BACKGROUND AND PURPOSE: In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization can improve patient outcome. Heart failure may result in reduction of brain perfusion, which limits the ability of the blood stream to wash out emboli. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. Most stroke patients with atrial fibrillation (AF) have elevated BNP levels. We investigated the relationships of plasma BNP levels before t-PA infusion and AF with early recanalization after t-PA infusion. METHODS: Patients with a major brain artery occlusion were studied prospectively. MRAs were performed before and within 60min after t-PA infusion. The relationship between BNP levels before t-PA infusion and the presence of AF with early recanalization was examined. RESULTS: Seventy-nine patients (49 men; mean age, 75.5+/-10.4years; ICA occlusion in 25 patients, M1 in 32, M2 in 13, PCA in 3, and BA in 6) were enrolled. Follow-up MRA within 60min after t-PA infusion revealed recanalization in 35 (44.3%) patients and no recanalization in 44 (55.7%). Patients with AF (57.1% vs. 75.0%, P=0.0294) and BNP>150pg/dl (39.0% vs. 73.7%, P=0.0019) less frequently had early recanalization than those without AF and with BNP</=150pg/dl. The combination of AF and BNP>150pg/ml was a useful predictor for no early recanalization (positive predictive value, 79.4%; negative predictive value, 62.2%; sensitivity, 61.4%; specificity, 80.0%). CONCLUSION: The presence of AF and elevated BNP was associated with no early recanalization after IV-t-PA therapy. We should need further study to ascertain its predictive ability.

The effect of a single injection of 17beta-estradiol (E2) was evaluated in the hermaphrodite fish Kryptolebias marmoratus. The fish [average body weight (BW), 0.15+/-0.01g] were injected with either two concentrations of E2 (1 and 100mug/g BW) once intraperitoneally. They were sampled at intervals of 7, 15, and 30 days after a single E2 injection. Gonadosomatic index (GSI), hepatosomatic index (HSI), the frequency of gonadal development, number of ovulated eggs, and plasma steroids levels were measured. The transcript abundances of vitellogenin (VTG) and estrogen receptors (ERalpha and beta) mRNA in the liver were also analyzed using quantitative real time polymerase chain reaction (real time PCR). GSI and the frequency of mature oocytes in the 100-mug E2-exposed group decreased compared to that of the control group during the experiment, and the number of ovulated eggs in the 100-mug E2-exposed group was lower when compared to the other groups. However, plasma E2 and 11-ketotestosterone (11-KT) levels were not significantly different between the experimental groups. On the other hand, plasma testosterone level and VTG mRNA abundance in the 100-mug E2-exposed group were significantly lower than the control group after 30 days. These results indicate that E2 stimulation at high concentration interferes with reproductive phenomena through delayed response. In addition, HSI in the 100-mug E2-exposed group and ERalpha mRNA abundance in the 1-mug E2-exposed group were significantly higher than the control group at 7 days after E2 injection, although there was no significant difference in HSI and ERalpha mRNA between all groups at 30 days. These results indicate temporal responses in reproductive parameters following high-dose E2 exposure in the hermaphrodite fish K. marmoratus.

PURPOSE: The effects of self-monitoring number of steps/day versus minutes of moderate to vigorous-intensity physical activity (MVPA/day) were compared to determine which is more effective for increasing physical activity levels. METHODS: A total of 18 participants of a university-based chronic disease prevention program (age 61 +/- 12 years) were enrolled in the 3-week intervention. Subjects were randomly assigned to a group (n = 8) that wore a New Lifestyles accelerometer (NL-1000) and were instructed to increase minutes of MVPA to 30 min/d or more (MIN) or to a group (n = 10) that wore a New Lifestyles pedometer (NL-800) and were instructed to increase the number of steps/day to 10,000 or more (STE). To objectively assess changes in physical activity levels, subjects in both groups simultaneously wore a Lifecorder-EX accelerometer (with display blank) during the intervention. RESULTS: The number of steps increased significantly in the MIN (10,810 +/- 3,211 to 13,355 +/- 3,498 steps/day) and STE (11,517 +/- 3,383 to 12,809 +/- 2,479 steps/day) from the first to fourth weeks, respectively. However, the time spent in MVPA increased significantly only in MIN group (36 +/- 11 to 52 +/- 15 min/d) but not in the STE group (32 +/- 7 to 37 +/- 11 min/d) from the first to fourth weeks, respectively. CONCLUSION: Data suggest that individuals with chronic disease conditions can more effectively increase levels of physical activity, expressed as both MVPA/day and steps/day, by self-monitoring MIN rather than STE. The effect of self-monitoring physical activity levels for longer periods and/or the effect of increasing minutes of MVPA/day versus steps/day on specific health outcomes have not yet been examined.

ABSTRACT: BACKGROUND: We previously reported that intrathecal injection of lysophosphatidylcholine (LPC) induced neuropathic pain through activation of the lysophosphatidic acid (LPA)-1 receptor, possibly via conversion to LPA by autotaxin (ATX). RESULTS: We examined in vivo LPA-induced LPA production using a biological titration assay with B103 cells expressing LPA1 receptors. Intrathecal administration of LPC caused time-related production of LPA in the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, spinal nerve or sciatic nerve. LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA3, but not LPA1 or LPA2 receptors. Similar time-related and LPA3 receptor-mediated production of LPA was observed following intrathecal administration of LPA. In an in vitro study using spinal cord slices, LPA-induced LPA production was also mediated by ATX and the LPA3 receptor. Intrathecal administration of LPA, in contrast, induced neuropathic pain, which was abolished in mice deficient in LPA1 or LPA3 receptors. CONCLUSIONS: These findings suggest that feed-forward LPA production is involved in LPA-induced neuropathic pain.

We monitored the contamination by environmental estrogens (EEs) of coastal areas in Korea and Japan using the wild grey mullet. The grey mullet were collected from Ansan, Jeju, Yeosu, Tongyeong, and Busan in Korea and Nagasaki, Omuta, and Fukuoka in Japan. Contamination by EEs was determined by measuring vitellogenin (VTG) levels in serum and identifying gonadal abnormalities histologically (i.e., testis-ova). In four sites in Korea (Ansan, Yeosu, Tongyeong, and Busan) and two sites in Japan (Nagasaki and Fukuoka), serum VTG in immature and male grey mullet was detected at levels greater than 1.0mug/ml, which is considered to be an abnormal level. Although, testis-ova were observed in some individuals collected in Ansan, Tongyeong, and Busan in Korea and Omuta in Japan, there was no correlation between individuals with testis-ova and individuals with abnormal levels of VTG. Furthermore, in Japan, serum VTG levels of fish collected from Nagasaki and Fukuoka were also greater than 1.0mug/ml. Although individuals with testis-ova were found in Omuta, these fish expressed normal levels of serum VTG. Our results suggest that the grey mullets living in these coastal areas are influenced by EEs in the environment. Furthermore, it appears that the production of VTG and the occurrence of testis-ova are caused by different mechanisms.

OBJECTIVES: Our aim was to determine whether a 600-mg loading dose of clopidogrel compared with 300 mg results in improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: A 600-mg loading dose of clopidogrel compared with 300 mg provides more rapid and potent inhibition of platelet activation. METHODS: In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI undergoing primary PCI were randomized to bivalirudin (n = 1,800) or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (n = 1,802). Randomization was stratified by thienopyridine loading dose, which was determined before random assignment. RESULTS: Patients in the 600-mg (n = 2,158) compared with the 300-mg (n = 1,153) clopidogrel loading dose group had significantly lower 30-day unadjusted rates of mortality (1.9% vs. 3.1%, p = 0.03), reinfarction (1.3% vs. 2.3%, p = 0.02), and definite or probable stent thrombosis (1.7% vs. 2.8%, p = 0.04), without higher bleeding rates. Compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin monotherapy resulted in similar reductions in net adverse cardiac event rates within the 300-mg (15.2% vs. 12.3%) and 600-mg (10.4% vs. 7.3%) clopidogrel loading dose subgroups (p(interaction)= 0.41). By multivariable analysis, a 600-mg clopidogrel loading dose was an independent predictor of lower rates of 30-day major adverse cardiac events (hazard ratio: 0.72 [95% confidence interval: 0.53 to 0.98], p = 0.04). CONCLUSIONS: In patients with STEMI undergoing primary PCI with contemporary anticoagulation regimens, a 600-mg loading dose of clopidogrel may safely reduce 30-day ischemic adverse event rates compared with a 300-mg loading dose.(Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

The nicotine metabolism of CYP2A6 (CYP2A6*1A,*1B, and *1C), and the cholecystokinin (CCK; which modulates the release of dopamine) and CCK-A receptor gene and personality traits for NEO-FFI, was investigated for the mechanism for elucidation of the smoking behavior in Japanese populations. The frequency of the CYP2A6*4C allele, which is a whole deleted allele of the human CYP2A6 gene, was higher, whereas that of CYP2A6*1A/*1B heterozygotes with higher nicotine metabolism activity was lower in nonsmokers than in smokers. There was also a significant difference between the current smoking and nonsmoking groups in the allele frequency of the CCK -45C/T polymorphism. It was also shown that the Openness (O) factor for smokers was significantly higher than that of nonsmokers; however, there were no significant differences in the Neuroticism (N), Extraversion (E), Agreeable (A), and Conscientiousness (C) scores among smokers than nonsmokers. It was suggested that the CYP2A6*4C allele may prevent the carrier from smoking, and being a CYP2A6*1A/*1B heterozygote and the CCK T allele may be risk factors for developing smoking behavior. Also, it is possible that persons with a low score in Openness may be refraining from smoking because they have a general negative impression toward smoking.

Plasticity related gene-1 (PRG-1) is a brain-specific membrane protein related to lipid phosphate phosphatases, which acts in the hippocampus specifically at the excitatory synapse terminating on glutamatergic neurons. Deletion of prg-1 in mice leads to epileptic seizures and augmentation of EPSCs, but not IPSCs. In utero electroporation of PRG-1 into deficient animals revealed that PRG-1 modulates excitation at the synaptic junction. Mutation of the extracellular domain of PRG-1 crucial for its interaction with lysophosphatidic acid (LPA) abolished the ability to prevent hyperexcitability. As LPA application in vitro induced hyperexcitability in wild-type but not in LPA(2) receptor-deficient animals, and uptake of phospholipids is reduced in PRG-1-deficient neurons, we assessed PRG-1/LPA(2) receptor-deficient animals, and found that the pathophysiology observed in the PRG-1-deficient mice was fully reverted. Thus, we propose PRG-1 as an important player in the modulatory control of hippocampal excitability dependent on presynaptic LPA(2) receptor signaling.

We investigated the relationship between the genetic polymorphism (s/l) of 5-HT2A receptors (A-1438G) and 5-HTT (s/l), and the drug effects among 31 patients who are administering olanzapine, as a help of the tailor made medical care in a time. As for the genetic polymorphism of 5-HT2AR, G/G group showed a significantly improvement tendency in the PANSS positive syndrome score in comparison with the group which did not have a G gene (AA and AG). It may be possible that this finding help to predict the drugs effect of olanzapine on the patients with excite state, who are used many antipsychotics together out of necessity.

There are gene polymorphisms changing the expression or activation of the serotonin (5-HT) receptors, which are associated with pain. This review showed an availability of 5-HT2A receptor gene polymorphism in analgesic sensitivity. To search gene polymorphisms related to analgesic sensitivity is important to further effective pain management. In future 5-HT2A receptor gene polymorphisms, together with polymorphisms of other genes, may greatly contribute to effective postoperative pain management and personalized medicine.