Predicting difficulty in extending the ileal pouch to the anus in restorative proctocolectomy: investigation of a simple predictive method using computed tomography.

AIM: This study aimed to assess the ability of preoperative axial computed tomography (CT) to predict surgical difficulty in bringing the ileal pouch to the level of the anus during restorative proctocolectomy (RPC). METHOD: Patients who underwent RPC with an ileal pouch-anal anastomosis (or ileal pouch-anal canal anastomosis) in our institution between January 2008 and April 2014 were enrolled. The patients were divided into two groups, including those in whom CT indicated potential difficulty in extending the pouch downwards (extension difficult (ED) group) and patients with no CT evidence of potential difficulty (normal group). The groups were compared for clinical factors and the thickness of the slices of CT showing the root of the superior mesenteric artery, the point of communication of the ileocaecal artery with the marginal artery (tICA) and the anal verge (AV). Receiver-operating characteristic analysis was performed, and a cut-off value was calculated for predicting the degree of difficulty in bringing the ileal pouch down to the anal canal. RESULTS: Thirty-four patients were entered in the study. The ED group included significantly taller patients and more with familial adenomatous polyposis than the normal group. The distance between tICA and AV was significantly longer in the ED group, with a cut-off of 21 cm giving a sensitivity of 100% and a specificity of 83.3%. CONCLUSION: The distance between tICA and AV measured by axial CT can be a useful predictor for the difficulty in bringing the ileal pouch down to the anus during RPC.

Three-step method for ultrasound-guided central vein catheterization.

BACKGROUND: The long-axis view and in-plane needle approach (LAX-IP) for ultrasound-guided central vein catheterization is considered ideal because of the quality of real-time imaging. We describe a novel technique, using a step-by-step procedure, to overcome the pitfalls associated with the LAX-IP. This study was undertaken to demonstrate the clinical utility of this approach. METHODS: All operators underwent training before participation in this study. One hundred patients were enrolled in this study and underwent central venous catheterization using this method. Using a portable ultrasound and vein catheterization kit, patients were appropriately positioned and a straight portion of the vein identified (Step 1). A needle guide was used (Step 2) and the vein imaged in real time in two directions (Step 3), to identify the true long axis and prevent damage to surrounding tissues. RESULTS: The overall success rate for catheterization was 100% with a median of one puncture for each patient. All catheterizations were performed within three punctures. Problems with the first puncture included difficult insertion of the guide-wire due to coiling, difficult anterior wall puncture, less experience with the procedure, and other reasons. There were no complications associated with the procedure. CONCLUSIONS: This three-step method is not dependent on an operator's ability to proceed based on spatial awareness, but rather depends on logic. This method can prevent difficulties associated with a two-dimensional ultrasound view, and may be a safer technique compared with others. Further clinical trials are needed to establish the safety of this technique.

Meige syndrome with apraxia of lid opening after the discontinuation of sulpiride treatment.

We report a case of Meige syndrome with apraxia of lid opening that lasted for about seven months after discontinuation of sulpiride treatment. To our knowledge, this is the first report demonstrating that Meige syndrome with apraxia of lid opening is induced by sulpiride, and that the condition persists.

Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain.

RATIONALE: Lithium is the most widely prescribed mood stabilizer, but the precise mechanism of lithium is unresolved. OBJECTIVE: We examine the effects of the administration of therapeutically relevant concentrations of lithium on the expression of brain-derived neurotrophic factor (BDNF) and its receptor, Trk B, as well as glia-derived neurotrophic factor (GDNF) and its receptors, RET and GDNFR-alpha, in the rat brain. In addition, we also examined the effect of another well-prescribed mood stabilizer, valproate, on the expression of BDNF and GDNF. METHODS: Rats were kept on a 0.2% lithium carbonate-containing diet for 1, 7, 14, or 28 days or treated with valproate (400 mg/kg per day i.p.) for 1 or 14 days. After the brains were rapidly removed, the levels of BDNF, GDNF, and their receptors were measured by ELISA or western blot analysis. RESULTS: Chronic lithium treatment for 14 and 28 days significantly increased the expression of BDNF in the hippocampus and temporal cortex. In addition, chronic lithium treatment for 14 days significantly increased the expression of BDNF in the frontal cortex. In contrast, acute or chronic dietary lithium treatment did not alter GDNF expression in these brain regions. In addition, acute or chronic lithium treatments did not change the levels of Trk B, RET, or GDNFR-alpha immunoreactivity. As well as lithium, repeated administration of valproate also increased the expression of BDNF in the frontal cortex and hippocampus. CONCLUSIONS: Our results suggest that the chronic administration of mood stabilizers may produce a neurotrophic effect mediated by the upregulation of BDNF in the rat brain.

Modulation of serotonin2A receptor function in rats after repeated treatment with dexamethasone and L-type calcium channel antagonist nimodipine.

1. It has been conceivable that the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity plays an important role in the pathophysiology of depression. In the present study, we have investigated the effect of repeated treatment with dexamethasone on serotonin (5-HT) 1A, 5-HT2A and alpha1-adrenergic receptors in the rat frontal cortex. Moreover, several studies have suggested the effectiveness of L-type calcium channel antagonist nimodipine for the treatment of depression. We also investigated the effect of repeated treatment with nimodipine on 5-HT2A receptor in rats with repeated dexamethasone treatment. 2. Repeated treatment with dexamethasone (1 mg/kg/day for 14 days) increased the density of 5-HT2A receptor, but not 5-HT1A and alpha1-adrenergic receptors in the rat frontal cortex. 3. The density of 5-HT2A receptor in the rat frontal cortex was significantly increased 1 day after repeated treatment with dexamethasone, but was not increased 7 or 14 days after repeated treatment. Wet dog shakes (WDS) induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), a 5-HT2A receptor agonist, in rats were significantly enhanced 1, 7 and 14 days after repeated treatment with dexamethasone, although the frequency of WDS gradually decreased after repeated treatment. 4. Repeated treatment with nimodipine (5 mg/kg/day for 14 days) attenuated DOI-induced WDS enhanced by repeated treatment with dexamethasone (1 mg/kg/day for 14 days), however, it did not change the density of 5-HT2A receptor. Repeated treatment with dexamethasone decreased locomotor activity and body weight, but repeated treatment with nimodipine did not recover these parameters. 5. The results of the present study suggest that repeated treatment with dexamethasone may selectively increase the 5-HT2A receptor in the rat frontal cortex and affect 5-HT2A receptor-mediated signal transduction. In addition, the intracellular calcium homeostasis by blocking calcium influx through L-type calcium channel may play an important role in the regulation of the 5-HT2A receptor function by dexamethasone.

Calf and shin muscle oxygenation patterns and femoral artery blood flow during dynamic plantar flexion exercise in humans.

The effects of dynamic plantar flexion exercise [40, 60, and 80 contractions.min-1 (cpm)] on calf and shin muscle oxygenation patterns and common femoral artery blood flow (Qfa) were examined in six female subjects [mean age 21 (SD 1) years] who exercised for 1 min at 33% of their maximal voluntary contraction at ankle angles between 90 degrees and 100 degrees. Spatially resolved near-infrared spectroscopy was used to measure medial gastrocnemius, lateral soleus (synergist) and anterior tibialis (antagonist) muscle oxygen saturation (SO2, %). Qfa was measured by ultrasound Doppler. The SO2 changed significantly only in the medial gastrocnemius and its decrease (up to about 30%) was independent of the contraction frequencies examined. The increase in Qfa, at the end of exercise, was highest at 80 cpm. When the exercise at 60 cpm was prolonged until exhaustion [mean 2.7 (SD 1.1) min], medial gastrocnemius SO2 decreased, reaching its minimal value [mean 30 (SD 10)%] within the 1st min, and had partially recovered before the end of the exercise with concomitant increases in total haemoglobin content and Qfa. These results suggest that the medial gastrocnemius is the muscle mostly involved in dynamic plantar flexion exercise and its oxygen demand with increases in contraction frequency and duration is associated with an up-stream increase in Qfa.

Characterization of 5-HT2A receptor desensitization and the effect of cycloheximide on it in C6 cells.

Effect of prolonged pretreatment with serotonin (5-HT) on 5-HT2A receptor desensitization was examined by the measurement of intracellular calcium ([Ca2+]i) mobilization in C6 cells. 5-HT-induced desensitization of [Ca2+]i mobilization was in a time and dose dependent manner and reached a plateau after 3 hr. After 1 and 3 hr 5-HT pretreatment, 5-HT concentration in the medium little changed. 5-HT pretreatment with cycloheximide, a protein synthesis inhibitor, produced an enhancement of the desensitization for 3 and 6 hr pretreatment. However, 5-HT pretreatment for 3 and 6 hr caused no marked change in the 5-HT2A receptor mRNA level or Galphaq/11 protein in this study, suggesting that 5-HT may decrease 5-HT-induced [Ca2+]i mobilization independent of 5-HT2A receptor mRNA or G-proteins. Endothelin-1-induced [Ca2+]i mobilization did not alter after 5-HT and/or cycloheximide pretreatment. These results showed that activation of the 5-HT2A receptor induced homologous desensitization and pretreatment with 5-HT and/or cycloheximide did not change the efficacy of the second messenger pathway from Gq to a [Ca2+]i rise.

Effect of acute lipopolysaccharide administration on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane-induced wet dog shake behavior in rats: comparison with body weight change and locomotor activity.

1. Several reports have shown that serotonin (5-HT)2A receptor density and its function are altered after physiological or pharmacological stress. To examine whether an acute administration of lipopolysaccharide (LPS), a bacterial endotoxin, affected 5-HT2A receptor function, wet dog shakes of male Wistar rats were observed after a subcutaneous injection of DOI, a 5-HT2A receptor agonist following LPS treatment. Body weight change and locomotor activity were also observed. 2. DOI (1 mg/kg)-induced WDS significantly decreased after 400 or 1000 microg/kg LPS treatment compared with that of control rats 1 and 3 hr after injection, and WDS completely recovered 8 hr after LPS treatment. Treatment with 10 mg/kg indomethacin (IND) or 1 mg/kg naltrexone (NLTX) canceled the effect of 400 microg/kg LPS on DOI-induced WDS. 3. Body weight decrease was significantly greater in LPS-treated rats compared with control rats 3, 5 and 8 hr after treatment. Treatment with IND (10 mg/kg) significantly recovered the reduction in body weight induced by 400 microg/kg LPS. Treatment with NLTX (1 mg/kg) also prevented the LPS effect on body weight decrease. 4. Eight hr after treatment with LPS (400 microg/kg), the rats showed significant attenuation of locomotor activity. IND (10 mg/kg) treatment abolished the inhibitory effect of LPS on locomotor activity, and NLTX (1 mg/kg) also improved the decrease in locomotion 8 hr after LPS treatment. 5. Plasma tumor necrosis factor (TNF)-alpha concentration dramatically increased 1 hr after the injection of 400 microg/kg LPS, and returned almost to the basal level 3 hr later. Next, rats were injected with 50 microg/kg TNF-alpha intraperitoneally, and body weight change and DOI-induced WDS was determined 3 hr after TNF-alpha injection. Body weight loss was significantly greater in rats treated with TNF-alpha. On the other hand, DOI-induced WDS was not altered when rats were treated with TNF-alpha. 6. These results suggest that acute treatment with LPS inhibited 5-HT2A receptor-mediated behavior via cyclooxygenase and opioid receptor activation, but that the inhibition of the WDS by LPS appears to be independent of TNF-alpha production.

Effect of beta-estradiol on voltage-gated Ca(2+) channels in rat hippocampal neurons: a comparison with dehydroepiandrosterone.

We investigated the effects of beta-estradiol, dehydroepiandrosterone and dehydroepiandrosterone sulfate on intracellular calcium concentration ([Ca(2+)](i)) increases induced by gamma-aminobutyric acid (GABA), high K(+) and N-methyl-D-aspartate acid (NMDA) in cultured hippocampal neurons. Acute treatment with beta-estradiol, dehydroepiandrosterone and dehydroepiandrosterone sulfate inhibited the GABA-induced [Ca(2+)](i) increases to the similar extent. Tamoxifen, an estrogen receptor antagonist, did not block the inhibitory effects of beta-estradiol. On the other hand, GABA type A (GABA(A)) receptor antagonists, picrotoxin and bicuculline, blocked the GABA-induced [Ca(2+)](i) increases. Previously, we demonstrated that GABA- and high K(+)-induced [Ca(2+)](i) increases were commonly mediated by voltage-gated calcium channels (VGCCs). Therefore, we examined the effects of these steroids on the high K(+)-induced [Ca(2+)](i) increases. The inhibitory effect of beta-estradiol on the high K(+)-induced [Ca(2+)](i) increases was much greater than that of dehydroepiandrosterone and dehydroepiandrosterone sulfate. beta-Estradiol inhibited the NMDA-induced [Ca(2+)](i) increases with an IC(50) of 51.8 microM and NMDA responses were reduced to half in the presence of 10 micro M nifedipine, indicating that the NMDA-induced [Ca(2+)](i) increases also involved VGCCs. Further, we examined the inhibitory effect of beta-estradiol on the high K(+)-induced [Ca(2+)](i) increases in the presence of a N-type VGCCs antagonist, 1 microM omega-conotoxin, or a L-type VGCCs antagonist, 10 microM nifedipine. The IC(50) value of beta-estradiol alone (45.5 microM) was similar to that of omega-conotoxin (33.1 microM), while the value combined with nifedipine was reduced to 2.2 microM. beta-Estradiol also abolished the positive modulatory effect of L-type VGCCs agonist, 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]pyridine-3-carboxylic acid methyl ester (Bay K 8644). Our results showed that the inhibitory mechanism of beta-estradiol is different from that of dehydroepiandrosterone and dehydroepiandrosterone sulfate and beta-estradiol may act primarily at L-type VGCCs.

Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan.

There are a number of investigations which indicate the important relationship between depression and cytokines. In this study, we investigated plasma interleukin (IL)-1beta, IL-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor (TNF)-alpha of depressed patients whose clinical evaluation was performed by the Hamilton Rating Scale for Depression (HAM-D) and the Profile of Mood States (POMS). They were compared with those of the control subjects, and before and after treatment with antidepressants. Before the treatment, plasma IL-1beta, IL-6, sIL-2R and TNF-alpha of the patients were not significantly different from those of the control subjects. sIL-2R was positively correlated with the POMS-tension-anxiety subscale and tended to have a positive correlation with HAM-D. After pharmacotherapy, TNF-alpha levels of the depressed patients increased, without any relationship between the change in the HAM-D or the POMS and the change in TNF-alpha. These results suggest that the plasma sIL-2R concentration is associated with mood state, and that the plasma TNF-alpha concentration is increased after pharmacotherapy in Japanese depressed patients.

Three sets of diagnostic criteria for major depression and correlations with serotonin-induced platelet calcium mobilization in cancer patients.

OBJECTIVE: Enhanced serotonin-induced platelet calcium mobilization has been proposed to be a biological marker for the pathophysiology of major depression in physically healthy patients. To determine the most appropriate method of diagnosing major depression in cancer patients, we compared serotonin-induced platelet calcium mobilization between patients with and without major depression diagnosed according to three different sets of diagnostic criteria (inclusive, substitutive and exclusive). METHODS: Among the cancer patients referred to our institution between June 1997 and March 1998, 24 patients diagnosed as having major depression according to the inclusive approach (in which the nine traditional symptoms of major depression contribute towards the diagnosis of depression regardless of its presumed etiology) participated in the study. Serotonininduced platelet calcium mobilization was examined in these patients and in the same number of non-depressed controls matched for age, sex, cancer stage and cancer site. The depressed patients were then re-evaluated using substitutive and exclusive criteria, and calcium mobilization comparisons with the relevant controls were repeated. RESULTS: Compared with the controls, an enhanced serotonin-induced platelet calcium response was only observed in the patients with major depression according to the exclusive criteria. No significant enhancement was observed when the inclusive or substitutive approaches were used. CONCLUSION: These findings, based on the use of enhanced serotonin-induced platelet calcium mobilization as a biological marker, suggest that the exclusive approach might be the most valid and appropriate method of diagnosing major depression in cancer patients, while the inclusive and substitutive approaches might overestimate the occurrence of major depression in these patients.

Neurotrophic action of interleukin 3 and granulocyte-macrophage colony-stimulating factor on murine sympathetic neurons.

We investigated neurotrophic effects of interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on cultured sympathetic neurons obtained from mouse superior cervical ganglia. After 1 day of culture with physiological concentrations of mouse recombinant IL-3 and GM-CSF, the numbers of process-bearing neurons were increased. Maximum responses were elicited by 10 U/ml IL-3 and 1 U/ml GM-CSF, which were equivalent to the action of a submaximal dose (5 ng/ml) of nerve growth factor (NGF). The effects of IL-3 and GM-CSF were completely blocked by their corresponding antibodies, but not by anti-NGF, indicting their action is specific and completely independent of NGF. IL-3 and, to a lesser extent, GM-CSF were also able to protect NGF-differentiated neurons from apoptotic cell death caused by NGF withdrawal. The mitogen-activated protein (MAP) kinase signal transduction pathway is known to be involved in action of IL-3 and GM-CSF on hemopoietic cells, and thus we examined the participation of this pathway in the neurotrophic activities of IL-3 and GM-CSF. IL-3 and GM-CSF stimulation of the differentiated neurons was found to result in a rapid elevation of MAP kinase activity, and PD98059, an inhibitor of MAP kinase kinase activity, blocked both the neuritogenic and neuroprotective effects of IL-3 and GM-CSF. Immunocytochemical studies showed that IL-3 and GM-CSF receptors were present on the differentiated neurons. Thus, IL-3 and GM-CSF appear to be able to stimulate sympathetic nerve growth, via specific cytokine receptors on neurons, which lead to activation of the MAP kinase pathway that then mediates the observed neurotrophic effects.

Effects of antidepressants on gamma-aminobutyric acid- and N-methyl-D-aspartate-induced intracellular Ca(2+) concentration increases in primary cultured rat cortical neurons.

We investigated the effects of antidepressants on the intracellular Ca2+ concentration ([Ca2+]i) increases induced by gamma-aminobutyric acid (GABA) or N-methyl-D-aspartate (NMDA) in primary cultured rat cortical neurons using fluorescence imaging. Acute treatment with imipramine inhibited GABA- and NMDA-induced increases in [Ca2+]i in a concentration-dependent manner. Doses of 30 microM clomipramine, desipramine, amoxapine and maprotiline also inhibited both the GABA- and NMDA-induced [Ca2+]i increases significantly. Both inhibitory effects of the five major antidepressants on the GABA- or the NMDA-induced [Ca2+]i increases were well-correlated. Imipramine could inhibit significantly high-K+-induced [Ca2+]i increases. Our previous study has already shown that the GABA-induced [Ca2+]i increase involves a similar pathway to high-K+-induced Ca2+ influx. In conclusion, imipramine and several other antidepressants have acute inhibitory effects on the GABA-, NMDA- and high-K+-induced [Ca2+]i increases, suggesting that these inhibitory effects are not related to specific receptors. One possibility is that these effects may be commonly mediated via part of the high-K+-induced [Ca2+]i pathway.

Effect of heat stress on serotonin-2A receptor-mediated intracellular calcium mobilization in rat C6 glioma cells.

This study was conducted to investigate an effect of heat stress at 44 degrees C for 30 min on intracellular Ca2+ signaling system and on heat shock protein (HSP)-70 expression. 5-HT-induced Ca2+ mobilization was reduced 1, 3 and 6 hrs after heat stress, and recovered to the control level 12 and 24 hrs after heat stress. One hr after heat stress, Ca2+ rise was significantly decreased when the cells were stimulated by any concentration of 5-HT. Thrombin-induced Ca2+ increase was also markedly reduced 1 hr after heat stress. HSP-70 level was increased 6 and 9 hr after heat stress. In HSP synthesis inhibitor quercetin-treated cells, HSP-70 expression was not enhanced after heat stress, and Ca2+ rise in response to 5-HT did not return to the control level. However, the Ca2+ rise induced by 5-HT was not restored to the control level after stress in Ac-Asp-Glu-Val-Asp-H (DEVD)-exposed cells while DEVD had little effect on heat stress-induced synthesis of HSP-70. Dexamethasone did not alter the change in HSP-70 expression or Ca2+ response after heat stress. These results indicate that heat stress attenuated 5-HT-induced Ca2+ mobilization and that HSP-70 expression played an important role in recovery from Ca2+ impairment, possibly via protease activity in C6 cells.

Oxygen supply-consumption balance in the thigh muscles during exhausting knee-extension exercise.

The purpose of this study was to investigate the difference in muscle oxygenation between the individual muscles involved in an exhaustive knee-extension exercise. Eight active women performed exercise by extending the knee joint from 90 degrees to 30 degrees (60 extensions min-1) at 20%, 30%, and 40% maximum voluntary contraction (MVC). Changes in oxy-(delta HbO2), deoxy-(delta Hb), and total (delta HbT) hemoglobin concentrations, and oxygen saturation (delta SO2NIRS = HbO2/HbT) in the vastus lateralis (VL) and rectus femoris (RF) muscles were measured with a spatially resolved near-infrared spectrometer (NIRS). The delta SO2NIRS in the VL and RF decreased rapidly from the pre-exercise control value (VL: 75.6 +/- 0.9%; RF: 81.6 +/- 1.6%) at the onset of exercise at three different intensities, although no significant difference in delta SO2NIRS was found between the two muscles at this time. However, the delta SO2NIRS decreased more rapidly thereafter and reached a lower value at exhaustion in the VL than in the RF. The difference in delta SO2NIRS between the VL (-10.3 +/- 1.7%) and RF (-4.0 +/- 1.0%) was significant (p < 0.05) when exercise intensity was 30% MVC. When the decreases in delta HbO2 and delta HbT (p < 0.05) were compared at different exercise intensities, the values at 30% and 40% MVC were significantly lower (delta HbO2: p < 0.01; delta HbT: p < 0.05) than those at 20% MVC in the VL, but there was no significant difference in any of the parameters in the RF, or in delta Hb in the VL. These results suggest that the muscle oxidative response to exhaustive knee-extension exercise differed between the VL and RF muscles. At exhaustion, oxygen saturation decreased to a lower level in the VL than in the RF, and an intensity-dependent difference in muscle oxygenation parameters was observed at 30% MVC in the VL but not in the RF muscles.

Chronic electroconvulsive shock decreases (+/-) 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI)-induced wet-dog shake behaviors of dexamethasone-treated rats.

Electroconvulsive shock (ECS) therapy is considered to be an effective treatment for depression, but its mechanism of action is still unknown. We investigated the effect of chronic ECS in rats treated for 14 days with dexamethasone (Dex), a glucocorticoid receptor agonist. Chronic injection of sesame oil decreased body weight change and increased serotonin (5-HT)-2A receptor number and DOI (5-HT-2A, 2C receptor agonist)-induced wet-dog shake (WDS) behaviors. Dex treatment for 14 days decreased body weight of rats, but repeated ECS did not reverse this decrease. Dex also abolished plasma corticosterone levels, and ECS failed to restore these levels. These results indicate that chronic ECS does not antagonize the effect of Dex. The treatment with Dex increased 5-HT-2A receptor binding density of rat frontal cortex and the number of DOI-induced WDS behaviors. Chronic ECS reduced the enhanced WDS behaviors by Dex but had little effect on receptor density. These results suggest that chronic ECS might suppress 5-HT-2A receptor function at the postreceptor signaling level rather than at the receptor itself, without changing HPA axis function in Dex-treated rats.

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.

Effect of lithium carbonate on the enhancement of serotonin 2A receptor elicited by dexamethasone.

The purpose of this study was to investigate whether chronic dexamethasone (Dex) administration induces serotonin (5-HT) 2A receptor supersensitivity and if chronic lithium carbonate (Li) administration contributes to the normalization of 5-HT2A receptor supersensitivity induced by Dex in rat brain. We investigated the effects of a 14-day administration of Dex and/or Li on changes in body weight (BW), on plasma corticosterone levels, on plasma lithium levels, on 5-HT2A receptor binding sites, and on (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI)-induced wet dog shake (WDS), which is mediated by 5-HT2A receptor in rats. Dex significantly reduced the BW of rats. Li did not have any effect on BW gain and did not prevent the BW loss induced by Dex. The plasma corticosterone levels of rats treated with Dex were too low to be detected. Li did not have any effect on corticosterone levels and did not prevent the decrease in the corticosterone levels induced by Dex. Six hours after the last treatment, the plasma lithium levels of rats treated with Li were significantly higher than those of rats treated with Dex/Li. Chronic Dex administration resulted in a significant increase in the density (B(max)) of the 5-HT2A receptor without a significant change in the affinity (K(d)). The increase in the B(max) induced by Dex was not prevented by chronic combined treatment with Dex and Li. Chronic Dex administration potentiated the WDS, and this increase was prevented by chronic combined treatment with Dex and Li. Chronic Li administration did not have any effect on WDS. These results indicate that chronic Li administration may improve the supersensitivity of the 5-HT2A receptor elicited by chronic Dex administration without decreasing the density of the 5-HT2A receptor, and the effect of Li was also independent of hypothalamo-pituitary-adrenal axis function.

Risperidone treatment of neuroleptic-induced tardive extrapyramidal symptoms.

Tardive extrapyramidal symptoms (EPS) induced by neuroleptic treatment, and particularly EPS which persist after withdrawal of the drugs, are clinically serious problems. We describe a patient with four types of tardive and persistent EPS such as dystonia, dyskinesia, choreatic movement and myoclonus, induced by haloperidol. These EPS were remarkably inhibited by 3 mg/day risperidone. This is the first published case demonstrating simultaneous development of these four types of tardive EPS induced by a neuroleptic and then reduced by low-dose risperidone treatment. ( Int J Psych Clin Pract 2000; 4: 241 - 243).