The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.     

Association of interleukin (IL)-4 gene intron 3 VNTR polymorphism with multiple sclerosis in Turkish population

Objective

Genetic risk factors are known to contribute to the etiology of multiple sclerosis (MS). Interleukin (IL)-4 gene polymorphisms have been associated with immune-mediated diseases. The aim of this study was to explore the frequency of IL-4 gene intron 3 VNTR (variable number tandem repeat) polymorphism in a cohort of Turkish patients with MS.

Methods

The study included 125 patients with MS and 160 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the IL-4 gene intron 3 VNTR polymorphism.

Results

The distribution of genotype and allele frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between MS patients and control group (p = 0.003 and p = 0.002, respectively). There were no statistically significant association between IL-4 VNTR polymorphism and clinical and demographical characteristics of MS patients.

Conclusion

The results of this study suggest that intron 3 VNTR polymorphism of the IL-4 gene was positively associated with predisposition to develop MS in Turkish population.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

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.     

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.