Thrombosis is reduced by inhibition of COX-1, but unaffected by inhibition of COX-2, in an acute model of platelet activation in the mouse

Background

Clinical use of selective inhibitors of cyclooxygenase (COX)-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI₂, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice.

Methodology/Principal Findings

A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control) diclofenac (1 mg.kg⁻¹, i.v.) and parecoxib (0.5 mg.kg⁻¹, i.v.) on thrombus formation induced by collagen or the thromboxane (TX) A₂-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist.

Conclusions/Significance

Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA₂, but not that induced by U46619, which is independent of platelet TXA₂. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis.     

The micronucleus assay as a biological dosimeter in hospital workers exposed to low doses of ionizing radiation

The health risk associated with low levels of ionizing radiation is still a matter of debate. A number of factors, such as non-target effects, adaptive responses and low-dose hypersensitivity, affect the long-term outcome of low-dose exposures. Cytogenetic bio-dosimetry provides a measure of the absorbed dose, taking into account the individual radiation sensitivity. The aim of the present study is to evaluate the value of the micronucleus (MN) test as a bio-dosimeter in hospital workers exposed to low doses of ionizing radiation. Blood samples were obtained from 30 subjects selected among workers exposed to X- and gamma-radiation, and 30 controls matched for sex, age and smoking from the same hospital. Micronucleus frequencies were analyzed by use of the cytokinesis-block method. The MN frequency was compared among the groups considering the confounding factors and the length of employment. No increase in the number of bi-nucleated cells with MN (BNMN), but a significant increase in the number of mono-nucleated cells with micronuclei (MOMN) was observed in exposed subjects compared with the controls. The relationship between MN frequency and accumulated dose (mSv) was evaluated. The length of employment did not affect the extent of MN frequency, but an increase of BNMN and MOMN cells was observed based on the accumulated radiation dose. Our study shows the sensitivity of the MN test in the detection of cytogenetic effects of cumulative exposure levels, suggesting the potential usefulness of this assay in providing a biological index in medical surveillance programs.     

Higher somatic cells counted by the electronic counter method do not influence renneting properties of goat milk

Laws of different countries regarding SCC of goat milk are not in agreement with each other and sometimes they fix a threshold for the enhancement of dairy products. The aim of this study was to assess if renneting properties of goat milk are influenced by higher somatic cell count (SCC) measured by an electronic cell counter. Milk samples, taken throughout the lactation of 169 goats from three farms, were analyzed for chemical, physical, hygienic and renneting properties. Samples were divided into three levels on the basis of their SCC: L: low level, samples with SCC lower than 10⁶ cells/ml; M: medium, between 10⁶ and 2 × 10⁶ cells/ml; H: high, higher than 2 × 10⁶ cells/ml. Milk clotting time was between 12.07 and 13.31 min, curd firming time between 1.68 and 2.05 min and curd firmness between 41.66 and 48.97 mm. All the three renneting properties were not affected by the SCC level but they were highly correlated with other factors as protein content and pH. Furthermore, the microbial count showed a high positive correlation with SCC. These results showed that in goat milk, contrarily to other dairy species, higher SCC did not affect renneting properties and that counting of somatic cells by using electronic cell counters might be not suitable for the improvement of dairy products.     

Levels of Metallic Elements and Their Potential Relationships to Cognitive Function among Elderly from Federal Land Development Authority (FELDA) Settlement in Selangor Malaysia

Exposure to toxic metals and excessive amount of trace elements is a risk factor of cognitive decline. Continuous monitoring of these elements by the use of metabolically inactive tissues such as fingernails may help in taking preventive measures to delay the cognitive decline process. In this study, the cognitive function of 54 elderlies (60–72 years old) from FELDA Sungai Tengi, Selangor, was evaluated using the Malay version of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The levels of arsenic (As), cadmium (Cd), copper (Cu), manganese (Mn), lead (Pb), and zinc (Zn) in fingernail were detected using Inductively Coupled Plasma-Mass Spectrometry. Results showed that (92.6 %) our population was cognitively impaired based on the MoCA with mean score of 18.07?±?5.11. The mean level of elements in fingernails for As, Cd, Cu, Mn, Pb, and Zn were 16.68?±?3.52, 4.26?±?0.91, 4.81?±?1.16, 1.00?±?0.23, 1.83?±?0.47, and 40.86?±?10.81 μg/g, respectively. Significant inverse correlations were observed between MoCA with age (r?=??0.543, p?<?0.01), Cu level (r?=??0.330, p?<?0.05), and Mn level (r?=??0.496, p?<?0.01). MMSE was correlated to age (r?=??0.346, p?<?0.05) only. In conclusion, besides aging, the progression of cognitive decline among the elderly FELDA population was associated with increased levels of copper and manganese.     

De Novo Transcriptomic and Life-History Responses of Moina Micrura Under Stress Environment Conditions

Marine Biotechnology - Moina micrura represents a promising model species for ecological and ecotoxicological investigations in tropical freshwater ecosystems. Illumina NovaSeq™ 6000...