Influence of amino acids on the formation of mutagenic/carcinogenic heterocydic amines in a model system

Mixtures of creatinine, glucose and various single amino acids were heated at 180°C for 10 min in an aqueous model system. The heated mixtures all showed mutagenic activity, ranging from 80 to 2400 TA98 revertant colonies/μmol creatinine with metabolic activation. Testing of HPLC fractions for mutagenic activity showed each mixture to contain several mutagenic components, some of which corresponded to known heterocyclic amines and others to unknown compounds. The presence of 2-amino-3-methyl-imidazo[4,5-f]quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline in most of the samples was established using HPLC with photodiode array detection and liquid chromatography/mass spectrometry with electrospray interface and single ion monitoring. In addition, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 3-amino-1,4-di-methyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the co-mutagenic compounds 9H-pyrido[3,4-bindole and 1-methyl-9H-pyrido[3,4-b]indole were detected in some sample

Across-country test-day model evaluations for Holstein, Nordic Red Cattle, and Jersey

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Health gains and fi nancial risk protection aff orded by public fi nancing of selected interventions in Ethiopia: an extended cost-eff ectiveness analysis

Background The way in which a government chooses to fi nance a health intervention can aff ect the uptake of health interventions and consequently the extent of health gains. In addition to health gains, some policies such as public fi nance can insure against catastrophic health expenditures. We aimed to evaluate the health and fi nancial risk protection benefi ts of selected interventions that could be publicly fi nanced by the government of Ethiopia. Methods We used extended cost-eff ectiveness analysis to assess the health gains (deaths averted) and fi nancial risk protection aff orded (cases of poverty averted) by a bundle of nine (among many other) interventions that the Government of Ethiopia aims to make universally available. These nine interventions were measles vaccination, rotavirus vaccination, pneumococcal conjugate vaccination, diarrhoea treatment, malaria treatment, pneumonia treatment, caesarean section surgery, hypertension treatment, and tuberculosis treatment. Findings Our analysis shows that, per dollar spent by the Ethiopian Government, the interventions that avert the most deaths are measles vaccination (367 deaths averted per $100 000 spent), pneumococcal conjugate vaccination (170 deaths averted per$100 000 spent), and caesarean section surgery (141 deaths averted per $100 000 spent). The interventions that avert the most cases of poverty are caesarean section surgery (98 cases averted per$100 000 spent), tuberculosis treatment (96 cases averted per $100 000 spent), and hypertension treatment (84 cases averted per$100 000 spent). Interpretation Our approach incorporates fi nancial risk protection into the economic evaluation of health interventions and therefore provides information about the effi ciency of attainment of both major objectives of a health system: improved health and fi nancial risk protection. One intervention might rank higher on one or both metrics than another, which shows how intervention choice—the selection of a pathway to universal health coverage—might involve weighing up of sometimes competing objectives. This understanding can help policy makers to select interventions to target specifi c policy goals (ie, improved health or fi nancial risk protection). It is especially relevant for the design and sequencing of universal health coverage to meet the needs of poor populations

Ultrasound screening for asymptomatic carotid stenosis in subjects with calcifications in the area of the carotid arteries on panoramic radiographs: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Directed ultrasonic screening for carotid stenosis is cost-effective in populations with > 5% prevalence of the diagnosis. Occasionally, calcifications in the area of the carotid arteries are incidentally detected on odontological panoramic radiographs. We aimed to determine if directed screening for carotid stenosis with ultrasound is indicated in individuals with such calcifications.</p> <p>Methods</p> <p>This was a cross-sectional study. Carotid ultrasound examinations were performed on consecutive persons, with findings of calcifications in the area of the carotid arteries on panoramic radiography that were otherwise eligible for asymptomatic carotid endarterectomy.</p> <p>Results</p> <p>Calcification in the area of the carotid arteries was seen in 176 of 1182 persons undergoing panoramic radiography. Of these, 117 fulfilled the inclusion criterion and were examined with carotid ultrasound. Eight persons (6.8%; 95% CI 2.2-11.5%) had a carotid stenosis - not significant over the 5% pre-specified threshold (p = 0.232, Binomial test). However, there was a significant sex difference (p = 0.008), as all stenoses were found in men. Among men, 12.5% (95%CI 4.2-20.8%) had carotid stenosis - significantly over the 5% pre-specified threshold (p = 0.014, Binomial test).</p> <p>Conclusions</p> <p>The incidental finding of calcification in the area of the carotid arteries on panoramic radiographs should be followed up with carotid screening in men that are otherwise eligible for asymptomatic carotid endarterectomy.</p> <p>Trial Registration</p> <p>The study was registered at <url>http://www.clinicaltrials.gov</url>; <a href="http://www.clinicaltrials.gov/ct2/show/NCT00514644">NCT00514644</a></p

Life expectancy gains from dietary modifications: a comparative modeling study in 7 countries

Background: Eating healthier is associated with a range of favorable health outcomes. Our previous model estimated the impact of dietary changes on life expectancy gains but did not consider height, weight, or physical activity. Objectives: We aimed to estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary changes, more feasible dietary modifications, and optimized vegan dietary changes in China, France, Germany, Iran, Norway, the United Kingdom, and the United States. Methods: Our modeling study used data from meta-analyses presenting dose-response relationships between intake of 15 food groups and mortality. Background mortality data were from the Global Burden of Disease Study. We used national food intake data and adjusted for height, weight, and physical activity level. Results: For 40-y-olds, estimated life expectancy gains ranged from 6.2 y (with uncertainty interval [UI]: 5.7, 7.5 y) for Chinese females to 9.7 y (UI: 8.1, 11.3 y) for United States males following sustained changes from typical country-specific dietary patterns to longevity-optimized dietary changes, and from 5.2 y (UI: 4.0, 6.5 y) for Chinese females to 8.7 y (UI: 7.1, 10.3 y) for United States males following changes to optimized vegan dietary changes. Conclusions: A sustained change from country-specific typical dietary pattern patterns to longevity-optimized dietary changes, more feasible dietary changes, or optimized vegan dietary changes are all projected to result in substantial life expectancy gains across ages and countries. These changes included more whole grains, legumes, and nuts and less red/processed meats and sugars and sugar-sweetened beverages. The largest gains from dietary changes would be in the United States

Postoperative Analgesia after Radical Retropubic Prostatectomy

Background: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study. Methods: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patientcontrolled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 g/ml fentanyl, and 2 g/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and &quot;deep&quot; visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl. Results: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P &lt; 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P &lt; 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0 -48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group ؋ time interaction was found in the Short Form-36. Conclusions: The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient

Nanovesicles from Malassezia sympodialis and Host Exosomes Induce Cytokine Responses – Novel Mechanisms for Host-Microbe Interactions in Atopic Eczema

BACKGROUND: Intercellular communication can occur via the release of membrane vesicles. Exosomes are nanovesicles released from the endosomal compartment of cells. Depending on their cell of origin and their cargo they can exert different immunoregulatory functions. Recently, fungi were found to produce extracellular vesicles that can influence host-microbe interactions. The yeast Malassezia sympodialis which belongs to our normal cutaneous microbial flora elicits specific IgE- and T-cell reactivity in approximately 50% of adult patients with atopic eczema (AE). Whether exosomes or other vesicles contribute to the inflammation has not yet been investigated. OBJECTIVE: To investigate if M. sympodialis can release nanovesicles and whether they or endogenous exosomes can activate PBMC from AE patients sensitized to M. sympodialis. METHODS: Extracellular nanovesicles isolated from M. sympodialis, co-cultures of M. sympodialis and dendritic cells, and from plasma of patients with AE and healthy controls (HC) were characterised using flow cytometry, sucrose gradient centrifugation, Western blot and electron microscopy. Their ability to stimulate IL-4 and TNF-alpha responses in autologous CD14, CD34 depleted PBMC was determined using ELISPOT and ELISA, respectively. RESULTS: We show for the first time that M. sympodialis releases extracellular vesicles carrying allergen. These vesicles can induce IL-4 and TNF-α responses with a significantly higher IL-4 production in patients compared to HC. Exosomes from dendritic cell and M. sympodialis co-cultures induced IL-4 and TNF-α responses in autologous CD14, CD34 depleted PBMC of AE patients and HC while plasma exosomes induced TNF-α but not IL-4 in undepleted PBMC. CONCLUSIONS: Extracellular vesicles from M. sympodialis, dendritic cells and plasma can contribute to cytokine responses in CD14, CD34 depleted and undepleted PBMC of AE patients and HC. These novel observations have implications for understanding host-microbe interactions in the pathogenesis of AE