Malondialdehyde,Antioxidant Enzymes,and Renal Tubular Functions in Children with Iron Deficiency or Iron-Deficiency Anemia

We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-d-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3–9 years, and adolescents 10–15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.     

Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies

Flavonoids are one of the largest classes of plant secondary metabolites and are known to possess a number of significant biological activities for human health. In this study, we examined in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of four flavonoid derivatives - quercetin, rutin, kaempferol 3-O-β-d-galactoside and macluraxanthone. The in vitro results showed that quercetin and macluraxanthone displayed a concentration-dependant inhibition of AChE and BChE. Macluraxanthone showed to be the most potent and specific inhibitor of both the enzymes having the IC₅₀ values of 8.47 and 29.8 μM, respectively. The enzyme kinetic studies revealed that quercetin inhibited both the enzymes in competitive manner, whereas the mode of inhibition of macluraxanthone was non-competitive against AChE and competitive against BChE. The inhibitory profiles of the compounds have been compared with standard AChE inhibitor galanthamine. To get insight of the intermolecular interactions, the molecular docking studies of these two compounds were performed at the active site 3D space of both the enzymes, using ICM-Dock™ module. Docking studies exhibited that macluraxanthone binds much more tightly with both the enzymes than quercetin. The calculated docking and binding energies also supported the in vitro inhibitory profiles (IC₅₀ values). Both the compounds showed several strong hydrogen bonds to several important amino acid residues of both the enzymes. A number of hydrophobic interactions could also explain the potency of the compounds to inhibit AChE and BChE.     

Migration potential and gene expression profile of human mesenchymal stem cells induced by CCL25

Recruitment of mesenchymal stem cells (MSC) to tissue damages is a promising approach for in situ tissue regeneration. The physiological mechanisms and regulatory processes of MSC trafficking to injured tissue remain poorly understood. However, the pivotal role of chemokines in MSC recruitment has already been shown.The aim of this study was to determine the migratory potential and the gene expression profile of MSC stimulated with the CC chemokine CCL25 (TECK). Bone marrow derived human MSC were exposed to different doses of CCL25 in a standardized chemotaxis assay. Microarray gene expression profiling and pathway analysis were performed for CCL25 stimulated MSC.Maximum migration of MSC towards CCL25 was observed at 10³ nM. Microarray analysis revealed an induction of molecules directly involved in chemotaxis and homing of bone marrow cells (CXCL1-3, CXCL8, PDE4B), cytoskeletal and membrane reorganisation (CXCL8, PLD1, IGFBP1), cellular polarity (PLD1), and cell movement (CXCL1-3, CXCL6, CXCL8, PTGS2, PDE4B, TGM2). Respective chemokine secretion was confirmed by protein membrane-array analysis. The activation of CXCR2 ligands (CXCL1-3, CXCL5-6, CXCL8) and a LIF-receptor/gp130 ligand (LIF) indicated an involvement of the respective signaling pathways during initiation of chemotaxis and migration.These results suggest CCL25 as a new potential candidate for further in situ regeneration approaches.     

Serum leptin is not a diagnostic marker for familial Mediterranean fever attacks

The aim of our study is to determine whether there is a relationship between familial Mediterranean fever (FMF) attacks and serum leptin levels. We enrolled 25 patients (22 males and 3 females) and 25 healthy controls (21 males and 4 females) with a mean age of 24.42 +/- 1.22 (Mean +/- SEM) years and 24.30 +/- 1.19 years (Mean +/- SEM), respectively. We investigated serum levels of leptin, interleukin-6 (IL-6) erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),fibrinogen, and leukocyte counts before the attack and 8-12 hours after the attack started. The same parameters have been investigated in the control subjects. The mean serum leptin levels before the attacks were 6.45 +/- 1.05 (Mean +/- SEM) and during the attacks were 7.59 +/- 1.3 (Mean +/- SEM) in FMF group,respectively. There was a slight increase in serum leptin levels during the attacks but it was not statistically significant (P > .05). The mean serum leptin levels were 16.12 +/- 2.81 in the control group which were not different from the mean serum leptin levels before and during the attack periods in the study group (P > .05). However, there were statistical differences in the serum levels of IL-6, ESR, CRP, fibrinogen, and leukocyte counts before and during the attack periods (P > .05). No correlation was found between serum leptin levels and IL-6, ESR, CRP, fibrinogen, and leukocyte counts (P > .05). Serum leptin levels do not increase during FMF attacks and therefore it is not useful for diagnostic purposes and follow-up during treatment.     

Turkish freshwater and marine macrophyte extracts show in vitro antiprotozoal activity and inhibit FabI, a key enzyme of Plasmodium falciparum fatty acid biosynthesis.

The ethanolic extracts of a number of Turkish freshwater macrophytes (Potamogeton perfoliatus, Ranunculus tricophyllus and Cladophora glomerata) and marine macroalgae (Dictyota dichotoma, Halopteris scoparia, Posidonia oceanica, Scinaia furcellata, Sargassum natans and Ulva lactuca) were assayed for their in vitro antiprotozoal activity. Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum were used as test organisms. The cytotoxicity of the extracts was also assessed against primary rat skeletal myoblasts (L6 cells). Whereas none of the extracts were active against T. cruzi, all crude extracts displayed appreciable trypanocidal activity against T. brucei rhodesiense, with S. natans being the most active one (IC(50) 7.4microg/ml). Except for the marine alga H. scoparia, all extracts also possessed leishmanicidal potential. The best antileishmanial activity was exerted by U. lactuca and P. oceanica (IC(50)'s 5.9 and 8.0microg/ml, respectively). Five extracts that demonstrated inhibitory activity towards P. falciparum (IC(50)'s 18.1-48.8microg/ml) were simultaneously assayed against FabI, a crucial enzyme of the fatty acid system of P. falciparum, to find out whether FabI was their target. The extracts of C. glomerata and U. lactuca efficiently inhibited the FabI enzyme with IC(50) values of 1.0 and 4.0microg/ml, respectively. None of the extracts were cytotoxic towards mammalian L6 cells. This work reports for the first time antiprotozoal activity of some Turkish marine and freshwater algae, as well as a target-based antiplasmodial screening for the identification of P. falciparum FabI inhibitors from aquatic and marine macrophytes.     

In vitro antiprotozoal activity of the lipophilic extracts of different parts of Turkish Pistacia vera L.

Thirteen lipophilic extracts prepared with n-hexane from various parts of Pistacia vera L. tree (Anacardiaceae) growing in Turkey were screened for their in vitro activity against four parasitic protozoa, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Melarsoprol, benznidazole, miltefosine, artemisinin and chloroquine were used as reference drugs. The cytotoxic potentials of the extracts on rat skeletal myoblast (L6) cells were also assessed and compared to that of podophyllotoxin. The screening method employed was medium-throughput, where the extracts were tested at two concentrations, at 0.8 and 4.8 μg/ml (T. brucei rhodesiense, L. donovani and Plasmodium falciparum), or at 1.6 and 9.7 μg/ml (T. cruzi and L6 cells). At 4.8 μg/ml concentration, the branch extract of Pistacia vera (PV-BR) significantly inhibited (77.3%) the growth of L. donovani, whereas the dry leaf extract (PV-DL) was active against Plasmodium falciparum (60.6% inhibition). The IC₅₀ values of these extracts were determined as 2.3 μg/ml (PV-BR, L. donovani) and 3.65 μg/ml (PV-DL, Plasmodium falciparum). None of the extracts possessed cytotoxicity on mammalian cells.     

Ixodid ticks (Acari: Ixodidae) infesting humans in Tokat Province of Turkey: species diversity and seasonal activity

Ixodid ticks (Acari: Ixodidae) are the major vectors of pathogens threatening animal and human health. Tokat Province, Turkey, is a suitable habitat for extended tick activity with its moderate climate and vegetation. In the present study, we surveyed humans visiting health centers to determine the species diversity, geographical distribution, and seasonal activity of ixodid ticks infesting them. Out of 5,999 adult ticks collected from humans from April to September, 2008, 800 ticks were identified to species, while the remaining were identified to genus according to their distinct morphological characteristics. Hyalomma marginatum, Hyalomma detritum, Rhipicephalus bursa, Rhipicephalus (Boophilus) annulatus, Haemaphysalis punctata, Dermacentor marginatus, and Ixodes laguri were the most prevalent tick species among 24 ixodid tick species infesting humans in the region. One of these tick species, Hyalomma isacii was identified as a new record for the ixodid tick fauna of Turkey. Hyalomma species were the most abundant in summer, while Dermacentor and Ixodes species displayed the lowest frequency. Hyalomma aegyptium infestation was very common on humans in the province. Results indicated that a variety of ixodid tick species infest humans depending on the season in the target area. It is possible that a variety of ixodid tick species may contribute to the spread of tick‐borne diseases such as Crimean‐Congo haemorrhagic fever virus (CCHFV), which is endemic in the region.     

Cholinesterase inhibitory and antioxidant properties of Verbascum mucronatum Lam. and its secondary metabolites

The aqueous extract of Verbascum mucronatum Lam. along with its fractions and secondary metabolites were assessed for their antioxidant, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities. The antioxidant activity was evaluated by three methods: as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferrous ion-chelating effect, and ferric-reducing antioxidant power (FRAP) tests. The AChE activity was determined by the Ellman method using an ELISA microplate reader. Phytochemical investigations revealed the presence of four iridoid glucosides, ajugol (1), aucubin (2), lasianthoside I (3) and catalpol (4), two saponins, ilwensisaponin A (5) and C (6), and a phenylethanoid glycoside, verbascoside (7), in Verbascum mucronatum. Their structures were elucidated by spectral techniques. The aqueous extract and fractions including the phenylethanoid glycoside 7 showed DPPH scavenger effect and had the best FRAP. Besides these results, one of the phenylethanoid fractions displayed the highest ferrous ion-chelating effect. While only 7 was found to possess moderate AChE inhibition, the extract, fractions, and all other tested compounds did not inhibit AChE and BChE.     

Synthesis,characterization and antiglaucoma activity of a novel proton transfer compound and a mixed-ligand Zn(II) complex

A novel proton transfer compound, pyridin-2-ylmethanaminium 2,4-dichloro-5-sulfamoylbenzoate (1), and a mixed-ligand Zn(II) complex, bis(2,4-dichloro-5-sulfamoylbenzoate)(2-aminomethylpyridine)aquazinc(II) monohydrate (2), have been synthesized from the same free ligands, which are 2,4-dichloro-5-sulfamoylbenzoic acid (Hsba) and 2-aminomethylpyridine (amp). They have been characterized by elemental, spectral (¹H NMR, IR and UV–vis.) and thermal analyses. Additionally, magnetic measurement and single crystal X-ray diffraction technique were applied to compound 2. In the complex, Zn(II) ion exhibits a distorted octahedral configuration coordinated by O1 and O1ⁱ atoms of two mono dentante sba anions and N1, N2, N2ⁱ atoms of bidentante amp anion and a water molecule (O1w). The free ligands Hsba and amp, and the products 1 and 2, and acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibitor effects on human Carbonic Anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cell by affinity chromatography for their hydratase and esterase activities. The IC₅₀ values of products 1 and 2 for hydratase activity are 0.26 and 0.13 μM for hCA I and 0.30 and 0.15 μM for hCA II, respectively. The IC₅₀ values of the same inhibitors for esterase activity are 0.32 and 0.045 μM for hCA I and 0.29 and 0.23 μM for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (K_i) were also determined and found 0.25 and 0.058 μM on hCA I and 0.22 and 0.24 μM on hCA II for 1 and 2, respectively. The comparison of the inhibition studies of newly synthesized compounds 1 and 2 to parent compounds Hsba and amp and to AAZ indicated that 1 and 2 have effective inhibitory activity on hCA I and II, and might be used potential inhibitors.