İbrahim Halil Türkbeyler

Serum leptin, resistin and TNF-α levels in patients with systemic sclerosis: the role of adipokines in scleroderma

Systemic sclerosis (SSc) is a chronic fibrotic collagen tissue disease. Leptins role in regulating immune and inflammatory response has become increasingly evident. Resistin has pro‐inflammatory properties and also is associated with inflammatory markers in some rheumatologic diseases. The purpose of this study was to determine serum leptin, resistin and tumor necrosis factor alpha (TNF‐α) in SSc patients and evaluate their association with other frequently used laboratory and clinic findings.

Drug- and herb-induced liver injury: a case series from a single center.

BACKGROUND/AIMS Drug-induced liver injury (DILI) is common worldwide and has a potentially fatal outcome. It accounts for more than half of the cases of acute liver failure in the United States. Herb-induced liver injury (HILI) is a less documented condition but a growing problem. We present here the clinical characteristics and outcome of patients with drug- and herb-induced liver injury from our center. MATERIALS AND METHODS In this 4-year retrospective study, 82 patients in whom there was a causal or highly probable relationship between herbal medicine or drug use and liver disease are presented. RESULTS The mean age of patients was 43.1±14.8 years; sexual distribution was 53 females and 29 males. The major cause of hepatotoxicity was drugs (87.8%), with herbal medicine accounting for 12.2%. The leading causative agents were nonsteroidal anti-inflammatory drugs (NSAIDs) (23.1%), followed by antibiotics (19.5%). The pattern of hepatotoxicity was hepatocellular in 35 patients (42.6%), mixed in 28 (34.1%), and cholestatic in 19 patients (23.1%). Teucrium polium (known popularly as felty germander), which is a traditionally used herbal medicine of the Labiatae family in our region, was the most common cause of herb-induced liver injury and responsible in 7 of 10 herbal hepatotoxic cases. Acute liver failure developed in 3 patients (two patients related with flurbiprofen and diclofenac and one patient due to an isoniazid-rifampicin combination). CONCLUSION Antibiotics and NSAIDs were the most common etiologic agents for drug-induced liver injury. Surprisingly, herbs follow these groups of drugs and must be questioned more carefully.

Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50–125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.

The Efficiency of a Urotensin II Antagonist in an Experimental Lung Fibrosis Model

Pulmonary fibrosis is a chronic disease. Urotensin II (U-II) is a new peptide with angiogenic and profibrotic features. Therefore, we aim to evaluate the antagonism of U-II with palosuran in an animal model and plan to measure U-II, endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1) and their association with lung fibrosis. Thirty Wistar male rats were used in the study and were divided into three groups: group 1, control; group 2, bleomycin-induced lung fibrosis group; and group 3, bleomycin-induced lung fibrosis with treatment palosuran group. U-II level (nanograms per milliliter) was 2.957 ± 0.159 in group1, 3.188 ± 0.122 in group 2, and 2.970 ± 0.165 in group 3 (p = 0.002). The ET-1 level (picograms per milliliter) was 4.486 ± 0.376 in group 1, 9.086 ± 1.850 in group 2, and 4.486 ± 0.376 in group 3 (p < 0.001). The TGF-β1 (nanograms per milliliter) level was 73.143 ± 9.96 in group 1, 84.81 ± 4.73 in group 2, and 77.86 ± 5.77 in group 3 (p = 0.006). Finally, the fibrosis score was 0.7 ± 0.48 in group 1, 4.4 ± 1.34 in group 2, and 3.2 ± 0.63 in group 3 (p < 0.001). There is a statistically significant positive relationship between fibrosis scores and the UT-II, ET-1, and TGF-β1 levels of the experimental lung fibrosis model. We believe U-II is an important mediator in lung fibrosis models, and its antagonism with palosuran could be a new treatment choice for interstitial lung fibrosis, but further studies need to be conducted to verify the findings of the current study.

An evaluation of oxidative stress and antioxidant capacity in patients with myofascial pain syndrome.

Abstract Objective. To evaluate total antioxidant capacity (TAC) and total oxidative stress (TOS) values in patients with myofascial pain syndrome (MPS). Method. The study comprised 38 patients diagnosed with MPS and 30 healthy volunteers. The age, body mass index (BMI) and pain scores (evaluation by visual analogue scales) of all the participants were recorded. The TAC, TOS and oxidative stress index (OSI) levels were compared between the MPS and control groups. Results. There was no significant difference between the MPS and control groups in respect of demographic characteristics. The TAC levels were determined to be significantly lower and TOS levels and OSI values, significantly higher in the MPS patients than in the control group. Conclusion. The results of this study determined that the oxidant/antioxidant balance was impaired in MPS patients and thus MPS can be considered to be related to an increase in oxidative stress.

Possible anti-metastatic effect of Iloprost in a patient with systemic sclerosis with lung cancer: a case study

Systemic Sclerosis (SSc) is a chronic disease of unknown etiology which affects the vascular system and connective tissue. A wide series of studies showed an increased prevalence of cancer in patients with SSc than the normal population. Prostacyclin (PGI2) is an endogenously produced element that is basically synthesized by arachiodonic acid through prostacyclin synthesis in vascular system endothelial cells. Iloprost is a stable analogue of PGI2 which is used in the treatment of pulmonary arterial hypertension (PAH). In a limited number of animal models, the anti-metastatic activity of PGI2 is observed. Herein, we report iloprost treatment of a 60-year-old-woman with SSc, who lately developed PAH as a complication of her disease and lung adenocarcinoma as a co-incidence simultaneously. These two mortal complications were both treated successfully with inhaled iloprost until her death due to gastrointestinal complications of SSc.

Safety of Tamoxifen During Pregnancy: 3 Case Reports and Review of the Literature

Dear Editors, Tamoxifen is one of the treatment options for estrogen receptor (ER)-positive breast cancers, and it is considered to be a teratogenic agent. Animal models have shown that tamoxifen can cause genitourinary developmental defects [1]. Although there is 1 case report showing that tamoxifen can cause genital defects in humans [2], other case studies report delivery of healthy babies by women using tamoxifen [3, 4]. Here we report on 3 breast cancer patients who became pregnant while undergoing tamoxifen therapy. The first case, a 32-year-old woman, presented with a left breast lump in 2007; incisional biopsy revealed infiltrative ductal carcinoma. The disease was staged as cT4cN2M1. The patient had bone metastasis at the time of diagnosis. Immunohistochemical analysis showed this tumor to be ER-positive (100%(+)), progesterone receptor (PR) 100% (+), and HER2-negative. The patient received adjuvant tamoxifen following adjuvant chemotherapy including paclitaxel, carboplatin and doxorubicin and radiotherapy. The patient became pregnant in 2009 while on a 6-month tamoxifen therapy. She discontinued tamoxifen when she discovered she was pregnant, so tamoxifen therapy lasted only 1.5 months. The patient delivered a healthy baby in 2010. After birth, positron emission tomography-computed tomography revealed regression of bone metastases. The second case, a 23-year-old woman, underwent right modified radical mastectomy for infiltrating ductal carcinoma in 2009. The disease was staged as T2N0M0. Immunohistochemical analysis showed this tumor to be ER 5% (+), PR 50% (+), and HER2-positive (3+). The patient received adjuvant chemotherapy including paclitaxel, carboplatin, doxorubicin and trastuzumab. Adjuvant tamoxifen and leuprolide were also recommended. No radiotherapy was administered. The patient received tamoxifen for 26 months and discontinued treatment of her own accord. 1 month after that she became pregnant and took no further therapy. She delivered a healthy baby in October 2012, and is herself in good health at present. The third case, a 35-year-old woman, underwent breast-conserving surgery and sentinel lymph node dissection for infiltrating ductal carcinoma in 2011. The disease was staged as T1N0M0. Immunohistochemical analysis showed this tumor to be ER 90% (+), PR 10% (+), and HER2-positive (2+), confirmed by fluorescent in situ hybridization. She did not receive any adjuvant chemotherapy except tamoxifen following radiotherapy. The patient became pregnant while taking tamoxifen for 6 months in 2011. She discontinued tamoxifen when 4 weeks pregnant and had a voluntary medical abortion at 6 weeks gestation. She subsequently continued tamoxifen treatment. Tamoxifen is a non-steroidal anti-estrogen agent used in the treatment of ER-positive breast cancers. It is contraindicated during pregnancy due to teratogenic effects, and recommended non-hormonal contraceptive methods may cause patients to get pregnant while on tamoxifen therapy. Von Schoultz et al. [5] have suggested that women taking tamoxifen who wish to become pregnant should stop tamoxifen at least 2 months prior to conception because of the drugs long half-life. Although there is insufficient knowledge regarding the use of tamoxifen and pregnancy outcomes in humans, there are some case reports indicating healthy deliveries [3, 4]. In contrast, there is 1 case report of a baby with ambiguous genitalia suggestive of a tamoxifen effect on the fetus [2]. Another case report showed a baby with congenital cranio-facial defects, who was exposed to cocaine, marijuana, and a bone scan along with tamoxifen during fetal development. The effects of tamoxifen during pregnancy were described in the study by Braems et al. [6], based on records provided by AstraZeneca. The AstraZeneca Safety Database registered 11 babies with congenital malformations out of 44 live births, which is 1 infant with malformations for every 4 live births. In fact, the actual number of malformations was even higher, because there were 6 terminations and 2 stillbirths with fetal defects, compared with 17 terminations and 1 stillbirth without fetal defects, which is a total rate of nearly 1 in 3 births [6]. We herein report 3 breast cancer cases in which the patients became pregnant while taking tamoxifen therapy. In the first case, the patient had a healthy baby who is now 2 years old and has no abnormalities. The second patient had an uncomplicated pregnancy and a normal healthy baby. The patient in the last case had an elective abortion after a discussion with her physician regarding the possible side effects of the chemotherapy. To conclude, due to the lack of long-term data on outcome and studies showing teratogenicity, use of tamoxifen during pregnancy is contraindicated despite reports of healthy babies after tamoxifen exposure. Premenopausal breast cancer patients who are taking tamoxifen should practice meticulous use of contraception, and they must be informed about the possible teratogenic effects of tamoxifen as well as the lack of long-term data on this subject.

Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review

Rheumatoid arthritis (RA) is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV) is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patients colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reaction-positive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patients complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis.

Effectiveness of Palosuran in Bleomycin-Induced Experimental Scleroderma

Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups—group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-β1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-β1 levels (p < 0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-β1 levels (p > 0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.

Ascites as an initial presentation of spontaneously ruptured hydatid cyst

We describe the diagnosis of a 77-year-old woman admitted to our outpatient department with a 3-month history of abdominal bloating and distension. Abdominal computed tomography revealed a large cystic lesion in the posterior segment of the right hepatic lobe, with a separated germinal layer and widespread ascites with dense internal echoes and septal appearance. The result of a serum Echinococcus indirect haemagglutination test was positive and findings were indicative of the spontaneous rupture of a hydatid cyst into the peritoneal cavity without trauma. Ascites is rarely seen in the course of hydatid disease, but can result from cyst rupture into the peritoneal cavity. This should be considered in the differential diagnosis of ascites, especially in areas such as Turkey, where hydatid disease in endemic.