~(123)I-MIBG心肌显像预测依那普利对扩张型心肌病患者治疗效果的临床价值

目的探讨123I-MIBG心肌显像在治疗前预测依那普利对扩张型心肌病(DCM)患者治疗效果的临床价值。方法对24例DCM患者于依那普利治疗前行早期(20min)及延迟(3h)123I-MIBG心肌显像,采用心/上纵隔(H/M)比和心脏放射性洗脱率(WR)作为相对半定量计数分析,与超声心功能参数进行对比。根据123I-MI-BG心肌显像延迟相的H/M分为3组延迟H/M≥1.7为组Ⅰ,1.5<延迟H/M<1.7为组Ⅱ,延迟H/M≤1.5为组Ⅲ。组Ⅰ和组Ⅱ在平均治疗4.5个月后重复以上检查。结果治疗前3组间超声心功能参数比较均无统计学差异。治疗后组Ⅰ的左室射血分数(LVEF)和左室收缩末径(LVDs)明显改善,早期H/M和延迟H/M均明显改善(P<0.05),而WR无明显变化。治疗后组Ⅱ的延迟H/M明显改善(P<0.05),而早期H/M和WR均无明显变化,心功能参数也无改善。组Ⅰ和组Ⅱ患者均能耐受依那普利治疗,而组Ⅲ患者均不能耐受依那普利治疗。结论123I-MIBG心肌显像在治疗前预测依那普利对DCM患者的治疗效果方面有一定价值。     

A suspicious case of central neurosarcoidosis, manifesting as a progressive gait disturbance with a lesion in the central gray matter of the midbrain, accompanying an elevated level of angiotensin converting enzyme in the cerebrospinal fluid]

We present a suspicious case of central neurosarcoidosis that presented with progressive gait disturbance probably caused by central vestibular dysfunction. And this case showed elevated level of angiotensin converting enzyme (ACE) in the cerebrospinal fluid, compared with the average level of two cases with acute inflammatory demyelinating neuropathy syndrome and four cases of multiple sclerosis. A 33-year-old man was admitted to our hospital with chief complaint of a gait disturbance that had appeared 3 years prior to the admission. And the symptom had exacerbated in these 3 months. Except for the gait disturbance and positive Romberg's sign, no neurological abnormality was detected. The findings of the cerebrospinal fluid test supported the diagnosis of meningitis. An increased level of angiotensine converting enzyme was detected when compared with our previous samplings from two cases of Guillain Barré syndrome and four cases of multiple sclerosis. With T1 weighted imaging of brain MRI, a high intensity lesion with gadolinium enhancement was identified in the central gray matter of the midbrain. Scan of the chest confirmed bilateral hilar lymphadenopathy. Based on these findings and the patient's clinical course, central neurosarcoidosis was suspected. The patient's symptoms improved dramatically after the administration of corticosteroid. The enhancement of the central gray matter ameliorated, and the ACE level of the CSF was decreased to the level of the demyelinating disorders.     

The fates of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice

In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, ³H-FX or ³H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given ³H-FX, but mainly via the feces in mice given ³H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of ³H-FX or ³H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in ³H-FX-administered than ³H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with ³H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.     

Linkage guide for rotational alignment during total knee arthroplasty

A linkage guide was devised for use in conjunction with knee arthroplasty instruments to achieve proper component rotation. The femoral component was rotationally aligned to the surgical epicondylar axis using one guide. The other guides were used after all bone surfaces were cut and soft tissue balancing was completed. A Kirschner wire was guided into the proximal tibial aspect parallel to the sagittal plane of the femoral component with the patella in its normal position and the knee in full extension. The wire was used as a reference to determine tibial component rotation. The relative rotational alignment of 21 knees in 19 patients who had undergone cruciate-retaining total knee arthroplasty utilizing this guide was assessed using the modified Eckhoff method. The results of radiographic analysis were compared with those in a control group of 25 knees where the guide was not employed. The external rotation of the femoral component relative to the tibial component was 1.3° ± 2.0° (mean ± SD) in the guided group and 1.1° ± 4.4° in the control group. The relative rotational angle was significantly more consistent using the guide. Implant malrotation can be reduced using our technique.     

Structural changes and cell viability of cultured epithelium after freezing storage

Numerous clinical reports have shown the utility of cultured epithelial grafting in the field of plastic and reconstructive surgery. Recently, freezing storage of the cultured epithelium has been tried and has successfully grafted after thawing. It is clinically convenient if it is possible for cultured epithelium to keep its normal structure and viability. However, few papers have described the structural changes in cultured epithelium after freezing storage. In the present study, the morphological changes and cell viability of cultured mucosal epithelial sheets after freezing were studied in comparison with cultured epidermal sheets. Furthermore, we discuss the effect of storage temperature and cryoprotectants.As a result, there were some structural changes such as vacuolar degeneration in the cultured mucosal sheets using dimethyl sulphoxide (DMSO) as a cryoprotectant. Such changes were more clearly observed at −80°C than at −196°C with DMSO. However, little morphological change was observed in both epithelial sheets cultured with glycerin. The cell viability analysed by flow cytometry showed that more than 62% of the cells kept their viability after freezing storage. These results suggest that the optimum conditions of freezing for cultured epithelium were −196°C storage by slow cooling methods with glycerin as a cryoprotectant.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Polyclonal anti-desmosine antiserum is specific to desmosine molecule: no cross-reaction to pyridinoline

Inhibition ELISA assay was used to examine the cross-reaction of the polyclonal anti-desmosine antiserum produced in rabbit against molecules possessing a "pyridinium ring" as their core structure i.e. isodesmosine, pentasine, pyridinoline and 2'-deoxypyridinoline, highly purified with column chromatography, and structurally unrelated substances, i.e. cysteic acid, taurine and 2-aminopyridine (core structure of desmosine). No cross-reaction was observed to the pyridinoline, 2'-deoxypyridinoline possessing "pyridinium ring" and derived from collagen cross-links, structurally unrelated cysteic acid and taurine, nor core structure of 2-aminopyridine. The antiserum specifically recognized the molecules derived from the elastin cross-links. Using the ELISA assay system with antisera and amino acids analysis, 10 micrograms of desmosine were extracted from 1.0 mg of the hydrolysate of commercial elastin.     

Microarray analysis on Phase II drug metabolizing enzymes expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile or phenobarbital

We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.