br Materials and methods br Results The clinical

Materials and methods
Results The clinical characteristics of the two selected groups are shown in Table 1. As shown in Table 1, the enzyme activity of ATX in CSF of MS patients (59.90±3.09nmol/min/ml±SEM) was significantly higher (p<0.0001) than those patients afflicted with other neurological disorders (24.85±2.19nmol/min/ml±SEM). In Fig. 1A, the association of ATX activity with MS has schematically been shown. In serum samples obtained from both groups, it was shown that the activity of ATX in MS patients (12.11±1.42nmol/min/ml±SEM) was statistically higher than controls (7.05±1.51nmol/min/ml±SEM) (p<0.0001). This association has been shown in Fig. 1B. Although we did find a strong association between ATX activity and MS, we could not find any association between the disease and EDSS of patients with MS (p=0.9).
Discussion Numerous studies have so far shown that ATX takes part in inflammation and inhibition of this enzyme may open a new horizon to therapeutic approaches used for the treatment of autoimmune diseases. This idea is brought up by the inhibitory role of FTY-720, a bona fide drug for the treatment of MS (Mehling et al., 2008), on LPA formation. It has been shown that FTY-720 can not only act as an agonist at S1P receptors but also hinder ATX activity when it becomes phosphorylated by sphingosine kinase 2 (Pitman et al., 2012). Seemingly, FTY-720 is able to “kill two Nucleozin with one stone”. Although Hammack et al. (2004) found that ATX is expressed in CSF of MS patients and not in patients with OND, they did not measure the activity of ATX in MS patients. Our results show that ATX is also expressed in patients with OND (ATX shows activity), however; the ATX activity in CSF of MS patients was much higher in comparison to the control group. This discrepancy may be due to small sample size of their study (only 3 patients were included as a control group). Another study carried out by Fuss et al. (1997) revealed decreased expression levels of PD-Ia/ATX in the brain and spinal cord of EAE mice, the animal model of multiple sclerosis, at onset of clinical symptoms, i.e., prior to signs of demyelination. Thus it would be conceivable that ATX expression is solely elevated in disease flare-up and may not be seen in the remission phase of MS disease. Another study performed by Nakasaki et al. (2008) showed that ATX activity is involved in lymphocyte–endothelial interactions suggesting that it might be responsible for the recruitment of autoreactive immune cells into the blood–brain barrier. One of the possibilities of high ATX activity in the CSF of MS patients may be due to the reactivation of Epstein–Barr virus (EBV) in MS relapse. The results from a myriad of studies have shown that EBV reactivation in MS is strongly associated with clinical disease activity in MS patients (Wandinger et al., 2000). This hypothesis is strengthened by a study performed by Baumforth et al. (2005) showing that EBV is able to induce the autotaxin enzyme in order to promote the growth and survival of Hodgkin lymphoma cells. Although ATX activity was strongly correlated with MS disease, we could not find any association with the EDSS. This might be due to a small sample size and the disease complexity. Small sample size and lack of patients with other inflammatory CNS diseases were the limitations of our study.
Acknowledgments The financial support of this study has been provided by the Tehran University of Medical Sciences (91-02-54-18065). We would like to thank all the patients for helping us out in doing this research.
Introduction Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, is a pregnancy-specific liver disorder with onset mainly in the third trimester of pregnancy. ICP is characterized by pruritus, elevated serum fasting bile salts and transaminases and an increased risk of adverse fetal outcomes [1], [2], [3]. This disorder typically affects 0.2–2% of all pregnant women. The incidence of ICP, however, varies considerably with ethnicity and geographical location, with the highest rates observed in Northern Europe and Southern America [2], [4]. Pruritus is the defining symptom of ICP, which progressively worsens as pregnancy advances. Pruritus may considerably reduce quality of life, lead to sleep deprivation, depressed mood, and even suicidal ideation in more severe cases. In contrast to other more commonly observed pruritic dermatoses of pregnancy [5], a concern in ICP is the increased risk of adverse fetal outcomes [1], [2]. ICP increases the risk of fetal distress, cardiotocography abnormalities, preterm labour and sudden intrauterine death, particularly in those women with total serum fasting bile salt (TBS) levels exceeding 40μmol/L [3], [4], [6], [7]. Therefore, a proper diagnosis is essential to enable pharmacological treatment with ursodeoxycholic acid (UDCA), close antenatal monitoring and potentially the induction of labour after 37weeks, with the aim of reducing fetal distress and intrauterine death [8], [9].