Sabina Lim

Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes.

Chloroquine has been used for many decades in the prophylaxis and treatment of malaria. It is metabolized in humans through theN-dealkylation pathway, to desethylchloroquine (DCQ) and bisdesethylchloroquine (BDCQ), by cytochrome P450 (CYP). However, until recently, no data are available on the metabolic pathway of chloroquine. Therefore, the metabolic pathway of chloroquine was evaluated using human liver microsomes and cDNA-expressed CYPs. Chloroquine is mainly metabolized to DCQ, and its Eadie-Hofstee plots were biphasic, indicating the involvement of multiple enzymes, with apparent Km and Vmax values of 0.21 mM and 1.02 nmol/min/mg protein 3.43 mM and 10.47 nmol/min/mg protein for high and low affinity components, respectively. Of the cDNA-expressing CYPs examined, CYP1A2, 2C8, 2C19, 2D6 and 3A4/5 exhibited significant DCQ formation. A study using chemical inhibitors showed only quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4/5 inhibitor) inhibited the DCQ formation. In addition, the DCQ formation significantly correlated with the CYP3A4/5-catalyzed midazolam 1-hydroxylation (r=0.868) and CYP2C8-catalyzed paclitaxel 6α-hydroxylation (r = 0.900). In conclusion, the results of the present study demonstrated that CYP2C8 and CYP3A4/5 are the major enzymes responsible for the chloroquineN-deethylation to DCQ in human liver microsomes.

Deqi Sensation Between the Acupuncture-Experienced and the Naïve: A Korean Study II

Previous experience of acupuncture is believed to affect peoples expectation of future treatments. Therefore, subjects who have had acupuncture are generally excluded from sham-controlled acupuncture clinical trials. However, this assumption has not been proven, but just accepted because of the lack of evidence to the contrary. To investigate the difference in frequency and intensity of acupuncture sensation between subjects who have had acupuncture and those who have not, 36 acupuncture-experienced subjects were invited to take part in the study. After informed consent was obtained, participants were asked to complete the acupuncture sensation scale (ASS) according to what they expected needling to feel like. The needling was done at the left Hegu (LI 4) point and consisted of insertion, stimulation for 30 seconds and removal. After needling, the subjects were asked to complete the same ASS according to what they actually experienced. Adverse events were monitored. The frequency of each sensation expected and experienced, as well as acupuncture sensation scores were compared. More than 60% of the subjects expected to feel sensations of penetrating (87.6% to 100%), aching (71.2% to 95.5%), tingling (87.6% to 100%), pricking (79.7% to 99.2%) and throbbing (64.2% to 91.4%). In fact, the subjects experienced sharp (60.9% to 89.1%), intense (60.9% to 89.1%), radiating (71.2% to 95.5%) and heavy (74.8% to 97.4%) sensations just as much. The subjects expected more hurting (p = 0.001), tingling (p < 0.001), pricking (p = 0.010), stinging (p = 0.012), burning (p = 0.001) and pulsing (p = 0.009) than they experienced, while more heaviness (p = 0.011) was experienced than expected. The same outcome measures were also compared between experienced and naive groups. Apart from the fact that the acupuncture-experienced participants expected to feel pricking (p = 0.030) and stinging (p = 0.002), and experienced hurting (p = 0.022) and stinging (p = 0.028) significantly less than those who had not had acupuncture before, there was no significant difference between first time and experienced subjects. The results indicate that previous experience does not affect the peoples expectation and does not hinder people from experiencing Deqi. In addition, a constellation of Deqi-related acupuncture-specific sensations is more than just a general pain intensity dimension, which requires a biochemical and physiological exploration.

Effect of acupuncture on 6-hydroxydopamine-induced nigrostratal dopaminergic neuronal cell death in rats.

In this study, we investigated the effect of acupuncture at the Zusanli acupoint (ST36) on the nigrostriatal dopaminergic neuronal cell death in the rats with Parkinsons disease. Two weeks after unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum, an apomorphine-induced rotational behavior test showed significant rotational asymmetry in the rats with Parkinsons disease. Immunostaining for tyrosine hydroxylase demonstrated a dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. Acupuncture at the ST36 for 14 days significantly inhibited rotational asymmetry in the rats with Parkinsons disease, and also protected against 6-OHDA-induced nigrostriatal dopaminergic neuronal loss. These effects of acupuncture were not observed for the non-acupoint (hip) acupuncture. The present study shows that acupuncture at the ST36 acupoint can be used as a useful strategy for the treatment of Parkinsons disease.

A combined extract of Cinnamomi Ramulus, Anemarrhenae Rhizoma and Alpiniae Officinari Rhizoma suppresses production of nitric oxide by inhibiting NF‐κB activation in RAW 264.7 cells

An herbal mixture prepared with Cinnamomi Ramulus, Anemarrhenae Rhizoma and Alpiniae Officinari Rhizoma (CAA) is used in oriental medicine for treating several ailments. The purpose of this study was to determine the mechanisms by which CAA elicits an antiinflammatory effect on nitric oxide (NO) production in the mouse macrophage cell line RAW 264.7 cells. The results indicated that lipopolysaccharide (LPS)‐induced NO production was inhibited by CAA in a dose‐dependent manner. Western blotting and RT‐PCR analysis demonstrated that CAA decreased LPS‐induced inducible nitric oxide synthase (iNOS) protein and gene expression in RAW 264.7 cells. Furthermore, CAA inhibited the LPS‐induced DNA binding activity of nuclear factor‐kappa B (NF‐κB) and this effect was mediated through inhibiting the degradation of inhibitory factor‐κBα (IκBα). Therefore, the results demonstrate that CAA inhibits LPS‐induced production of NO and expression of iNOS by blocking NF‐κB activation. CAA might be a potential therapeutic candidate for treating inflammatory diseases such as arthritis. Copyright

Transforming growth factor beta receptor II (TGFBR2) polymorphisms and the association with nonsegmental vitiligo in the Korean population

The precise cause of vitiligo is unknown. However, autoimmunity is considered the most likely aetiology, especially in nonsegmental vitiligo (NSV). In this study we determined whether or not the transforming growth factor beta receptor II (TGFBR2) gene contributes to susceptibility for NSV in the Korean population. Blood samples were collected from 415 controls and 233 cases. We selected three single nucleotide polymorphisms (SNPs) in the TGFBR2 gene. The genotypes of the SNPs were determined using direct sequencing. All of the SNPs were significantly different between the vitiligo patients and controls (rs2005061, co‐dominant, dominant, recessive, P < 0.05; rs3773645, co‐dominant, dominant, recessive, P < 0.05; rs3773649, co‐dominant, recessive, P < 0.05). In addition, haplotype 1 (CG) and haplotype 2 (GA) of the linkage disequilibrium (LD) block were also associated with a risk of NSV. The present study suggests that TGFBR2 might be related to NSV.

Acupuncture modulates expressions of nitric oxide synthase and c-Fos in hippocampus after transient global ischemia in gerbils

The effects of acupuncture on the expressions of nitric oxide synthase (NOS) and c-Fos in the hippocampus of gerbils after transient ischemia were investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and Fos immunohistochemistry. In animals of the ischemia-induction groups, both common carotid arteries were occluded for 5 minutes. Animals of the acupunctued groups were given acupunctural treatment at Zusanli twice daily for 9 consecutive days. Acupuncture was shown to decrease NADPH-d and c-Fos levels in both the sham-operation group and the ischemia-induction group. These results suggest that acupuncture modulates the expressions of NOS and c-Fos in the hippocampus.

fMRI Study on the Brain Activity Induced by Manual Acupuncture at BL62

Recently, the effect of acupuncture was approved not only in the East but also in the West, so the interest on acupuncture has greatly been improved. Especially, functional magnetic resonance imaging (fMRI) was embossed as the tool for studying the mechanism of acupuncture noninvasively and many studies on the mechanism of acupuncture using fMRI were carried out. Here, we acquired 9 fMRI results from 6 persons (age 20–30, 4 male and 2 female) to study the brain activity for motor function by acupuncture at the left BL62. We employed the block design for mapping brain activity. We proceeded to study the brain activity for motor function by acupuncture at BL62. In the result of this study, the regions showed significant activation in the cerebellum was centered on the spinocerebellum in the anterior lobe, so we presumed that this result showed the input of stimulation by acupuncturing on BL62. Unexpectedly basal ganglia and cerebral cortex showed the regions of significant activation in the left rather than in the right. This result explains that acupuncture on BL62 could have an influence on the motor function of cerebellum and could affect the right side through the activation of the left basal ganglia and cerebral cortex. We think of this result as the evidence which could explain the theory of crossing needling at collaterals.