Estimating the spectral radius of a graph by the second Zagreb index

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Diet-Induced Obesity and Ghrelin Effects on Pituitary Gonadotrophs: Immunohistomorphometric Study in Male Rats

Objective: The close relationship between energy metabolism, nutritional state, and reproductive physiology suggests that nutritional and metabolic disorders can disrupt normal reproductive function and fertility. Considering the importance of leptin and ghrelin effects in regulation of the hypothalamic-pituitary-gonadal axis, the objective of this study was to investigate the influence of obesity and centrally applied ghrelin on immunohistochemical appearance and quantitative morphology of the pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) producing cells in adult male rats. Materials and Methods: In this experimental study, animals were given two different diets: normal-fat (NF) and high-fat (HF), for 4 weeks, corresponding to normal and positive energy balance (n=2×14), respectively. Each group was subsequently divided into two subgroups (n=7) receiving intracerebroventricular (ICV) injections of either ghrelin [G, 1 μg/5 μL phosphate buffered saline (PBS)] or vehicle (5 μL PBS, control group) every 24 hours for five consecutive days. Results: Morphometric analyses showed that in HF control group, the percentage of FSH cells per unit volume of total pituitary gland tissue (in μm3), i.e. volume density (Vvc), was increased (P<0.05) by 9.1% in comparison with the NF controls. After ICV treatment with ghrelin, volume (Vc) and volume density (Vvc) of FSH cells in ghrelin+NF (GNF) and ghrelin+HF (GHF) groups remained unchanged in comparison with NF and HF controls. Volume of LH cells in HF control group was increased by 17% (P<0.05), but their Vvc was decreased by 8.3% (P<0.05) in comparison with NF controls. In GNF group, the volume of LH cells increased by 7% (P<0.05), in comparison with the NF controls, but in GHF group, the same parameter remained unchanged when compared with HF controls. The central application of ghrelin decreased the Vvc of LH cells only in GNF group by 38.9% (P<0.05) in comparison with the NF control animals. Conclusion: The present study has shown that obesity and repetitive ICV administration of low doses of ghrelin, in NF and HF rats, modulated the immunohistomorphometric features of gonadotrophs, indicating the importance of obesity and ghrelin in regulation of the reproductive function

Prospects for wider energetic utilization of subgeothermal water resources: Eastern Serbia case study

Intenzivno korišćenje fosilnih goriva širom sveta uzrok je ozbiljnih zagađenja prirode i utiče na globalno zagrevanje. Otuda je jedan od glavnih ciljeva energetske politike evropskih zemalja korišćenje efikasnije 'zelene' energije iz obnovljivih i sopstvenih izvora. Generalno, geotermalna energija predstavlja vid obnovljivih izvora energije. Ipak, i dalje se smatra da korišćenje subgeotermalne energije niske entalpije (temperature podzemnih voda od 30°C i niže) za potrebe grejanja nije u potpunosti ekonomski opravdano. Standardna tehnologija za primenu ovog vida energije zahteva velike površine pod panelima sa cevima koje provode toplu vodu i/ili upotrebu toplotnih pumpi sa visokim stepenom iskorišćenja. Razvoj kaskadne toplotne pumpe i njena šira primena omogućila bi daleko efikasniju upotrebu 'lako' dostupnih podzemnih vodnih resursa temperature između 10-30°C i stoga je u više projekata realizovanih poslednjih godina analizirana i razvijana ova tehnologija. Hidrogeološki uslovi u terenima istočne Srbije, su veoma povoljni sa aspekta eksploatacije subgeotermalnih resursa. Područje se odlikuje značajnim količinama podzemnih voda i terestičnim toplotnim tokom u okviru geoloških formacija u osnovnim geo-strukturnim jedinicama ovog regiona (Karpato-Balkanidi i Dakijski basen). Blizina urbanizovanih naselja i manjih gradova i postojanje razvijenog i centralizovanog grejanja su činjenice koje povoljno utiču na mogućnost eksploatacije subgeotermalnih vodnih resursa. Održivo korišćenje podzemnih vodnih resursa podrazumevalo bi i potrebnu termalnu rekonstrukciju i bolju izolaciju postojećih građevinskih objekata, kao i donošenje novih zakonskih propisa u Srbiji u cilju podsticaja korišćenja obnovljivih izvora energije. U području istočne Srbije, procenjene količine energije koje se mogu dobiti iz subgeotermalnih voda iznose oko 33 MWt, što bi predstavljalo oko 16% ukupnih energetskih potreba nekoliko odabranih većih naselja za koje je ova analiza vršena. I pored činjenice da se ne očekuje potpuno iskorišćenje ovog potencijala, evidentno je da je on daleko veći od 4 % koliko je u planovima energetskog razvoja predviđeno da bi moglo iznositi učešće geotermalnih vodnih resursa na nivou cele Srbije.Extensive worldwide usage of fossil energy sources causes high pollution and contributes to global warming. Hence, achieving energy independence by stimulating efficient use of energy and environmentally friendly exploitation of renewable sources is a main orientation of European countries. Geothermal energy is generally treated as a renewable and inexhaustible energy source. Nonetheless, direct use of low enthalpy subgeothermal resources, i.e. groundwater of 30.C or lower, for heating is commonly viewed as economically unjustified. To enable its usage, large panel surfaces or a high-temperature heat pump with excellent efficiency is required. The development of a cascade type heat pump and its wide application would enable more efficient utilization of widely available and easy replenished groundwater sources with temperatures of 10-30.C. The hydrogeological conditions in eastern Serbia are particularly favourable for exploitation of subgeothermal resources due to rich aquifer systems and notable terrestrial heat flow formed into the main geo-structures of the region (Carpathian-Balkan arch and Dachian basin). More intensive exploitation of subgeothermal sources additionally justifies the existence of a number of urbanized small and medium-size cities with a heating infrastructure already developed and centralized. Sustainable use of groundwater resources should be followed by thermal reconstruction of the previously constructed buildings as well as new legislation which supports and encourages development of renewable energy sources. It is estimated that the total potential thermal power which can be generated from subgeothermal waters in the study area is around 33 MWt, which corresponds to some 16 % of the total heat requirements

Early Left Ventricular Systolic and Diastolic Dysfunction in Patients with Newly Diagnosed Obstructive Sleep Apnoea and Normal Left Ventricular Ejection Fraction

The aim of the study was to evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolic and regional systolic dysfunction in newly diagnosed OSA with normal left ventricle ejection fraction. Methods. 125 consecutive patients were prospectively enrolled in the study. Control group consisted of 78 asymptomatic age-matched healthy subjects who did not have any cardiovascular and respiratory diseases. All patients had undergone overnight polysomnography and standard transthoracic and tissue Doppler imaging echocardiogram. Results. The E/A ratio and the peak E wave at mitral flow were significantly lower and the peak A wave at mitral flow was significantly higher in OSA patients compared with control subjects. Left ventricle isovolumetric relaxation time (IVRT) and mitral valve flow propagation (MVFP) were significantly longer in OSA patients than in controls. Tissue Doppler derived S′ amplitude of lateral part at mitral valve (S′Lm) and E′ wave amplitudes both at the lateral (E′Lm) and septal parts of the mitral valve (E′Sm) were significantly lower in OSA patients compared to controls. Conclusion. Newly diagnosed OSA patients with normal global LV function have significantly impaired diastolic function and regional longitudinal systolic function. OSA is independently associated with these changes in LV function

AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C

We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G(2)/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells. (c) 2009 Elsevier Inc. All rights reserved

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1 beta, IFN-gamma) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1 beta, IL-6, IFN-gamma, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-beta remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 mu g/day) for five consecutive days significantly reduced TNF, IL-1 beta and IFN-gamma levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of 1FN-gamma, IL-17,1L-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. (C) 2011 Elsevier Inc. All rights reserved

Unacylated ghrelin suppresses grelin-induced neuronal activity in the hypothalamus and brainstem of male rats

Ghrelin, the endogenous growth hormone secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and unacylated (UAG). Many studies suggest different roles for these two forms of ghrelin in energy balance regulation. In the present study, we compared the effects of acute intracerebroventricular administration of AG, UAG and their combination (AG+UAG) to young adult Wistar rats on food intake and central melanocortin system modulation. Although UAG did not affect food intake it significantly increased the number of c-Fos positive neurons in the arcuate (ARC), paraventricular (PVN) and solitary tract (NTS) nuclei. In contrast, UAG suppressed AG-induced neuronal activity in PVN and NTS. Central UAG also modulated hypothalamic expression of Mc4r and Bmp8b, which were increased and Mc3r, Pomc, Agrp and Ucp2, which were decreased. Finally, UAG, AG and combination treatments caused activation of c-Fos in POMC expressing neurons in the arcuate, substantiating a physiologic effect of these peptides on the central melanocortin system. Together, these results demonstrate that UAG can act directly to increase neuronal activity in the hypothalamus and is able to counteract AG-induced neuronal activity in the PVN and NTS. UAG also modulates expression of members of the melanocortin signaling system in the hypothalamus. In the absence of an effect on energy intake, these findings indicate that UAG could affect energy homeostasis by modulation of the central melanocortin system