Childhood Attention Deficit in the Patients with Bipolar Disorder and CHRNA7 Gene Polymorphisms / 대한정신약물학회지

OBJECTIVE: Patients with bipolar disorder have attention deficit during even euthymic status. Bipolar disorder patients showed more childhood attention deficit and other ADHD like feature. Alpha 7 nicotinic receptor (CHRNA7) gene has been known to play roles in attention and sensory gating, and association between CHRNA7 gene and bipolar disorder has been reported. Therefore, we investigated a possible association between childhood attention deficit of bipolar disorder and CHRNA7 gene polymorphisms. METHODS: We included 122 patients with bipolar disorder (89 subjects of bipolar disorder type I, 33 subjects of bipolar disorder type II). Childhood attention deficit was measured by Wender Utah Rating Scale (WURS). Factor analysis was done for WURS to extract inattention factor from childhood ADHD like feature. Three factors were extracted: Impulsivity, Inattention, and Mood instability. All subjects were ethnically Korean. Genotyping was done for three intronic Single Nucleotide Polymorphism (SNPs) of CHRNA7 gene: rs2337506 (A/G), rs6494223 (C/T), and rs12916879 (A/G). Analysis of association was done by UNPHASED version 3.1.4, a free software for genetic statistics. RESULTS: Genetic association tests found no association between factor score of inattention and any SNP or combination of SNPs of CHRNA7. Positive association between WURS total score and SNP rs6494223 (p=0.043), factor score of impulsivity and SNP rs2337506 (p=0.038) as well as SNP rs6494223 (p=0.043) was revealed. These positive associations were survived after 1,000 permutation tests. Combination of SNPs association tests performed for total WURS and factor scores could not find any significant association. CONCLUSION: We could not find association between CHRNA7 gene and childhood attention deficit in bipolar disorder. However, we found CHRNA7 gene involved in childhood impulsivity of bipolar disorder, another ADHD like feature. Further studies with larger sample and denser polymorphisms are necessary to clarify genetic role of CHRNA7 in attention and impulsivity of bipolar disorder.

Inhibition of Angiotensin II-Induced Vascular Smooth Muscle Cell Hypertrophy by Different Catechins

A cumulative evidence indicates that consumption of tea catechin, flavan-3-ol derived from green tea leaves, lowers the risk of cardiovascular diseases. However, a precise mechanism for this cardiovascular action has not yet been fully understood. In the present study, we investigated the effects of different green tea catechins, such as epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC), epicatechin-3 gallate (ECG), and epicatechin (EC), on angiotensin II (Ang II) -induced hypertrophy in primary cultured rat aortic vascular smooth muscle cell (VSMC). [3H]-leucine incorporation was used to assess VSMC hypertrophy, protein kinase assay, and western blot analysis were used to assess mitogen-activated protein kinase (MAPK) activity, and RT-PCR was used to assess c-jun or c-fos transcription. Ang II increased [3H]-leucine incorporation into VSMC. However, EGCG and ECG, but not EGC or EC, inhibited [3H]-leucine incorporation increased by Ang II. Ang II increased phosphorylation of c-Jun, extracellular-signal regulated kinase (ERK) 1/2 and p38 MAPK in VSMC, however, EGCG and ECG, but not EGC or EC, attenuated c-Jun phosphorylation increased by Ang II. ERK 1/2 and p38 MAPK phosphorylation induced by Ang II were not affected by any catechins. Ang II increased c-jun and c-fos mRNA expression in VSMC, however, EGCG inhibited c-jun but not c-fos mRNA expression induced by Ang II. ECG, EGC and EC did not affect c-jun or c-fos mRNA expression induced by Ang II. Our findings indicate that the galloyl group in the position 3 of the catechin structure of EGCG or ECG is essential for inhibiting VSMC hypertrophy induced by Ang II via the specific inhibition of JNK signaling pathway, which may explain the beneficial effects of green tea catechin on the pathogenesis of cardiovascular diseases observed in several epidemiological studies.

Compartmental analysis of RBC circulation through the rabbit kidney

This experiment involved 12 rabbits of both sexes, weighing 2.1 kg. After anesthesia, the kidneys were exposed, isolated and cannulated in the renal artery, ureter and sometimes in the vein as well. The kidney were perfused through the renal artery with Krebs-Henseleit solution, which were then filtered to be free of particles, gased with 95% O2-5% CO2, and kept at 37 degrees C. We measured RBCs concentrations by means of Coulter Counter in the venous outflow collected, and plotted them against the volume perfused. Using 2 different flow rates, 9 ml/min (group I) and 19 ml/min (group II), we found that the RBCs decreased in a multiexponential decay fashion and a biophysical model for each flow rate was constructed. These models indicated that there were more cell stores (2.20 x 10(10)) in the fast compartment of group II than in group I (1.72 x 10(10)). This difference is not statistically significant, but certainly coincides with urine flow collected from ureter cannula during perfusion. Our present data clearly suggest that in order to clear 99% blood cells out of 10-12 gm rabbit kidneys, at least 3-6 ml of cell free perfusate is required while clearing the whole blood cells out of human kidneys (200-240 gm) may need 600 ml or more. Thus, we recommend that at least 600 ml of perfusate should be used to clear most of the blood cells in the renal vasculature before renal transplantation is performed.