Oktay Özdemir

Impaired haemostatic kinetics and endothelial function in Behçet's disease

Objectives. This study was planned to explore the alterations of endothelial functions in the prethrombotic state of Behçets disease (BD) patients.

In vivo hemostatic effect of the medicinal plant extract Ankaferd Blood Stopper in rats pretreated with warfarin.

Aim: Ankaferd comprises a mixture of Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) has been approved in the management of bleedings. This study aimed to evaluate in vivo hemostatic effect of ABS in rats pretreated with warfarin. Materials and methods: Wistar rats (210-270 g) were treated either with warfarin (2 mg/kg) or vehicle (0.9% NaCl) orally before bilateral hind leg amputation. ABS was administered topically to one of the amputed legs. The duration of bleeding and the amount of bleeding were measured to evaluate the hemostatic effect of ABS. Results: Topical ABS administration to amputed leg shortened the duration of bleeding markedly in both untreated and warfarin-treated rats by 31.9% [1.42 min (95% CI: 0.35-2.49)] and 43.5% [5.12 min (95% CI: 2.16-8.07)] respectively. The amount of bleeding in ABS-administered amputed leg showed a decrease by 53.8% in warfarin-treated group. Conclusions: ABS has in vivo hemostatic actions that may provide a therapeutic potential for the management of patients with deficient primary hemostasis in clinical medicine.

Ultrastructural and Morphological Analyses of the In Vitro and In Vivo Hemostatic Effects of Ankaferd Blood Stopper

Ultrastructural and morphological analyses of a novel hemostatic agent, Ankaferd Blood Stopper (ABS), in comparison to its in vitro and in vivo hemostatic effects were investigated. High-resolution scanning electron microscopy (SEM) images accompanied with morphological analysis after topical application of ABS revealed a very rapid (<1 second) protein network formation within concurrent vital erythroid aggregation covering the classical coagulation cascade. Histopathological examination revealed similar in vivo ABSinduced hemostatic network at the porcine hepatic tissue injury model. Instantaneous control of bleeding was achieved in human surgery-induced dental tissue injury associated with primary and secondary hemostatic abnormalities. Ankaferd Blood Stopper could hold a great premise for clinical management of surgery bleedings as well as immediate cessation of bleeding on external injuries based on upcoming clinical trials.

The efficacy of Ankaferd Blood Stopper in antithrombotic drug-induced primary and secondary hemostatic abnormalities of a rat-bleeding model

Ankaferd comprises a standardized mixture of plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) as a medicinal product has been approved in the management of external hemorrhage and dental surgery bleedings in Turkey. This study aimed to evaluate the in-vivo hemostatic effect of ABS in rats pretreated with acetylsalicylic acid or enoxaparin. Wistar rats (210–270 g) of both sexes were used in this study. The animals were pretreated with acetylsalicylic acid (10 mg/kg) orally for 4 days or enoxaparin sodium (8 mg/kg) subcutaneously for 3 days or did not receive any anticoagulant before tail cut at 4th day. ABS was administered topically [a total of 4 ml (1 ml/puff × 4)] to the cut tail in the studied animals. The duration of bleeding and the amount of bleeding were measured in order to evaluate the hemostatic effect of ABS. In acetylsalicylic acid-treated animals, topical ABS reduced both the duration and also the amount of bleeding volume by 68.4 and 54.6%, respectively. It was also effective in shortening the duration of bleeding (30.6%) and decreasing the amount of bleeding (32.8%) in enoxaparin-treated animals. ABS, a traditional folkloric medicinal plant extract, has in-vivo hemostatic actions, which may provide a therapeutic potential for the management of patients with deficient hemostasis in the clinical medicine.

Oral Systemic Administration of Ankaferd Blood Stopper Has No Short-Term Toxicity in an In Vivo Rabbit Experimental Model

Background: Ankaferd blood stopper (ABS) is a standardized herbal extract obtained from 5 different plants. In Turkey, it has been approved for local topical applications in external postsurgical and postdental surgery bleedings. Ankaferd blood stopper, besides its hemostatic activity, has in vitro anti-infectious and antineoplastic actions. Objective: The aim of this study was to assess short-term hematological and biochemical safety following the oral systemic administration of ABS to rabbits. Methods: Twelve rabbits (aged 6-12 months) were included to test the safety of oral ABS. Animals were divided into 4 groups, which had ABS administered orally at doses of 1, 3, 6, and 9 mL, irrespective of their weight. The general well-being and feeding patterns of the animals were observed for a period of 7 days. Blood samples (5.5 mL) were obtained just before oral administration, on days 1 and 4. Results: During the observation period of 7 days, none of the animals showed any abnormal behavior or deviation from the normal. Acute mucosal toxicity, hematotoxicity, hepatotoxicity, nephrotoxicity, and biochemical toxicity were not observed during the short-term follow-up of the animals. Conclusions: No signs of toxicity were observed in rabbits during short-term study with oral ABS administration.

Megakaryocyte-Related Interleukins in Reactive Thrombocytosis versus Autonomous Thrombocythemia

The primary thrombocytosis (thrombocythemia) associated with myeloproliferative disorders is believed to be due to autonomous platelet production. Secondary or reactive thrombocytosis can be observed in a number of clinical circumstances, and may be related to persistent overproduction of some thrombocytopoietic factors acting on megakaryocytes. Several cytokines, including IL-6, IL-1 and IL-4 have been shown to act alone or in concert, to affect various cellular stages of megakaryocytopoiesis in humans. The aim of this study is to assess the serum concentrations of these cytokines in myeloproliferative disorders (MPD) with thrombocythemia and in rheumatoid arthritis (RA) with marked reactive thrombocytosis. Twenty-two patients (14 men, 8 women) with MPD and thrombocythemia (platelet counts > 500 x 10(9)/1; range 507-996 x 10(9)/1), 33 RA patients (28 women, 5 men) with marked thrombocytosis (platelet counts > 500 x 10(9)/1; range 500-745 x 10(9)/ 1), 27 RA patients (24 women, 3 men) with normal platelet counts (range 168-399 x 10(9)/1) and 15 healthy volunteers (8 women, 7 men) with normal platelet counts (range 161-385 x 10(9)/1) enrolled in the study. Serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations were measured in these four groups. Of the 22 patients with MPD, 10 had chronic myelogenous leukemia, 5 had polycythemia vera, 6 had essential thrombocytosis and 1 had osteomyelofibrosis. Serum interleukin concentrations in patients with MPD and thrombocythemia were either suppressed or similar to those of normal subjects, whereas IL-6, IL-1 beta and IL-4 levels were increased in RA patients with reactive thrombocytosis. We conclude that thrombocythemia associated with MPD is an autonomous phenomenon, and is not regulated by cytokines which affect megakaryocytopoiesis.

Correlation of in vitro fluconazole susceptibility with Clinical outcome for severely ill patients with oropharyngeal candidiasis

We investigated the correlation between in vitro susceptibility to fluconazole and clinical response in severely ill patients with oropharyngeal candidiasis treated with fluconazole. The study included 48 adult patients, of whom 23 were neutropenic (absolute neutrophil count, < 500/mm3). Forty-eight isolates (20 Candida albicans, 12 Candida krusei, 10 Candida kefyr, 3 Torulopsis glabrata, and 3 Candida tropicalis) were tested for susceptibility to fluconazole with use of the macrodilution method of the National Committee for Clinical Laboratory Standards. A strain was considered to be susceptible to fluconazole if the MIC was < or = 8 micrograms/mL and resistant if the value was > or = 64 micrograms/mL. All but one of the resistant strains were C. krusei isolates. Species of causative Candida, persistent neutropenia, and susceptibility to fluconazole were significant predictors of clinical response by univariate analysis. Logistic regression analysis indicated that the only significant factor was the species of Candida isolates, validating the recently recommended MIC breakpoint and the correlation between clinical outcome and in vitro antifungal susceptibility.

Perianal infections in patients with leukemia

PURPOSE: This study was performed to evaluate relations among neutrophil count (including its course), type of lesion, treatment, and prognosis in patients with leukemia and perianal infection. METHODS: Medical records of patients with acute and chronic leukemia who were followed during the last five years were reviewed retrospectively. RESULTS: The incidence of perianal infections was found to be 7.3 percent in 259 patients with acute leukemia. Only 1 of 108 patients with chronic leukemia suffered from this problem. Twenty percent of all patients with this complication died as a result of sepsis. Perianal abscess was the sole and obligatory indication for surgical treatment in our patients. There were ten patients in each treatment group. The operative group had better results (9 cures, 1 complicationvs. 3 cures, 7 complications). However, median neutrophil count at diagnosis was notably higher in the operative group 1,280/mm3vs. 96/mm3;P=0.075). Also, significantly more frequent abscess formations and, consequently, operative treatments were performed in patients with a period of normal neutrophil counts during the infection compared with continuously neutropenic patients (9 operative, 4 nonoperativevs. 1 operative, 6 nonoperative;P=0.057). Ten cures, three complicationsvs. two cures, five complications (3 mortalities) were present in patients with and without normal neutrophil counts, respectively (P=0.062). When only severely neutropenic patients were considered, four patients in the surgery group had normal neutrophil counts before or shortly after surgery. However, only two of eight patients with perianal cellulitis had normal counts during full-course infection (P=0.06). CONCLUSIONS: The course of the neutrophil count during infection was an important factor affecting the perianal lesion, and indirectly, choice of treatment and prognosis. A period of normal counts during infection usually led to well bordered and fluctuant lesions, and the prognosis was acceptable with operative treatment. However, continuously neutropenic patients developed nonfluctuating indurations. We found disappointing results with nonoperative treatment of such patients. In all studies, regarding treatment of perianal infections in neutropenic patients, the course of the neutrophil count and indications for surgery should be clarified to get reliable results.

Soluble Thrombomodulin and Fibrinolysis in Behçet’s Disease

Behcet’s disease is a chronic relapsing systemic vasculitis in which recurrent urogenital ulceration is a prominent feature. The precise reason underlying the thrombotic tendency in Behcet’s disease i

FIBRINOLYTIC SYSTEM IN PLASMA AND PLEURAL FLUID IN MALIGNANT PLEURAL MESOTHELIOMA

The two major fibrinolytic activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) may play role in tumor spread and metastasis. Malign pleural mesothelioma (MPM) is a kind of tumor with predominantly local invasion and low incidence of distant metastasis. In this study, u-PA, t-PA and PA activator-1 (PAI-1) antigen and activity were measured in plasma and pleural fluid samples from patients with MPM, lung cancer and benign effusion. When compared to the control group, in MPM group, plasma u-PA and t-PA antigen levels were higher, but plasma u-PA and t-PA activity were comparable. PAI-1 antigen was also higher in MPM group. These findings were in contrast to the lung cancer group, in which both activity and immunologic measurement of u-PA and t-PA were higher, but PAI-1 antigen was similar as compared to the control group. It is concluded that excess t-PA and u-PA are balanced in complexes with PAI-1 in MPM, whereas the amount of PAI-1 in plasma is insufficient to overcome the elevated t-PA and u-PA, in lung cancer. Based on these findings, it may be suggested that the balanced fibrinolytic system is responsible for the low incidence of distant metastasis in MPM.