Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.

We investigated the effect of CYP2D6 genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 88 Japanese schizophrenic inpatients being treated with HAL. Some subjects carrying CYP2D6*5 allele (CYP2D6*1/CYP2D6*5, CYP2D6*5/CYP2D6*10) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D6*5 allele seemed to have higher plasma concentrations of HAL (1.14+/-0.69 ng/ml/mg) and RHAL (1.10+/-1.05 ng/ml/mg) than the other groups. Among those without CYP2D6*5 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D6*10 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.69+/-0.14 ng/ml/mg, RHAL=0.40+/-0.09 ng/ml/mg), although there was a tendency of higher plasma concentration of RHAL in those with two CYP2D6*10 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D6*10 allele(s) showed significantly higher plasma concentrations of RHAL (0.43+/-0.23 ng/ml/mg, 0.34+/-0.16 ng/ml/mg) than those without CYP2D6*10 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D6*10 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D6*10 allele with CYP2D6*5 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.     

蘡Ao中分离的多酚化合物

目的分离鉴定蘡Ao地上部分的化学成分。方法通过硅胶柱色谱，Sephadex LH-20及制备HPLC方法分离，对其进行理化常数和光谱分析确定结构。结果自蘡Ao地上部分分离得到11个多酚化合物，均属首次分离。结论化合物1为新化合物，经鉴定其结构为3，5-二甲氧基-4-羟基苯丙醇-9-氧-β-D-吡喃葡萄糖苷。     

Systemic inflammatory response syndrome and acute renal failure associated with Hemophilus influenzae septic meningitis

Sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis.     

Triggers of hair cell regeneration in the avian inner ear

We performed an in vitro study in order to determine possible triggers of hair cell regeneration in the chick basilar papilla following degeneration. We compared the response of sensory epithelium damaged by collagenase treatment with that damaged by acoustic trauma. The former exhibited no proliferative activity, but the latter did. The basilar papillae damaged by acoustic trauma could have proliferating activity in medium containing fetal bovine serum (FBS) or epidermal growth factor (EGF) but not in the medium without FBS or EGF. These findings indicate that regeneration of basilar papillae depends on the manner of cell death and that FBS or EGF is required for regeneration.     

A Question and Answer E-Mail System for Responding to Query from the General Public with Which the System Manager Can Identify Delayed Replies

We constructed a question and answer system for direct delivery of E-mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two sub-systems; one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days.     

(+)-cis-ε-Viniferin的结构确证

用光化学沟通方法确证了从葡萄科植物蘡薁Vitis thunbergii(Vitaceae)中分离得到的( )-cis-ε-viniferin的结构；并纠正了文献核磁共振氢谱(^1H-NMR)数据。     

Uptake of99mTc-tetrofosmin,99mTc-MIBI and201TI in malignant thymoma

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.     

Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels.

PURPOSE: There are no available tumor markers detecting primary melanoma at an early stage. The identification of such serum markers would be of significant benefit for an early diagnosis of melanoma. We recently identified glypican-3 (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby, we focused out attention on secreted protein acidic and rich in cysteine (SPARC) overexpressed in melanoma as another candidate for tumor marker. EXPERIMENTAL DESIGN: Secreted SPARC protein was quantified using ELISA in the sera from 109 melanoma patients, five patients with large congenital melanocytic nevus, 61 age-matched healthy donors, and 13 disease-free patients after undergoing a surgical removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples and compared these markers for their diagnostic value. RESULTS: The serum SPARC concentrations in melanoma patients were greater than those in healthy donors (P = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the healthy donors, the serum SPARC was found to have increased in the sera of 36 of the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased SPARC levels were in stages 0 to II. The serum SPARC level decreased under the cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an early stage (0-II). CONCLUSIONS: SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage.     

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.