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The anticonvulsant carbamazepine is an effective treatment both for epilepsy and for bipolar affective disorder, but the molecular mechanism(s) underlying its therapeutic effects have not been identified. We have found that carbamazepine exerts significant inhibitory effects on the cyclic AMP (cAMP) generating system. Within the clinical therapeutic range (-~5Oj.tM), carbamazepine inhibited both basal and forskolin-stimulated cAMP production, without having any significant effects on phosphodiesterase activity. Carbamazepine also exerted its inhibitory effects on the cAMP generating system in pertussis toxin-treated cells, suggesting that the action of carbamazepine was likely mediated through an inhibitory guanine nucleotide binding protein-independent mechanism. A forskolin affinity purification column was used to purify adenylyl cyclases from rat cerebral cortex, and we found that. carbamazepine inhibited both basal and forskolin-stimulated activity of purified adenylyl cyclase. We also investigated the effects of carbamazepine on the levels of the transcription factor, cAMP response element binding protein in the phosphorylated (active) state, and found that carbamazepine significantly inhibited forskolin-induced phosphorylation of the cAMP response element binding protein. The data indicate that carbamazepine inhibits adenylyl cyclase activity as well as the downstream effects of activation of adenylyl cyclase. Key Words: Carbamazepine-Adenylyl cyclase-Seizure-Mania-Anticonvulsant--Cyclic AMP response element binding protein.

The in-plane resistivity and thermal conductivity of the heavy-fermion superconductor Ce 2 PdIn 8 single crystals were measured down to 50 mK. A field-induced quantum critical point, occurring at the upper critical field H c2 , is demonstrated from the ðTÞ $ T near H c2 and ðTÞ $ T 2 when further increasing the field. The large residual linear term 0 =T at zero field and the rapid increase of ðHÞ=T at low field give evidence for nodal superconductivity in Ce 2 PdIn 8 . The jump of ðHÞ=T near H c2 suggests a first-order-like phase transition at low temperature. These results mimic the features of the famous CeCoIn 5 superconductor, implying that Ce 2 PdIn 8 may be another interesting compound to investigate for the interplay between magnetism and superconductivity. The interplay between magnetism and superconductivity has been a central issue for heavy-fermion superconductors [1], high-T c cuprates [2], and iron pnictides [3]. Among them, one particularly interesting case is the heavy-fermion superconductor CeCoIn 5 , with T c ¼ 2:3 K at ambient pressure [4]. Its superconducting gap has d-wave symmetry [5,6]. While there is no static magnetism in CeCoIn 5 at zero field, a field-induced antiferromagnetic (AF) quantum critical point (QCP) has been clearly demonstrated by resistivity and specific heat measurements [7,8]. Initially, it was very puzzling why the AF QCP is located right at the upper critical field H c2 .Meanwhile, the observations of first-order phase transition at low temperature and H c2 and a second magnetization and specific heat anomaly well inside the superconducting state have been interpreted as the signature of a Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) superconducting state [5,[9][10][11][12]. The novel FFLO state with broken spatial symmetry was predicted in the 1960s [13,14], but it has never been experimentally verified before. The possible FFLO state at the low-temperaturehigh-field (LTHF) corner of the H À T phase diagram of CeCoIn 5 has stimulated extensive studies [15].More recently, NMR, neutron scattering, and muon spin rotation ( SR) experiments have provided clear evidence for a field-induced magnetism in this LTHF part of the phase diagram [16][17][18][19][20][21]. It was identified as a spin-density wave (SDW) order with an incommensurate modulation Q ¼ ð0:44; 0:44; 0:5Þ. Interestingly, this SDW order disappears in the normal state above H c2 , showing that magnetic order and superconductivity in CeCoIn 5 are directly coupled [16,17]. While this has nicely explained the field-induced AF QCP at H c2 [7,8], the physical origin of this LTHF superconducting Q phase is still under debate. For example, Yanase and Sigrist have suggested that the incommensurate SDW order is stabilized in the FFLO state by the appearance of the Andreev bound state localized around the zeros of the FFLO order parameter [22]. Aperis, Varelogiannis, and Littlewood have argued that the Q phase is a pattern of coexisting condensates: a d-wave singlet superconducting state, a staggered -triplet superconducting s...

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Asian Pac J Cancer Prev, 15 (21), 9185-9190 IntroductionColorectal cancer (CRC) is one of the most common malignant tumors of the gastrointestinal tract. With an estimated 140 thousand new cases and over 50 thousand deaths in 2013, colorectal cancer (CRC) is the fourth most common cancer that leads to mortality in the United States (Committee et al., 2013). In addition, the incidence and mortality of colorectal cancer has continued to rise rapidly in China over the past few decades. The incidence of CRC has increased by an annual average of 5.73% from 1992 to 2005 (13.06 to 23.54/100000) in the Nangang District of Harbin, China (Hu et al., 2013). Though the exact mechanism of CRC is still unknown, it has been well established that smoking, obesity, red meat consumption, excessive alcohol consumption, and chronic intestinal inflammation are risk factors for CRC; (Wang et al., 2010;Theodoratou et al., 2012;Burn et al., 2013). Of these risk factors, chronic intestinal inflammation has been considered one of the most significant causes of colon cancer (Wang and Dubois, 2010).Many studies have confirmed the relationship of cyclooxygenase-2 (Cox-2) and the CRC development and progression leading to chronic inflammation (Williams et al., 1999). Cox-2 is an early inflammation response gene, previously shown to be up-regulated in 40-50% of colorectal adenomas and 85% of CRC, leading to AbstractCyclo-oxygenase-2(Cox-2), a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth. Therefore, a better understanding of the regulatory mechanisms of Cox-2 could lead to novel targeted cancer therapies. MicroRNAs are strongly implicated in colorectal cancer but their specific roles and functions have yet to be fully elucidated. MiR-1297 plays an important role in lung adenocarcinoma and laryngeal squamous cell carcinoma, but its significance in colorectal cancer (CRC) has yet to be reported. In our present study, we found miR-1297 to be down regulated in both CRC-derived cell lines and clinical CRC samples, when compared with normal tissues. Furthermore, miR-1297 could inhibit human colorectal cancer LOVO and HCT116 cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo by targeting Cox-2. Moreover, miR-1297 directly binds to the 3`-UTR of Cox-2, and the expression level was drastically decreased in LOVO and HCT116 cells following overexpression of miR-1297. Additionally, Cox-2 expression levels are inversely correlated with miR-1297 expression in human colorectal cancer xenograft tissues. These results imply that miR-1297 has the potential to provide a new approach to colorectal cancer therapy by directly inhibiting Cox-2 expression.