conception and pregnancy rates in heifers given a CIDR (65.1 and 61.4%) were higher (P<0.01) than those fed MGA (49.6 and 40.4%), but not different from controls (62.2 and 54.9%, respectively). In Experiment 3, 616 heifers received a once- or twice-used CIDR for 7 days, beginning 13+/-1 days after TAI, with or without a concurrent injection of 150 mg of P4 (2 x 2 factorial design). Pregnancy rate to TAI was 47.2%. In heifers that returned to estrus, there was no significant difference between a once- or twice-used CIDR for rates of estrus (68.8%, P < 0.3), conception (65.9%, P < 0.6) and pregnancy (45.3%, P < 0.8). Injecting progesterone at CIDR insertion increased the median interval from CIDR removal to onset of estrus (P < 0.05) and reduced rates of estrus (63.8% versus 73.8%, P<0.05), conception (60.5% versus 70.6%, P = 0.1) and pregnancy (38.6% versus 52.2%, P < 0.02). In a field trial, 983 heifers received a once-used CIDR for 7 days, beginning 13 +/- 1 days after TAI. Pregnancy rate to TAI was 55.2%. The median (and mode) of the interval from CIDR removal to estrus was 2.5 days. Estrus, conception and pregnancy rates were 78.2, 70.3 and 55.0% (overall pregnancy rate to TAI and rebreeding, 78.7%). In summary, a once- or twice-used CIDR for 7 days, starting 13 +/- 1 days after TAI resulted in the majority of nonpregnant heifers detected in estrus over a 4-day interval, with acceptable conception rates; however, injecting progesterone at CIDR insertion significantly reduced both estrus and pregnancy rates, and estradiol treatment after CIDR removal was associated with a decreased pregnancy rate to TAI. Fertility was higher in heifers resynchronized with a once-used CIDR than with MGA.


Subject(s)
Breeding/methods , Cattle/physiology , Estrus Synchronization/methods , Fertility/drug effects , Progestins/pharmacology , Reproduction/drug effects , Animals , Drug Implants , Estradiol/administration & dosage , Estradiol/analogs & derivatives , Female , Insemination, Artificial/veterinary , Pregnancy , Pregnancy Rate , Progesterone/administration & dosage , Prostaglandins F/administration & dosage , Random Allocation , Time Factors
15.
Theriogenology ; 61(6): 1115-24, 2004 Apr 15.
Article in English | MEDLINE | ID: mdl-15036999

ABSTRACT

The objectives were to determine pregnancy rates following fixed-time AI (FTAI) in heifers: (1). given GnRH or estradiol cypionate (ECP) to synchronize follicular wave emergence and ovulation in a CIDR-based protocol; and (2). fed diets supplemented with flax or sunflower seeds. At two locations, Angus and crossbred Angus heifers (n=983) were examined ultrasonically to confirm reproductive maturity and randomly allocated to six synchronization groups in a 2 x 3 factorial design. On Day 0 (start of synchronization treatments), heifers received a CIDR and either 100 microg GnRH i.m. (n=492) or 1mg ECP plus 50 mg progesterone i.m. (n=491); in these groups, CIDR removal and PGF treatment were done concurrently on Days 7 and 8.5, respectively. Heifers were re-randomized to receive 0.5 mg ECP i.m. at CIDR removal or 24 h later (with FTAI 58-60 h after CIDR removal in both groups), or 100 microg GnRH i.m. concurrent with FTAI (52-54 h after CIDR removal). The heifers were fed a barley silage-based diet for 50 days (from Day -25 to 25) supplemented with 1kg/heifer per day of flax seed (n=321), sunflower seed (n=324), or no oilseed (n=338). Pregnancy rate to FTAI (overall, 56.2%) was not affected by treatment at CIDR insertion (P = 0.96) but was higher (P < 0.05) in heifers given ECP 24h after CIDR removal (216/330, 65.4%) than in those given either ECP at CIDR removal (168/322, 52.1%) or GnRH at AI (169/331, 51.1%). Overall, there was no effect of diet on pregnancy rates (P = 0.46). In summary, pregnancy rate to FTAI was not significantly affected by treatment at CIDR insertion to synchronize follicular wave emergence, but 0.5mg ECP 24h after CIDR removal (to synchronize ovulation) resulted in the highest pregnancy rate.


Subject(s)
Cattle/physiology , Diet , Estradiol/analogs & derivatives , Estradiol/administration & dosage , Fertilization , Gonadotropin-Releasing Hormone/administration & dosage , Insemination, Artificial/veterinary , Animals , Dietary Fats, Unsaturated/administration & dosage , Female , Flax , Helianthus , Insemination, Artificial/methods , Linoleic Acid/administration & dosage , Ovulation Induction/veterinary , Pregnancy , Seeds , alpha-Linolenic Acid/administration & dosage
16.
Anim Reprod Sci ; 81(1-2): 25-34, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14749046

ABSTRACT

The objective was to compare pregnancy rates following fixed-time AI (FTAI) in beef cattle given a new or previously used CIDR insert and injections of estradiol, with or without progesterone, to synchronize follicular wave emergence. In Experiment 1, heifers (n=616) received a new or once-used CIDR insert for 9 days and were given 1mg estradiol cypionate (ECP), with or without 100 mg of a commercial progesterone preparation (CP4), at CIDR insertion. Heifers were treated with PGF at CIDR removal and 0.5 mg ECP i.m. 24h later, with FTAI 55 to 60 h after CIDR removal. Pregnancy rate was not affected by either the number of CIDR uses (P=0.59; 48.3% versus 46.2% for new versus once-used CIDRs, respectively) or the addition of progesterone (P=0.42; 45.6% versus 48.8% for ECP+CP4 and ECP, respectively). In Experiment 2 (replicated at two locations), heifers (n=56) and lactating beef cows (n=307) received a once- or twice-used CIDR and an i.m. injection of 1mg estradiol benzoate (EB), with or without 100 mg progesterone, at CIDR insertion. Cattle received PGF in the ischiorectal fossa at CIDR removal (Day 7) and 1mg EB i.m. 24h later, with FTAI 52 to 56 h after CIDR removal. Pregnancy rate was affected by location (P<0.002; 46.0% versus 61.1% for Locations A and B, respectively), parity (P<0.04; 67.9% versus 53.1% in heifers and cows, respectively), and numbers of times the CIDR had been used (P<0.03; 62.4% versus 48.4% for once- and twice-used CIDRs, respectively). However, the addition of progesterone to the injection of EB at CIDR insertion did not affect pregnancy rate (P=0.6). In Experiment 3, heifers (n=187) received one new, one once-used, one twice-used or two twice-used CIDRs for 7 days and 2 mg EB plus 50 mg of CP4 at the time of CIDR insertion. Heifers were treated with PGF at CIDR removal and 1mg EB i.m. 24 h later, with FTAI 52-56 h after CIDR removal. Pregnancy rate was not affected by treatments (P=0.28, 57.5, 63.8, 47.9, 47.9% for one new, one once-used, one twice-used, or two twice-used CIDRs, respectively). In summary, pregnancy rate to FTAI did not differ between cattle synchronized with a new or once-used CIDR, but pregnancy rate was lower in cattle synchronized with a twice-used CIDR; however, the insertion of two twice-used CIDRs did not affect pregnancy rates. The addition of an injection of progesterone to the estradiol treatment at CIDR insertion did not enhance pregnancy rate to FTAI.


Subject(s)
Cattle/physiology , Equipment Reuse/veterinary , Estradiol/administration & dosage , Fertility , Progesterone/administration & dosage , Administration, Intravaginal , Animals , Female , Pregnancy
17.
J Microbiol Methods ; 55(3): 709-16, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14607413

ABSTRACT

Identification of bacterial species by profiling fatty acid methyl esters (FAMEs) has commonly been carried out by using a 20-min capillary gas chromatographic procedure followed by library matching of FAME profiles using commercial MIDI databases and proprietary pattern recognition software. Fast GC (5 min) FAME procedures and mass spectrometric methodologies that require no lipid separation have also been reported. In this study, bacterial identification based on the rapid (2 min) infrared measurement of FAME mixtures was demonstrated. The microorganisms investigated included Gram positive bacteria Staphylococcus aureus, Listeria monocytogenes, Bacillus anthracis, and Bacillus cereus, and Gram negative bacteria from the family Enterobacteriacae: Yersinia enterocolitica, Salmonella typhimurium, Shigella sonnei, and Escherichia coli (four strains of E. coli), and non-Enterobacteriacae: Vibrio cholerae, Vibrio vulnificus, and Vibrio parahemolyticus. Foodborne bacterial mixtures of FAMEs were measured by using an attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopic procedure and discriminated by multivariate analysis. Results showed that the Enterobacteriacae could be discriminated from the vibrios. The identification was at the level of species (for the Bacillus and Vibrio genera) or strains (for the E. coli species). A series of bacterial FAME test samples were prepared and analyzed for accuracy of identification, and all were correctly identified. Our results suggest that this infrared strategy could be used to identify foodborne pathogens.


Subject(s)
Fatty Acids/analysis , Food Microbiology , Gram-Negative Bacteria/metabolism , Gram-Positive Bacteria/metabolism , Spectroscopy, Fourier Transform Infrared/methods , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Multivariate Analysis
18.
Regul Toxicol Pharmacol ; 36(3): 280-6, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12473412

ABSTRACT

According to the American Association of Poison Control Centers, exposures to excessive doses of iron supplements still occur in children less than 6 years of age. Since 1998, there has been one death among U.S. children in this age group. Exposures, including adverse events, to iron supplements and iron-containing vitamins for the years 1999 and 2000 were 23,215 and 24,249, respectively. To reduce the potential seriousness of such exposures, carbonyl iron (Fe(0)) has been suggested as a possible replacement for ferrous sulfate (FeSO(4)). Carbonyl Fe is a unique form of elemental iron because of its small particle size. It is highly bioavailable when used to correct iron deficiency anemia. There is also current interest in using sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA) for food fortification. In this study both NaFeEDTA and carbonyl Fe were compared with FeSO(4), the most common form of iron for dietary supplements, to obtain information relevant to the acute toxicological profile in young rats. With FeSO(4) and NaFeEDTA, total liver nonheme iron increased with increasing dose, but the response was approximately 50% lower with NaFeEDTA compared with FeSO(4). Serum iron peaked at approximately 0.5 to 1 h for both FeSO(4) and carbonyl Fe, while NaFeEDTA was elevated up to 4 h. FeSO(4) had an LD(50) of 1.1 g Fe/kg and was approximately 45 times more toxic than carbonyl Fe, which had an LD(50) greater then 50 g Fe/kg. NaFeEDTA had an LD(50) of 1.3 g Fe/kg and, when compared with FeSO(4), had approximately the same level of toxicity.


Subject(s)
Adjuvants, Immunologic/toxicity , Edetic Acid/toxicity , Ferric Compounds/toxicity , Ferrous Compounds/toxicity , Iron Chelating Agents/toxicity , Organometallic Compounds/toxicity , Adjuvants, Immunologic/pharmacokinetics , Animals , Chemistry, Pharmaceutical , Delayed-Action Preparations , Dietary Supplements/poisoning , Edetic Acid/pharmacokinetics , Ferric Compounds/pharmacokinetics , Ferrous Compounds/pharmacokinetics , Humans , Iron Carbonyl Compounds , Iron Chelating Agents/pharmacokinetics , Lethal Dose 50 , Male , Organometallic Compounds/pharmacokinetics , Poisoning/prevention & control , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species
19.
Br J Nutr ; 86(5): 587-92, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11737956

ABSTRACT

The effects of increasing levels of Fe on serum fatty acids, cholesterol, triacylglycerol, liver and heart were examined in male Sprague-Dawley rats fed either Fe-deficient or carbonyl Fe-supplemented diets with 35 (control), 350, 3500 and 20 000 microg Fe/g for 12 weeks. As intake of Fe increased, serum total cholesterol increased from 2.0 mmol/l in controls to 5.2 mmol/l at the highest level of Fe. Also, the total serum phospholipid fatty acids increased from 609 mg/dl in controls to 1292 mg/l at the highest level of Fe. Except for the highest dose of Fe, the ratio of saturated to unsaturated phospholipid fatty acids increased from 1.2 to 1.7. The serum total free fatty acid levels remained constant among all groups with a range from 162 to 228 mg/l, while a ratio of 0.6 to 0.8 for saturated to unsaturated fatty acids was maintained. A dose-related increase in liver non-haem Fe from 18 to 3500 microg/g correlated with increases in lipid peroxidation (r 0.87), measured by the lipid-conjugated diene assay. Oxidative changes in the liver may have resulted in alterations in sterol synthesis, leading to increased serum cholesterol levels with increases in serum phospholipids and changes in the ratios of their saturated to unsaturated fatty acids. Animals with heart damage showed myocardial degeneration and cardiomyopathy with haemosiderin in interstitial macrophages or myocardial fibres and, when these were coupled with the findings of increased non-haem Fe in the heart and lipid peroxidation in the liver, suggested that oxidative stress is involved in the pathogenesis of the lesions.


Subject(s)
Iron, Dietary/administration & dosage , Lipids/blood , Analysis of Variance , Animals , Cholesterol/blood , Chromatography, Thin Layer/methods , Dose-Response Relationship, Drug , Fatty Acids/blood , Lipid Peroxidation/drug effects , Liver/drug effects , Male , Myocardium , Rats , Rats, Sprague-Dawley , Spectrophotometry/methods , Triglycerides/blood
20.
J Am Coll Cardiol ; 38(6): 1741-7, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11704390

ABSTRACT

OBJECTIVES: We tested the hypothesis that cardioprotection with ischemic preconditioning (PC) is lost in the aging, or senescent, heart. BACKGROUND: Although infarct size reduction with PC has been documented in virtually all models, a purported exception to this paradigm is the aging heart, the population in which cardioprotection is most relevant. However, no previous studies have assessed the concept of an age-associated loss in the efficacy of PC in an in vivo model of acute myocardial infarction in which definitive hallmarks of cardiovascular aging were demonstrated and a reduction of infarct size, the "gold standard" of PC, served as the primary end point. METHODS: Using the in vivo rabbit model, three cohorts of animals were studied: adult (4 to 6 months old), middle-aged ( approximately 2 years old) and old ( approximately 4 years old) rabbits. Within each cohort we assessed: 1) infarct size (measured by tetrazolium staining and expressed as percent myocardium at risk) in control and PC groups; and 2) morphologic and functional hallmarks of cardiovascular aging (progressive myocyte hypertrophy, increased myocardial fibrosis and attenuated responsiveness to beta-adrenergic stimulation). RESULTS: In adult animals, infarct size was significantly smaller in the PC group than in the control group (29 +/- 4% vs. 57 +/- 2%; p < 0.01). Although middle-aged and old rabbits exhibited all three archetypal indexes of cardiovascular aging, a comparable (approximately 50%) reduction in infarct size with PC was evident in both cohorts. CONCLUSIONS: These data provide the first in vivo evidence that infarct size reduction with PC is not precluded by increased cardiovascular age, per se.


Subject(s)
Aging/physiology , Ischemic Preconditioning, Myocardial/methods , Myocardial Infarction/pathology , Analysis of Variance , Animals , Cardiotonic Agents/pharmacology , Hemodynamics/drug effects , Isoproterenol/pharmacology , Rabbits
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