Effect of a combined treatment with angiotensin converting enzyme inhibitor and aldosterone antagonist on insulin sensitivity and serum leptin concentration in patients with type 2 diabetes mellitus

WSTĘP. Układ renina-angiotensyna-aldosteron odgrywa kluczową rolę w patogenezie nadciśnienia tętniczego i jego powikłań narządowych. Wyniki wielu badań klinicznych wskazują również na znaczenie układu w kontroli glikemii i rozwoju cukrzycy. Jego blokada na 2–3 poziomach, poza działaniem hemodynamicznym, może wywierać różny efekt metaboliczny. Celem niniejszej pracy była ocena wpływu skojarzonego leczenia inhibitorem konwertazy angiotensyny i antagonistą aldosteronu na insulinowrażliwość i stęśenie leptyny u chorych na cukrzycę typu 2, długotrwale leczonych inhibitorem konwertazy angiotensyny. MATERIAŁ I METODY. Do badania włączono 25 chorych, których kolejność dobierano losowo. Wyjściowo oraz po dwóch 6-tygodniowych okresach terapii pacjentom podawano spironolakton w dawce 25 mg/d. lub placebo. Oznaczano stężenie glukozy, insuliny, leptyny, białka C-reaktywnego w surowicy, wskaźnik insulinowrażliwości (HOMA-S) oraz monitorowano ciśnienie tętnicze przez całą dobę. WYNIKI. Po 6 tygodniach stosowania spironolaktonu obserwowano istotny statystycznie (w porównaniu z placebo) wzrost stężenia leptyny w surowicy oraz redukcję stężenia białka C-reaktywnego i wartości średniego ciśnienia têtniczego w okresie wczesnej aktywności porannej. Całodobowe ciśnienie tętnicze nie uległo istotnym zmianom, podobnie jak stężenie glukozy, insuliny, wartość HOMA-S i masa ciała. WNIOSKI. Skojarzone leczenie inhibitorem konwertazy angiotensyny i małą dawką spironolaktonu w porównaniu z terapią samym inhibitorem konwertazy angiotensyny istotnie zmniejsza nasilenie stanu zapalnego i aferentną regulację łaknienia, ale nie wpływa na insulinowrażliwość. Wydaje się, że efekty te są niezależne od zmian całodobowego ciśnienia tętniczego.INTRODUCTION. The renin–angiotensin–aldosterone system plays a key role in the pathogenesis of arterial hypertension and its complications. Many clinical trials have proven also its role in the development of diabetes and control of glycemia. A double or even triple blockade of that system may besides the hemodynamic effect induce various metabolic alterations. The aim of the study was to assess the influence of the combined therapy with the angiotensin-converting enzyme inhibitor and aldosterone antagonist on insulin sensitivity and serum leptin concentration in patients with type 2 diabetes on a long-term angiotensin-converting enzyme inhibitor therapy. MATERIAL AND METHODS. Twenty five patients were included. At baseline and after two 6-week long periods in which in a random order either spironolactone (25 mg/day) or placebo were given, serum levels of insulin, glucose, leptin, C-reactive protein, insulin sensitivity index (HOMA-S) and 24-hour blood pressure were assessed. RESULTS. Six weeks of spironolactone therapy induced a statistically significant increase of serum leptin concentration. The same was not observed after placebo administration. Serum C-reactive protein decreased after spironolactone as well as blood pressure during the early morning activity. The mean 24-hour blood pressure was not changed as well as serum levels of glucose and insulin, HOMA-S and body mass. CONCLUSIONS. The combined treatment with an angiotensin-converting enzyme inhibitor and low-dose spironolactone compared to the treatment with the angiotensin-converting enzyme inhibitor alone may significantly decrease inflammation and afferent regulation of apetite but do not influence insulin resistance. Those effects do not seem to be related to the change of 24-hour blood pressure

Reachable by walking: inappropriate integration of near and far space may lead to distance errors

Our experimental results show that infants while learning to walk intend to reach for unreachable objects. These distance errors may result from inappropriate integration of reaching and locomotor actions, attention control and near/far visual space. Infants during their first months are fairly immobile, their attention and actions are constrained to near (reachable) space. Walking, in contrast, lures attention to distal displays and provides the information to disambiguate far space. In this paper, we make use of a reward-mediated learning to mimic the development of absolute distance perception. The results obtained with the NAO robot support further our hypothesis that the representation of near space changes after the onset of walking, which may cause the occurrence of distance errors

Reaching for the Unreachable: Reorganization of Reaching with Walking

Previous research suggests that reaching and walking behaviors may be linked developmentally as reaching changes at the onset of walking. Here we report new evidence on an apparent loss of the distinction between the reachable and nonreachable distances as children start walking. The experiment compared non-walkers, walkers with help, and independent walkers in a reaching task to targets at varying distances. Reaching attempts, contact, leaning, and communication behaviors were recorded. Most of the children reached for the unreachable objects the first time it was presented. Non-walkers, however, reached less on the subsequent trials showing clear adjustment of their reaching decisions with the failures. On the contrary, walkers consistently attempted reaches to targets at unreachable distances. We suggest that these reaching errors may result from inappropriate integration of reaching and locomotor actions, attention control and near/far visual space. We propose a rewardmediated model implemented on a NAO humanoid robot that replicates the main results from our study showing an increase in reaching attempts to nonreachable distances after the onset of walking

Integration of Static and Self-motion-Based Depth Cues for Efficient Reaching and Locomotor Actions

The common approach to estimate the distance of an object in computer vision and robotics is to use stereo vision. Stereopsis, however, provides good estimates only within near space and thus is more suitable for reaching actions. In order to successfully plan and execute an action in far space, other depth cues must be taken into account. Self-body movements, such as head and eye movements or locomotion can provide rich information of depth. This paper proposes a model for integration of static and self-motion-based depth cues for a humanoid robot. Our results show that self-motion-based visual cues improve the accuracy of distance perception and combined with other depth cues provide the robot with a robust distance estimator suitable for both reaching and walking actions

Reachable by walking: inappropriate integration of near and far space may lead to distance errors

Our experimental results show that infants while learning to walk intend to reach for unreachable objects. These distance errors may result from inappropriate integration of reaching and locomotor actions, attention control and near/far visual space. Infants during their first months are fairly immobile, their attention and actions are constrained to near (reachable) space. Walking, in contrast, lures attention to distal displays and provides the information to disambiguate far space. In this paper, we make use of a reward-mediated learning to mimic the development of absolute distance perception. The results obtained with the NAO robot support further our hypothesis that the representation of near space changes after the onset of walking, which may cause the occurrence of distance errors

Cadmium inhibitory action leads to changes in structure of ferredoxin:NADP+ oxidoreductase

This study deals with the influence of cadmium on the structure and function of ferredoxin:NADP(+) oxidoreductase (FNR), one of the key photosynthetic enzymes. We describe changes in the secondary and tertiary structure of the enzyme upon the action of metal ions using circular dichroism measurements, Fourier transform infrared spectroscopy and fluorometry, both steady-state and time resolved. The decrease in FNR activity corresponds to a gentle unfolding of the protein, caused mostly by a nonspecific binding of metal ions to multiple sites all over the enzyme molecule. The final inhibition event is most probably related to a bond created between cadmium and cysteine in close proximity to the FNR active center. As a result, the flavin cofactor is released. The cadmium effect is compared to changes related to ionic strength and other ions known to interact with cysteine. The complete molecular mechanism of FNR inhibition by heavy metals is discussed. Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9262-z) contains supplementary material, which is available to authorized users

Language development beyond the here‐and‐now: Iconicity and displacement in child‐directed communication

Most language use is displaced, referring to past, future, or hypothetical events, posing the challenge of how children learn what words refer to when the referent is not physically available. One possibility is that iconic cues that imagistically evoke properties of absent referents support learning when referents are displaced. In an audio‐visual corpus of caregiver–child dyads, English‐speaking caregivers interacted with their children (N = 71, 24–58 months) in contexts in which the objects talked about were either familiar or unfamiliar to the child, and either physically present or displaced. The analysis of the range of vocal, manual, and looking behaviors caregivers produced suggests that caregivers used iconic cues especially in displaced contexts and for unfamiliar objects, using other cues when objects were present

Synthesis of 1-(3-(benzyloxy)-2 -methyl-phenyl)-piperazine as potential inhibitors of cholinesterase and antagonists of serotonin 5 -HT6 receptor

W części teoretycznej pracy przedstawiono ogólne wiadomości na temat budowy, występowania i funkcji receptorów 5-HT6 oraz przyczyn i leczenia choroby Alzheimera. Omówione zostały również wybrane przykłady selektywnych antagonistów receptora 5-HT6.Zgodnie z przedstawionym celem pracy, badania własne obejmowały syntezę nowych związków, pochodnych 1-(3-(benzyloksy)-2-metylofenylo)piperazyny. Związki zostały otrzymane czterema różnymi metodami. W wyniku przeprowadzonych prac otrzymano następujące związki:•N-benzylo-3-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)propan-1-aminę (BG-7)•N-benzylo-5-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)pentan-1-aminę (BG-8)•N-benzylo-5-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)-N-metylo-pentan-1-aminę (BG-9)•N-benzylo-4-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)-N-metylo-butan-1-aminę (BG-10)•N-benzylo-4-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)butan-1-aminę (BG-13)•N-(3-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)-propylo)-1,2,3,4- tetrahydroakrydyno-9-aminę (BG-14)•1-benzylo-N-(2-(4-(3-(benzyloksy)-2-metylofenylo)piperazyn-1-ylo)etylo) piperydyno-4-aminę (BG-16)Tożsamość i czystość wszystkich otrzymanych pochodnych potwierdzono za pomocą analizyLC-MS, 1H NMR, oraz, w przypadku związków finalnych, 13C NMRThe theoretical part of the theses presents general information on the construction, distribution and function of 5-HT6 receptors and the causes and treatment of Alzheimer's disease. Some examples of selective antagonists of 5-HT6 receptor are also presented.According to the aim of the study, the research included synthesis of new compounds derived from 1-(3-(benzyloxy)-2-methyl-phenyl)-piperazine. The compounds were obtained by four different methods.As a result of the work the following compounds were obtained:•N-benzyl-3-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)propan-1-amine (BG-7)•N-benzyl-5-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)pentan-1-amine (BG-8)•N-benzyl-5-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)-N-methyl-pentan-1-amine (BG-9)•N-benzyl-4-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)-N-methyl-butan-1-amine (BG-10)•N-benzyl-4-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)butan-1-amine (BG-13)•N-(3-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)-propyl)-1,2,3,4-tetrahydroacrid-9-amine (BG-14)•1-benzyl-N-(2-(4-(3-(benzyloxy)-2-methyl-phenyl)piperazin-1-yl)ethyl)piperidine-4-amie (BG-16)The identity and purity of all the derivatives obtained were confirmed by analysis usingLC-MS, 1H NMR, and in the case of the final compounds by 13CNMR