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.

Sudden death is a major health problem all over the world. The most common causes of sudden death are cardiac but there are also other causes such as neurological conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine toxicity, etc. A common feature of all these diverse pathologies underlying sudden death is the imbalance of the autonomic nervous system control of the cardiovascular system. This paper reviews different pathologies underlying sudden death with emphasis on the autonomic nervous system contribution, possibilities of early diagnosis and prognosis of sudden death using various clinical markers including autonomic markers (heart rate variability and baroreflex sensitivity), present possibilities of management and promising prevention by electrical neuromodulation.

Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA–DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA–DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5 mg/kg), HPMA–DOX (5 mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA–DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer–drug conjugate and other nano-sized-drug constructs.

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The questionnaire about knowledge of ACE inhibitors' adverse effects is a reliable and probably valid instrument for measuring patients' knowledge about adverse effects of ACE inhibitors.

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Epidermis stem cells have a crucial role through the processes of proliferation and differentiation, to replace cells that are constantly lost during tissue turnover or following injury. On the other hand, thyroid hormones regulate the proliferation and differentiation of epidermal cells and thus significantly influence the homeostasis of the skin. It is well known that maternal hypothyroidism during pregnancy leads to impaired development of many organ systems in their offspring. However, there is a lack of data about the influence of maternal subclinical hypothyroidism during pregnancy and lactation on the development of the skin and its derivatives in the litter. The aim of this study was to investigate the effects of maternal thyroid dysfunction on the development of the skin and its derivatives in their offspring in the early postnatal period. Antithyroid substance 6-n-propyl-2-thiouracil was added into the drinking water to female Albino Oxfords rats from the beginning of pregnancy and during lactation, with the aim to induce subclinical and overt form of hypothyroidism. Skin samples were taken from male pups within twenty-four hours and seven days after birth. The main findings of this investigation were that both forms of maternal hypothyroidism lead to serious damage of the epidermis in pups in terms of pronounced hyperkeratosis and reduction of the germinal layer along with a reduced number of hair follicles and their delayed morphogenesis. Epidermal impairments were more pronounced in pups with the overt form of hypothyroidism while offspring with the subclinical form had impairments that were less pronounced and delayed in occurrence.