Comparison of the anti-cancer activity of 5-aminolevulinic acid-mediated photodynamic therapy after continuous wave and pulse irradiation in different histological types of canine mammary sarcoma tumors.

Canine mammary sarcoma tumors (CMST) are the most aggressive tumors with poor prognosis in dogs. Due to inadequate treatment options for CMST, recent studies have focused on alternative treatment strategies. We previously determined the optimized protocol of 5-ALA-based photodynamic therapy (PDT) in canine liposarcoma. However, its molecular mechanisms in the treatment of different histological types of CMST remain unclear.In this context, we, for the first time, assessed 5-aminolevulinic acid (5-ALA)-PDT-mediated anti-cancer activity and its molecular mechanism after continuous wave (CW) and pulse radiation (PR) on three different histological types (liposarcoma, chondrosarcoma, and osteosarcoma) of CMST cells by WST-1, Annexin V, ROS, acridine orange/propidium iodide staining, RT-PCR, and western blot analysis.Our findings showed that 5-ALA/PDT significantly suppressed the proliferation of CMST cells (p < 0.01) and induced apoptosis via increased ROS level and overexpression of Caspase-9 and Caspase-3 mRNA and cleaved protein levels in especially liposarcoma and chondrosarcoma cells following CW and PR irradiation at 9 J/cm2. However, the response of CMST cells to 5-ALA was different upon CW and PR irradiation due to differences in their origin.Collectively, our findings provided the first evidence that 5-ALA-based PDT could be used as an alternative treatment strategy, especially liposarcoma and chondrosarcoma. However, further in vitro and in vivo studies are required to elucidate the underlying molecular mechanism of the efficacy of 5-ALA in CMST cells at the molecular level.

The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy

Purpose Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. Methods After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. Results Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. Conclusion Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population (AU)

The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. METHODS: After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. RESULTS: Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. CONCLUSION: Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population.

Effectiveness of 5-Fluorouracil and gemcitabine hydrochloride loaded iron­based chitosan-coated MIL-100 composite as an advanced, biocompatible, pH-sensitive and smart drug delivery system on breast cancer therapy.

This study was planned to evolve the bioavailability and therapeutic efficiency of Gemcitabine (GEM) and 5-Fluorouracil with decreased side effects using MIL-100 nano-composite as carrier. Impregnation approach was used for encapsulation of 5-Fluorouracil alone and with GEM inside the MIL-100. The formed 5-Fluorouracil@MIL-100 and 5-Fluorouracil-GEM@MIL-100 were then coated with chitosan, sequentially chelated with iron(III) and conjugated with quercetin, eventually obtaining a multifunctional MIL-100 nanocarrier. The hybrid nanocarrier nascency was verified by different characterization results. pH-sensitive releases of 5-Fluorouracil and GEM were observed because of the inherent pH-dependent stability of MIL-100. Additionally, we evaluated the anti-cancer activity of these nanocarriers through WST-1 analysis and acridine orange staining in MCF-7 human breast cancer and HUVEC control cell lines. Our findings showed that all nanocarriers exhibited anti-cancer activity and induced apoptosis in MCF-7 cells. However, 5-Fluorouracil@MIL-100 and chitosan-coated 5-Fluorouracil@MIL-100 with quercetin were more effective than other nanocarriers in MCF-7 cells (p < 0.05). Moreover, we observed cytotoxicity in HUVEC cells due to the adverse side effects of chemotherapy drugs. However, chitosan coated nanocarriers with quercetin were less toxic on HUVEC cells at particularly 1 µg/mL. Therefore, MIL-100 could be used for a promising chemotherapeutic drugs delivery and chitosan coated drugs with quercetin could be useful for reducing toxicity on normal cells.

Efficacy of 5-aminolevulinic acid-based photodynamic therapy in different subtypes of canine mammary gland cancer cells.

Canine mammary gland tumors (CMGTs) are heterogeneous disease and subclassified [sarcomas (S), carcinomas (C), and carcinosarcomas (CS)] according to histopathological differentiation. Photodynamic therapy (PDT) is a promising treatment strategy based on the use of a photosensitizer (PS) activated by light. However, the therapeutic potential of PDT in the treatment of CMGTs has not been investigated, yet. Therefore, the aim of this study was to determine the in vitro protocol of 5-ALA-based-PDT for the treatment of three subtypes of CMGTs, for the first time. The intracellular PpIX florescence intensity was measured for 5-ALA (0.5 and 1 mM). After irradiation with different light doses (6, 9, 12, 18, and 24 J/cm2) for two different modes [continuous wave (CW) and pulse radiation (PR)], the cytotoxic effects of 5-ALA (0.5 and 1 mM) on the subtypes (C, S, and CS) of CMGTs were analyzed by WST-1. Finally, the optimal PDT treatment protocol was validated through Annexin V and AO/EtBr staining. Our results showed that 1 mM 5-ALA for 4-h incubation was the best treatment condition in all subtypes of CMGTs due to higher intracellular PpIX level. After irradiation with different light doses, PR mode was more effective in S primary cells at 9 J/cm2. However, a significant decrease in the viability of C and CS cells was detected at 12 /cm2 in CW mode (p < 0.05). Additionally, 1 mM 5-ALA induced apoptotic cell death in each subtype of CMGTs. Our preliminary findings suggest that (i) each subtype of CMGTs differentially responds to PDT and (ii) the light dose and mode could play an important role in the effective PDT treatment. However, further studies are needed to investigate the role of the different light sources and PDT-based apoptotic cell death in CMGTs cells.

Immunotherapeutic role of cabazitaxel treatment in the activation of TLR3 signalling in metastatic castration-resistant prostate cancer in vitro.

BACKGROUND: The activation of toll like receptors (TLR) potentially affect the inflammatory tumor microenvironment and thus is associated with tumor growth or inhibition. Cabazitaxel (CAB) has been effectively used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the immune regulatory role of CAB in the tumor microenvironment is not clear. In this context, we for the first time assessed the immunotherapeutic role of CAB in the TLR3 signalling following activation of Poly I:C in mCRPC cells. METHODS AND RESULTS: The cytotoxic and apoptotic effects of CAB with the induction of Poly I:C were determined by WST-1, Annexin V, acridine orange, RT-PCR analysis, ELISA assay and immunofluorescence staining in DU-145 mCRPC and HUVEC control cells. Our findings showed that CAB treatment with Poly I:C significantly suppressed the proliferation of DU-145 cells through the induction of apoptosis and caspase activation. Additionally, higher concentration of CAB mediated the activation of TLR3 via increased cytoplasmic and nuclear expression of TLR3, TICAM-1 and IRF-3 in mCRPC cells. CONCLUSIONS: Co-treatment of CAB and Poly I:C was more effective in mCRPC cells with less toxicity in control cells. However, further investigations are required to elucidate the molecular mechanisms of TLRs signalling upon CAB treatment at the molecular level to further validate the immunotherapeutic efficacy of CAB in mCRPC.

Regulation of valproic acid induced EMT by AKT/GSK3ß/ß-catenin signaling pathway in triple negative breast cancer.

Valproic acid (VPA) is a selective histone deacetylation (HDAC) inhibitor and exerts anti-cancer properties in different types of cancer. The epithelial-to-mesenchymal transition (EMT) mediating by different signaling cascade can be a potential target in aggressive human cancers. Therefore, we aimed to clarified the unravel relationship between AKT/GSK3ß/ß-catenin signalling pathway and VPA-induced EMT in triple negative breast cancer (TNBC). The cytotoxicity of VPA in MDA-MB-231 TNBC and MCF-10A control cells was evaluated. Alterations in the expression levels of Snail, E-cadherin, AKT, GSK3ß, ß-catenin were analyzed by RT-PCR. Additionally, Annexin V, cell cycle and wound healing assays were performed. Our results showed that VPA remarkably inhibited the growth of TNBC cell and triggered apoptotic cell death through G0/G1 arrest. Furthermore, VPA increased cell migration and activated the EMT process through significantly increasing Snail expression and in turn downregulation of E-cadherin and GKS3ß levels. However, the level of AKT and ß-catenin was reduced after treatment of VPA. Our data showed that VPA induced EMT process and cell migration in TNBC cells. However, AKT/GSK3ß/ß-catenin signaling pathway did not mediate EMT activation.

Evaluation of the Effects of Nobiletin on Toll-Like Receptor 3 Signaling Pathways in Prostate Cancer In Vitro.

Nobiletin as a nontoxic dietary citrus flavonoid has anticancer effects in cancer. Toll-like receptor three has a role in prostate cancer progression. However the relationship among NOB and TLR3 signaling in PCa has not been elucidated, yet. Therefore, we aimed to evaluate the effects of NOB on the activation of TLR3 signaling pathways in PCa In Vitro. PC-3, LNCaP and HUVEC cells were used for comparison of NOB-mediated TLR3 signaling pathways. After treatment with NOB and Poly I:C alone and NOB + Poly I:C, RT-PCR, western blotting and ELISA assay were performed to evaluate changes in gene and protein expression level, as well as CASP8. NOB potentially induced TLR3/IRF3 signaling pathway and the activation of TLR3/IRF3 signaling pathway by both NOB and Poly I:C was more profound in LNCaP than PC-3 cells. However, the level of TRIF protein and CASP8 decreased after both NOB and Poly I:C incubation. NOB could mediate TLR3 signaling pathways. NOB + Poly I:C could improve the activation of TLR3/IRF3 signaling pathway. However, the activation of TRIF/RIPK1/FADD signaling pathway reduced. Therefore, the elucidation of molecular mechanisms of TLR3 signaling pathways and the combination effects of NOB + Poly I:C on apoptotic cell death are further studied.

Anti-inflammatory effects of nobiletin on TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in prostate cancer cells.

Background: Toll-like receptors (TLRs) are often expressed in natural immune cells as well as in tumor cells. TLR4 exhibits both tumor promoting and tumor-suppressing roles and higher TLR9 expression is an important marker of poor prognosis in prostate cancer (PCa). Nobiletin (NOB) is an O-methylated flavonoid and NOB has been proven to have anti-cancer effect in PCa cells. However, there is no study in the literature investigating the potential anti-inflammatory effects of NOB on the TLR signaling pathways in cancer. Therefore, we aimed to explore the potential anti-inflammatory effects of NOB on the TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in different types of PCa cell lines, for the first time.Material and methods: In the current study, the cytotoxic effect of NOB PC-3 (hormone-independent and metastatic) and LNCaP cells (hormone-dependent) was evaluated by WST-1 assay. Furthermore, the inhibitory effects of NOB on TLR4/TRIF/IRF3 and TLR9/IRF7signaling pathway were determined by RT-PCR, western blotting and ELISA analysis.Results: NOB demonstrated an inhibitory effect on PCa cell growth and LNCaP cells were more sensitive to NOB than PC-3 cells due to androjen receptor status. Furthermore, NOB alone could suppress TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways through the downregulation of their associated pathways (mRNA and related protein levels) and the release of IFN-α and IFN-ß compared to LPS or CpG-ODN stimulated PCa cells.Conclusions: NOB potentially inhibited TLR4 and TL9-dependent signaling pathway in PCa cells. However, the efficacy of NOB was different in PCa cells due to the hormone status and aggressive features.

Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer.

Curcumin has a therapeutic potential activity through modulation of different signaling pathways in various types of cancer. However, the relationship between the efficacy of curcumin and the homologous recombination (HR) mechanism which plays important roles in the repair of double strand DNA (dsDNA) breaks remains uncertain. Herein, we explored curcumin-dependent dsDNA breaks and the association of curcumin with HR mechanism in triple negative breast cancer (TNBC). The cytotoxic and therapeutic activity of curcumin on HCC1937 (BRCA1 mutant), MDA-MB-231 (BRCA1 wild type) TNBC and HUVEC control cell lines were assessed. Then, the expression level and subcellular localization of H2AX, PARP1, BRCA1 and RAD51 were detected by RT-PCR and immunofluorescence analysis. Furthermore, ultrastructural changes of cell death were observed by TEM. Our findings for the first time demonstrated that curcumin's therapeutic activity was more pronounced in HCC1937 cells through the suppression of HR mechanism and the induction of dsDNA breaks. Consequently, curcumin based therapy could benefit in patients with TNBC particularly especially in women with a BRCA1 mutation.

Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells.

PURPOSE: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated.  For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. METHODS: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay.  The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. RESULTS: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-α/ß) levels induced by LPS. However, curcumin was more efficient in MDA- MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS- enhanced TLR4 signaling pathway. Furthermore, IFN-α/ß levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. CONCLUSIONS: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin's anti-inflammatory activities on TLR4/MyD88/NF-κB as well as other signaling pathways downstream of TLRs in breast cancer.

Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells.

Objective: Herein we, for the first time, investigated a potential synergistic effect of nobiletin (NOB) and sorafenib (SOR) on PC-3 prostate cancer and HUVEC control cell lines. Methods: In order to determine the cytotoxic and apoptotic effects of the combination of NOB and SOR, WST-1, Annexin V, and cell cycle analysis were performed. The potential molecular mechanism of apoptotic cell death was assessed by Bax, Bcl-2, CCDN1, Rb1, and CDKN1A gene expression and acridine orange (AO) and DAPI staining. Results: Our results indicated that NOB and SOR combination had a significant inhibitory effect on the viability of PC-3 cells with less toxicity on HUVEC cells than SOR alone (P < 0.01). NOB and SOR combination significantly caused much more apoptotic cell death and cell cycle arrest at G0/G1 phase by up-regulation of Bax, Rb1, and CDKN1A levels in PC-3 cells (P < 0.01). Therefore, strong synergistic effects between NOB and SOR were analyzed (CI < 1). Conclusion: NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells.

Anti-inflammatory and antioxidative properties of honey bee venom on Freund's Complete Adjuvant-induced arthritis model in rats.

The aim of this study was to assess anti-inflammatory, anti-oxidant, anti-genotoxic and immunomodulatory effects of honey bee venom (HBV) on adjuvant-induced arthritis in rats. Thirty-five rats were equally divided into a negative control (NC), a positive control (PC) and low, moderate and high doses (2, 4 and 20 mg/kg, respectively) of HBV treatment groups. Freund's Complete Adjuvant (FCA) was given to the rats to form arthritis. The treatment groups were treated with HBV for 3 consecutive weeks. After the treatment, plasma IL-1ß, IL-6, TNF-α, IFN-γ and TGF-ß1, total oxidant status (TOS), total antioxidant status (TAS) and myeloperoxidase (MPO) activities and mononuclear leukocyte (MNL) DNA damage levels were measured. Oxidative stress index (OSI) was calculated. IL-1ß, IL-6, TNF-α, TGF-ß1, IFN-γ, TOS, OSI, DNA damage levels and MPO activities were significantly higher and TAS levels were lower in the PC group than the NC. After low-doses of HBV treatment IL-1ß, IL-6, TNF-α, TGF-ß1, TOS, OSI, MPO and MNL-DNA damage levels significantly decreased according to the PC, while IFN-γ and TAS levels increased. The differences in moderate and high-dose HBV treatment groups were not as significant as low HBV doses. Low-doses of HBV has been shown to treat RA with anti-inflammatory and antioxidant effects, by preventing DNA damage. However, these effects have not been observed as strong at higher doses of HBV. In summary, HBV may be an effective option to ameliorate RA, but the optimization of the therapeutic dose has a crucial role.

Effect of high-dose fluoride on antioxidant enzyme activities of amniotic Fluid in rats.

OBJECTIVE: To investigate the effect of high-dose fluoride on antioxidant enzyme activities of amniotic fluid and fluoride of serum in rats. METHODS: The experimental study was conducted from January 8, 2008, to December 14, 2010, at the Suleyman Demirel University Experimental Animals Laboratory and the Medical Biochemistry Department Research Laboratory, Isparta, Turkey. Impregnated Wistar albino rats were divided into two equal groups. Group I had controls, while Group II rats were exposed to high-dose fluoride. Group I was given drinking water mixed with 0.1 mg/kg/b.w./day of natrium fluoride, while group II was given drinking water mixed with 10 mg/kg/b.w./day of natrium fluoride for 18 days. At the end of 18 days, amniotic fluid and blood samples were collected from control and experimental groups of pregnancy. Superoxide dismutase, glutathione peroxidase, catalase activities and thiobarbituric acid reactive substances as antioxidant enzymes in amniotic fluid and levels of fluoride in serum samples were investigated. RESULTS: There were 14 rats, with 7(50%) in each group. Foetal weight in group II significantly decreased compared to the control group (p< 0.05). Antioxidant enzyme activities in amniotic fluid were significantly higher in group II than group I (p< 0.05) although thiobarbituric acid reactive substances in amniotic fluid and serum fluoride levels were significantly lower in group II than group I (p< 0.05). CONCLUSIONS: Fluoride that created oxidative stress inhibited lipid peroxidation and apparently increased the antioxidant defence system.

Serum Prolidase Activity as a Biomarker for Choroid Plexus Calcification.

The choroid plexus (CP) performs multiple functions such as secretion and reabsorption. CP also acts as the blood-cerebrospinal fluid barrier. Prolidase plays an important role in collagen metabolism by degrading imidodipeptides, in which proline or hydroxyproline residue is located at the C-terminal end. Serum prolidase activity (SPA) may reflect the degree of fibrosis and inflammation. Choroid plexus calcification (CPC) is considered as the physiological calcification of the brain, and CPC is diagnosed by the presence of calcification in the anatomical region on computed tomography (CT). Here, CPC and non-calcified CP were defined by Hounsfield Units (HU) values of > 150 and < 50, respectively. We aimed to measure SPA in subjects with CPC and those with non-calcified CP. This study included 89 subjects who were admitted to the neurology clinic and underwent CT: 44 subjects with CPC and 45 subjects with non-calcified CP. The neurological examination of all subjects was normal; namely, the subjects with CPC were asymptomatic. The SPA level was significantly higher in the CPC group than that in the non-calcified CP group (p < 0.002), and there was a significant positive correlation between vitamin D and SPA levels in the CPC group. In contrast, the vitamin D and parathyroid hormone levels were higher in the CPC group, but the difference was not statically significant (p > 0.05). These findings indicate that SPA is a biomarker for CPC that may be predictive of future brain disease.

DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture.

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%, p = 0.049; 38.15% versus 16.2%, p = 0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097-3.863; p = 0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041-2.129; p = 0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101-1.992; p = 0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

Refractive errors in patients with newly diagnosed diabetes mellitus.

BACKGROUND AND OBJECTIVE: Diabetes mellitus is a complex metabolic disorder that involves the small blood vessels, often causing widespread damage to tissues, including the eyes' optic refractive error. In patients with newly diagnosed diabetes mellitus who have unstable blood glucose levels, refraction may be incorrect. We aimed to investigate refraction in patients who were recently diagnosed with diabetes and treated at our centre. METHODS: This prospective study was performed from February 2013 to January 2014. Patients were diagnosed with diabetes mellitus using laboratory biochemical tests and clinical examination. Venous fasting plasma glucose (fpg) levels were measured along with refractive errors. Two measurements were taken: initially and after four weeks. The last difference between the initial and end refractive measurements were evaluated. RESULTS: Our patients were 100 males and 30 females who had been newly diagnosed with type II DM. The refractive and fpg levels were measured twice in all patients. The average values of the initial measurements were as follows: fpg level, 415 mg/dl; average refractive value, +2.5 D (Dioptres). The average end of period measurements were fpg, 203 mg/dl; average refractive value, +0.75 D. There is a statistically significant difference between after four weeks measurements with initially measurements of fasting plasma glucose (fpg) levels (p<0.05) and there is a statistically significant relationship between changes in fpg changes with glasses ID (p<0.05) and the disappearance of blurred vision (to be greater than 50% success rate) were statistically significant (p<0.05). Also, were detected upon all these results the absence of any age and sex effects (p>0.05). CONCLUSIONS: Refractive error is affected in patients with newly diagnosed diabetes mellitus; therefore, plasma glucose levels should be considered in the selection of glasses.

Effect of hot-smoked rainbow trout (Oncorhynchus mykiss) diets on the protein levels of liver tissue in rats.

AIMS: Free radicals may not only affect the denatured cell structure but also reduce protein levels. These mechanisms are critical and need to be clarified as a high priority. Because of the limited information on this subject, in this respect, the effects on protein levels of liver tissue in rats fed hot-smoked rainbow trout (Oncorhynchus mykiss) were investigated. METHODS: Four diets containing fresh and hot-smoked rainbow trout flesh and vitamins were prepared and commercial pellet food was purchased. Four groups of female Wistar rats were fed the diets for 28 days. The rats were killed by decapitation, and the hepatic tissue was removed. Total protein and detection of protein bands using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were evaluated. RESULTS: The liver protein level in rats fed a hot-smoked rainbow trout flesh + vitamin diet was increased significantly compared with the other diet groups (p < 0.001, p < 0.009 and p < 0.011). 10 protein bands were visualized on rat gels. The molecular weights of protein bands detected were 200, 130, 70, 50, 42, 38, 26, 25, 24 and 14 kDa, respectively. The 25-kDa band of group V had a dense appearance. Also, the 14-kDa band appeared as very dense in groups V, B and K, but this band did not have a dense appearance in group D. CONCLUSION: Nourishment with smoked fish diets containing antioxidant substances reduced the harmful effects of free radicals and positive effects were observed on protein metabolism.

The effects of different treatments on prolidase and antioxidant enzyme activities in patients with bronchial asthma.

The effects of two different treatment combinations of bronchial asthma on antioxidant defense systems and serum prolidase activity were investigated. The groups were organized as follows: the first group (control) consisted of healthy subjects. The second group (treatment 1) consisted of patients with bronchial asthma inhaling budesonide (2×400mcg/d, as puff)+formaterol (2×9mcg/d, as puff). In the third group (treatment 2) patients with bronchial asthma were treated with montelukast (1×10mg/d, as pill)+budesonide (2×400mcg/d, as puff)+formaterol (2×9mcg/d, as puff). The medical therapy of the patients in treatment 1 and treatment 2 lasted 12 weeks. Before and after treatment in all three groups blood samples were taken and the level of thiobarbituric acid-reactive substances (TBARS) and the activities of prolidase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-Rd) and catalase (CAT) were measured. Prolidase activity was found to be significantly higher in patients compared to control (p<0.05). Treatment 2 was successfully reduced the prolidase activity (p<0.05). Before treatments, SOD activity was significantly decreased whereas TBARS level and other antioxidant enzymes were increased in both treatment groups comparing with control (p<0.05). Both of different treatments given in treatment 1 and treatment 2 groups caused significant increase in SOD whereas decrease in TBARS, CAT, GSSG-Rd, GSH-Px (p<0.05). When compared the treatment groups after treatments, SOD activity was significantly higher in treatment 2 group than treatment 1 group (p<0.05). No significant difference was seen in other parameters. The balance between oxidant-antioxidant system is impaired in patients with asthma.