Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis. Using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), we aimed to clarify the role of myeloid-specific AMPK signaling in male and female mice made acutely atherosclerotic by injection of AAV vector encoding a gain-of-function mutant PCSK9 (PCSK9-AAV) and WD feeding. After 6 weeks of WD feeding, mice received a daily injection of either the AMPK activator A-769662 or a vehicle control for an additional 6 weeks. Following this (12 weeks total), we assessed myeloid cell populations and differences between genotype or sex were not observed. Similarly, aortic sinus plaque size, lipid staining, and necrotic area did not differ in male and female MacKO mice compared with their littermate floxed controls. Moreover, therapeutic intervention with A-769662 showed no treatment effect. There were also no observable differences in the amount of circulating total cholesterol or triglyceride, and only minor differences in the levels of inflammatory cytokines between groups. Finally, CD68+ area and markers of autophagy showed no effect of either lacking AMPK signaling or AMPK activation. Our data suggest that while defined roles for each catalytic AMPK subunit have been identified, complete deletion of myeloid AMPK signaling does not significantly impact atherosclerosis. Additionally, these findings suggest that intervention with the first-generation AMPK activator A-769662 is not able to stem the progression of atherosclerosis.     

Anti Diabetic effect of CL 316,243 (A β3-Adrenergic Agonist) by Down Regulation of Tumour Necrosis Factor (TNF-α) Expression

Objective

Obesity is a risk factor for the development of insulin resistance and is one of the most important contributors to the pathogenesis of type2 diabetes, which acts mainly through the secretion of adipokines such as TNF-α that may influence insulin sensitivity. TNF-α affects many aspects of adipocyte function, such as adipocyte development and lipid metabolism.

Material and Methods

We demonstrated that there is a correlation between the expressions of TNF-α in retroperitoneal WAT and insulin-resistance in 8 genetically obese fa/fa rats. Treatment of animals with CL 316,243, a β3-adrenergic agonist, showed an improvement of insulin-resistance that was linked with the suppression of TNF-α mRNA expression in WAT.

Results

These results confirm the association between TNF-α expression and the insulin-resistant condition in rats. Our finding indicates that the hyperglycaemia and hyperinsulinemia induced by insulin-resistance correlated positively with the expression of TNF-α mRNA in an abdominal WAT depot.

Conclusion

We conclude that CL 316,243 possesses both anti-diabetic effects and anti-obesity effects in rodents.     

A comparison of symmetry and flatness measurements in small electron fields by different dosimeters in electron beam radiotherapy

BackgroundSymmetry and flatness are two quantities which should be evaluated in the commissioning and quality control of an electron beam in electron beam radiotherapy. The aim of this study is to compare symmetry and flatness obtained using three different dosimeters for various small and large fields in electron beam radiotherapy with linac.Materials and methodsBeam profile measurements were performed in a PTW water phantom for 10, 15 and 18 MeV electron beams of an Elekta Precise linac for small and large beams (1.5 × 1.5 cm² to 20 × 20 cm² field sizes). A Diode E detector and Semiflex-3D and Advanced Markus ionization chambers were used for dosimetry.ResultsBased on the obtained results, there are minor differences between the responses from different dosimeters (Diode E detector and Semiflex-3D and Advanced Markus ionization chambers) in measurement of symmetry and flatness for the electron beams. The symmetry and flatness values increase with increasing field size and electron beam energy for small and large field sizes, while the increases are minor in some cases.ConclusionsThe results indicate that the differences between the symmetry and flatness values obtained from the three dosimeter types are not practically important.     

A Monte Carlo study on dose distribution evaluation of Flexisource 192Ir brachytherapy source

Aim

The aim of this study is to evaluate the dose distribution of the Flexisource ¹⁹²Ir source.

Background

Dosimetric evaluation of brachytherapy sources is recommended by task group number 43 (TG. 43) of American Association of Physicists in Medicine (AAPM).

Materials and methods

MCNPX code was used to simulate Flexisource ¹⁹²Ir source. Dose rate constant and radial dose function were obtained for water and soft tissue phantoms and compared with previous data on this source. Furthermore, dose rate along the transverse axis was obtained by simulation of the Flexisource and a point source and the obtained data were compared with those from Flexiplan treatment planning system (TPS).

Results

The values of dose rate constant obtained for water and soft tissue phantoms were equal to 1.108 and 1.106, respectively. The values of the radial dose function are listed in the form of tabulated data. The values of dose rate (cGy/s) obtained are shown in the form of tabulated data and figures. The maximum difference between TPS and Monte Carlo (MC) dose rate values was 11% in a water phantom at 6.0 cm from the source.

Conclusion

Based on dosimetric parameter comparisons with values previously published, the accuracy of our simulation of Flexisource ¹⁹²Ir was verified. The results of dose rate constant and radial dose function in water and soft tissue phantoms were the same for Flexisource and point sources. For Flexisource ¹⁹²Ir source, the results of TPS calculations in a water phantom were in agreement with the simulations within the calculation uncertainties. Furthermore, the results from the TPS calculation for Flexisource and MC calculation for a point source were practically equal within the calculation uncertainties.     

The impact of the flower mite Aceria acroptiloni on the invasive plant Russian knapweed,Rhaponticum repens,in its native range

Rhaponticum repens (L.) Hidalgo is a clonal Asteraceae plant native to Asia and highly invasive in North America. We conducted open-field experiments in Iran to assess the impact of the biological control candidate, Aceria acroptiloni Shevchenko & Kovalev (Acari, Eriophyidae), on the target weed. Using three different experimental approaches, we found that mite attack reduced the biomass of R. repens shoots by 40–75 %. Except for the initial year of artificial infestation by A. acroptiloni of R. repens shoots, the number of seed heads was reduced by 60–80 % and the number of seeds by 95–98 %. Morphological investigations of the mite complex attacking R. repens at the experimental field site revealed that A. acroptiloni was by far the dominant mite species. We conclude that the mite A. acroptiloni is a promising biological control candidate inflicting significant impact on the above-ground biomass and reproductive output of the invasive plant R. repens.