Yunus Ugan

Hypericum perforatum modulates apoptosis and calcium mobilization through voltage-gated and TRPM2 calcium channels in neutrophil of patients with Behcet's disease.

Behcet’s disease (BD) is a chronic, inflammatory, and multisystemic condition although its pathogenesis is uncertain. Main component of St. John’s wort (Hypericum perforatum, HP) is hyperforin and induces antiinflammatory and antioxidant properties. We aimed to investigate effects of HP on oxidative stress, apoptosis, and cytosolic-free Ca2+ [Ca2+]i concentration in neutrophil of BD patients. Nine new-diagnosed active patients with BD and nine control subjects were included in the study. Disease activity was considered by clinical findings. Neutrophil samples were obtained from the patients and controls. The neutrophils from patients were divided into three subgroups and were incubated with HP, voltage-gated calcium channel (VGCC) blockers, (verapamil+dilitiazem) and non-specific TRPM2 channel blocker (2-aminoethyl diphenylborinate, 2-APB), respectively. The neutrophils were stimulated by fMLP as a Ca2+-concentration agonist and oxidative stress former. Caspase-3, caspase-9, apoptosis, lipid peroxidation, and [Ca2+]i values were high in the patient groups, although cell viability, glutathione (GSH), and glutathione peroxidase (GSH-Px) values were low in patient group. However, the [Ca2+]i, caspase-3, and caspase-9 values decreased markedly in patient+HP group although GSH and GSH-Px values increased in the group. The [Ca2+]i concentration was also decreased in the patient group by V+D, 2-APB, and HP incubations. In conclusion, we observed the importance of neutrophil Ca2+ entry, apoptosis, and oxidative stress through gating VGCC and TRPM2 channels in the neutrophils in the pathogenesis and activation of the patients with BD. HP induced protective effects on oxidative stress by modulating Ca2+ influx in BD patients.Graphical Abstract

Catastrophic antiphospholipid syndrome treated with rituximab: A case report

Catastrophic antiphospholipid syndrome (CAPS) is a rare and fatal condition that is characterized by diffuse venous and/or arterial thromboembolism within a short period of time and histopathological confirmation of small-vessel occlusion in at least one organ or tissue in the presence of positive antiphospholipid antibodies. Here we report the case of a 19-year-old woman with CAPS. During the first week of her hospitalization, she was diagnosed with CAPS on the basis of skin necrosis, pulmonary artery thrombosis, cerebral venous sinus thrombosis, and positive lupus anticoagulant. She was treated with corticosteroids, intravenous immunoglobulins, plasmapheresis, and anticoagulants. Forty days after the onset of CAPS, cutaneous lesions were recurred during skin surgery. She required a high dose of corticosteroids, intravenous immunoglobulins, and rituximab. No further thrombotic events occurred. Rituximab may be an effective treatment option for patients with CAPS.

Sacroiliitis and Polyarteritis Nodosa in a Patient with Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an autoinflammatory disorder with autosomal recessive inheritance, characterized by recurrent fever and episodes of serositis. The condition is known to be caused by mutations in the MEFV (Mediterranean FeVer) gene, located in the short arm of chromosome 16. While more than 310 sequence variants in the MEFV gene have been described to date, the diagnosis is still established clinically. FMF may be accompanied by sacroiliitis and various forms of vasculitis. The most common forms of associated vasculitis are Henoch-Schonlein purpura and polyarteritis nodosa (PAN). We have presented here a fairly rare case of FMF, accompanied by both sacroiliitis and PAN.

Protective Effects of Caffeic Acid Phenethyl Ester on Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

We investigated the protective effect of caffeic acid phenethyl ester (CAPE) on cyclophosphamide‐induced hemorrhagic cystitis in rats in comparison with 2‐mercaptoethane sulfonate (MESNA). Forty male rats were randomized into four groups: group 1 (control), group 2 (cyclophosphamide), group 3 (cyclophosphamide + MESNA), group 4 (cyclophosphamide + CAPE). Cyclophosphamide injection increased malondialdehyde levels indicating oxidative stress, whereas CAPE and MESNA ameliorated malondialdehyde levels in the bladder (p < 0.05). Only catalase activities were decreased significantly in both groups (cyclophosphamide + MESNA and cyclophosphamide + CAPE, p < 0.05). Pretreatment with CAPE (p < 0.01) resulted in a significant decrease in nitric oxide levels when compared with the cyclophosphamide group. When we consider the studies that show the critical importance of increased nitric oxide levels in pathogenesis of cyclophosphamide‐induced hemorrhagic cystitis, we suggest that it would be more beneficial to use MESNA with CAPE to prevent histological damage.

A clinical threat in patients with granulomatosis polyangiitis in remission: Subglottic stenosis

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing granulomatous disease that involves small- and medium-sized arteries and affects the main respiratory tracts and kidneys. Upper respiratory tract involvement usually occurs in 90% of patients, who most frequently present with symptoms of chronic sinusitis. Subglottic stenosis (SS) is a rare and severe complication that is usually observed in approximately 15% of patients. Here we present a case of SS in a patient with limited form of GPA during remission.

AB0894 The Significance of Urinary Beta-2 Microglobulin Level for Differential Diagnosis of Familial Mediterranean Fever and Acute Appendicitis

Background The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. Objectives The present study aims to investigate the urinary beta-2 microglobulin (U-β2M) level as a potential parameter to identify these two diseases mimicking each other. Methods A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1–1.5mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens urinary Beta-2 Microglobulin, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. Results U-β2M levels were significantly higher in acute appendicitis group compared to FMF group during attack period, FMF group during attack free period, and control groups (p<0.001, p<0.001, and p<0.001 respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF group during attack period, and FMF group during attack free period compared to controls (U-NAG p<0.001, p=0.016, p=0.004, microalbuminuria p<0.001, p<0.001, p<0.001 respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF group during attack period (p=0.004). Conclusions Determination of U-β2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment, and acute appendicitis. However, this finding should be substantiated with other studies. Disclosure of Interest None declared

AB0800 Neutrophil: Lymphocyte Ratio and Mean Platelet Volume in Patients with Gout: Table 1.

Background Gout is a clinical syndrome with increased uric acid concentration, which is caused by inflammatory response against mono sodium urate (MSU) crystals. In gout, neutrophils are involved in inflammatory response and neutrophil activation is dependent to local cytokine production. Mean platelet volume (MPV) and neutrophil:lymphocyte ratio (NLR) are considered as inflammatory markers in several diseases and it is reported that they may have prognostic significance. Objectives According to current literature, there is no study evaluating MPV and NLR in gout. In this retrospective study, we investigated role of MPV and NLR in determination of inflammation in gout disease. Methods In this retrospective study, 106 patients with gout (91 men and 15 women) meeting inclusion criteria by patients records and 148 age- and sex-matched healthy controls (128 men and 20 women) were included. Laboratory data during attacks (group I) and intercritical period (group II) were collected in the patient group. Results Mean age was 59.46±12.93 years in the patient group whereas 59.00±11.33 years in the control group. Age at first attack was 52.00±12.77 years and mean time interval between first 2 attacks was 6.00±5.52 months. There was tophus in 9 patients (8.5%) and family history of gout in 17 patients (16.0%). Compared to group 2 (intercritical period) and control, no significant difference in MPV levels was found in the group 1 (during attack). MPV was similar among three groups. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were found to be significantly higher in the group I compared to group II. There was significant difference in NLR among three groups. When classified according to presence of tophus, it was seen that MPV and NLR were similar in both groups.Table 1. Parameters evaluated in the groups Parametre Group I Group II Control p (during attack period) (during intercritical period) n=148 n=106 n=106 MPV (f/L) 8.1 (5.9–10.7) 8.2 (5.4–12) 8.3 (6.7–12.9) 0.054 NLR 2.88 (1.21–21.16) 2.19 (0.69–21.82) 1.72 (0.78–11.25) <0.001† ESR (mm/h) 36 (24–65) 12.5 (2–30) – <0.001 CRP (mg/dL) 35 (19–60) 3.2 (1.6–4.7) – <0.001 CRP: C-reactive protein, Normal reference range: 0–10 mg/dL. ESR: erythrocyte sedimentation rate, MPV: mean platelet volume; NLR: neutrophil:lymphocyte ratio; †There are statistically significant differences in all groups. Conclusions The finding of increased NLR during attacks and intercritical period shows that patients with gout are subjected to chronic inflammation. Thus, NLR can be simple, inexpensive and useful diagnostic marker in gout. Studies comparing cytokine levels with NLR will be helpful in elucidating this topic. Disclosure of Interest None declared

AB0895 Effects of Colchicine on Neutrophil Apoptosis in Patients with Familial Mediterranean Fever: Table 1.

Background Familial mediterranean fever (FMF) is an autoinflammatory disease associated with a self-limiting attacks of fever and serositis. Objectives We aimed to investigate the assessment of apoptosis during acute attack and the effect of colchicine on apoptosis in patients with familial mediterranean fever (FMF). Methods This study was performed on 7 FMF patients during acute attack period and 7 age-sex matched healthy persons. Caspase 3 and caspase 9 were studied as the markers of apoptosis. Caspase 3–9 were studied again after neutrophils were incubated with colchicine in cell culture. Results Apoptosis level (0.21±0.009 versus 0.17±0.009, p<0.05) and markers of apoptosis (caspase 3 and 9) was significantly higher in FMF group during attack period than the control group (p<0.001). After the incubation with colchicine, apoptosis markers were found to provide a significantly decrease in comparison with attack period (p<0.001).Table 1. Apoptosis, caspase 3 and caspase 9 levels in between groups Parameters FMF (n=7) Control (n=7) P Apoptosis 0.21±0.009 0.17±0.009 <0.05 Caspase 3 14.33±0.69 8.01±0.18 <0.001 Caspase 9 12.54±1.57 6.17±0.83 <0.001 FMF (n=7) FMF + Colchicine (n=7) P Apoptosis 0.21±0.009 0.15±0.014 <0.01 Caspase 3 14.33±0.69 9.16±1.99 <0.001 Caspase 9 12.54±1.57 7.11±1.99 <0.001 Conclusions Changing the structure of pyrin after mutation can cause failure in the regulation of inflammation and apoptosis. We suggest that defects in the regulation of apoptosis may play a role in the pathogenesis of FMF. Colchicine may reduces apoptosis as well as other mechanisms of action. More studies are needed to clarify the pathogenetic mechanisms of apoptosis in FMF. Disclosure of Interest None declared

AB0162 Protective Effects of Caffeic Acid Phenethyl Ester (CAPE) on Cyclophosphamide Induced Hemorrhagic Cystitis in Rats

Background Cyclophosphamide (CP) is commonly used chemotherapeutic agent in malignancies and rheumatic diseases. Hemorrhagic cystitis (HC) is a serious complication of CP treatment. CAPE, antioxidant and anti-inflammatory molecule, is a major component of honeybee propolis and structurally similar to flavonoids. Objectives We investigated the protective effect of Caffeic asit phenyl ester (CAPE) on cyclophosphamide (CP) induced hemorrhagic cystitis (HC) in rats in comparison with mesna Methods Forty male Wistar rat ages between 8-12 weeks were divided into four groups by random sampling method. HC induction was performed using an urotoxic dose of 100 mg/kg CP. Group 1 (Control) animals were injected with the same amount of saline and served as controls. Group 2 (CP) received only CP, group 3 (CP+mesna) received 100 mg/kg CP and mesna in dosage of 21,5 mg/kg which was given 20 minutes before, 4 and 8 hours after CP injection. Group 4 (CP+CAPE) received 100mg/kg CP and pretreated with CAPE (10 μmol/kg/day) at 48 and 24 hours and also 20 minutes before CP injection. All drugs were administered intraperitoneally. The bladder tissues were cut into two equal pieces from top to the bottom. One half was stored at -80°C for determination of SOD and CAT activities with MDA and NO concentration and the other half was fixed for 24 hr in 10% buffered formaldehyde for histological evaluation. Results Control animals had histologically normal bladders. CP caused severe microscopic mucosal injury in the bladder. Mesna exhibited significant histological protection against bladder damage of CP. CAPE had minimal protective effect on histological damage. CP injection which caused HC increased MDA levels indicating oxidative stres while CAPE and mesna ameliorated MDA levels in the bladder (p>0.05). SOD and CAT activities were decreased in the tissue samples of CP+mesna and CP+CAPE group. However, only CAT activities were decreased significantly in both groups (CP+mesna and CP+CAPE p<0.05). Pretreatment with CAPE (p<0.01) resulted in significant decrease in NO level when compared with CP group. Conclusions When we consider the studies which show the critical importance of increased NO levels in the pathogenesis of cyclophosphamide induced hemorrhagical cystitis, we suggest that it would be more benefical to use mesna with CAPE to prevent histological damage. References Korkmaz A, Oter S, Deveci S, Ozgurtas T, Topal T, Sadir S, Bilgic H. Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of cyclophosphamide induced hemorrhagic cystitis in rats. J Urol 2003;170:2498– 2502 Natarajan K, Singh S, Burke TR, Grunberger D, Aggrawal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996:20;93(17): 9090–9095. Disclosure of Interest None declared