Extracellular magnesium ion modifies the actions of volatile anesthetics in area CA1 of rat hippocampus in vitro

BACKGROUND: Magnesium ion (Mg2+) is involved in important processes as modulation of ion channels, receptors, neurotransmitter release, and cell excitability in the central nervous system. Although extracellular Mg2+ concentration ([Mg2+]o) can be altered during general anesthesia, there has been no evidence for [Mg2+]o-dependent modification of anesthetic actions on neural excitability in central nervous system preparations. The purpose of current study was to determine whether the effects of volatile anesthetics are [Mg2+]o-dependent in mammalian central nervous system. METHODS: Extracellular electrophysiologic recordings from CA1 neurons in rat hippocampal slices were used to investigate the effects of [Mg2+]o and anesthetics on population spike amplitude and excitatory postsynaptic potential slope. RESULTS: The depression of population spike amplitudes and excitatory postsynaptic potential slopes by volatile anesthetics were significantly dependent on [Mg2+]o. The effects were attenuated in the presence of a constant [Mg2+]o/extracellular Ca2+ concentration ratio. However, neither N-methyl-d-aspartate receptor antagonists nor a non-N-methyl-d-aspartate receptor antagonist altered the [Mg2+]o-dependent anesthetic-induced depression of population spikes. Volatile anesthetics produced minimal effects on input-output (excitatory postsynaptic potential-population spike) relations or the threshold for population spike generation. The effects were not modified by changes in [Mg2+]o. In addition, the population spike amplitudes, elicited via antidromic (nonsynaptic) stimulation, were not influenced by [Mg2+]o in the presence of volatile anesthetics. CONCLUSIONS: These results provide support that alteration of [Mg2+]o modifies the actions of volatile anesthetics on synaptic transmission and that the effects could be, at least in part, a result of presynaptic Ca2+ channel-related mechanisms.     

Continuous epidural analgesia with intensive monitoring of cardiovascular system for vaginal delivery in a patient with Marfan's syndrome

We report here the management of labor for a 33-year-old woman with Marfan's syndrome. She was diagnosed as Marfan's syndrome at the age of 5 and experienced corrective surgery for abdominal aortic aneurysm at 28 years of age. As there was no progression of cardiovascular lesion, she was allowed to be pregnant. She was planned to proceed with vaginal delivery, since she was in trouble of circulation during her gestational period. In order to prevent catastrophe such as aortic dissection or aortic regurgitation elicited by hypertension related with labor pain, we performed continuous epidural anesthesia to control labor pain under the invasive blood pressure monitoring. Two epidural catheters were inserted into the epidural space via the L 2-3 and the L 5-S 1 intervertebral space, and mixed solutions containing both 0.125% bupivacaine and 0.0002% fentanyl were administered continuously. After 7 hours and 47 minutes from the start of her labor, she delivered her baby vaginally with the aid of forceps technique due to attenuated abdominal muscle activity. No cardiovascular mishaps occurred during her labor and she was discharged 6 days after the delivery. Thus, continuous epidural anesthesia with intensive monitoring of circulation may be useful for vaginal delivery in a patient with Marfan's syndrome by avoiding cardiovascular complications due to labor pain.     

CD3-zetachain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients

BACKGROUND: Impaired or reduced CD3 zeta chain (CD3-zeta) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The clinical significance of CD3-zeta chain expression in tumor-infiltrating lymphocytes (TILs) in gastric carcinoma remains unclear. METHODS: The authors immunohistochemically investigated CD3-zeta expression in TILs in 185 patients who had undergone curative gastrectomy. CD3-zeta/CD3 epsilon (CD3-epsilon) ratios were calculated. Patients were divided into two groups: a normal CD3-zeta group (n = 121) and a reduced CD3-zeta group (n = 64). Patients with a zeta per epsilon ratio of greater than 66% were placed in the normal CD3-zeta group. RESULTS: Patients in the normal CD3-zeta group had fewer lymph node metastasis (P < 0.01) and a shallower depth of invasion (P < 0.05) than those in the reduced CD3-zeta group. The 5-year survival rate was 72% in the normal CD3-zeta group, which was significantly better than that in the reduced CD3-zeta group (55%; P < 0.01). When stratified according to clinical stage, the prognostic value was significantly different only in Stage IV patients. Multivariate analysis showed that CD3-zeta expression was an independent prognostic factor (P = 0.03) next to depth of invasion and lymph node involvement. CONCLUSIONS: Reduced CD3-zeta expression in TILs was strongly correlated with progressive disease in gastric carcinomas. CD3-zeta expression in TILs is considered an immunologic, independent prognostic marker in gastric carcinoma patients. CD3-zeta normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients.     

Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo

Cyclooxygenase-2 (COX-2) is expressed within neovascular structures that support many human cancers. Inhibition of COX-2 by celecoxib delays tumor growth and metastasis in xenograft tumor models as well as suppresses basic fibroblast growth factor 2 (FGF-2)-induced neovascularization of the rodent cornea. The present studies were undertaken to evaluate possible mechanisms of the antiangiogenic and anticancer effects of celecoxib. Prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TXB(2)) were increased in rat corneas implanted with slow-release pellets containing FGF-2 (338.6 ng of PGE(2)/g and 17.53 ng of TXB(2)/g) compared with normal rat corneas (63.1 ng of PGE(2)/g and 2.0 ng of TXB(2)/g). Celecoxib at 30 mg/kg/day p.o. inhibited angiogenesis (78.6%) and prostaglandin production by 78% for PGE(2) (72.65 ng/g) and 68% for TXB(2) (5.55 ng/g). Decreased prostaglandin production in corneas was associated with a 2.5-fold cellular increase in apoptosis and a 65% decrease in proliferation. Similar reductions in proliferation were observed in neovascular stroma (65-70%) of celecoxib-treated (dietary 160 ppm/day) xenograft tumors as well as in tumor cells (50-75%). Apoptosis was also increased in the tumor cells (2.2-3.0-fold) in response to celecoxib. Thus, the antitumor activity of celecoxib may be attributable, at least in part, to a direct effect on host stromal elements, such as the angiogenic vasculature.     

Selective suppression of hippocampal region hyperexcitability related to seizure susceptibility in epileptic El mice by the GABA-transporter inhibitor tiagabine

High seizure susceptibility in El mice is associated with disinhibition in the dentate gyrus (DG) and paired-pulse facilitation in the CA3 area in hippocampal slices [Brain Res. 745 (1997) 165; Brain Res. 779 (1998) 324]. A decrease in gamma-aminobutyric acid (GABA)-mediated inhibition and an increase in excitatory inputs to the major neurons seem to be the responsible mechanisms, respectively, for these phenomena. In this study, we examined the effects of tiagabine, an inhibitor of GABA transporter, on hyperexcitation in vivo and in slice preparations. Tiagabine (0.3-0.5 mg/kg) suppressed the occurrence of seizures to about 20% of controls with an ED(50) value of about 0.17 mg/kg. In addition, perfusion of hippocampal slices with tiagabine (20 microM) counteracted the paired-pulse facilitation in the CA3 region over the entire range of interpulse intervals (P<0.05, two-way ANOVA) and reduced the disinhibition in the DG measured at 10 and 20 ms during short interpulse intervals (P<0.005, paired t-test). The CA1 region in the El mice, as well as in a non-epileptic parental strain of ddY mice did not respond to the drug. However, frequency potentiation of CA3 was enhanced in both strains (P<0.05, paired t-test). Our results suggest that within the hippocampus the antiepileptic action of tiagabine is selectively suppressive for hyperexcitability of DG and CA3, which are responsible for seizure-susceptibility in El mice.     

Feasibility of early ambulation three hours after transfemoral angiography using a 4 French sheath

PURPOSE: Our objective was to evaluate the feasibility of early resumption of ambulation 3 hours after transfemoral angiography using a 4 French sheath. SUBJECTS AND METHODS: This prospective study was carried out in a selected group of men and women without impaired blood clotting (prothrombin time > 15 sec) or thrombocytopenia (platelet < 55,000/mm3). The subjects consisted of 66 men and 34 women with a mean age of 62.3 years (range 27-90 years). Incidences of rebleeding or hematoma at the site of femoral catheter insertion were investigated before and after ambulation. Rebleeding was defined as bleeding that required recompression. Hematoma was defined as a palpable, firm collection of subcutaneous blood. RESULTS: Of 100 patients who resumed full ambulation after three hours of bed rest, none (0%) had acute groin hematoma and only three (3%) showed rebleeding that had to be manually compressed. The remaining 97 patients (97%) had no problem after ambulation. CONCLUSION: Supervised resumption of ambulation 3 hours after angiography with a 4 French sheath is safe and feasible in most ambulatory patients undergoing transfemoral angiography.     

Comparison of multishot echo-planar fluid-attenuated inversion-recovery imaging with fast spin-echo fluid-attenuated inversion-recovery and T2-weighted imaging in depiction of white matter lesions

PURPOSE: To compare a multishot echo-planar fluid-attenuated inversion-recovery (EPI-FLAIR) sequence with fast spin-echo FLAIR (F-FLAIR) and fast spin-echo T2-weighted (FSE-T2W) sequences in depiction of white matter lesions. METHODS: Thirty-five patients with various white matter lesions were included in this prospective study. Two independent readers for lesion detection (lesion size, >2 mm) compared sequences quantitatively. In 22 patients, contrast was calculated between periventricular hyperintensity (PVH) and the cerebrospinal fluid (CSF). RESULTS: EPI-FLAIR revealed more lesions than FSE-T2W (p < 0.01). However, F-FLAIR revealed more lesions than EPI-FLAIR (p < 0.01). For PVH-to-CSF contrast, EPI-FLAIR demonstrated significantly higher contrast than FSE-T2W. There were no differences in PVH-to-CSF contrast between EPI-FLAIR and F-FLAIR. CONCLUSIONS: This study shows that EPI-FLAIR has distinct advantages over FSE-T2W in the depiction of white matter lesions. Although EPI-FLAIR reduces imaging time by more than 60% relative to F-FLAIR, it cannot replace F-FLAIR for the detection of lesions in the cerebral white matter.     

Discovery of novel [Arg49]phospholipase A2 isozymes from Protobothrops elegans venom and regional evolution of Crotalinae snake venom phospholipase A2 isozymes in the southwestern islands of Japan and Taiwan.

Protobothrops (formerly Trimeresurus) elegans, a Crotalinae snake, inhabits Ishigaki and Iriomote islands of the Sakishima Islands of Japan which are located between Okinawa island of Japan and Taiwan. Two phospholipase A(2) (PLA(2)) isozymes were purified to homogeneity from P. elegans venom and sequenced. This led to a discovery of novel PLA(2) isozymes with Arg at position 49, that is, [Arg(49)]PLA(2) forms, named PeBP(R)-I and PeBP(R)-II. They are polymorphic at position 3, Val for PeBP(R)-I and Ile for PeBP(R)-II. The cDNAs encoding PeBP(R)-I and PeBP(R)-II were cloned. The cDNA encoding an [Asp(49)]PLA(2) named PePLA(2) was also obtained. In contrast to PLA(2) isozymes from Protobothrops genus with 122 amino acid residues, PeBP(R)-I and PeBP(R)-II are composed of 121 amino acid residues due to lack of Pro at position 90. They exhibited necrotic and edema-inducing activities but no hemorrhagic activity was detected. A phylogenetic tree constructed for venom PLA(2) isozymes of Protobothrops genus and of related genera in the southwestern islands of Japan and Taiwan revealed that PeBP(R)-I and PeBP(R)-II of P. elegans are evolutionarily much closer to PmK49PLA(2), a [Lys(49)]PLA(2), from P. mucrosquamatus (Taiwan) than BPI and BPII, both [Lys(49)]PLA(2) forms, from P. flavoviridis (Amami-Oshima and Tokunoshima islands of Japan). Such evolutionary relationships are also seen in neutral [Asp(49)]PLA(2) isozymes from the three Protobothrops species. Thus, P. elegans is the species much closer to P. mucrosquamatus than P. flavoviridis. Their evolutionary distances seem to be well related to geological history of the islands where they have lived. In addition, it was clearly noted that Ovophis okinavensis (Amami-Oshima), which had formerly belonged to the Trimeresurus genus, and Trimeresurus stejnegeri (Taiwan) are the species fairly distant from Protobothrops genus.     

Lithium chloride inhibits thrombin-induced intracellular calcium mobilization in C6 rat glioma cells

In this study, the authors have demonstrated the effect of lithium, a typical mood stabilizer, on thrombin-evoked Ca2+ mobilization in C6 cells to elucidate the action mechanisms of the drug. Thrombin-induced Ca2 mobilization was reduced 24 hr after 1 or 10 mM lithium chloride (LiCl) pretreatment. The Ca2+ rise was reduced in a time-dependent manner, and the significant inhibition was observed 9 hr pretreatment with 10 mM LiCl. On the other hand, pretreatment of the cells with 10 mM LiCl for 24 hr did not alter the amount of Galphaq/11 significantly. Pretreatment with 10 mM LiCl for 24 hr failed to reduce the 5-HT-induced Ca2+ mobilization or to affect the desensitization of the 5-HT signal. Finally, thrombin-elicited Ca2+ rise was markedly inhibited in the presence of 0.05 U/ml plasmin, however, the Ca2+ rise was not further attenuated in the presence of plasmin in C6 cells pretreated with LiCl for 24 hr. These results indicate that pretreatment with LiCl attenuated thrombin-evoked intracellular Ca2+ mobilization in plasmin sensitive manner in C6 rat glioma cells. Thus, it is important to investigate the effect of lithium on thrombin-induced cellular responses to clarify the action mechanism of lithium in relation to some abnormality in thrombin-evoked Ca2+ rise observed in bipolar disorders.