Publications by authors named "Ertugrul Kaya"

36 Publications

Determination of amatoxin concentration in heat-treated samples of Amanita phalloides by high-performance liquid chromatography: A forensic approach.

J Forensic Leg Med 2021 02 7;78:102111. Epub 2021 Jan 7.

Department of Forensic Science, Punjabi University, Patiala, Punjab, 147002, India. Electronic address:

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http://dx.doi.org/10.1016/j.jflm.2020.102111DOI Listing
February 2021

Toxin components and toxicological importance of Galerina marginata from Turkey.

Toxicon 2020 Nov 28;187:29-34. Epub 2020 Aug 28.

Department of Natural, Herbal and Cosmetic Products, Duzce University, Duzce, Turkey.

Amatoxins, most of which are hepatotoxic, can cause fatal intoxication. While mushrooms in the amatoxin-containing Galerina genus are rare, they can poison humans and animals worldwide. Few studies have profiled the toxicity of Galerina marginata. In addition, many studies indicate that macrofungi can have different characteristics in different regions. In this study, the quantities of toxins present in G. marginata from different provinces in Turkey were analysed using reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-HPLC-UV) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). G. marginata samples were collected from three different regions of Turkey. The taxonomic categorization of mushrooms was based on their micro- and macroscopic characteristics. The presence of toxins α-amanitin (AA), β-amanitin (BA), γ-amanitin (GA), phalloidin (PHD) and phallacidin (PHC) quantities were measured using RP-HPLC-UV and then were confirmed using LC-ESI-MS/MS. BA levels were higher than AA levels in G. marginata mushrooms collected from all three regions. Moreover, the levels of GA were below the detection limit and no phallotoxins were detected. This is the first study to identify and test the toxicity of G. marginata collected from three different regions of Turkey using RP-HPLC-UV. This is also the first study to confirm the UV absorption of amatoxins in G. marginata using LC-ESI-MS/MS, which is a far more sensitive process. More studies evaluating the toxicity of G. marginata in other geographic regions of the world are needed.
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http://dx.doi.org/10.1016/j.toxicon.2020.08.017DOI Listing
November 2020

First Report of a Neotropical Agaric (, Agaricales, Basidiomycota) Containing Lethal α-Amanitin at Toxicologically Relevant Levels.

Front Microbiol 2020 11;11:1833. Epub 2020 Aug 11.

Department of Pharmacology, Faculty of Medicine, Duzce University, Duzce, Turkey.

A recent collection of from the Dominican Republic is presented here. Macro- and micromorphological features of are described in detail, and its evolutionary (phylogenetic) position within sect. , in the subincarnata/brunneoincarnata clade, is assessed on the basis of a combined nrLSU + nrITS + + analysis. Additionally, high levels of deadly amatoxins were detected and quantified in for the first time by HPLC analysis; in particular, α-amanitin was found at concentrations up to approximately 4 mg/g dry weight, which render a potentially lethal mushroom, if ingested.
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http://dx.doi.org/10.3389/fmicb.2020.01833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432468PMC
August 2020

Two new species of Amanitasect.Phalloideae from Africa, one of which is devoid of amatoxins and phallotoxins.

MycoKeys 2019 6;53:93-125. Epub 2019 Jun 6.

Meise Botanic Garden, 38 Nieuwelaan, 1860 Meise, Belgium Meise Botanic Garden Meise Belgium.

Two new species of Amanitasect.Phalloideae are described from tropical Africa (incl. Madagascar) based on both morphological and molecular (DNA sequence) data. was collected, associated with , in Rwanda, Burundi and Tanzania. It is consumed by local people and chemical analyses showed the absence of amatoxins and phallotoxins in the basidiomata. Surprisingly, molecular analysis performed on the same specimens nevertheless demonstrated the presence of the gene sequence encoding for the phallotoxin phallacidin (PHA gene, member of the MSDIN family). The second species, was collected in Tanzania and Madagascar. It is also characterised by a complete PHA gene sequence and is suspected to be deadly poisonous. Both species clustered together in a well-supported terminal clade in multilocus phylogenetic inferences (including nuclear ribosomal partial LSU and ITS-5.8S, partial -α, and β-tubulin genes), considered either individually or concatenated. This, along with the occurrence of other species in sub-Saharan Africa and their phylogenetic relationships, are briefly discussed. Macro- and microscopic descriptions, as well as pictures and line drawings, are presented for both species. An identification key to the African and Madagascan species of Amanitasect.Phalloideae is provided. The differences between the two new species and the closest species are discussed.
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http://dx.doi.org/10.3897/mycokeys.53.34560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565643PMC
June 2019

Determination of histological, immunohistochemical and biochemical effects of acute and chronic grayanotoxin III administration in different doses in rats.

Environ Sci Pollut Res Int 2019 Jan 13;26(2):1323-1335. Epub 2018 Nov 13.

Faculty of Medicine Histology-Embryology Department, Bozok University, Yozgat, Turkey.

Grayanotoxin (GTX)-III is a Na-channel neurotoxin. Grayanotoxins can be found in the nectar, pollen, and other plant parts of the Rhododendron genus plants from the Ericaceae family. It is widely believed that honey produced from these plants, which are concentrated in the Black Sea region, is traditionally characterized as enhancing sexual performance. It is thought that the effective factor is dose for this compound, which has both beneficial and toxic effects reported. Therefore, it is aimed to evaluate the histological, immunohistochemical, and biochemical effects of acute and chronic impact of GTX-III in different doses on testes tissue in this study. For this purpose, 100 Sprague-Dawley male rats were divided into 5 separate groups for acute and chronic research. While dose groups were (control, 0.1, 0.2, 0.4, ve 0.8 μg/kg/bw) for experimental groups, a single dose (i.p.) was administered for acute impact whereas the same doses were administered daily for 3 weeks to assess chronic effect. At the end of the experiment, Johnsen testicular biopsy scoring was performed on testicular tissue samples, seminiferous tubule diameters were measured, and apoptotic cells were evaluated by TUNEL method. Testosterone, LH, and FSH levels were measured by ELISA method in serum and tissue specimens. It was found that Johnsen score of acute doses was significantly lower than the control group, and the diameter of the seminiferous tubules decreased significantly in acute and chronic dose-administered groups compared to the control. Hemorrhage, epithelial shedding, irregularity in seminiferous epithelium, and vacuolization were observed in acute and chronic dose-administered groups, and increase in apoptotic cells was determined. Hormone levels varied depending on the dose. In conclusion, it was found that dose-dependent acute and chronic effects of GTX-III are different, and this factor should be taken into account in studies to be carried out due to the adverse effects of high doses.
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http://dx.doi.org/10.1007/s11356-018-3700-9DOI Listing
January 2019

Omentin Val/Val genotype increases predisposition to acne vulgaris without changing omentin serum level.

Cell Mol Biol (Noisy-le-grand) 2018 Sep 30;64(12):81-86. Epub 2018 Sep 30.

Department of Medical Biology and Genetics, Duzce University Institute of Health Science, Duzce, Turkey.

Acne vulgaris is the most frequent and multifactorial inflammatory skin disorder in all races. Obesity is considered to be a risk factor for acne due to its contribution to inflammation. The involvements of inflammatory (leptin and resistin) and anti-inflammatory (adiponectin) adipokines in the pathogenesis of acne were reported. Omentin resembles adiponectin in terms of having inhibitory effect on tumor necrosis factor-α (TNF-α) induced inflammation, a vital process in the acne formation. This study was designed to investigate the putative involvement of omentin in acne formation. The genotyping was performed by restriction fragment length polymorphism (RFLP) method. Serum omentin protein levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Serum omentin level was not significantly changed between groups. However, the decreased serum omentin level was observed as the mean value of BMI increased. The Asp/Asp, Val/Asp and Val/Val genotypes distributions for control and patient groups (19[17.4%], 22[20.2%], and 3[2.8%] respectively, vs. 31[28.4%], 25[22.9%], and 9[8.3%], respectively) were obtained. The Val/Val (mutant homozygote) genotype was found nearly 1.8 times more in the patient group (p=0.403, OR=1.839 (0.442-7.653)). This is the first time to clarify a linkage between anti-inflammatory omentin and acne vulgaris. Omentin Val109Asp polymorphism affects the overall function of the protein. In conclusion, omentin Val/Val (mutant homozygote) genotype increases predisposition to acne vulgaris by probably disrupting overall protein function of omentin.
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September 2018

Evaluation of the corrosion inhibiting efficacy of a newly synthesized nitrone against St37 steel corrosion in acidic medium: Experimental and theoretical approaches.

Mater Sci Eng C Mater Biol Appl 2018 Dec 13;93:539-553. Epub 2018 Aug 13.

Corrosion Research Laboratory, Department of Mechanical Engineering, Faculty of Engineering, Düzce University, 81620 Düzce, Turkey.

A novel amphiphilic nitrone, N-phenyl-1-(4-((11-(pyridin-1-ium-1yl) undecanoyl) oxy)phenyl)methanimine oxide bromide (NP-1-4-11-PUOPMOB) has been synthesized from a fatty acid derivative as a starting material. Structural characterization of the new compound has been realized by spectroscopic techniques (FTIR, H NMR, and C NMR). The corrosion inhibition effect of the compound for St37 steel corrosion in 1 M HCl medium has been investigated using experimental (weight loss, electrochemical impedance spectroscopy, potentiodynamic polarization, dynamic electrochemical impedance spectroscopy) and theoretical approaches complemented by surface morphological examination using energy dispersive X-ray spectroscopy, scanning electron microscope, and atomic force spectroscopy. Results from both chemical and electrochemical techniques reveal that the presence of the nitrone in the acid solution impedes St37 steel corrosion. The inhibition efficiency obtained at 125 ppm and 150 ppm concentrations for all methods is found to be over 90%. NP-1-4-11-PUOPMOB behaves as a mixed type corrosion inhibitor according to the potentiodynamic polarization studies. The adsorption of NP-1-4-11-PUOPMOB molecules onto the metal surface follows Langmuir adsorption isotherm and the calculated K (equilibrium constant of the adsorption process) value reflects strong interaction. There is evidence of NP-1-4-11-PUOPMOB adsorption on the metal surface from SEM, EDAX, and AFM studies. Experimental and theoretical results are in good agreement.
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http://dx.doi.org/10.1016/j.msec.2018.08.031DOI Listing
December 2018

Gum Arabic-silver nanoparticles composite as a green anticorrosive formulation for steel corrosion in strong acid media.

Carbohydr Polym 2018 Feb 14;181:43-55. Epub 2017 Oct 14.

Corrosion Research Laboratory, Department of Mechanical Engineering, Faculty of Engineering, Duzce University, 81620 Duzce, Turkey.

A green anticorrosive composite (GA-AgNPs) has been formulated for steel in 15% HCl and 15% HSO media. Characterization of GA-AgNPs is achieved via FTIR, UV-vis, EDAX, and SEM. Gravimetric, electrochemical (EIS, EFM, DEIS, & TP), and surface assessment (SEM, EDAX, AFM, & XPS) techniques have been deployed in the anticorrosion studies. Results from all applied methods potray GA-AgNPs as effective anticorrosive agent. Inhibition is by adsorption mechanism and follows Langmuir isotherm. GA-AgNPs acts as mixed type inhibitor in 15% HSO solution but as anodic type in 15% HCl solution. Results from surface techniques confirm adsorption of GA-AgNPs molecules on specimen surface. Oxides, hydroxides, carbonates, and sulphates (HSO medium) or chlorides (HCl medium) are the corrosion products in the free corrodent according to XPS results. In the presence of composite, both ionic and neutral forms of GA-AgNPS are adsorbed. AgNPs are present on the surface in the form: Ag°, AgO, and AgO.
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http://dx.doi.org/10.1016/j.carbpol.2017.10.051DOI Listing
February 2018

A Case Study: What Doses of Amanita phalloides and Amatoxins Are Lethal to Humans?

Wilderness Environ Med 2015 Dec 9;26(4):491-6. Epub 2015 Oct 9.

Department of Pharmacology, Duzce University School of Medicine, Duzce, Turkey (Dr Kaya).

There are few data estimating the human lethal dose of amatoxins or of the toxin level present in ingested raw poisonous mushrooms. Here, we present a patient who intentionally ingested several wild collected mushrooms to assess whether they were poisonous. Nearly 1 day after ingestion, during which the patient had nausea and vomiting, he presented at the emergency department. His transaminase levels started to increase starting from hour 48 and peaking at hour 72 (alanine aminotransferase 2496 IU/L; aspartate aminotransferase 1777 IU/L). A toxin analysis was carried out on the mushrooms that the patient said he had ingested. With reversed-phase high-performance liquid chromatography analysis, an uptake of approximately 21.3 mg amatoxin from nearly 50 g mushroom was calculated; it consisted of 11.9 mg alpha amanitin, 8.4 mg beta amanitin, and 1 mg gamma amanitin. In the urine sample taken on day 4, 2.7 ng/mL alpha amanitin and 1.25 ng/mL beta amanitin were found, and there was no gamma amanitin. Our findings suggest that the patient ingested approximately 0.32 mg/kg amatoxin, and fortunately recovered after serious hepatotoxicity developed.
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http://dx.doi.org/10.1016/j.wem.2015.08.002DOI Listing
December 2015

Effect of Montelukast on Spinal Cord Ischemia- Reperfusion Injury.

Turk Neurosurg 2015 ;25(5):757-65

Ankara Numune Education and Research Hospital, Department of Cardiovascular Surgery, Ankara, Turkey.

Aim: Paraplegia due to ischemia-reperfusion (I/R) injury of the spinal cord is a devastating complication of thoracoabdominal aortic surgery. Cysteinyl leukotrienes are potent mediators of inflammation that are associated with I/R injury. The present study was designed to investigate the role of montelukast, a selective reversible CysLT1 receptor antagonist, on spinal cord I/R injury in an experimental model.

Material And Methods: Twenty-one male Sprague-Dawley rats were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion and montelukast administration), G2 (45 min. aortic occlusion; no montelukast administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast administration). After neurologic evaluation using the Motor Deficit Index (MDI) score at the 48th hour of reperfusion, lumbar spinal cords were removed for histopathological evaluation and immunohistochemical staining for HSP70, interleukin-6 and myeloperoxidase (MPO).

Results: All rats in the G1 group had a normal neurological status and their MDI score was 0 (p < 0.05). The MDI score of G3 was significantly lower than G2 group (2.8 vs. 5.5; p < 0.05). Vacuolar congestion was found to be significantly lower in G1 than the other groups (p=0.0001). The interleukin-6 receptor level was found to be significantly lower in G3 group than the control group (p=0.013). There was no statistically significant difference found among the groups in terms of the degree of HSP70 and MPO staining.

Conclusion: Increased generation of leukotrienes in postischemic organs play an important role in I/R injury. The findings of the current study demonstrated that montelukast improved motor recovery and decreased IL-6 levels in spinal cord I/R injury.
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http://dx.doi.org/10.5137/1019-5149.JTN.11499-14.2DOI Listing
May 2016

Comparison of Changes in Anxiety and Depression Level Between Dabigatran and Warfarin Use in Patients With Atrial Fibrillation.

Clin Appl Thromb Hemost 2017 Mar 9;23(2):164-167. Epub 2016 Jul 9.

6 Department of Pharmacology, Duzce University, Medical School, Duzce, Turkey.

We hypothesized that patients taking warfarin require frequent hospital follow-up and they are at higher risk for complications, so the incidence of depression and anxiety is higher in patients with atrial fibrillation (AF) in the period of taking warfarin compared to the period of taking dabigatran. Fifty patients having AF without valvular diseases under treatment of warfarin in whom a transition to dabigatran was planned were consecutively enrolled in this study and followed up prospectively between July 2013 and July 2014. All patients completed Beck Depression Inventory and Hamilton Anxiety Scale (HAS) at the initiation of study and 6 months after initiation of study. Of the patients enrolled in the study, age, gender, smoking status, and comorbidities were questioned. A total of 50 patients (28 women; mean age 74.6 ± 8.7 years) treated with warfarin in whom a transition to dabigatran was planned were included. Basal mean value of BDS (15.6 ± 7.8 vs 11.5 ± 4.8, P < .001) and HAS (16.8 ± 10.4 vs 12.6 ± 8.1, P < 0.001) was significantly higher in patients when they used warfarin than when they switched to dabigatran. In categorical analysis, frequency of patients with depression (mild, moderate, and severe) was significantly higher in period of warfarin use than after dabigatran transition (n = 24, 48% vs n = 14, 28%, P = .039). Our study demonstrates that patients with nonvalvular AF under treatment of dabigatran had lower BDS and HAS scores compared to warfarin. These findings suggest that dabigatran may increase quality of life and decrease morbidity and mortality due to reduction in anxiety and depression.
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http://dx.doi.org/10.1177/1076029615600792DOI Listing
March 2017

Erythropoietin stimulates patellar tendon healing in rats.

Knee 2015 Dec 9;22(6):461-8. Epub 2015 Jun 9.

Düzce University Medical School, Department of First Aid and Emergency, Düzce, Turkey.

Background: Erythropoietin (EPO), regulating erythropoiesis, is used to provide protective and regenerative activity in non-haematopoietic tissues. There is insufficient knowledge about the role of EPO activity in tendon healing. Therefore, we investigated the effect of EPO treatment on healing in rat patellar tendons.

Methods: One hundred and twenty-six, four-month-old male Sprague-Dawley rats were randomly assigned to three experimental groups: 1, no treatment; 2, treatment with isotonic saline (NaCl) and 3, treatment with EPO. Each group was randomly subdivided into two groups for sacrifice at three (1a, 2a, 3a) or six weeks (1b, 2b, 3b). Complete incision of the left patellar tendon from the distal patellar pole was performed. We applied body casts for 20 days after the incised edges of the patellar tendon were brought together with a surgical technique. Both legs were harvested and specimens from each group underwent histological, biomechanical, and protein mRNA expression analyses.

Results: There were statistically significant differences in the ultimate breaking force between the EPO group and others at both weeks three and six (p<0.05); significant differences in fibroblast proliferation, capillary vessel formation, and local inflammation were found between groups 1a and 3a, and 2a and 3a (p<0.05). There were statistical differences between 1a, 3a and 2a, 3a for Col III, TGF-β1, and VEGF and between 1b, 3b and 2b, 3b for Col I, Col III, TGF-β1, and VEGF mRNA expressions.

Conclusion: EPO had an additive effect with surgery on the injured tendon healing process in rats compared to the control groups biomechanically, histopathologically and with tissue protein mRNA expression.

Clinical Relevance: This is the first experimental study to analyze the relationship between EPO treatment and the patellar tendon repair process by biomechanical, histopathological, and tendon tissue mRNA expression methodologies.
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http://dx.doi.org/10.1016/j.knee.2015.01.011DOI Listing
December 2015

Erythropoietin stimulates patellar tendon healing in rats.

Knee 2015 Dec 9;22(6):461-8. Epub 2015 Jun 9.

Düzce University Medical School, Department of First Aid and Emergency, Düzce, Turkey.

Background: Erythropoietin (EPO), regulating erythropoiesis, is used to provide protective and regenerative activity in non-haematopoietic tissues. There is insufficient knowledge about the role of EPO activity in tendon healing. Therefore, we investigated the effect of EPO treatment on healing in rat patellar tendons.

Methods: One hundred and twenty-six, four-month-old male Sprague-Dawley rats were randomly assigned to three experimental groups: 1, no treatment; 2, treatment with isotonic saline (NaCl) and 3, treatment with EPO. Each group was randomly subdivided into two groups for sacrifice at three (1a, 2a, 3a) or six weeks (1b, 2b, 3b). Complete incision of the left patellar tendon from the distal patellar pole was performed. We applied body casts for 20 days after the incised edges of the patellar tendon were brought together with a surgical technique. Both legs were harvested and specimens from each group underwent histological, biomechanical, and protein mRNA expression analyses.

Results: There were statistically significant differences in the ultimate breaking force between the EPO group and others at both weeks three and six (p<0.05); significant differences in fibroblast proliferation, capillary vessel formation, and local inflammation were found between groups 1a and 3a, and 2a and 3a (p<0.05). There were statistical differences between 1a, 3a and 2a, 3a for Col III, TGF-β1, and VEGF and between 1b, 3b and 2b, 3b for Col I, Col III, TGF-β1, and VEGF mRNA expressions.

Conclusion: EPO had an additive effect with surgery on the injured tendon healing process in rats compared to the control groups biomechanically, histopathologically and with tissue protein mRNA expression.

Clinical Relevance: This is the first experimental study to analyze the relationship between EPO treatment and the patellar tendon repair process by biomechanical, histopathological, and tendon tissue mRNA expression methodologies.
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http://dx.doi.org/10.1016/j.knee.2015.01.011DOI Listing
December 2015

A Case Study: Rare Lepiota brunneoincarnata Poisoning.

Wilderness Environ Med 2015 Sep 12;26(3):350-4. Epub 2015 Mar 12.

Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey (Drs Kose and Guler).

Amatoxin poisoning from the genus Lepiota may have a deadly outcome, although this is not seen as often as it is from the genus Amanita. In this report, we present a patient who was poisoned by a sublethal dose of Lepiota brunneoincarnata mushrooms. The patient was hospitalized 12 hours after eating the mushrooms. The patient's transaminase levels increased dramatically starting on day 4. Aspartate transaminase peaked at 78 hours. Starting at 1265 IU/L, alanine transaminase peaked at 90 hours at 5124 IU/L. The patient was discharged on day 8 to outpatient care, and his transaminase levels returned to normal ranges in the subsequent days. A toxin analysis was carried out on the mushrooms that the patient claimed to have eaten. Using reversed-phase high-performance liquid chromatography analysis, an uptake of approximately 19.9 mg of amatoxin from nearly 30 g of mushrooms was calculated. This consisted of 10.59 mg of α-amanitin, 9.18 mg of β-amanitin, and 0.16 mg of γ-amanitin. In conclusion, we present a patient from Turkey who was poisoned by L. brunneoincarnata mushrooms.
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http://dx.doi.org/10.1016/j.wem.2014.12.025DOI Listing
September 2015

Polymorphisms in MMP-2 and TIMP-2 in Turkish patients with prostate cancer.

Turk J Med Sci 2014 ;44(5):839-43

Aim: Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of cancer deaths in the Western male population. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) modulate the remodeling of the extracellular matrix (ECM). The imbalance between MMPs and TIMPs may lead to an emergence of pathological processes such as cancer. In this study, the association between TIMP-2 (-418 G/C) and MMP-2 (-1306 C/T) polymorphisms and prostate cancer in the Turkish population was investigated.

Materials And Methods: Sixty-one prostate cancer patients and 46 healthy subjects were included in the study. DNA was isolated from 2 mL of peripheral blood taken from subjects, and genotypes were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method.

Results: The TIMP-2 -418 (GC) genotype was found in 15 cases (32.6%) in the control group and in 9 cases (14.8%) in the patients group, and statistical significance was determined (P = 0.037, OR = 0.346). The MMP-2 -1306 (CT) genotype was found 2.17 times more in the patient group than in the control group (P = 0.149, OR = 2.17).

Conclusion: Our results show that the TIMP-2 -418 (GC) genotype had a putative protective effect against prostate cancer.
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January 2015

Evaluation and comparison of alpha- and beta-amanitin toxicity on MCF-7 cell line.

Turk J Med Sci 2014 ;44(5):728-32

Background/aim: Alpha- and beta-amanitins are the main toxins of the poisonous Amanita phalloides mushroom. Although there are many studies available concerning alpha-amanitin, there are limited data about beta-amanitin in the literature. Therefore, this study is aimed at comparing the toxic effects of alpha- and beta-amanitin on the MCF-7 cell line.

Materials And Methods: The alpha- and beta-amanitins used for this research were purified from Amanita phalloides by preparative high-performance liquid chromatography. The MCF-7 breast cancer cell line was used, and specific concentrations of the toxins (100, 10, 1, 0.1, and 0.01 μg/mL) were applied to the cells. The MTT test was performed to determine the level of toxicity, and the quantity of protein in the cell was measured using the biuret test.

Results: The aLpha-amanitin showed a higher toxicity at 36 h, while the highest inhibition of protein synthesis by the beta-amanitin was observed at 24 h.

Conclusion: It was shown that the beta-amanitin may be responsible for toxicity, like alpha-amanitin, in Amanita phalloides mushroom poisoning. The early inhibition of protein synthesis for beta-amanitin might be useful for future experiments and research.
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January 2015

Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen-activated protein kinases and NF-ĸB signaling pathways in human chondrocytes.

Cell Biol Int 2015 Jan 31;39(1):104-12. Epub 2014 Jul 31.

Department of Medical Biology, Kahramanmaras Sutcu Imam University Medical Faculty, Kahramanmaras, Turkey.

Elucidation of the causes of inflammation has vital importance in the development of new approaches for the treatment of arthritic diseases. The degradation of aggrecan by upregulated disintegrin and metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have been demonstrated, thus linking leptin to arthritic diseases, but the mechanism has not been clarified. This study investigated the putative role of signaling pathways (p38, JNK, MEK1, NF-ĸB, and PI3) involved in leptin-induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000 ng/mL doses for 6, 12, 24, and 48 h, after which ADAMTS-4, -5, and -9 genes expression were determined by real time-polymerase chain reaction (RT-PCR) and Western Blot methods. The signaling pathways involved in leptin-induced ADAMTSs upregulation were also investigated by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs expression level was peaked at 1000 ng/mL doses for 48 hours, and MAPKs (p38, JNK, and MEK) and NF-ĸB signaling pathways involving in leptin triggered ADAMTSs upregulation. Obesity as a risk for RA and OA may contribute to the inflammation of both RA and OA diseases by secreting adipokines like leptin. We hypothesize that leptin is involved in the development of RA and OA accompanied with obesity by increasing ADAMTS-4, -5, and -9 genes expression via MAPKs and NF-ĸB signaling pathways.
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http://dx.doi.org/10.1002/cbin.10336DOI Listing
January 2015

Clinical importance of toxin concentration in Amanita verna mushroom.

Toxicon 2014 Sep 7;87:68-75. Epub 2014 Jun 7.

Duzce University School of Medicine, Department of Anatomy, Duzce, Turkey.

Poisoning from Amanita group of mushrooms comprises approximately 3% of all poisonings in our country and their being responsible for nearly the entire fatal mushroom poisonings makes them important. These mushrooms contain primarily two types of toxins, amatoxins and phallotoxins. Phallotoxins have a more limited toxicity potential and they primarily consist of phalloidin (PHN) and phallacidin (PCN). Amatoxins, on the other hand, are very toxic and they primarily consist of alpha-amanitin (AA), beta-amanitin (BA) and gamma-amanitin (GA). Toxin levels can vary among various species, even among varieties of the same species, of Amanita mushroom family. Revealing the differences between the toxin compositions of the Amanita species that grow in our region may contribute to the clinics of poisonings. Our study aims at showing in detail the toxin levels in various parts of Amanita verna mushroom. A. verna mushrooms needed for toxin analysis were collected from Kozak Plateau near Ayvalik county of Balıkesir, Turkey in April 2013. The mushrooms were divided into their parts as pileus, gills, stripe and volva. Following the procedures required before the analysis, the AA, BA, GA, PHN and PCN levels were measured using the RP-HPLC method. While the lowest level of amatoxin was in the volva of the mushroom, the highest was measured in the gills. This was followed by pileus and stripe where the levels were close to each other. Similarly, the highest level of phallotoxin was measured in the gills. Gamma toxin and phalloidin were at lower amounts than the other toxins. A. verna is frequently confused with edible mushrooms with white caps due to its macroscopic similarity. If just one of them is eaten by mistake by an adult person with no mushroom experience, it can easily poison them. The amount of amatoxin is more as compared to Amanita phalloides and A. phalloides var. alba. Particularly, the AA and BA levels are approximately three times higher, whereas GA levels are lower. Similarly, the level of PCN is approximately four times higher as compared to A. phalloides and A. phalloides var. alba; by contrast, the level of PNH is about a half of theirs. In summary, it can be said that A. verna is a more toxic mushroom than A. phalloides and has a higher rate of mortality. With our study, the amatoxin and phallotoxin concentrations and distribution in A. verna mushrooms were shown in detail for the first time and it would be useful to carry out more similar studies with other members of Amanita family growing in various parts of the world.
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http://dx.doi.org/10.1016/j.toxicon.2014.05.019DOI Listing
September 2014

Effect of nifedipine on hippocampal neuron number in penicillin-induced epileptic rats.

Turk Neurosurg 2014 ;24(2):234-40

Bozyaka Education and Research Hospital, Department of Medical Pharmacology, Izmir, Turkey.

Aim: Epileptic seizures lead to neuronal loss in the hippocampus. Experimental epilepsy can be induced by direct application of various chemicals to cerebral cortex. Nifedipine is an L-type voltage-dependent calcium channel blocker. In spite of several studies that show the seizure-suppressing effects of nifedipine, it has been shown that nifedipine does not suppress but conversely increases epileptic seizures. Similarly, contradictory effects of nifedipine have been reported, such as neuroprotection, failed neuroprotection and neurotoxicity. We therefore aimed to investigate the effect of nifedipine on hippocampal neuronal loss in penicillin induced epileptic rats in this study.

Material And Methods: The effect of nifedipine on total hippocampal neuron number was estimated by using the optical fractionator method (an unbiased stereological method) in penicillin-G induced epileptic rats.

Results: The total number of hippocampal neurons in the control group was 183687 ± 3184. In the penicillin-induced group, the total neuron number significantly decreased to 146318 ± 3042 compared to the control group. In the nifedipine group, the neuron number significantly decreased to 128873 ± 1157 compared to both control and penicillin-induced groups.

Conclusion: Nifedipine increased neuronal loss and did not suppress epileptic seizures in penicillin-induced epileptic rats. Nifedipine could not protect against hippocampal neuronal loss in penicillin-induced epileptic rats.
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http://dx.doi.org/10.5137/1019-5149.JTN.8428-13.2DOI Listing
February 2015

Extracorporeal shockwave increases the effectiveness of systemic antibiotic treatment in implant-related chronic osteomyelitis: experimental study in a rat model.

J Orthop Res 2014 Jun 20;32(6):752-6. Epub 2014 Feb 20.

Department of Orthopaedics and Traumatology, Sakarya University Medical School, Sakarya, Turkey.

Implant-related chronic osteomyelitis is a serious complication of orthopedic surgery requiring implant removal and radical debridement. Extracorporeal shockwave (ESW) have demonstrated significant bactericidal effectiveness in vitro and effectiveness and safety were evaluated in an animal model of osteomyelitis. In this experimental study, we aimed to test our hypothesis that the use of ESW together with systemic antibiotic treatment will provide synergy for the treatment of implant-related chronic osteomyelitis caused by methicillin-susceptible Staphylococcus aureus (MSSA). The proximal tibia of 32 rats was contaminated with (10) 8 CFU/ml methicillin-sensitive S. aureus (MSSA-ATCC 29213) and Kirschner-wires were placed into the medulla of the tibia. After 4 weeks, Kirschner-wires were removed and the rats were randomly divided into four groups: group I, untreated contaminated control group; group II, receiving only ESW therapy; group III, receiving only systemic teicoplanin; group IV, treated with a combination of ESW and systemic teicoplanin. ESW was applied twice to the infected limbs and all rats were sacrificed at the end of 8th week. The degree of tibial osteomyelitis was assessed by quantitative culture analysis. Bacterial counts in groups III and IV were significantly reduced relative to the control (p=0.002 and 0.001, respectively). The decrease in bacterial counts was more pronounced and significant in group IV compared to group III (p=0.024). In group II, bacterial counts also decreased, but the differences were in significant (p=0.068). Our experimental model suggests that ESW provides significant synergy for systemic antibiotic treatment. However, further clinical trials are required in order to use this treatment modality safely in patients, even though our study demonstrated successful results in the treatment of implant-related chronic osteomyelitis in rats.
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http://dx.doi.org/10.1002/jor.22604DOI Listing
June 2014

Association of omentin Val109Asp polymorphism with coronary artery disease.

Anadolu Kardiyol Derg 2014 Sep 19;14(6):511-4. Epub 2013 Dec 19.

Department of Medical Biology and Genetics, Institute of Health Science, Faculty of Medicine, Düzce University, Düzce-Turkey.

Objective: Coronary artery disease (CAD) is the most important morbidity and mortality disease in the world. It is also one of the leading causes of death in Turkey. Omentin, a recently found adipocytokine, is reported to regulate insulin sensitivity. It has anti-inflammatory properties and is inversely associated with CAD. Omentin gene polymorphism in patients with CAD has not been studied yet. The aim of this study is to investigate the relationship between omentin Val109Asp polymorphism and CAD.

Methods: This is an observational study on genetic association. 157 consecutive patients who had undergone coronary angiography were included in the study. Seventy-five of them had CAD and the rest serves the control group. Val109Asp polymorphism was analyzed and compared. Chi-square test was used in comparison of genotype frequencies, whereas ANOVA and chi-square tests were used in comparison of clinical characteristics according to the genotypes.

Results: There was no significant difference between CAD patients and control subjects regarding omentin Val109Asp polymorphism. However, a 2.5 fold increase in Val/Val (homozygous mutant) genotype was detected in patients with CAD. The OR (80% Cl) for Val/Val genotype was 3.46 (1.14-10.49).

Conclusion: Although no significant difference was detected regarding omentin Val109Asp polymorphism, Val/Val genotype frequency was found to be more in patient group than control group. In conclusion, it may be speculated that Val/Val genotype increases the tendency for CAD, but this experiment should done with larger population to clarify this issue.
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http://dx.doi.org/10.5152/akd.2013.4932DOI Listing
September 2014

Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis.

Int J Dermatol 2014 May 10;53(5):601-5. Epub 2013 Dec 10.

Department of Dermatology, Duzce University Medical Faculty, Duzce, Turkey.

Background: Psoriasis is a chronic inflammatory disease of uncertain pathogenesis. Omentin is a new adipokine with anti-inflammatory properties; however, the relationship between psoriasis and omentin has not been fully established yet.

Objectives: This study was designed to evaluate the relationship between psoriasis and omentin serum levels and Val109Asp polymorphism in exon 4 of the omentin gene.

Methods: Forty-nine patients with plaque-type psoriasis and 39 healthy subjects were included in the study. Omentin concentrations were determined by using enzyme-linked immunosorbent assay. Val109Asp polymorphism in exon 4 of the omentin gene was assessed by the polymerase chain reaction-restriction fragment length polymorphism method. Genotypes were determined according to the bands formed in agarose electrophoresis gels. In the statistical analysis, the level of significance was set at P < 0.05.

Results: The serum omentin levels of the patients with psoriasis (354.2 ± 152.0) were found to be significantly lower than those in the control group (488.7 ± 190.3) (P = 0.001). A moderate level negative correlation was determined between serum omentin level and body mass index and waist circumference. No significant differences were observed between the patient and control groups in terms of the genotype and allele frequency of Val109Asp polymorphism in exon 4 of the omentin gene (P > 0.05).

Conclusions: Omentin serum levels were determined to be low in patients with psoriasis. No significant difference was found regarding Val109Asp polymorphism of the omentin gene. To the best of our knowledge, our study is the first clinical study to examine the relationship between psoriasis and omentin in terms of serum and genomic levels.
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http://dx.doi.org/10.1111/ijd.12306DOI Listing
May 2014

Polymorphisms in the promoters of MMP-2 and TIMP-2 genes in patients with acne vulgaris.

Int J Clin Exp Med 2013 25;6(10):967-72. Epub 2013 Oct 25.

Department of Medical Genetics, Faculty of Medicine, Duzce University Duzce, Turkey.

Acne, a chronic inflammatory skin disease, can be seen at any age but it most often occurs in adolescents and young people. Several factors, including increased sebum production, abnormal cornification of the pilosebaceous units, proliferation of Propionibacterium acne, and extracellular matrix (ECM) remodeling, are thought to be associated with the pathogenesis of the acne. The remodeling of the ECM is regulated by a balance between matrix metalloproteinases (MMPs) and their inhibitors called tissue inhibitors of metalloproteinases (TIMPs). The current study investigated the potential association between MMP-2 (-1306 C/T) and TIMP-2 (-418 G/C) polymorphisms and the risk for acne in a Turkish population. The study was conducted with 85 subjects who presented to the Dermatology Department of Duzce University Hospital. DNA was isolated from 2 ml of peripheral blood taken from each subject, and their genotypes were analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CC, CT, and TT genotypes for MMP-2 (-1306 C/T) polymorphism were similar between the patient and control group (24 [55.8%], 17 [39.5%], and 2 [4.7%], respectively, vs. 21 [50%], 18 [42.9%], and 3 [7.1%], respectively). However, the distribution of the GG, GC, and CC genotypes for TIMP-2 (-418 G/C) polymorphism were different between the patient and control group (30 [69.8%], 9 [14.8%] and 4 [9.3%], respectively, vs. 26 [61.9%], 14 [33.3%], and 2 [4.8%], respectively). The results demonstrated that the TIMP-2 (-418 CC) genotype was nearly two times more common in the patient group compared to the control group (p=0.686, OR=1.45). It may be possible that the TIMP-2 (-418 CC) genotype increases the tendency to develop acne vulgaris by disrupting the balance between MMPs and TIMPs. Further investigations are needed to clarify more precisely the relationship between acne and MMP-TIMP genes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832336PMC
November 2013

Amanitin and phallotoxin concentration in Amanita phalloides var. alba mushroom.

Toxicon 2013 Dec 15;76:225-33. Epub 2013 Oct 15.

Duzce University School of Medicine, Department of Pharmacology, Duzce, Turkey.

Although rarely seen, Amanita phalloides var. alba, a variety of A. phalloides type mushrooms, causes mushroom poisoning resulting in death. Since it is frequently confused with some edible mushrooms due to its white colored cap and macroscopic appearance, it becomes important in toxicological terms. Knowledge of the toxin amount contained in this mushroom type is invaluable in the treatment of cases involving poisoning. In this study, we examined the toxin levels of various parts of the A. phalloides var. alba mushroom growing Duzce region of Turkey. Toxin analyses were carried out for A. phalloides var. alba, which were collected from the forests Duzce region of Turkey in 2011, as a whole and also separately in its spore, pileus, gills, stipe and volva parts. The alpha amanitin, beta amanitin, gamma amanitin, phalloidin and phallacidine analyses of the mushrooms were carried out using the RP-HPLC method. A genetic analysis of the mushroom showed that it had similar genetic characteristics as A. phalloides and was a variety of it. The lowest toxins quantity was detected in spores, volva and stipe among all parts of the mushroom. The maximum amount of amatoxins was measured in the gills. The pileus also contained a high amount of amatoxins. Generally, amatoxins and phallotoxin concentrations were lower as compared to A. phalloides, but interestingly all toxins other than gamma toxin were higher in the spores of A. phalloides var. alba. The amount of toxin in all of its parts had sufficient concentrations to cause death. With this study, the amatoxin and phallotoxin concentrations in A. phalloides var. alba mushroom and in its parts have been revealed in detail for the first time.
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http://dx.doi.org/10.1016/j.toxicon.2013.10.008DOI Listing
December 2013

Sedoanalgesia in pediatric daily surgery.

Int J Clin Exp Med 2013 1;6(7):576-82. Epub 2013 Aug 1.

Department of Pediatric Surgery, School of Medicine, University of Duzce Duzce, Turkey.

Purpose: The present report was focused on clinical advantages of sedoanalgesia in the pediatric outpatient surgical cases.

Method: Sedoanalgesia has been used to sedate patients for a variety of pediatric procedures in our department between 2007 and 2010. This is a retrospective review of 2720 pediatric patients given ketamine for sedation with midazolam premedication. Ketamine was given intravenously (1-2 mg/kg) together with atropine (0.02 mg/kg) and midazolam (0.1 mg/kg) + a local infiltration anesthetic 2 mg/kg 0.5% bupivacaine hydrochloride.

Result: Median age of the patients included in the study was 5.76 ± 2.12 (0-16 years). The main indications for ketamine include circumcision (69%), inguinal pathologies (inguinal hernia (17%), orchidopexy (2.68%), hydrocele (3.38%), hypospadias (1.94%), urethral fistula repair (0.33%), urethral dilatation (0.25%), and other conditions. All of our patients were discharged home well. In this regard, we have the largest group of patients ever given ketamine.

Conclusion: Sedoanalgesia might be used as a quite effective method for daily surgical procedures in children.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731190PMC
August 2013

Dermal absorption and toxicity of alpha amanitin in mice.

Cutan Ocul Toxicol 2014 Jun 14;33(2):154-60. Epub 2013 Jun 14.

Department of Medical Pharmacology and.

The fungus Amanita phalloides is known to contain two main groups of toxins: amanitins and phallotoxins. The amanitins group effectively blocks the RNA polymerase II enzyme found in eukaryotic cells. As alpha amanitin has a lethal effect on the majority of eukaryotic cells, it can be valuable as an antiparasitic or antifungal drug. It can be used externally against ectoparasites. It is critical that percutaneous applications of the alpha amanitin toxin are not harmful to the recipient. In this study, the absorption and the toxicity of percutaneous and intraperitoneal (ip) applications of 1 mg/kg alpha amanitin to mice were compared. Potential skin, liver and kidney toxicities were investigated through pathological examination. HPLC analysis was used to determine the amount of the toxin. No toxicity or toxin were found in the skin, liver, or kidneys of the mice in the control group. Interestingly, the percutaneous application group also showed no toxicity, and the toxin was not present in this group. After 24 h, Councilman-like bodies and pyknotic cells were observed in the mice in which alpha amanitin was applied intraperitoneally, demonstrating the presence of toxicity. Peak levels of alpha amanitin (µg/mL) in the liver, kidney, and blood in the ip application group were measured at 3.3 (6 h), 0.2 (6 h) and 1.2 (1 h), respectively. The results demonstrated that the toxin was not absorbed through the skin of the mice and that the percutaneous application of alpha amanitin did not have any toxic effects. Thus, alpha amanitin may be administered percutaneously for therapeutic purposes.
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http://dx.doi.org/10.3109/15569527.2013.802697DOI Listing
June 2014

Amatoxin and phallotoxin concentration in Amanita phalloides spores and tissues.

Toxicol Ind Health 2015 Dec 29;31(12):1172-7. Epub 2013 May 29.

Department of Emergency Medicine, School of Medicine, Düzce University, Düzce, Turkey.

Most of the fatal cases of mushroom poisoning are caused by Amanita phalloides. The amount of toxin in mushroom varies according to climate and environmental conditions. The aim of this study is to measure α-, β-, and γ-amanitin with phalloidin and phallacidin toxin concentrations. Six pieces of A. phalloides mushrooms were gathered from a wooded area of Düzce, Turkey, on November 23, 2011. The mushrooms were broken into pieces as spores, mycelium, pileus, gills, stipe, and volva. α-, β-, and γ-Amanitin with phalloidin and phallacidin were analyzed using reversed-phase high-performance liquid chromatography. As a mobile phase, 50 mM ammonium acetate + acetonitrile (90 + 10, v/v) was used with a flow rate of 1 mL/min. C18 reverse phase column (150 × 4.6 mm; 5 µm particle) was used. The least amount of γ-amanitin toxins was found at the mycelium. The other toxins found to be in the least amount turned out to be the ones at the spores. The maximum amounts of amatoxins and phallotoxin were found at gills and pileus, respectively. In this study, the amount of toxin in the spores of A. phalloides was published for the first time, and this study is pioneering to deal with the amount of toxin in mushrooms grown in Turkey.
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http://dx.doi.org/10.1177/0748233713491809DOI Listing
December 2015

Iododerma following topical povidone-iodine application.

Cutan Ocul Toxicol 2013 Oct 8;32(4):339-40. Epub 2013 Apr 8.

Department of Dermatology, Duzce University Medical Faculty, Konuralp, Duzce, Turkey .

A 43-year-old male patient presented with two well-demarcated, elevated plaques, measuring 4 cm in diameter, with yellow-black crusts over it that appeared 3 d earlier. With the help of history, physical examination and histopathological features, the patient was diagnosed with iododerma secondary to topical povidone-iodine use. Iododerma develops frequently after oral or intravenous but rarely after topical use of iodine. Its pathogenesis is not well-known though it is widely believed that it is a delayed hypersensitivity reaction.
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http://dx.doi.org/10.3109/15569527.2013.780181DOI Listing
October 2013

Efficacy of iloprost and montelukast combination on spinal cord ischemia/reperfusion injury in a rat model.

J Cardiothorac Surg 2013 Apr 4;8:64. Epub 2013 Apr 4.

Background: The thoracic or thoracoabdominal aortic aneurysm surgery may cause spinal cord ischemia because of aortic cross-clamping and may result in severe postoperative complications caused by spinal cord injury. Ischemia/reperfusion injury may directly or indirectly be responsible for these complications. In this study we sought to determine whether combination of iloprost and montelukast can reduce the ischemia/reperfusion injury of spinal cord in a rat model.

Methods: Medulla spinalis tissue concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO) and heat shock protein 70 (HSP-70) were determined in 3 groups of Spraque Dawley rats: control group (operation with cross clamping and intraperitoneal administration of 0.9% saline, n = 7), sham group (operation without cross clamping, n = 7), and study group (operation with cross-clamping and intraperitoneal administration of iloprost (25 ng/kg) and montelukast (1 mg/kg), n = 7). The abdominal aorta was clamped for 45 minutes, with a proximal (just below the left renal artery) and a distal (just above the aortic bifurcation) clip in control and study groups. Hindlimb motor functions were evaluated at 6, 12, 24, and 48 hours using the Motor Deficit Index score. All rats were sacrificed 48 hours after the procedure and spinal cord tissue levels of myeloperoxidase, interleukin-6, and heat shock protein (HSP-70) were evaluated as markers of oxidative stress and inflammation. Histopathological analyses of spinal cord were also performed.

Results: The tissue level of HSP-70 was found to be similar among the 3 groups, however, MPO was highest and IL-6 receptor level was lowest in the control group (p = 0.007 and p = 0.005; respectively). In histopathological examination, there was no significant difference among the groups with respect to the neuronal cell degeneration, edema, or inflammation, but vascular congestion was found to be significantly more prominent in the control group than in the sham or in the study group (p = 0.05). Motor deficit index scores at 24 and 48 hours after ischemia were significantly lower in the study group than in the control group.

Conclusion: This study suggests that combined use of iloprost and montelukast may reduce ischemic damage in transient spinal cord ischemia and may provide better neurological outcome.
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http://dx.doi.org/10.1186/1749-8090-8-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639838PMC
April 2013

Branch retinal vein occlusion associated with tamoxifen use.

Semin Ophthalmol 2013 Mar;28(2):88-90

Duzce University Medical Faculty, Department of Ophthalmology, Duzce, Turkey.

Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of hormone-responsive breast cancer. Tamoxifen-induced ocular complications are very rare. A post-menopausal woman with carcinoma of the left breast had presented with sudden loss of vision. The patient had been on tamoxifen therapy 20 mg daily for the last three years. Fundus examination showed left branch retinal vein occlusion. Fluorescein angiography and optical coherence tomography confirmed the diagnosis. Tamoxifen therapy was discontinued. Although branch retinal vein occlusion is rare, careful evaluation of patients on tamoxifen therapy with visual symptoms is required.
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http://dx.doi.org/10.3109/08820538.2012.760618DOI Listing
March 2013
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