A kinetic model for the relative contribution of waterborne and dietary cadmium and zinc in the common carp (Cyprinus carpio)

In this work, the uptake and whole-body accumulation of Cd and Zn by the common carp from water, diet, and a combination of both was studied using the radioactive tracers 09Cd and 65Zn. A three-compartment pharmacokinetic model was constructed and revealed metal- and exposure route-dependent accumulation profiles. Under the tested exposure conditions in water (0.1 microM Cd and 1 microM Zn), only 0.1 and 0.07%, respectively, of the total Cd and Zn load that passed the branchial surfaces was accumulated by the carp. In contrast, the carp accumulated 20 and 29% of the total ingested Cd and Zn load (mean concentrations in food of newly accumulated metals were 2.24 +/- 0.29 and 19.91 +/- 2.89 nmol/g wet weight, respectively). However, the contribution of the waterborne metals to the whole-body metal accumulation was higher than the metal uptake from food. The constructed model was used to simulate the effect of variable assimilation efficiency (AE) values on the relative importance of dietary Cd and Zn exposure to the overall metal accumulation in common carp. This simulation was performed under a realistic exposure scenario and with Cd and Zn AE values ranging from 5 to 95%. Dissolved Zn levels were higher and Cd levels lower compared to the laboratory experiments. Levels in the midge larvae were much higher. The results show that under these conditions, even at the lowest Cd and Zn AEs, almost 40% of the total body Cd and Zn concentrations originated from dietary Cd and Zn exposure. Taking into account the Cd and Zn AE of the laboratory experiments, respectively, 31 and 55%, more than 85% of the total body Cd and Zn was taken up from the food.     

Unawareness and undertreatment of asthma and allergic rhinitis in a general population

The aim of this study was to determine the extent of unawareness and undertreatment of asthma and allergic rhinitis in an adolescent and adult population in Copenhagen, Denmark. METHODS: Patients with asthma and rhinitis were recruited by a standardised asthma and rhinitis screening questionnaire. Out of a random sample of 10,877 subjects aged 14-44 years, 1149 subjects were treated or reported symptoms of asthma or rhinitis and agreed to participate. Those subjects were assessed on history, lung function tests, and skin prick tests. Disease severity and optimal treatment were decided according to the GINA and ARIA guidelines. RESULTS: A total of 726 participants suffered from asthma and/or allergic rhinitis. Concomitant upper and lower airways disease was found in 47%. Seventy-five per cent were allergic and 44% with a known allergy had been tested previously. Asthma was undiagnosed and untreated in 50% of all the asthmatics. According to the guideline recommendation, 76% of asthmatics were undertreated. Rhinitis was undiagnosed in 32% of patients and 83% with moderate to severe rhinitis were undertreated. Patient knowledge about self-care and education was low. CONCLUSIONS: In this population a large proportion of patients were unaware of having asthma or rhinitis. The pharmaceutical treatment and management practice were inadequate. Our study emphasises the need for additional intervention.     

Increased colorectal permeability in patients with severe sepsis and septic shock

Objective To develop a method for the assessment of colorectal permeability in septic patients.Design and setting Observational study in ICUs at two university hospitals.Participants Nine patients with septic shock and abdominal focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy subjects.Measurements and results Colorectal permeability was assessed as the initial appearance rate of ^99mTc-DTPA in plasma after instillation into the rectal lumen and as the cumulative systemic recovery at 1 h. To calculate the latter, volume of distribution and renal clearance of ^99mTc-DTPA was estimated by an i. v. bolus of ⁵¹Cr-EDTA. The initial rate of permeability was increased in patients with septic shock and severe sepsis compared with controls [29.0 (3.7–83.3), 20.6 (3.6–65.5) and 6.0 (2.2–9.6) cpm ml⁻¹ min⁻¹, respectively, p < 0.05)] with a positive linear trend (r ² = 0.27, p = 0.01) and correlated to L-lactate concentrations in the rectal lumen (r ² = 0.39, p < 0.05). The cumulative permeability was also increased in patients with septic shock and severe sepsis compared with controls [2.07 (0.05–15.7), 0.32 (0.01–1.2) and 0.03 (0.01–0.06)‰, respectively, p < 0.01] and correlated to the initial permeability rate (r ² = 0.26, p = 0.01).Conclusions In septic patients, the systemic recovery of a luminally applied marker of paracellular permeability was increased and related to the luminal concentrations of L-lactate and possibly to disease severity. This suggests that the assessment of colorectal permeability by systemic recovery of ^99mTc-DTPA is valid and that metabolic dysfunction of the mucosa contributes to increased permeability of the large bowel in patients with severe sepsis and septic shock.     

Hb Bronovo, a new globin gene mutation at alpha2 103 (His->Leu) associated with an alpha thalassemia phenotype

Mild alpha-thalassemia, a common condition in many ethnic groups, presents with hematologic abnormalities almost identical to those found in iron deficiency. We report a new alpha globin chain variant associated with an alpha-thalassemia phenotype in two members of a Turkish family.     

Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity

OBJECTIVE: Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity. DESIGN Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). RESULTS The mean weight loss was 5.1 kg (range -15.3 to +1.3 kg). BMI decreased from 36.5 to 34.9 kg/m(2) (P=0.003). Saturated FA (SFA) decreased 11% (P=0.0001). Polyunsaturated FA (PUFA)n-6 increased 4% (P =0.003). Long-chain PUFAn-3 increased 51% (P= 0.0001), mainly due to a 75% increase (P<0.0001) in docosahexaenoic acid. Changes in HOMA-IR correlated significantly with changes in long-chain PUFAn-3 (R=-0.57, P< 0.01), SFA (R=0.58, P<0.01) and waist circumference (R=0.46, P<0.05). A multivariate linear regression analysis that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R(2)=0.33, P<0.01). CONCLUSIONS: A hypocaloric low-fat dietary intervention programme increased incorporation of long-chain PUFAn-3 and reduced SFA in skeletal muscle membrane phospholipids of obese subjects, a setting that may impact on insulin action.     

Listeria monocytogenes: maternal-foetal infections in Denmark 1994-2005

Maternal-foetal infection by Listeria monocytogenes is a rare complication in pregnancy. In the period 1994-2005, 37 culture-confirmed cases of maternal-foetal Listeria monocytogenes infections were reported in Denmark. We examined 36 patients' files in order to evaluate risk factors, clinical and laboratory findings, response to therapy, and outcome for maternal-foetal listeriosis. Patient data and bacteriological findings were divided into 2 groups for comparison: 1 group with children born alive (n=24) and another group with abortion or stillbirth (n=12). 23 of the 36 children survived the acute infection, as did all the mothers. The mothers were generally only mildly affected by the infection. In contrast, among the children born alive, 15 were diagnosed with bacteraemia/septicaemia, 3 children with pneumonia, 3 with neonatal meningitis, and 3 were unaffected. Despite the high frequency of illness only 1 of the live-born children died from the infection and none of the surviving children showed signs of permanent damage at the time they were discharged from hospital. Listeriosis during pregnancy is a serious threat to the unborn child. One-third of culture-confirmed cases of maternal-foetal infections resulted in abortion or stillbirth; however, the prognosis for live-born children is good, even in severely ill newborns.     

Contrast harmonic intravascular ultrasound: a feasibility study for vasa vasorum imaging

OBJECTIVE: We sought to investigate feasibility of vasa vasorum imaging using the novel technique of contrast harmonic intravascular ultrasound. METHODS: Prototype intravascular ultrasound (IVUS) instrumentation was developed for the sensitive detection of micro-bubble contrast agents. The technique, "harmonic" imaging, involves transmitting ultrasound at 20 MHz (fundamental) and detecting contrast signals at 40 MHz (second harmonic). Phantom experiments were conducted to investigate the detection of a small vessel in the wall surrounding a larger vessel. In vivo experiments were conducted in atherosclerotic rabbit abdominal aortas. RESULTS: The phantom experiments showed improved small vessel detection in harmonic mode relative to fundamental mode. For the in vivo experiments, harmonic imaging enabled the visualization of contrast agent outside the aortic lumen through a statistically significant (P < 0.001) enhancement of image power, consistent with the detection of adventitial microvessels. These microvessels were not detected in fundamental imaging mode. CONCLUSIONS: These results indicate the feasibility of contrast harmonic intravascular ultrasound as a new technique for vasa vasorum imaging.     

Unmet needs in oral antiplatelet therapy with ADP receptor blocking agents

Antiplatelet agents like aspirin and clopidogrel are treatment cornerstones for acute coronary syndromes (ACS). Drawbacks of dual therapy with these agents include slow onset and offset of effect and wide response variability. Clopidogrel may provide little benefit if administered too close to percutaneous coronary intervention (PCI) and increase major bleeding risk if given too close to coronary artery bypass grafting (CABG) or other surgery. It may not provide sufficient antiplatelet coverage prior to CABG if stopped too long before intervention and leave patients without antiplatelet coverage due to hyporesponsiveness. Prasugrel has made steps towards addressing these limitations by exhibiting more efficient metabolism, more rapid onset of effect, and greater and more consistent platelet inhibition than clopidogrel. The TRITON-TIMI38 trial in ACS patients undergoing PCI showed prasugrel produced greater ischemic event protection than clopidogrel but significantly increased major bleeding risk. AZD6140, the first reversible oral P2Y₁₂ inhibitor, provides more rapid onset of effect and greater and more consistent platelet inhibition than clopidogrel. In DISPERSE2, a phase II trial in ACS patients, AZD6140 did not increase bleeding risk, reduced bleeding risk among CABG patients, and produced numerical reductions in myocardial infarction risk. AZD6140 is being compared with clopidogrel in PLATO, a phase III trial in approximately 18000 ACS patients.