Heart rate dynamics in doxorubicin-induced cardiomyopathy.

The clinical use of doxorubicin, an effective chemotherapeutic is hampered by the development of irreversible cardiotoxicity. Here we test time-frequency analysis of heart rate (HR) variability (HRV) for early detection of doxorubicin-induced cardiotoxicity. Experiments were conducted in adult male Wistar rats treated for 15 days with doxorubicin (DOXO, total dose 15 mg kg(-1), i.p.) or saline (CONT). DOXO rats exhibited cardiotoxicity confirmed by histological examination without developing heart failure as estimated by echocardiography. However, HR variability increase reflected subtle microscopic changes of cardiac toxicity in DOXO rats. The results recommend time-frequency analysis of HRV for early detection of doxorubicin-induced cardiomyopathy.

Cadmium in meat and edible offal of free-range reared Swallow-belly Mangulica pigs from Vojvodina (northern Serbia).

The aim of this study was to determine the cadmium concentration in four muscles and 10 edible offal items of 15 free-range reared Swallow-belly Mangulica pigs from Vojvodina, by flame atomic absorption spectrometry after mineralisation by dry ashing. All individual concentrations in muscles and heart, tongue, spinal cord, back fat and leaf fat were below the limit of detection (LOD = 0.050 mg/kg). In lungs, spleen and brain, cadmium concentrations ranked from below LOD, 0.055 and 0.058 to 0.057, 0.065 and 0.074 mg/kg, respectively. The concentration of cadmium in liver and kidney ranged from 0.089 to 0.116 mg/kg and from 0.204 to 0.440 mg/kg, respectively. Cadmium concentrations in liver and kidney of free-range reared Swallow-belly Mangulica pigs slaughtered at about 20 months of age were lower than in liver and kidney of commercial pigs from Vojvodina, slaughtered at about 6 months of age.

Dipeptidyl peptidase IV (DPP4) deficiency increases Th1-driven allergic contact dermatitis.

BACKGROUND: CD26 or dipeptidyl peptidase IV (DPP4) is known to be involved in several immunological processes and has recently been reported to play a crucial role in the allergic responses of the lungs. OBJECTIVES: To explore the impact of DPP4 on the allergic response of the skin. METHODS: Skin biopsies from patients suffering from atopic dermatitis (AD) and healthy controls were investigated for the expression of CD26/DPP4. Furthermore, the functional impact of CD26 was investigated in two models of contact hypersensitivity using CD26/DPP4-deficient and wild-type rats. Dinitrochlorobenzene (DNCB) was used to induce a T helper type 1 (Th1)-dominated inflammation and toluene-2,3-diisocyanate for a Th2-pronounced inflammation. The inflammatory responses were determined by histological quantification, flow cytometry [fluorescence-activated cell sorting (FACS)], and an enzyme-linked immunosorbant assay (ELISA). RESULTS: CD26/DPP4-expression was up-regulated in the lesional skin biopsies of patients compared with healthy controls as well as in both models of contact hypersensitivity. However, in the more Th2-driven model, a reduced inflammatory skin response was found in CD26/DPP4-deficient rats, analogous to the effects observed recently in a rat model of asthma. In partial contrast, there was an aggravation of local skin inflammation in CD26/DPP4-deficient rats under conditions of Th1-like skin inflammation. CONCLUSION AND CLINICAL RELEVANCE: The up-regulation of CD26 in atopic dermatitis represents a new finding, which has also been seen in other inflammatory skin diseases. However, tissue expression of CD26/DPP4 in immunological skin response can either be beneficial or aggravating, depending on a possible Th1/Th2 shift. This might have consequences for humans suffering from diabetes mellitus treated by DPP4 inhibitors, who have eczematous skin diseases as a co-morbidity.