Ertugrul Kaya

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

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.

Amanitin and phallotoxin concentration in Amanita phalloides var. alba mushroom

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.

Amatoxin and phallotoxin concentration in Amanita phalloides spores and tissues.

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.

Clinical importance of toxin concentration in Amanita verna mushroom.

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.

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

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.

Association of omentin Val109Asp polymorphism with coronary artery disease.

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.

Allergic contact dermatitis to para-phenylenediamine in a tattoo: a case report

It is highly popular among children and young adults to have temporary henna tattoos on their bodies in different colors and figures. Henna is a greenish natural powder obtained from the flowers and dry leaves of Lawsonia alba plant and its allergenicity is very low. Henna is also used in combination with other coloring substances such as para-phenylenediamine in order to darken the color and create a permanent tattoo effect. Para-phenylenediamine is a substance with high allergenicity potential and may cause serious allergic reactions. Here, we aimed to draw attention to the potential harms of para-phenylenediamine containing temporary tattoos by presenting a child patient who developed allergic contact dermatitis after having a scorpion-shaped temporary tattoo on his forearm.

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

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.

Dermal absorption and toxicity of alpha amanitin in mice

Abstract 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.

Neutrophilic eccrine hidradenitis induced by cetuximab

Cetuximab is an epidermal growth factor receptor inhibitor used in metastatic colorectal cancer, and head and neck cancers. Several cutaneous side effects due to cetuximab such as acne-like rash, pruritus, dry skin, desquamation, hypertrichosis, and paronychia have been reported so far. A 59-year-old male patient with metastatic colon cancer referred to our outpatient clinic for his lesions on the dorsal surfaces of his hands and wrists, and on thighs developing after the chemotherapy. He was diagnosed as neutrophilic eccrine hydradenitis related to cetuximab in the light of clinical and histopathological findings. According to our knowledge, this is the first reported case of neutrophilic ecrine hydradenitis due to cetuximab.