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β-D-glukan, lektin, linoleik asit ve β-karoten; hayvansal, bitkisel ve bakteriyel kaynaklarda bulunan, biyolojik olarak aktif bileşiklerdir. Glokom, dünya genelinde körlüğe neden olma bakımından katarakttan sonra ikinci sırada gelen bir hastalıktır. Karbonik anhidraz (CA) inhibitörleri uzun yıllardır glokom tedavisinde kullanılmaktadır. Ancak, inhibitör ajanların yan etkileri azımsanmayacak derecede çoktur. Yeni CA inhibitörlerinin geliştirilmesi üzerine çeşitli araştırma grupları çalışmalar yapmaktadırlar. Doğal kaynaklı bileşiklerin CA inhibitörü olarak kullanımının araştırılması da son yıllarda popülerlik kazanmıştır. Bu çalışmada, β-D-glukan, lektin, linoleik asit ve β-karoten bileşiklerinin, insan eritrosit CA izoenzimleri olan hCA I ve hCA II üzerine etkileri in vitro koşullarda araştırılmıştır. Bileşiklerin Ki değerleri hCA I için 0.45±0.09 µM − 37.02±17.85 µM aralığında, hCA II için 3.12±1.38 µM − 61.23±25.46 µM aralığındadır., β-D-glucan, lectin, linoleic acid and β-carotene are biologically active compounds and they are found in animal, herbal and bacterial sources. Glaucoma is the second most common cause of blindness worldwide after cataract. Carbonic anhydrase (CA) inhibitors have been used in the treatment of glaucoma for years. However, inhibitory agents have a lot of side effects. Research groups have been working on the development of new CA inhibitors. Research into the use of compounds of natural origin as CA inhibitors has also gained popularity in recent years. In this study, the inhibitory effects of β-D-glucan, lectin, linoleic acid and β-carotene on human erythrocyte carbonic anhydrase isoenzymes, hCA I and hCA II, have been studied in vitro. The Ki values of the compounds were in the range of 0.45±0.09 µM − 37.02±17.85 µM for hCA I, and 3.12±1.38 µM − 61.23±25.46 µM for hCA II.

Hücresel yapılar için önemli metabolik görevleri olan enzimler çeşitli amaçlarla kullanılmak üzere gündelik ve ekonomik hayata girmiştir. Son yıllarda lipazlar ile katı ve sıvı yağların enzimatik modifikasyonu giderek önem kazanmıştır. Endüstrinin hemen her alanında kullanılan lipazlar genellikle mikroorganizma ve son zamanlarda da yağlı bitki tohumlarından elde edilmektedir. Kolay bulunabilmeleri, katalitik aktivitelerinin çok yüksek olmaları, istenmeyen yan ürün oluşturmamaları gibi avantajları bulunan bitkisel kaynaklı lipazlar gıda, deterjan ve ilaç endüstrilerinde kullanılabilmektedir. Yağların hidrolizlenme yeteneklerinden dolayı lipazlar evlerde deterjan ürünlerinde temizleme etkilerini arttırabilmek amacı ile katkı maddesi olarak kullanılmaktadır. Bu çalışmada bol yağlı bir bitki tohumu olan Antep fıstığı tercih edilmiş ve saflaştrıma işlemleri sonucunda enzim aktiviteleri belirlenmiştir. Yağsızlaştırma işlemi sonucunda amonyum sülfat çöktürmesinde %30 doygunlukta ilk çökelme gözlemlenmiş ve en yüksek enzim aktivitesi %50 ve %60 doygunlukta 5 ml NaOH eklendiğinde olmuştur. Kinetik özellikleri belirlenen Antep fıstığı bitki tohumu lipazının stabil ve optimum sıcaklık ve pH değerleri tespit edilip deterjan endüstrisinde kullanılan diğer lipaz enzimleri kinetik özellikleri ile karşılaştırılıp yorumlanmıştır. Antep fıstığı lipaz enzimi kinetik özelliklerinin deterjan endüstrisinde kullanımı uygun bulunmuştur.

INTRODUCTION: Many regulations for aeromedical assessments state that a ratio between forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of < 0.7 should be evaluated by a pulmonary specialist. The Global Lung Initiative (GLI) reference values introduced the lower limit of normal (LLN 2.5), in which the lowest 2.5% of the population is regarded as abnormal, instead of a fixed ratio. This study assesses the impact of adopting GLI reference values on aeromedical evaluation and referrals.METHODS: The Royal Netherlands Air Force performed 7492 aeromedical assessments between February 2012 and April 2017. Cases with FEV1/FVC < 0.7 from three groups were selected: 1) men < 25 yr; 2) men > 40 yr; and 3) women, with twice as many matched controls. Pearson's Chi-squared and Fisher’s exact tests were used to analyze the data.RESULTS: From the database, 23 (group 1), 62 (group 2), and 7 (group 3) cases were selected, with 184 controls. Respectively, 17%, 84%, and 29% would not be referred using the GLI. In the controls, this would lead to one additional referral (group 1). Qualitative analysis of the cases who would not be referred using the GLI showed that no significant diagnoses would have been missed.DISCUSSION: Using the GLI LLN 2.5 reference values for pulmonary function tests leads to significantly fewer referrals to a pulmonary specialist without missing relevant pulmonary pathology in our aircrew. This would reduce resources spent on the assessment of aircrew without compromising flight safety.Wingelaar-Jagt YQ, Wingelaar TT, Bülbül M, vd Bergh PP, Frijters E, Staudt E. The effect of using the lower limit of normal 2.5 in pulmonary aeromedical assessments. Aerosp Med Hum Perform. 2020; 91(8):636–640.

Sulfonamides represent an important class of biologically active compounds. A sulfonamide possessing carbonic anhydrase (CA) inhibitory properties obtained from a pyrazole based sulfonamide, ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate (1), and its metal complexes with the Ni(II) for (2), Cu(II) for (3) and Zn(II) for (4) have been synthesized. The structures of metal complexes (2–4) were established on the basis of their elemental analysis, 1H NMR, IR, UV–Vis and MS spectral data. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes I and II, with 1 and synthesized complexes (2–4) and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. The complexes 2, 3 and 4 showed inhibition constant in the range 0.1460–0.3930 µM for hCA-I and 0.0740–0.0980 µM for hCA-II, and they had effective more inhibitory activity on hCA-I and hCA-II than corresponding free ligand 1 and than AAZ. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group., This work was supported by Scientific and Technological Research Council of Turkey (TUB€ İTAK) with Grant No. TBAG-104T406.

Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR, 1H-NMR, 13C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein−1, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein−1. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied in vitro. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC50 values of compounds for esterase activity are in the range of 118.4 ± 7.0 μM–257.5 ± 5.2 μM for hCA I and 86.7 ± 3.0 μM–249.4 ± 10.2 μM for hCA II, respectively.

WOS: 000392591100016, PubMed: 28100079, A novel proton transfer compound (SMHABT) (+)(HDPC)(-) (1) obtained from 2-amino-6-sulfamoylbenzothiazole (SMABT) and 2,6-pyridinedicarboxylic acid (H2DPC) and its Fe(III), Co(II), Ni(II) complexes (2-4), and Fe(II) complex of SMABT (5) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to complexes (2-4). All complexes (2-4) have distorted octahedral conformations and the structure of 5 might be proposed as octahedral according to spectral and analytical results. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. The synthesized compounds have remarkable inhibitory activities on hCA I and hCA II. Especially, the inhibition potentials of the salt and the metal complexes (1-5) are comparable with AAZ. Inhibition data have been analyzed by using a one-way analysis of variance for multiple comparisons (p < .0001)., Dumlupinar University Research Fund [2014/18], This work was supported by the Dumlupinar University Research Fund [(grant No. 2014/18)].

WOS: 000352274500004, PubMed ID: 24758349, A novel proton transfer compound (HClABT)(+)(HDPC.H2DPC)(-) (1) and its Fe(III), Co(II), Ni(II) and two different Cu(II) complexes (2-6) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to all complexes. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. The comparison of the inhibition studies of 1-6 to parent compounds, ClABT and H2DPC, indicates that 1-6 have superior inhibitory effects. The inhibition effects of 2-6 are also compared to the inhibitory properties of the simple metal complexes of ClABT and H2DPC, revealing an improved transfection profile. Data have been analysed by using a one-way analysis of variance for multiple comparisons., Dumlupynar University Research Fund [2012/16], The authors acknowledge the support provided by Dumlupynar University Research Fund (grant No. 2012/16).

Novel sulfonamide derivatives 6a–i, as new carbonic anhydrase inhibitors which candidate for glaucoma treatment, were synthesized from the reactions of 4-amino-N-(4-sulfamoylphenyl) benzamide 4 and sulfonyl chloride derivatives 5a–i with high yield (71–90%). The structures of these compounds were confirmed by using spectral analysis (FT-IR, 1H NMR, 13C NMR, LC/MS and HRMS). The inhibition effects of 6a–i on the hydratase and esterase activities of human carbonic anhydrase isoenzymes, hCA I and II, which were purified from human erythrocytes with Sepharose®4B-l-tyrosine-p-aminobenzene sulfonamide affinity chromatography, were studied as in vitro, and IC50 and Ki values were determined. The results show that newly synthesized compounds have quite powerful inhibitory properties.

Bu çalışmada, ilk olarak sülfanilamit (sa) ve maleik anhidritin (mal) tepkimesinden (E)-3-(4- sülfamoyilfenil)amino)büt-2-enoik asit (Hsamal) bileşiği sentezlenmiş ve sonra bu bileşiğin 2-aminopiridin (ap) ile proton transfer tuzu (Hapsamal) hazırlanmıştır. Bu tuzun Fe(II), Co(II), Ni(II) ve Zn(II) geçiş metal kompleksleri sentezlenmiştir. Proton transfer tuzlarının yapısı elementel analiz, 1H-NMR, 13C-NMR, FT-IR, UV-Vis metotları ile aydınlatılmıştır. Amorf halde elde edilen geçiş metal komplekslerinin yapıları ise elementel analiz, ICP-OES, FT-IR, UV-Vis, manyetik duyarlılık ve molar iletkenlik sonuçları dikkate alınarak önerilmiştir. Ayrıca, sentezlenen maddelerin insan eritrosit hCA I ve hCA II izoenzimleri üzerindeki inhibisyon etkilerini belirlemek üzere in vitro çalışmalar yapılmıştır. Yeni sentezlenen maddelerin izoenzimlerin esteraz aktivitesini inhibe ettiği tespit edilmiştir. Bu maddelerin inhibisyon değerlerinin kontrol bileşiği asetazolamid (AAZ) değerleri ile kıyaslanabilir büyüklükte olduğu tespit edilmiştir. In this study, first (E)-4-oxo-4-(4-sulfamoylphenylamino)but-2-enoic acid (Hsamal) have been synthesized from the reaction between sulfanilamide (sa) and maleic anhydride (mal) and second, proton transfer salt (Hapsamal) has been prepared from 2-aminopyridine (ap) and Hsamal. Four transition metal complexes [Fe(II), Co(II), Ni(II) and Zn(II)] of the salt have also been synthesized. The structure of proton transfer compounds have been proposed by using elemantal analysis, 1H-NMR, 13C-NMR, FT-IR, UV-Vis techniques. The structure of amorphous metal complexes have been proposed by using elemantal analysis, ICP-OES, FT-IR, UV-Vis, magnetic susceptibility and molar conductivity techniques. In addition, in vitro studies have been performed to determine the inhibition effects of synthesized compounds on human erythrocyte hCA I and hCA II isoenzymes. It has been observed that synthesized compounds have affected esterase activities of hCA I and hCA II and the inhibition values of these compounds are comparable with the inhibition values of control compound acetazolamide (AAZ).

We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase inhibitor, administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided into three groups. First group was used as control. 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days, respectively. Both dose of Tenoxicam administration resulted in significant increase in the glutathione peroxidase activity, reduced glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration. Vitamin A and ß-carotene concentration was not affected by the administration. There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system. © 2008 Springer Science+Business Media, LLC.

WOS: 000342056900013, PubMed ID: 24148087, A novel proton transfer compound (HMeOABT) (+) (HDPC)(-) (1) and its Fe(III), Co(II), Ni(II) and Cu(II) complexes (2-5) have been prepared and characterized by spectroscopic techniques. Complex 4 has distorted octahedral conformation revealed by single crystal X-ray diffraction method. Structures of the other complexes might be proposed as octahedral according to experimental data. All compounds were also evaluated for their in vitro inhibition effects on hCA I and II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. Data have been analyzed by using a one-way analysis of variance. The comparison of the inhibition studies of 1-5 to parent compounds indicates that 1-5 have superior inhibitory effects. The inhibition effects of 2-5 are also compared to inhibitory properties of the metal complexes of MeOABT and H2DPC, revealing an improved transfection profile., Dumlupinar University Research Fund [2012/16], The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2012/16). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

WOS: 000336311600008, PubMed ID: 23808804, A novel proton transfer compound (HABT)(+)(Hdipic)(-) (1) obtained from ABT and H(2)dipic and its metal complexes (2-5) have been prepared and characterized by spectroscopic techniques. Single crystal X-ray diffraction method has also been applied to 2 and 5. While complex 2 has a distorted octahedral conformation, 5 exhibits a distorted square pyramidal structure. The structures of 3 and 4 might be proposed as octahedral according to experimental data. All compounds were also evaluated for their in vitro inhibition effects on hCA I and II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. The comparison of the inhibition studies of 1-5 to parent compounds indicates that 1-5 have superior inhibitory effects. The inhibition effects of 2-5 are also compared to inhibitory properties of the metal complexes of ABT and H(2)dipic, revealing an improved transfection profile., Dumlupinar University [2010/2], The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2010/2). In addition, the authors would like to thank the Medicinal Plants and Medicine Research Center of Anadolu University, for allowing us to use the X-ray facility.

Mannich bases 2a-f derived from 3,4-dimethylphenol (1), formaldehyde and different amines are prepared and subjected to spectral (IR, 1H and 13C NMR) and elemental analyses. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with 1 and synthesized Mannich bases 2a-f and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. In relation to hydratase and esterase activities of the half maximal inhibitory concentration (IC50) and the inhibition equilibrium constants (Ki)values were determined. Only two compounds (2a and 2e)exhibit weak hCA II inhibitory effects on esterase activity. IC50 and Ki values for 2a and 2e with respect to esterase activity of hCA II are0.88 × 103 and 6.3-7.6 µM and 0.44 × 103 and 19.0-96.4 µM,respectively. On the contrary, compounds 2b and 2d might be used as CA activators due to increasing esterase activity of hCA I and hCA II isozymes. © 2013 Informa UK, Ltd., This work was supported by grant (Grant No: 2008-1) from the Dumlupınar University Research Foundation and carried out in the Department of Chemistry of the Dumlupınar University.

Novel dioxoacridine sulfonamide compounds were synthesized from reaction of cyclic 1,3-diketones, sulfanilamide (4-amino benzene sulfonamide) and aromatic aldehydes. The structures of these compounds were confirmed by using spectral analysis (IR, H-NMR, 13C-NMR, and mass). Human carbonic anhydrase isoenzymes (hCA I and hCA II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of sulfanilamide, acetazolamide (AAZ), and newly synthesized sulfonamides on hydratase and esterase activities of these isoenzymes have been studied in vitro. The IC50 values of compounds for esterase activity are 0.710.11 M for hCA I and 0.450.12 M for hCA II, respectively. The Ki values of these inhibitors were determined as 0,380,008 M for hCA I and 0,190,001 M for hCA II, respectively. © 2012 Informa UK, Ltd., Fundamental Research Fund of Shandong University: 2008-4, The authors are very grateful to Dumlupinar University Research Fund for providing financial support for this project (Grant No. 2008-4).

Three novel metal complexes of N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxamide which possess strong carbonic anhydrase (CA) inhibitory properties have been synthesised. The structure of these compounds has been investigated by elemental analysis, FT-IR, LC/MS, UV-vis spectrophotometric method and magnetic susceptibility. Human carbonic anhydrase isoenzymes hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of newly synthesized complexes and acetazolamide (AAZ) as a control compound on hydratase and esterase activities of these isoenzymes have been studied in vitro by comparing IC50 and Ki values and it has been found that the newly synthesised complexes behave as very powerful inhibitors against hCA-I and hCA-II than parent ligand (1) and than AAZ. © 2013 Informa UK, Ltd., National Council for Scientific Research, This work was supported by The Scientific and Research Council of Turkey (TÜBİTAK) with Grant No. TBAG-104T406.

Two novel proton transfer compounds were prepared between 2,4-dichloro-5-sulphamoylbenzoic acid (lasamide) (Hsba) and ethylenediamine (en), namely ethane-1,2-diaminium 2,4-dichloro-5-sulphamoylbenzoate (1), and also between Hsba and 2-amino-3-methylpyridine (2-amino-3-picoline) (amp), namely 2-amino-3-methylpyridinium 2,4-dichloro-5-sulphamoylbenzoate (2). All these were characterised by elemental, spectral (IR and UV-vis), thermal analyses, and single crystal X-ray diffraction studies. Compounds 1 and 2 crystallised in the P-1 and P21/c space groups, respectively. Intermolecular non-covalent interactions, such as ion pairing, hydrogen bonding, and ?Ï€-?Ï€ stacking were observed for these ionic compounds. The free ligands Hsba, en and amp, the products 1 and 2, and acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibitor effects on the human carbonic anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cells by affinity chromatography for their hydratase and esterase activities. The half maximal inhibitory concentration (IC50) values for products 1 and 2 with respect to hydratase activity are 0.15 and 0.32 µ M for hCA I and 0.06 and 0.15 µ M for hCA II, respectively. The IC50 values of the same inhibitors for esterase activity are 0.13 and 0.8 µ M for hCA I and 0.14 and 0.1 µ M for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (Ki) were also determined and found to be 0.137 and 0.99 µ M on hCA I and 0.157 and 0.075 µ M on hCA II for 1 and 2, respectively. The comparison of the inhibition studies of the newly synthesised compounds 1 and 2 to the parent compounds Hsba and amp and also to AAZ indicated that 1 and 2 have an effective inhibitory activity on hCA I and II, and might be used as potential inhibitors. © 2011 Informa UK, Ltd., Faculty of Arts and Sciences 2007/2, The authors acknowledge the support provided by Dumlupınar University Research Fund (grant No. 2007/2). In addition, the authors would like to thank the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for use of the Stoe IPDS-2 diffractometer purchased under grant F.279 of the University Research Fund.

In this study, some novel inhibitors were synthesised from the further stage reactions of 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulphonamide 1 (inhibitor 1). They were characterised by elemental and spectral (1H NMR, 13C NMR, IR) analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (2) and the 11 newly synthesised amides (8-18) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The Ki values for the new compounds (8-18) were observed to be well below that of the parent compound inhibitor 1 and were also compared to 2 under the same experimental conditions. The comparison of the newly synthesised amides to inhibitor 1 and to 2 indicated that the new derivatives preferentially inhibited hCA-II and were more potent inhibitors of hCA-II than the parent inhibitor 1 and 2. © 2011 Informa UK, Ltd., 106T180, This research was funded by TUBITAK (The Foundation of Scientific and Technological Research of Turkey, 106T180) (Ankara, Turkey).

Pyrazole carboxylic acid derivatives of 5-amino-1,3,4-thiadiazole-2- sulfonamide (inhibitor 1) were synthesized from ethyl 3-(chlorocarbonyl)-1-(3- nitrophenyl)-5-phenyl-1H-pyrazole-4-carboxylate compound. The inhibitory effects of inhibitor 1, acetazolamide (AAZ) and of 11 newly synthesized amides (5a-b, 6, 7a-g, and 8) on hydratase and esterase activities of carbonic anhydrase isoenzymes (hCA-I and hCA-II) have been studied in vitro. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives inhibit CA isoenzymes and they are more potent inhibitors than the parent inhibitor 1 and AAZ. © 2010 Elsevier Masson SAS. All rights reserved., Türkiye Bilimsel ve Teknolojik Araştirma Kurumu: 106T180 National Council for Scientific Research, This study was funded by The Scientific and Research Council of Turkey (TÜBITAK) with Grant No 106T180 .

Previous studies have shown that generation of free radicals is increased following pentylenetetrazol kindling, due to increased cytosolic Ca2+ concentrations. Topiramate, a voltage-gated calcium channel inhibitor, has an evident effect in the treatment of childhood epilepsy; however, topiramate may cause nephrotoxicity. We investigated the effects of topiramate and vitamin E administration on pentylenetetrazol-induced nephrotoxicity in rats by evaluation of lipid peroxidation, nitric oxide, glutathione peroxidase, catalase and superoxide dismutase values. Forty male Wistar rats were randomly divided into five equal groups. Group 1 was used as control and group II received a single dose of pentylenetetrazol. Fifty and 100 mg/kg topiramate daily were intragastrically administered to rats in groups III and IV for 7 days, respectively. Intragastric 100 mg topiramate (daily for 7 days) and intraperitoneal vitamin E (150 mg/kg, daily for 3 days) combination were given to animals in group V before a single-dose pentylenetetrazol administration. Serum and kidney samples were taken after 3 hr of pentylenetetrazol administration. Pentylenetetrazol resulted in a significant increase in nitric oxide levels of serum and kidney, and lipid peroxidation levels of kidney although superoxide dismutase and catalase activities in the kidney was reduced by pentylenetetrazol administration. The lipid peroxidation levels in serum and kidneys and the nitric oxide levels in kidneys of groups III, IV and V were decreased by topiramate although the superoxide dismutase and catalase activities in the kidneys were increased. Lipid peroxidation and nitric oxide levels were reduced by the topiramate and vitamin E combination compared to only topiramate. Glutathione peroxidase activity was not affect by pentylenetetrazol, topiramate and vitamin E administrations. In conclusion, topiramate and vitamin E have protective effects on pentylenetetrazol-induced nephrotoxicity by inhibition of free radicals and by support of the antioxidant redox system. © 2008 The Authors.

WOS: 000260847500020, PubMed: 18618324, Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide were synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride and 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride. Carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from human erythrocyte cells by the affinity chromatography method. The inhibitory effects of 5-amino-1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 and new synthesized amides on these isozymes have been studied in vitro. The I50 concentrations (the concentration of inhibitor producing a 50% inhibition of CA activity) against hydratase activity ranged from 1.2 to 2.2nM for hCA-I and from 0.4 to 2nM for hCA-II. The I50 values against esterase activity ranged from 1.4 to 8nM for hCA-I and from 1.3 to 6nM for hCA-II. The Ki values were observed between 8.210-5 to 6.210-4 M for hCA-I and between 2.910-4 to 8.210-4 M for hCA-II. The comparison of new synthesized amides to 5-amino-1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 indicated that the new synthesized compounds (18-23) inhibit CA activity more potently than the parent compounds., TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG- 2376], This research was funded by TUBITAK (The Foundation of Scientific and Technological Research of Turkey, TBAG- 2376) (Ankara/ Turkey).

WOS: 000269883900031, PubMed: 18843546, The metal accumulation levels for muscle, skin, gill, liver and intestine tissues of some Cyprinidae species (Carassius carassius, Condrostoma nasus, Leuciscus cephalus and Alburnus alburnus) in Enne Dame Lake (Kutahya/Turkey), which is mostly fed by hot spring waters, were investigated. Analyses were performed for copper (Cu), zinc (Zn), manganese (Mn), iron (Fe), cobalt (Co), magnesium (Mg), nickel (Ni), chrome (Cr) and boron (B) using inductively coupled plasma-optic emission spectroscopy (ICP-OES), and cadmium (Cd) using atomic absorption spectrophotometer (AAS) utilizing microwave digestion techniques. The concentrations of the heavy metals found in the fish varied in the follow ing ranges: Cu: < DL-7.04, Zn: 6.96-357.25, Mn: < DL-20.70, Ni: < DL-6.21, Fe: 9.62-2500.33, Cr: < DL-1.74, Co: < DL-0.54, Cd: 0.01-0.27 and Mg: 197.44-904.90 mg/kg wet weight. While B had the second highest concentration in the water of the lake, it was not encountered in any tissue of the investigated species. In all tissues and the species, While the bioaccumulation factors (BAFs) of Mn, Zn, Fe and Cu were remarkably high, the BAFs of Mg, Cr, Co, and B were also fairly low or none. Although the heavy metal accumulation levels for the muscle were generally lower than other tissues, there were some exceptions. Cd level in the muscle of C. carassius was higher than the permissible limit stated by Turkish legislation, FAO and WHO. The mean metal amounts for all the investigated tissues and species are statistically compared and discussed in this study., Research Fund of Dumlupinar University (Turkey)Dumlupinar University [2004-8], This study was supported (Project no: 2004-8) by the Research Fund of Dumlupinar University (Turkey). Others also thank Temir Ali Demir for Cd analysis with AAS.

In this study, the in vitro effects of some sulfonamide derivatives, which are carbonic anhydrase inhibitors, on the enzymes activities of glucose-6-phosphate dehydrogenase, 6-phospho gluconate dehydrogenase and glutathione reductase were investigated. For this purpose, these three enzymes were purified from human erythrocytes. Purification procedure composed of four steps; preparation of the hemolysate, ammonium sulfate precipitation, 2',5'-ADP Sepharose 4B affinity chromatography, and gel filtration chromatography on Sephadex G-200. 5-(3alpha-Hydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (1), 5-(3alpha,12alpha-Dihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (2), 5-(3alpha,7alpha,12alpha-Trihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (3), 5-(3alpha,Acetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (4), 5-(3alpha,7alpha,12alpha-Triacetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (5), 5-(3,7,12-Trioxo-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (6), acetazolamide, and dorzolamide were tested in this experiment. Compounds 3, 5, and dorzolamide showed inhibitory effects on the activity of 6-phosphogluconate dehydrogenase, and I(50) values and K(i) constants were calculated as 0.0601 mM, 0.00253 mM, and 1.41 mM and 0.0878 +/- 0.0274 mM, 0.0042 +/- 0.0009 mM, and 3.1446 +/- 0.2081 mM, respectively. Glutathione reductase was also inhibited by 1 and 2. I(50) values and K(i) constants were 0.0471 mM and 0.0723 +/- 0.0388 mM for 1 and 0.0045 mM and 0.0061 +/- 0.0014 mM, for 2. If these sulfonamide derivatives are proposed as drugs, some of which are being used in glaucoma treatment such as acetazolamide and dorzolamide, these results should be taken into consideration concerning via these enzymes.

Fatty acid composition, conjugated linoleic acid and cholesterol contents in the muscles of three freshwater fish species (Barbus plebejus escherichi, Capoeta capoeta capoeta and Rutilus rutilus) were determined under natural extreme temperate (July) and cold (January) conditions. The aim of the study was to determine whether there were differences in these components of the muscle lipids among these three fish species under extreme natural conditions. Samples were analyzed using gas chromatography. Palmitic, oleic, docosahexaenoic and eicosapentaenoic acids were the predominant fatty acids in all fish in both months. The percentages of polyunsaturated fatty acids, n - 3 polyunsaturated fatty acids, n - 6 polyunsaturated fatty acids and eicosapentaenoic + docosahexaenoic acids in the muscle of B. plebejus escherichi and C. capoeta capoeta were significantly higher in January (P < 0.05) than in July. The ratio of n - 6 to n - 3 polyunsaturated fatty acids was lower than 0.60 in all fish species, with C. capoeta capoeta showing the lowest ratio in January (0.36). The levels of cholesterol and conjugated linoleic acid ranged from 103.46 to 150.10 mg/100 g oil and from 16.27 to 35.45 mg/100 g oil, respectively, for all samples in both months. There were no statistical differences in cholesterol levels among the three fish species in July and January. Conjugated linoleic acid contents were significantly higher in January in B. plebejus escherichi and C. capoeta capoeta. Of the three species tested, the extreme temperate and cold conditions affected B. plebejus escherichi the most. © Springer Science+Business Media B.V. 2008.

Effects of nicotine, nicotine + vitamin E and nicotine + Hippophea rhamnoides L. extract (HRe-1) on muscle, heart, lungs, testicle, kidney, stomach, brain and liver carbonic anhydrase (CA; EC 4.2.1.1.) enzyme activities were investigated in vivo. Groups of rats were given nicotine (0.5 mg/kg/day, i.p.), nicotine + vitamin E (75 mg/kg/day, i.g.), nicotine + HRe-1 (250 mg/kg/day, i.g.) and a control group vehicle only. The results showed that nicotine inhibited the heart, lung, stomach and liver CA enzyme activities by approximately 80% (p < 0.001), approximately 94% (p < 0.001), approximately 47% (p < 0.001) and approximately 81% (p < 0.001) respectively, and activated muscle and kidney, but had no effects on the testicle and brain CA activities. Nicotine + vitamin E inhibited the heart and liver CA enzyme activities by approximately 50% (p < 0.001), and approximately 50% (p < 0.001), respectively, and nicotine + vitamin E activated the muscle CA activity. However, nicotine + vitamin E had no effect on lung, testicle, kidney, stomach and brain CA activities. Nicotine + HRe-1 inhibited the heart and stomach CA enzyme activities by approximately 51% (p < 0.001), and approximately 32% (p < 0.002), respectively, and activated the muscle and brain CA activities, but had no effects on the lung, testicle, kidney, and liver CA activities. In vitro CA inhibition results for similar experiments correlated well with the in vivo experimental results in lungs, testicles, kidney, stomach, brain and liver tissues.

The in vitro and in vivo inhibitory effects of 5-(3alpha, 12alpha-dihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (1), 5-(3alpha, 7alpha, 12alpha-trihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (2), 5-(3alpha, 7alpha, 12alpha-triacetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (3) and acetazolamide on rainbow trout (Oncorhynchus mykiss) (RT) erythrocyte carbonic anhydrase (CA) were investigated. The RT erythrocyte CA was obtained by affinity chromatography with a yield of 20.9%, a specific activity of 422.5EU/mg protein and a purification of 222.4-fold. The purity of the enzyme was confirmed by SDS-PAGE. Inhibitory effects of the sulfonamides and acetazolamide on the RT erythrocyte CA were determined using the CO2-Hydratase method in vitro and in vivo studies. From in vitro studies, it was found that all the compounds inhibited CA. The obtained I50 value for the sulfonamides (1), (2) and (3) and acetazolamide were 0.83, 0.049, 0.82 and 0.052 microM, respectively. From in vivo studies, it was observed that CA was inhibited by the sulfonamides (1), (2) and (3) and acetazolamide.