Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

A multicenter study on anaphylaxis caused by peanut, tree nuts, and seeds in children and adolescents.

Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.

Relationship between prolactin levels and subjective endocrine-related adverse effects in patients with schizophrenia receiving long-term treatment with amisulpride.

INTRODUCTION: We have investigated the categorical prevalence of hyperprolactinemia and examined the relationship between prolactin levels and subjective endocrine-related adverse effects in schizophrenia patients treated with amisulpride during a 1-year period. METHODS: A total of 111 patients with schizophrenia who were either started on or switched to amisulpride were assessed for prolactin levels and endocrine-related adverse effects using 6 items derived from the Liverpool University neuroleptic side-effect rating scale (LUNSERS) at baseline, 8 weeks, and 1 year. RESULTS: 10 were antipsychotic-naïve, 23 were antipsychotic free for 1 month, 54 discontinued their medication during 1 month prior to study, and 24 maintained their antipsychotics at baseline. At 1 year, hyperprolactinemia was found in 75.9% of men and 85.7% of women. Significant increases in mean prolactin levels at week 8 in both sexes were found; this was followed by a significant decrease over 1 year only in women. The proportions of both sexes with hyperprolactinemia increased from baseline to week 8 but remained unchanged at 1 year. Scores on the endocrine-related items of the LUNSERS improved significantly from baseline to week 8 in both sexes and then remained consistent during maintenance treatment. Prolactin levels were significantly higher in the group with baseline hyperprolactinemia than in the group without baseline hyperprolactinemia at all assessment points. CONCLUSIONS: Amisulpride commonly induces hyperprolactinemia. Although the percentage of patients with hyperprolactinemia remained unchanged during maintenance treatment, serum prolactin levels significantly decreased among women. Self-reported endocrine-related side effects were not associated with prolactin elevation during amisulpride treatment.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Mutational analysis of JAK1 gene in human hepatocellular carcinoma.

UNLABELLED: The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that is noncovalently associated with a variety of cytokine receptors and plays a nonredundant role in cell proliferation, survival, and differentiation. The mutated forms of JAK1 often altered the activation of JAK1 and then changed the activation of JAK1/STAT pathways, and this may contribute to cancer development and progression. Thus, to investigate whether genetic mutations of JAK1 gene are associated in hepatocellular carcinoma (HCC) progression, we analyzed genetic alterations of JAK1 gene in 84 human HCCs by single-strand conformational polymorphism (SSCP) and direct sequencing. Of 24 exons of JAK1 gene, 12 exons were previously reported to have mutations, we searched genetic alteration of JAK1 in these exons. Overall, one missense mutation (1.2%) was found. In addition, 12 cases (14%) were found to have single nucleotide polymorphism (14%) in exon 14. Taken together, we found one novel missense mutation of JAK1 gene in hepatocellular carcinomas with some polymorphisms. Although the functional assessment of this novel mutant remains to be completed, JAK1 mutation may contribute to the tumor development in liver cancer. KEYWORDS: JAK1 gene, hepatocellular carcinoma, mutation.

Low frequency mutation of the Ephrin receptor A3 gene in hepatocellular carcinoma.

EphA3 is a component of the Eph/ephrin tyrosine kinase system, which participates in vasculature development. This receptor/ligand system is associated with various signaling pathways related to cell growth and viability, cytoskeletal organization, cell migration, and anti-apoptosis. Accumulated evidence suggests that aberrant regulation of EphA3 and its genetic alterations are implicated in the development and progression of various cancers. However, despite a high incidence of EphA3 over-expression, no such investigation has been performed in hepatocellular carcinoma. Thus, we investigated genetic alterations of the EphA3 gene in 73 cases of hepatocellular carcinoma by single-strand conformational polymorphism and sequencing. One novel D219V missense mutation was found in the extracellular domain of EphA3, and two genetic alterations in the intracellular sterile-alpha-motif (SAM) domain of EphA3 appeared to be polymorphisms. Although the functional assessments of this mutant are incomplete, it is believed that this novel EphA3 mutation may contribute to the development of hepatocellular carcinoma.

Inhibitory effects of herbal decoction Ojeoksan on proliferation and migration in vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells plays a crucial role in pathogenesis of cardiovascular disease. The principal objective of this study was to determine the effects of Ojeoksan (OJS) on human aortic smooth muscle cell (HASMC) proliferation induced by tumor necrosis factor α (TNF-aα). Thymidine incorporation after TNF-α treatment was increased and this effect was inhibited significantly by OJS treatment. HASMC proliferation and migration by kinetic live cell imaging were also reduced by treatment with OJS. TNF-α induced the expression of cyclins/cyclin-dependent kinases (CDKs) and reduced the expression of p21waf1/cip1/p27kip1. However, OJS also attenuated the expression of TNF-α-induced cell-cycle regulatory proteins. The results of Western blot analysis demonstrated that the TNF-α treated HASMC secreted gelatinases, probably including MMP-2/-9, which may be involved in the invasion and migration of HASMC. Additionally, OJS suppressed the mRNA expression levels of matrix metalloproteinase-2/-9 (MMP-2/-9) in a dose-dependent manner. OJS inhibited the production of TNF-α-induced hydrogen peroxide (H2O2) and the formation of DCF-sensitive intracellular reactive oxygen species (ROS). Further, OJS suppressed the nuclear translocation and phosphorylation of inhibitor of kappa B-α (IκB-α) of nuclear factor κB (NF-κB) under TNF-α conditions. Our results demonstrate that OJS exerts inhibitory effects on TNF-α-induced HASMC proliferation and migration, suggesting the involvement of the inhibition of both MMP-2 and MMP-9 expressions, and the downregulation of ROS/NF-κB signaling. Thus, herbal decoction OJS may be a possible therapeutic approach to the inhibition of cardiovascular disease including atherosclerosis.

Prenatal vitamin C status is associated with placental apoptosis in normal-term human pregnancies.

Pregnancy is associated with increased susceptibility to oxidative stress. Deficiencies in antioxidants during pregnancy and placental oxidant-antioxidant imbalance may impair the development of the fetoplacental unit or the eventual offspring. In order to elucidate the association of prenatal status of vitamin C with the oxidative stress and apoptotic activity in normal full-term placentas, we evaluated the content of placental lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and the trophoblast apoptotic index in normal-term human pregnancies. Tissue samples of placentas obtained from 80 normal-term pregnancies were categorized into 40 cases with a lower level of prenatal vitamin C (< 8.997 microg/ml) and 40 cases with a higher level of prenatal vitamin C (> or =11.734 microg/ml). We evaluated the placental LOX-1 content and the trophoblast apoptotic index with Western blot analysis and immunohistochemistry, and then determined their correlation with the prenatal status of vitamin C. We confirmed that the trophoblast expression for the endothelial scavenger receptor LOX-1 and the apoptotic activity were significantly lower in the group with a higher prenatal level of vitamin C, indicating that placental oxidative stress and the apoptotic index were associated with the maternal status of vitamin C. We therefore postulate that the maternal status of antioxidant vitamins during pregnancy can affect fetal development.

Dysbindin gene variants are associated with bipolar I disorder in a Korean population.

The dysbindin gene (DTNBP1) has been associated with schizophrenia in several populations. Because the clinical characteristics of schizophrenia and bipolar disorder overlap in many respects and findings from genetic studies have suggested common genes between them, we conducted a case control association study of bipolar disorder in Korea to investigate the genetic association between DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350 controls were evaluated. We genotyped three single nucleotide polymorphisms of DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype associations with bipolar disorder. We found significant genotypic associations with P1763 and P1320, but no association with SNP A in the bipolar I group. When we included bipolar II and schizoaffective disorder in the affected phenotype, the significance decreased. A positive association was observed between the SNP A-P1763 haplotype and the bipolar I phenotype. This haplotype association was lost when we either broadened our phenotype or included P1320 in a haplotype. The positive results of the present study lost significance after a Bonferroni correction for multiple testing. These findings are consistent with previous findings that showed a positive association of DTNBP1 with bipolar disorders. Moreover, our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. Further comprehensive studies will be required to clarify these association, however, it seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.

Mantidis ootheca induces vascular relaxation through PI3K/AKT-mediated nitric oxide-cyclic GMP-protein kinase G signaling in endothelial cells.

Mantidis ootheca (Sang Piao Xiao) is well known mantis eggs in a foamy pouch. The purpose of the present study was to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of the aqueous extract of Mantidis ootheca (AMO) in rat aorta and vascular endothelial cells. AMO was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aortic rings. The roles of the nitric oxide (NO) signaling in the AMO-induced effects were tested in human umbilical vein endothelial cells (HUVECs). HUVEC treated with AMO produced higher amount of NO compared to control. However, AMO-induced increases in NO production were blocked by pretreatment with NG-nitro-L-arginine methylester (L-NAME) or wortmannin. AMO increased in phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt in HUVECs, which were attenuated by a NOS and Akt inhibitors. In aortic ring, AMO-induced dose-dependent relaxation of phenylephrine-precontracted aorta was abolished by removal of functional endothelium. Pretreatment with L-NAME, 1H-[1,2,4]-oxadiazolo-[4,3-alpha]-quinoxalin-1-one (ODQ), and KT5823 inhibited the AMO-induced vasorelaxation. Similarly, wortmannin and LY-294002, an inhibitors of the phosphatidylinositol 3-kinase (PI3K), an upstream signaling molecule of eNOS, attenuated the AMO-induced vasorelaxation. Moreover, AMO-induced increases in cGMP production were blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of AMO was attenuated by tetraethylammonium, 4-aminopyridine, and glibenclamide. We conclude that AMO relaxed vascular smooth muscle via endothelium-dependent activation of PI3K/Akt-mediated NO-cGMP-PKG signaling pathway and possible involvement of K+ channel.

Expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human preeclamptic placenta: possible implications in the process of trophoblast apoptosis.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was originally identified as a receptor for oxidatively modified low-density lipoprotein. It has been reported that oxidative stress and hyperlipidemia play important roles in the etiology of preeclampsia, and that placental oxidative stress may stimulate syncytiotrophoblast apoptosis in preeclampsia. In this study, we examined the expression of LOX-1 in the human placentas of normal pregnancies and in preeclampsia using immunohistochemistry and Western blot analysis, and proposed that LOX-1 has a role in trophoblast apoptosis. To analyze apoptotic activity, the expression of the specific caspase cleavage site within cytokeratin 18 was assessed immunohistochemically using the monoclonal antibody M30 CytoDeath. Both LOX-1 and M30 immunoreactivity occurred predominantly in syncytiotrophoblasts. A significantly higher number of LOX-1 and M30-positive cells were found in preeclamptic placentas than in normal placentas. The number of M30-positive cells correlated with the apoptotic index of trophoblasts determined by TdT-mediated dUTP nick-end labeling (TUNEL). Syncytiotrophoblasts showing apoptotic activity were immunopositive to LOX-1 by double immunohistochemical fluorescence. We suggest that the functional role of syncytiotrophoblasts in placental dysfunction results from the localization and upregulation of LOX-1 in the preeclamptic placenta, possible implications in upregulation of syncytiotrophoblast apoptotic activity in preeclampsia.

Determination of environmental factors influencing methane oxidation in a sandy landfill cover soil.

It is advantageous to use coarse soils as landfill cover because they allow better aeration of the biologically active zone. In this study, therefore, patterns of methane oxidation were investigated under various environmental conditions including soil moisture content, temperature, and the addition of NH4+ in a sandy landfill cover soil. The kinetics of CH4 oxidation was also studied at different moisture contents and temperatures. Soil moisture content of 10% (wt/wt) resulted in the maximum CH4 oxidation rate (19.2-22.4 nmol gsoil DW(-1) min(-1)). A Vmax value was not significantly different when the moisture content was more than 10%, but a Km value increased from 5.23 to 75.24 microM as the moisture content increased. The ratio of Vmax to Km was the highest at 10% moisture content. The CH4 oxidation rate increased as the incubation temperature increased, and Q10 values and optimum temperature were determined to be 2.57-2.69 and 30 degrees C, respectively. Both Vmax and Km values decreased at the temperatures below and above 30 degrees C. The addition of various levels of NH4+ resulted in increased or decreased CH4 oxidation rates, however, the initiation of appreciable CH4 oxidation was delayed with increasing amounts of NH4+ application in all samples tested. Among the environmental variables tested, moisture content control seems to be the most important and an efficient means of managing methane oxidation when sandy soils are used in landfill cover.

Induction of tetradecanoyl phorbol acetate-inducible sequence (TIS) genes by electroconvulsive shock in rat brain.

We studied the induction of tetradecanoyl phorbol acetate-inducible sequences (TIS)1, 7, 8, 11, and 21 in rat cerebral cortex, hippocampus, and cerebellum after electroconvulsive shock (ECS). These genes were reported to be induced by depolarization in PC-12 cells. Single ECS induced TIS1, 8, 11, and 21, but not TIS7 genes in the rat brain regions examined. In cerebral cortex and hippocampus, induction of TIS1, TIS8, and TIS21 reached peak at 30 or 45 min after ECS. The induced mRNA of TIS1 and 21 decreased rapidly and returned almost to the basal level by 90 min after ECS, whereas those of TIS8 and 11 lasted longer. In cerebellum, TIS genes were induced and disappeared more rapidly than in the other two regions. The 10 and 20 daily ECSs did not affect the inducibility of TIS1, 11, and 21 in cerebellum, but the induction of TIS8 was attenuated by 35% after 20 daily ECSs. Our study indicated that ECS could induce some of the TIS genes in various rat brain regions, but the induction patterns were different depending on the TIS genes and brain regions. Our study also suggested that chronic ECS could not attenuate the induction of some immediate early genes.

Electrocardiographic abnormalities in patients treated with clozapine.

BACKGROUND: Cardiovascular side effects of clozapine are not uncommon, but few systematic studies of these effects have been performed. In this study, we reviewed data on the electrocardiographic (ECG) abnormalities in patients treated with clozapine. METHOD: Sixty-one patients treated with clozapine were selected from the Seoul National University Hospital Treatment-Resistant Schizophrenia Clinic. A retrospective chart review was conducted to identify ECG abnormalities and cardiovascular side effects. RESULTS: The prevalence of ECG abnormalities in patients who had been using antipsychotics other than clozapine was 13.6% at baseline, which increased significantly to 31.1% after commencement of clozapine treatment. Among the 53 patients without baseline ECG abnormalities, 13 showed new-onset ECG abnormalities after using clozapine. Normal ECG under previous antipsychotic medication reduced the risk of new-onset ECG abnormalities, whereas increased age was found to increase the risk. The occurrence of orthostatic hypotension or tachycardia was not related to the development of ECG abnormalities. Most of the newly developed abnormalities had little clinical significance, and they tended to occur during the initial phase of treatment. In 10 patients, ECGs normalized despite the continued use of clozapine. Clozapine increased corrected QT interval (QTc) in a dose-dependent fashion; however, the clinical significance of this observation is uncertain. Pathologic prolongation of QTc was found to be rare. CONCLUSION: Although a substantial portion of patients treated with clozapine developed ECG abnormalities, most of the abnormalities were benign and did not hinder further treatment.

Efficacy of measles vaccine during the 1993 measles epidemic in Korea.

Immunization to eliminate measles is recommended at 15 months of age with the option of giving vaccine at 6 to 9 months of age during measles outbreaks in Korea. Because of the recent resurgence of measles and concern about the possibility of reduced vaccine efficacy caused by genomic differences between vaccine virus and contemporary wild measles viruses, we conducted a measles vaccine efficacy study involving children with household exposure ages 1 to 5 years during measles outbreak that had occurred 1993 in Seoul and Seong-nam city, with the demographic analysis of patients brought to the hospitals. A total of 380 patients (M:F = 216:164) were included in this study. Two hundred nine cases (55.0%) occurred in children less than 5 years of age, and 167 (43.9%) were younger than 16 months of age. The recorded age-specific incidence rates showed bimodal patterns, i.e. highest peak in those below 16 months of age and second peak in those ages 6 to 9 years of age. Only 9.6% (16 of 167) of the measles cases less than 16 months, 59.5% (25 of 42) of those 16 months to 4 years and 91.8% (157 of 171) of the cases in school age children have been vaccinated. Attack rates among the 122 vaccinated siblings and 12 unvaccinated siblings ages 1 to 5 years who contacted measles were 5.7 and 75%, respectively, and the clinical vaccine efficacy was 92.4% (95% confidence interval, 83.6, 96.4). The high vaccine efficacy in household exposures suggests that measles outbreaks in Korea are not caused by reduced vaccine efficacy.

A convenient method for the efficient removal of ruthenium byproducts generated during olefin metathesis reactions.

[reaction in text] An efficient method for removing ruthenium byproducts generated during olefin metathesis reactions with Grubbs catalysts is described. Treatment of the crude reaction products with triphenylphosphine oxide or dimethyl sulfoxide, followed by filtration through silica gel, was found to be a practical and effective method to remove colored ruthenium byproducts.

An N-methyl-D-aspartate antagonist, MK-801, preferentially reduces electroconvulsive shock-induced phosphorylation of p38 mitogen-activated protein kinase in the rat hippocampus.

Electroconvulsive shock (ECS) activates the mitogen-activated protein kinase (MAPK) family in the rat hippocampus, but the signaling pathways for this activation are not well understood. We investigated whether N-methyl-D-aspartate (NMDA) receptor mediated signaling is involved in the phosphorylation-activation of the MAPK family. The NMDA receptor antagonist, MK-801, dose-dependently reduced ECS-induced phosphorylation of p38 and its upstream kinase MKK6 up to 1 mg/kg. MK-801 also reduced the phosphorylation of ERK1/2 and MEK1, but only at high dosage, 2 mg/kg. Moreover, the reduction in the phosphorylation of p38 and MKK6 was greater than that of ERK1/2 and MEK1. Our results suggest that ECS activates p38 and ERK1/2 partly through an NMDA receptor-mediated signaling system in the rat hippocampus and that NMDA receptor mediated signaling is more responsible for the activation of the MKK6-p38 pathway than the MEK1-ERK pathway.

Differential activation of c-Jun N-terminal protein kinase and p38 in rat hippocampus and cerebellum after electroconvulsive shock.

Electroconvulsive shock (ECS), an effective treatment for psychiatric diseases, has been reported to induce immediate-early genes (IEGs) and to activate p42 and p44 MAPKs (ERK-1 and ERK-2) in rat brain. In this study, we examined the activation of the other members of MAPK family, c-Jun N-terminal protein kinase (JNK/SAPK) and p38. Following ECS, the phosphorylation of p38 was substantially increased in both hippocampus and cerebellum, but the increase of JNK phosphorylation was observed only in hippocampus. We also investigated the phosphorylation of their upstream kinases, SEK-1, MKK6 and MKK3. In both hippocampus and cerebellum, the phosphorylation of MKK6 showed closer correlation with p38 phosphorylation than that of MKK3. However, SEK-1, known as upstream kinase of JNK and p38 in vitro, corresponded with none of MAPKs. These results, with previous reports on the activation of ERK, indicate that ECS activates three MAPKs differentially in rat hippocampus and cerebellum, and suggest the possibility that unknown MAPKK may be involved in the activation of JNK in rat brain after ECS.

Non-linear dynamic analysis of clozapine-induced electroencephalographic changes in schizophrenic patients--a preliminary study.

1. In order to find the electroencephalographic (EEG) parameters that reflect the effect of clozapine in schizophrenic patients, the authors applied various non-linear analyses on multi-channel EEG data drawn from patients before and after a therapeutic trial of clozapine. 2. The correlation dimension was difficult to extract from our limited time series EEG data and the authors did not find a meaningful association with clozapine use. The primary Lyapunov exponent could be reliably calculated but also did not reflect the effect of clozapine. 3. However, the mutual cross-prediction (MCP) algorithm showed potentially meaningful results. The driving system was shifted to the frontal channels after a 4-week trial with clozapine. Moreover, MCP might have a value as a predictor of treatment response. 4. Although preliminary in nature, the MCP might have greater power for interpreting complex changes from channel to channel in EEG induced by clozapine.

Isoform-specific changes of adenylate cyclase mRNA expression in rat brains following chronic electroconvulsive shock.

1. Electroconvulsive shock (ECS) has been reported to regulate the cAMP signaling system at various levels, suggesting that the cAMP system is involved in the therapeutic mechanism. 2. Chronic ECS has been suggested to change the expressions of adenylate cyclase (AC) genes, which constitute at least 9 families. However, little is known about its effect on the expression of AC. Therefore, to understand how chronic ECS alters the expression of AC genes in the brain, the authors analyzed the expression of 9 AC isoforms at the transcriptional level in rat hippocampus and cerebellum by quantitative RT-PCR following chronic ECS treatment. 3. Chronic ECS treatment was found to induce differential changes in the expression of AC isoforms in an isoform- and brain region-specific manner in the rat hippocampus and cerebellum. 4. Thus, it is concluded that chronic ECS induces differential changes in the expression of AC isoform mRNA in an isoform- and brain region-specific manner in the rat hippocampus and cerebellum. This suggests that the differential expression of AC isoforms might be an important mechanism by which chronic ECS treatment regulates the cAMP signaling system in rat brains.