Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome proliferator activated receptor gamma (PPARG) modulator. Recently, we tested metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously hypertensive rats (SHR) fed a diet containing 60 % fructose, a widely used model of the metabolic syndrome. Surprisingly, we observed acute toxic effects of telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and treated with telmisartan exhibited rapid decrease in blood pressure when compared to the SHR fed a high fructose diet and treated with valsartan. Concentrations of both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR rats fed a high fructose diet were approximately 4 fold higher when compared to Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated telmisartan in the SHR were about 5 fold higher when compared to BN rats while plasma levels of telmisartan glucuronide were similar between the strains. Testing of other rat strains, diets, and the ARB valsartan showed that toxic effects of telmisartan in combination with high fructose diet are specific for the SHR. These results are consistent with the possibility that in some circumstances, SHR are predisposed to telmisartan toxicity possibly because of a genetically determined disturbance in telmisartan metabolism.
Huntingtonova choroba (HD) je autozomálně dominantní neurodegenerativní onemocnění způsobené zvýšením počtu polyglutaminových repetic (> 35 repetic) v genu pro protein huntingtin. HD je charakteristická pomalými progresivními změnami pohybového aparátu a osobnosti, kdy tyto změny jsou často doprovázeny ztrátou tělesné hmotnosti. Do dnešního dne není znám přesný mechanizmus patofyziologie choroby. Poruchy pohybových funkcí reflektují masivní poškození specifických částí mozku (striatum), které bylo popsáno u pacientů s HD. V roce 2013 Sbodio et al [1] popsali zvýšené množství proteinu Acyl‑CoA binding domain containing 3 (ACBD3) ve striatu HD pacientů. Protein ACBD3 hraje nezastupitelnou roli v mnoha buněčných procesech, a to především díky interakci s různými vazebnými partnery. ACBD3 je esenciální při neuronálním dělení, neurodegeneraci, udržení lipidové homeostáze, stresové odpovědi, virové replikaci, apoptóze, udržení struktury golgiho komplexu. V této práci jsme prokázali nepřítomnost proteinu ACBD3 v mitochondriích v lidských kožních fibroblastech a navíc jsme potvrdili, že změny celkové hladiny proteinu ACBD3 ve fibroblastech HD pacientů nejsou konzistentní., Huntington’s disease (HD) is an autosomal‑dominant neurodegenerative disease caused by the expansion of polyglutamine repeats (> 35 repeats) in the nuclear gene for the huntingtin protein. HD is characterized by slow progressive changes in motor behaviour and personality that are sometimes accompanied by weight loss. To date, the exact mechanisms of HD pathophysiology have not been defined. Impaired motor behaviour reflecting massive and selective destruction of the striatum has been observed in patients with HD. Sbodio et al. [1] reported in 2013 that Acyl‑CoA binding domain containing 3 (ACBD3) protein levels were elevated in the striatum of HD patients and connected with higher neurotoxicity in HD. The ACBD3 protein plays essential roles in many different cellular functions via interactions with a multitude of partners. ACBD3 is involved in neuronal stem cell self‑renewal, neurodegeneration, lipid homeostasis, stress resistance, intracellular vesicle trafficking, organelle maintenance, viral replication and the apoptotic response. Herein, we found that ACBD3 in not present in the mitochondria in skin fibroblasts. Moreover, our findings also revealed that the total cellular level of ACBD3 is not consistent among the fibroblasts of HD patients., and H. Kratochvíľová, M. Rodinova, J. Sladkova, J. Klempir, I. Liskova, J. Motlik, J. Zeman, H. Hansíková, M. Tesarova
In the last decade the health of young people in Ukraine as well as in many other countries of the world significantly deteriorated according to the results of screening tests. Because of this the main task of prophylactic medicine is development and introduction of new methods of early diagnostics of diseases. The aim of the work to assess the peculiarities of adaptation of students with different types of vegetative regulation. Material and methods: 415 second year students of Lugansk State Medical University were tested. The mechanisms of physiological functions of the body regulation were assessed by registration of cardiac rhythm variability (CRV). Analysis of CRV was performed by three methods: statistical, geometrical, and spectral analysis. The express method proposed by Shlyk, N.I. (2009) was later used to determine the prevailing type of vegetative regulation. To assess adaptability the method of R.M. Baevskij (1979) was used. Results: In the result of investigation 4 types of functional states of regulatory systems were determined: I type 295 (71 %) of tested, II in 14 (3 %), III in 96 (23 %) and IV only in 10 (2%). I type of functional state of regulatory systems in the wakeful state at rest was characterized by moderate prevalence of central regulation of heart rhythm (MPCR), decreased activity of autonomic regulation. It was noticed that some of the parameters of CRV (like RR, SDNN, RMSSD and pNN50) which characterize autonomic regulation, were statistically lowere (р≤0.01) compared to type III, and some (like AMo and SI) higher, in both female and male students. Summarized spectrum capacity and components of its wave structure (HF, LF, VLF) which characterize central regulation were statistically significantly lower (р≤0.01) for the I type of regulation compared to the III one which is characterized by moderate prevalence of autonomic regulation of the heart rhythm. In female students with type I autonomic regulation compared to male students such CRV parameters as RR and AМo were statistically significantly lower (р≤0.05), while the parameters of total potency (TP) and high frequency waves (HF) were higher (р≤0.05), which could point to more centralized heart rhythm regulation in male compared to female. The evaluation of regulatory systems overstress allowed to determine the state of adaptation and risk of overstress or breakdown in students with different types of autonomic regulation. Conclusions: Thus, evaluation of adaptation state in students with different types of autonomic regulation allows to characterize the current functional state and uncover the risk of disease development., Tatiana Tananakina, Natalya Lila, Anzhelika Ivasenko, Dmitrij Bolgov, Svetlana Mavrich, Yuliya Modna, and Literatura
Like adults, larvae of the myrmecophilous ladybird Coccinella magnifica are rarely attacked by Formica rufa ants on foraging trails, but more often attacked on ant-tended aphid colonies. Larvae of the non-myrmecophile Coccinella septempunctata, to which C. magnifica was compared, were more readily attacked by ants in both situations. To avoid or counter ant aggression when foraging for aphids, C. magnifica larvae exhibit three main tactics: they may feed on un- or non-tended aphids; when feeding on tended colonies they often carry prey away, minimising time spent there; and if attacked, they use limited chemical defence. No novel behaviours were found in C. magnifica larvae, not occurring to some extent in C. septempunctata. Coccinella magnifica eggs were laid distant to ant-tended aphids, although closer to un- or non-tended aphids.
In this paper, the finite-time stabilization problem of chained form systems with parametric uncertainties is investigated. A novel switching control strategy is proposed for adaptive finite-time control design with the help of Lyapunov-based method and time-rescaling technique. With the proposed control law, the uncertain closed-loop system under consideration is finite-time stable within a given settling time. An illustrative example is also given to show the effectiveness of the proposed controller.
This paper is concerned with the finite-time synchronization problem for a class of cross-strict feedback underactuated hyperchaotic systems. Using finite-time control and backstepping control approaches, a new robust adaptive synchronization scheme is proposed to make the synchronization errors of the systems with parameter uncertainties zero in a finite time. Appropriate adaptive laws are derived to deal with the unknown parameters of the systems. The proposed method can be applied to a variety of chaotic systems which can be described by the so-called cross-strict feedback systems. Numerical simulations are given to demonstrate the efficiency of the proposed control scheme.