Search results for: Engin Ceylan
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 42

Search results for: Engin Ceylan

12 Genotypic Variation in the Germination Performance and Seed Vigor of Safflower (Carthamus tinctorius L.)

Authors: Mehmet Demir Kaya, Engin Gökhan Kulan, Onur İleri, Süleyman Avcı

Abstract:

Due to variation in seed size, shape and oil content of safflower cultivars, germination and emergence performance have been severely influenced by seed characteristics. This study aimed to determine genotypic variation among safflower genotypes for one thousand seed weight, oil content, germination and seed vigor using electrical conductivity (EC) and cold test. In the study, safflower lines ES37-5, ES38-4, ES43-11, ES55-14 and ES58-11 which were developed by single seed selection method, and Dinçer and Remzibey-05 were used as standard varieties. The genotypes were grown under rainfed conditions in Eskişehir, Turkey with four replications. The seeds of each genotype were subjected to standard germination and emergence test at 25°C for 10 days with four replications and 50 seeds per replicate. Electrical conductivity test was performed at 25°C for 24 h to assess the seed vigor. Also, cold test were applied to each safflower genotype at 10°C for 4 days and 25°C for 6 days. Results showed that oil content of the safflower genotypes were different. The highest oil content was determined in ES43-11 with 36.6% while the lowest was 25.9% in ES38-4. Higher germination and emergence rate were obtained from ES55-14 with 96.5% and 73.0%, respectively. There was no significant difference among the safflower genotypes for EC values. Cold test showed that ES43-11 and ES55-14 gave the maximum germination percentages. It was concluded that genotypic factors except for soil and climatic conditions play an important role for determining seed vigor because safflower genotypes grown at the same condition produced various seed vigor values.

Keywords: Carthamus tinctorius L., germination, emergence, cold test, electrical conductivity

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11 Wind Energy Status in Turkey

Authors: Mustafa Engin Başoğlu, Bekir Çakir

Abstract:

Since large part of electricity generation is provided by using fossil based resources, energy is an important agenda for countries. Depletion of fossil resources, increasing awareness of climate change and global warming concerns are the major reasons for turning to alternative energy resources. Solar, wind and hydropower energy are the main renewable energy sources. Among of them, wind energy is promising for Turkey whose installed power capacity increases approximately eight times between 2008 - seventh month of 2014. Signing of Kyoto Protocol can be accepted as a milestone for Turkey's energy policy. Turkish government has announced 2023 Vision (2023 targets) in 2010-2014 Strategic Plan prepared by Ministry of Energy and Natural Resources (MENR). 2023 Energy targets can be summarized as follows: Share of renewable energy sources in electricity generation is 30% of total electricity generation by 2023. Installed capacity of wind energy will be 20 GW by 2023. Other renewable energy sources such as solar, hydropower and geothermal are encouraged with new incentive mechanisms. Share of nuclear power plants in electricity generation will be 10% of total electricity generation by 2023. Dependence on foreign energy is reduced for sustainability and energy security. As of seventh month of 2014, total installed capacity of wind power plants is 3.42 GW and a lot of wind power plants are under construction with capacity 1.16 GW. Turkish government also encourages the locally manufactured equipments. MILRES is an important project aimed to promote the use of renewable sources in electricity generation. A 500 kW wind turbine will be produced in the first phase of project. Then 2.5 MW wind turbine will be manufactured domestically within this project

Keywords: wind energy, wind speed, 2023 vision, MILRES, wind energy potential in TURKEY

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10 The Effects on Abomasal Emtying Rate of Erythromycin and Bethanechol in Healthy, Premature and Diarrheic Calves

Authors: Sebnem Canikli Engin, Mutlu Sevinc, Hasan Guzelbektes

Abstract:

In this study, we aim to define the effects of erythromycin and bethanechol which are prokinetic agents, on the value of abomasal discharge in healthy, diarrhea and premature calves. In the work, 5 healty calves, 12 diarrheaic calves and 12 premature calves, amounting to a total of 29 calves. In healty calves work; the same 5 calves were used for controlled, erythromycin and bethanechol studies (there was a 48-hour waiting period between each work). In diarrheic calves work; 12 diarrheic calves were used during the study (4 of them for control group, 4 of them bethanechol group and last 4 calves erythromycin group). In premature calves works; 12 premature calves were used during the study (4 of them for control group, 4 of them bethanechol group and last 4 calves erythromycin group). 10 mg/kg IM dose of erythromycin were applied to each erythromycin group, 0,07 mg/kg IM dose of bethanechol were applied on bethanechol group. No drugs were applied to the control group and substitution milk was given to all calves. 50 mg/kg acetominophen and 25 gram/L glucose have been added into the substitution milk to evaluate the speed of gastrointestinal motility with the test results of absorptions of acetominophen and glucose. The blood samples have been taken before substitution milk application and 30, 60, 90, 120, 180, 240 and 300 minutes after substitution milk application. Respiratory rates and number of heartbeats were also recorded during the test time. No changes were observed in the number of heartbeats, respiratory rates and general conditions for all groups after drug application. It is observed that, the feces of some calves became slightly watery and viscous and premature calves generaly defecated after 180 minutes. When Cmax, Tmax and AUC values of acetaminophen and glucose are compared with control group’s after applying erythromycin on the calves in the premature group, we obtain higher Cmax (P<0,05), shorter Tmax and greather AUC (P>0,05) values. In conclusion, according to clinical and laboratory findings, it may be stated that the application of 10 mg/kg doze of erythromycin IM has provided faster abomazal emptying in premature calves.

Keywords: abomazal emptying, bethanechol, calf, erythromycin

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9 Development of Carrageenan-Psyllium/Montmorillonite Clay Hybrid Hydrogels for Agriculture Purpose

Authors: D. Aydinoglu, N. Karaca, O. Ceylan

Abstract:

Limited water resources on the earth come first among the most alarming issues. In this respect, several solutions from treatment of waste water to water management have been proposed. Recently, use of hydrogels as soil additive, which is one of the water management ways in agriculture, has gained increasing interest. In traditional agriculture applications, water used with irrigation aim, rapidly flows down between the pore structures in soil, without enough useful for soil. To overcome this fact and increase the abovementioned limit values, recently, several natural based hydrogels have been suggested and tested to find out their efficiency in soil. However, most of these researches have dealt with grafting of synthetic acrylate based monomers on natural gelling agents, most probably due to reinforced of the natural gels. These results motivated us to search a natural based hydrogel formulations, not including any synthetic component, and strengthened with montmorillonite clay instead of any grafting polymerization with synthetic monomer and examine their potential in this field, as well as characterize of them. With this purpose, carrageenan-psyllium/ montmorillonite hybrid hydrogels have been successively prepared. Their swelling capacities were determined both in deionized and tap water and were found to be dependent on the carrageenan, psyllium and montmorillonite ratios, as well as the water type. On the other hand, mechanical tests revealed that especially carrageenan and montmorillonite contents have a great effect on gel strength, which is one of the essential features, preventing the gels from cracking resulted in readily outflow of all the water in the gel without beneficial for soil. They found to reach 0.23 MPa. The experiments carried out with soil indicated that hydrogels significantly improved the water uptake capacities and water retention degrees of the soil from 49 g to 85 g per g of soil and from 32 to 67%, respectively, depending on the ingredient ratios. Also, biodegradation tests demonstrated that all the hydrogels undergo biodegradation, as expected from their natural origin. The overall results suggested that these hybrid hydrogels have a potential for use as soil additive and can be safely used owing to their totally natural structure.

Keywords: carrageenan, hydrogel, montmorillonite, psyllium

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8 An Analysis of the Performances of Various Buoys as the Floats of Wave Energy Converters

Authors: İlkay Özer Erselcan, Abdi Kükner, Gökhan Ceylan

Abstract:

The power generated by eight point absorber type wave energy converters each having a different buoy are calculated in order to investigate the performances of buoys in this study. The calculations are carried out by modeling three different sea states observed in two different locations in the Black Sea. The floats analyzed in this study have two basic geometries and four different draft/radius (d/r) ratios. The buoys possess the shapes of a semi-ellipsoid and a semi-elliptic paraboloid. Additionally, the draft/radius ratios range from 0.25 to 1 by an increment of 0.25. The radiation forces acting on the buoys due to the oscillatory motions of these bodies are evaluated by employing a 3D panel method along with a distribution of 3D pulsating sources in frequency domain. On the other hand, the wave forces acting on the buoys which are taken as the sum of Froude-Krylov forces and diffraction forces are calculated by using linear wave theory. Furthermore, the wave energy converters are assumed to be taut-moored to the seabed so that the secondary body which houses a power take-off system oscillates with much smaller amplitudes compared to the buoy. As a result, it is assumed that there is not any significant contribution to the power generation from the motions of the housing body and the only contribution to power generation comes from the buoy. The power take-off systems of the wave energy converters are high pressure oil hydraulic systems which are identical in terms of their characteristic parameters. The results show that the power generated by wave energy converters which have semi-ellipsoid floats is higher than that of those which have semi elliptic paraboloid floats in both locations and in all sea states. It is also determined that the power generated by the wave energy converters follow an unsteady pattern such that they do not decrease or increase with changing draft/radius ratios of the floats. Although the highest power level is obtained with a semi-ellipsoid float which has a draft/radius ratio equal to 1, other floats of which the draft/radius ratio is 0.25 delivered higher power that the floats with a draft/radius ratio equal to 1 in some cases.

Keywords: Black Sea, buoys, hydraulic power take-off system, wave energy converters

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7 Determination of the Vaccine Induced Immunodominant Regions of Nucleoprotein Crimean-Congo Hemorrhagic Fever Virus

Authors: Engin Berber, Nurettin Canakoglu, Ibrahim Sozdutmaz, Merve Caliskan, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Aykut Ozdarendeli

Abstract:

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the family Bunyaviridae, genus Nairovirus. The CCHFV genome consists of three molecules of negative-sense single-stranded RNA, each encapsulated separately. The virion particle contains viral RNA polymerase (L segment), surface glycoproteins Gn and Gc (Msegment), and a nucleocapsid protein NP (S segment). CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Eastern Europe. Clinical CCHF was first recognized in Turkey in 2002. The numbers of CCHF cases have gradually increased in Turkey making the virus a public health concern. Between 2002 and 2014, more than 8000 the CCHF cases have been reported in Turkey and mortality rate is around 5%. So, Turkey is one of the countries where the epidemy has become spread to the wider geography and the biggest outbreaks of CCHF have occurred in the world. We have recently developed an inactivated cell-culture based vaccine against CCHF. We have showed that the Balb/c mice immunized with the CCHF vaccine induced the high level of neutralizing antibodies. In this study, we aimed to determine the immunodominant regions of nucleoprotein (NP) CCHFV Kelkit06 strain which stimulate T cells. For this purpose, pools of overlapping NP were used for an IFN- γ ELISPOT assay. Balb/c mice were divided into two groups for the experiment. Two groups (n = 10 each) were immunized via the intraperitoneal route with 5, or 10μg of the cell culture-based vaccine. The control group (n = 6) was mock immunized with PBS. Booster injections with the same formulation were given on days 21 and 42 after the first immunization. The higher reactivity against the CCHFV NP pools 31-40 and 80-90 was determined in the two dose groups. In order to analyze the vaccine-induced T cell responses in Balb/c mice immunized with varying doses of the vaccine, we have been also currently working on CD4+, CD8+ and CD3 + T cells by flow cytometry.

Keywords: Crimean-Congo hemorrhagic fever virus, immunodominant regions of NP, T cell response, vaccine

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6 Existence of Systemic Risk in Turkish Banking Sector: An Evidence from Return Distributions

Authors: İlhami Karahanoglu, Oguz Ceylan

Abstract:

As its well-known definitions; systemic risk refers to whole economic system down-turn movement even collapse together in very severe cases. In fact, it points out the contagion effects of the defaults. Such a risk is can be depicted with the famous Chinese game of falling domino stones. During and after the Bear & Sterns and Lehman Brothers cases, it was well understood that there is a very strong effect of systemic risk in financial services sector. In this study, we concentrate on the existence of systemic risk in Turkish Banking Sector based upon the Halkbank Case during the end month of 2013; there was a political turmoil in Turkey in which the close relatives of the upper politicians were involved in illegal trading activities. In that operation, the CEO of Halkbank was also arrested and in investigation, Halkbank was considered as part of such illegal actions. That operation had an impact on Halkbanks stock value. The Halkbank stock value during that time interval decreased remarkably, the distributional profile of stock return changed and became more volatile as well as more skewed. In this study, the daily returns of 5 leading banks in Turkish banking sector were used to obtain 48 return distributions (for each month, 90-days-back stock value returns are used) of 5 banks for the period 12/2011-12/2013 (pre operation period) and 12/2013-12/2015 (post operation period). When those distributions are compared with timely manner, interestingly; the distribution of the 5 other leading banks in Turkey, public or private, had also distribution profiles which was different from the past 2011-2013 period just like Halkbank. Those 5 big banks, whose stock values are monitored with sub index in Istanbul stock exchange (BIST) as BN10, had more skewed distribution just following the Halkbank stock return movement during the post operation period, with lover mean value and as well higher volatility. In addition, the correlation between the stock value return distributions of the leading banks after Halkbank case, where the returns are more skewed to the left, increased (which is measured in monthly base before and after the operation). The dependence between those banks was stronger under the case where the stock values were falling compared with the normal market condition. Such distributional effect of stock returns between the leading banks in Turkey, which is valid for down sub-market (financial/banking sector) condition, can be evaluated as an evidence for the existence of contagious effect and systemic risk.

Keywords: financial risk, systemic risk, banking sector, return distribution, dependency structure

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5 Environmental Interactions in Riparian Vegetation Cover in an Urban Stream Corridor: A Case Study of Duzce Asar Suyu

Authors: Engin Eroğlu, Oktay Yıldız, Necmi Aksoy, Akif Keten, Mehmet Kıvanç Ak, Şeref Keskin, Elif Atmaca, Sertaç Kaya

Abstract:

Nowadays, green spaces in urban areas are under threat and decreasing their percentages in the urban areas because of increasing population, urbanization, migration, and some cultural changes in quality. An important element of the natural landscape water and water-related natural ecosystems are exposed to corruption due to these pressures. A landscape has owned many different types of elements or units, a more dominant structure than other landscapes as good or bad perceptible extent different direction and variable reveals a unique structure and character of the landscape. Whereas landscapes deal with two main groups as urban and rural according to their location on the world, especially intersection areas of urban and rural named semi-urban or semi-rural present variety landscape features. The main components of the landscape are defined as patch-matrix-corridor. The corridors include quite various vegetation types such as riparian, wetland and the others. In urban areas, natural water corridors are an important elements of the diversity of the riparian vegetation cover. In particular, water corridors attract attention with a natural diversity and lack of fragmentation, degradation and artificial results. Thanks to these features, without a doubt, water corridors are the important component of all cities in the world. These corridors not only divide the city into two separate sides, but also assured the ecological connectivity between the two sides of the city. The main objective of this study is to determine the vegetation and habitat features of urban stream corridor according to environmental interactions. Within this context, this study will be realized that 'Asar Suyu' is an important component of the city of Düzce. Moreover, the riparian zone touched contiguous area borders of the city and overlaid the urban development limits of the city, determining of characteristics of the corridor will be carried out as floristic and habitat analysis. Consequently, vegetation structure and habitat features which play an important role between riparian zone vegetation covers and environmental interaction will be determined. This study includes first results of The Scientific and Technological Research Council of Turkey (TUBITAK-116O596; 'Determining of Landscape Character of Urban Water Corridors as Visual and Ecological; A Case Study of Asar Suyu in Duzce').

Keywords: corridor, Duzce, landscape ecology, riparian vegetation

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4 A New Approach for Preparation of Super Absorbent Polymers: In-Situ Surface Cross-Linking

Authors: Reyhan Özdoğan, Mithat Çelebi, Özgür Ceylan, Mehmet Arif Kaya

Abstract:

Super absorbent polymers (SAPs) are defined as materials that can absorb huge amount of water or aqueous solution in comparison to their own mass and retain in their lightly cross-linked structure. SAPs were produced from water soluble monomers via polymerization subsequently controlled crosslinking. SAPs are generally used for water absorbing applications such as baby diapers, patient or elder pads and other hygienic product industries. Crosslinking density (CD) of SAP structure is an essential factor for water absortion capacity (WAC). Low internal CD leads to high WAC values and vice versa. However, SAPs have low CD and high swelling capacities and tend to disintegrate when pressure is applied upon them, so SAPs under load cannot absorb liquids effectively. In order to prevent this undesired situation and to obtain suitable SAP structures having high swelling capacity and ability to work under load, surface crosslinking can be the answer. In industry, these superabsorbent gels are mostly produced via solution polymerization and then they need to be dried, grinded, sized, post polymerized and finally surface croslinked (involves spraying of a crosslinking solution onto dried and grinded SAP particles, and then curing by heat). It can easily be seen that these steps are time consuming and should be handled carefully for the desired final product. If we could synthesize desired final SAPs using less processes it will help reducing time and production costs which are very important for any industries. In this study, synthesis of SAPs were achieved successfully by inverse suspension (Pickering type) polymerization and subsequently in-situ surface cross-linking via using proper surfactants in high boiling point solvents. Our one-pot synthesis of surface cross-linked SAPs invovles only one-step for preparation, thus it can be said that this technique exhibits more preferable characteristic for the industry in comparison to conventional methods due to its one-step easy process. Effects of different surface crosslinking agents onto properties of poly(acrylic acid-co-sodium acrylate) based SAPs are investigated. Surface crosslink degrees are evaluated by swelling under load (SUL) test. It was determined water absorption capacities of obtained SAPs decrease with the increasing surface crosslink density while their mechanic properties are improved.

Keywords: inverse suspension polymerization, polyacrylic acid, super absorbent polymers (SAPs), surface crosslinking, sodium polyacrylate

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3 A Study on Green Building Certification Systems within the Context of Anticipatory Systems

Authors: Taner Izzet Acarer, Ece Ceylan Baba

Abstract:

This paper examines green building certification systems and their current processes in comparison with anticipatory systems. Rapid growth of human population and depletion of natural resources are causing irreparable damage to urban and natural environment. In this context, the concept of ‘sustainable architecture’ has emerged in the 20th century so as to establish and maintain standards for livable urban spaces, to improve quality of urban life, and to preserve natural resources for future generations. The construction industry is responsible for a large part of the resource consumption and it is believed that the ‘green building’ designs that emerge in construction industry can reduce environmental problems and contribute to sustainable development around the world. A building must meet a specific set of criteria, set forth through various certification systems, in order to be eligible for designation as a green building. It is disputable whether methods used by green building certification systems today truly serve the purposes of creating a sustainable world. Accordingly, this study will investigate the sets of rating systems used by the most popular green building certification programs, including LEED (Leadership in Energy and Environmental Design), BREEAM (Building Research Establishment's Environmental Assessment Methods), DGNB (Deutsche Gesellschaft für Nachhaltiges Bauen System), in terms of ‘Anticipatory Systems’ in accordance with the certification processes and their goals, while discussing their contribution to architecture. The basic methodology of the study is as follows. Firstly analyzes of brief historical and literature review of green buildings and certificate systems will be stated. Secondly, processes of green building certificate systems will be disputed by the help of anticipatory systems. Anticipatory Systems is a set of systems designed to generate action-oriented projections and to forecast potential side effects using the most current data. Anticipatory Systems pull the future into the present and take action based on future predictions. Although they do not have a claim to see into the future, they can provide foresight data. When shaping the foresight data, Anticipatory Systems use feedforward instead of feedback, enabling them to forecast the system’s behavior and potential side effects by establishing a correlation between the system’s present/past behavior and projected results. This study indicates the goals and current status of LEED, BREEAM and DGNB rating systems that created by using the feedback technique will be examined and presented in a chart. In addition, by examining these rating systems with the anticipatory system that using the feedforward method, the negative influences of the potential side effects on the purpose and current status of the rating systems will be shown in another chart. By comparing the two obtained data, the findings will be shown that rating systems are used for different goals than the purposes they are aiming for. In conclusion, the side effects of green building certification systems will be stated by using anticipatory system models.

Keywords: anticipatory systems, BREEAM, certificate systems, DGNB, green buildings, LEED

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2 Improved Morphology in Sequential Deposition of the Inverted Type Planar Heterojunction Solar Cells Using Cheap Additive (DI-H₂O)

Authors: Asmat Nawaz, Ceylan Zafer, Ali K. Erdinc, Kaiying Wang, M. Nadeem Akram

Abstract:

Hybrid halide Perovskites with the general formula ABX₃, where X = Cl, Br or I, are considered as an ideal candidates for the preparation of photovoltaic devices. The most commonly and successfully used hybrid halide perovskite for photovoltaic applications is CH₃NH₃PbI₃ and its analogue prepared from lead chloride, commonly symbolized as CH₃NH₃PbI₃_ₓClₓ. Some researcher groups are using lead free (Sn replaces Pb) and mixed halide perovskites for the fabrication of the devices. Both mesoporous and planar structures have been developed. By Comparing mesoporous structure in which the perovskite materials infiltrate into mesoporous metal oxide scaffold, the planar architecture is much simpler and easy for device fabrication. In a typical perovskite solar cell, a perovskite absorber layer is sandwiched between the hole and electron transport. Upon the irradiation, carriers are created in the absorber layer that can travel through hole and electron transport layers and the interface in between. We fabricated inverted planar heterojunction structure ITO/PEDOT/ Perovskite/PCBM/Al, based solar cell via two-step spin coating method. This is also called Sequential deposition method. A small amount of cheap additive H₂O was added into PbI₂/DMF to make a homogeneous solution. We prepared four different solution such as (W/O H₂O, 1% H₂O, 2% H₂O, 3% H₂O). After preparing, the whole night stirring at 60℃ is essential for the homogenous precursor solutions. We observed that the solution with 1% H₂O was much more homogenous at room temperature as compared to others. The solution with 3% H₂O was precipitated at once at room temperature. The four different films of PbI₂ were formed on PEDOT substrates by spin coating and after that immediately (before drying the PbI₂) the substrates were immersed in the methyl ammonium iodide solution (prepared in isopropanol) for the completion of the desired perovskite film. After getting desired films, rinse the substrates with isopropanol to remove the excess amount of methyl ammonium iodide and finally dried it on hot plate only for 1-2 minutes. In this study, we added H₂O in the PbI₂/DMF precursor solution. The concept of additive is widely used in the bulk- heterojunction solar cells to manipulate the surface morphology, leading to the enhancement of the photovoltaic performance. There are two most important parameters for the selection of additives. (a) Higher boiling point w.r.t host material (b) good interaction with the precursor materials. We observed that the morphology of the films was improved and we achieved a denser, uniform with less cavities and almost full surface coverage films but only using precursor solution having 1% H₂O. Therefore, we fabricated the complete perovskite solar cell by sequential deposition technique with precursor solution having 1% H₂O. We concluded that with the addition of additives in the precursor solutions one can easily be manipulate the morphology of the perovskite film. In the sequential deposition method, thickness of perovskite film is in µm and the charge diffusion length of PbI₂ is in nm. Therefore, by controlling the thickness using other deposition methods for the fabrication of solar cells, we can achieve the better efficiency.

Keywords: methylammonium lead iodide, perovskite solar cell, precursor composition, sequential deposition

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1 Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

Abstract:

Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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