A possibility of the prognosis factor of serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) as a marker of bone metastasis

We measured ICTP in 126 patients suffering from cancer in our palliative care unit to investigate the clinical significance of serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and divided them into 2 groups according to the absence or presence of bone metastasis. 1) There was a relationship that of ICTP = -22.6Loge (Ccr) + 111.4 (r = 0.63, p < 0.01) between ICTP and creatinine clearance (Ccr) in non-metastasis group. The ICTP increased as renal function deteriorated. 2) In cancer patients with normal renal function of 40 ml/min/1.73 m2, ICTP was significantly higher in the group of metastasis than non-metastasis group. 3) In cancer patients who died, ICTP was high in both metastasis and non-metastasis groups and no difference was found between 2 groups. Duration of disease was significantly short in non-metastasis group than in metastasis group. These results suggest that ICTP is one of markers of bone metastasis, but higher value of ICTP is influenced by various factors such as renal function and may reflect the prognosis.     

Bile acids influence hepatic chemiluminescence in normal and oxidative-stressed rats†

The aim of the present study was to clarify whether bile acids influence chemiluminescence (CL) in the liver in vivo. Hepatic CL was determined on the surface of the liver of anaesthetized rats by using a photon counter. In normal rats, hepatic CL was significantly decreased 30 min after enteral administration of chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA), but returned to its initial level 3 h later, after part of the CDCA administered was metabolized. Ursodeoxycholic acid (UDCA) and cholic acid had no effect on CL. In contrast, hepatic CL was markedly increased 30 min after CDCA or DCA administration in rats given either buthionine sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, or diethyldithiocarbamate (DDC), an inhibitor of both superoxide dismutase and glutathione peroxidase. Chenodeoxycholic acid further increased the CL of BSO- or DDC-treated rats during inhalation of oxygen via a tracheal cannula. Coadministration of UDCA eliminated the effects of CDCA on the hepatic CL of normal and BSO- or DDC-treated rats with or without oxygen inhalation. We conclude that cytotoxic bile acids, such as CDCA, increase CL in the antioxidants-depleted or oxidative-stressed liver in vivc, but that UDCA prevents CDCA from developing CL.     

THE EFFECT OF ALTHESIN (CT1341) ON THE OXYHAEMOGLOBIN DISSOCIATION CURVE IN VITRO

Blood from non-smoking donors was incubated with Althesin andthe Po2 for half-saturation of haemoglobin at standard pH, Pco₂and temperature (P₆₀) was measured. The mean P₆₀ values of bloodwith blood concentrations of Althesin of 0.14ml/dl and 0.42ml/dl were greater (1.14 ± 0.31 (SEM) mm Hg (p< 0.005)and 2.22 ± 0.35 (SEM) mm Hg (P< 0.001), respectively)than that of control blood. These increases were dose-dependent(P< 0.05). Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentrationswere not significantly different between the Althesin-treatedand the control blood. Although a decrease in the affinity ofhaemoglobin for oxygen in vitro in the presence of Althesinwas statistically significant, this would have no clinical significanceif the drug was being used for the induction of anaesthesiaonly.     

Brain perfusion differences between Parkinson's disease and multiple system atrophy with predominant parkinsonian features

BACKGROUND: The patterns of regional cerebral blood flow in Parkinson's disease and multiple system atrophy remain inconsistent. OBJECTIVES: To compare brain perfusion images of 123I-IMP SPECT between Parkinson's disease, multiple system atrophy with predominant parkinsonian features (MSA-P) and controls. METHODS: Eighty-two patients with Parkinson's disease, 10 patients with MSA-P and 14 controls were studied. We performed 3D-SSP and volume of interest analysis using 123I-IMP scintigraphy. RESULTS: Occipital perfusion of MSA-P increased compared to that of Parkinson's disease and perfusion in the cerebellum and primary sensorimotor cortex of Parkinson's disease increased compared to that of MSA-P. Perfusion in the putamen of MSA-P decreased compared to that of Parkinson's disease. CONCLUSION: Our study demonstrated perfusion differences in 123I-IMP SPECT between the two diseases.     

Assessment of statistic analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example

The murine local lymph node assay (LLNA) is used for the identification of chemicals that have the potential to cause skin sensitization. However, it requires specific facility and handling procedures to accommodate a radioisotopic (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA based on BrdU incorporation to avoid a use of RI. Although this alternative method appears viable in principle, it is somewhat less sensitive than the standard assay. In this study, we report investigations to determine the use of statistical analysis to improve the sensitivity of a non-RI LLNA procedure with alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the alternative non-RI method required HCA concentrations of greater than 25% to elicit a positive response based on the criterion for classification as a skin sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the alternative method were consistent in both experiments and we examined whether the use of an endpoint based upon the statistical significance of induced changes in LNC turnover, rather than an SI of 3 or greater, might provide for additional sensitivity. The results reported here demonstrate that with HCA at least significant responses were, in each of two experiments, recorded following exposure of mice to 25% of HCA. These data suggest that this approach may be more satisfactory-at least when BrdU incorporation is measured. However, this modification of the LLNA is rather less sensitive than the standard method if employing statistical endpoint. Taken together the data reported here suggest that a modified LLNA in which BrdU is used in place of radioisotope incorporation shows some promise, but that in its present form, even with the use of a statistical endpoint, lacks some of the sensitivity of the standard method. The challenge is to develop strategies for further refinement of this approach.     

Axillary dissection can be avoided in selected patients with breast cancer

Acknowledgment  This study was supported by the Grant for Scientific Research Expenses for Health and Welfare Programs (Second Term Comphrehensive 10-Year Strategy for Cancer Control).     

Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals

We performed the Hershberger assay of 12 chemicals based on the OECD draft protocol. The chemicals tested by the Hershberger assay were phthalic acid di-n-hexyl ester, phthalic acid di-n-amyl ester, phthalic acid di-n-propyl ester, diethylstilbestrol, 17beta-estradiol, tamoxifen, 5alpha-dihydrotestosterone, dichlorodiphenyldichloroethane, cyproterone acetate, 6alpha-methyl-17alpha-hydroxy-progesterone, atrazine, and spironolactone. Phthalic acid di-n-hexyl ester, phthalic acid di-n-amyl ester, and phthalic acid di-n-propyl ester are phthalates; diethylstilbestrol and 17beta-estradiol are estrogenic chemicals; tamoxifen is partial estrogen receptor antagonist with mainly estrogenic properties; 5alpha-dihydrotestosterone is an androgen derivatives; dichlorodiphenyldichloroethane is a reference androgen antagonistic chemical; cyproterone acetate, 6alpha-methyl-17alpha-hydroxy-progesterone, and spironolactone have an androgenic steroid structure and are known as androgen antagonistic chemicals; and atrazine is a reference endocrine disruptor. We also subjected these chemicals to the receptor binding assay for androgen. A clear androgen agonistic effect was detected in 5alpha-dihydrotestosterone, and an androgen antagonistic effect was observed in five chemicals: cyproterone acetate, spironolactone, 6alpha-methyl-17alpha-hydroxy-progesterone, phthalic acid di-n-amyl ester, and dichlorodiphenyldichloroethane. By contrast, diethylstilbestrol, 17beta-estradiol, tamoxifen, 5alpha-dihydrotestosterone, dichlorodiphenyldichloroethane, cyproterone acetate, 6alpha-methyl-17alpha-hydroxy-progesterone, and spironolactone were positive in the receptor binding assay for androgen. Three estrogenic chemicals, diethylstilbestrol, 17beta-estradiol, and tamoxifen, were negative in the Hershberger assay with receptor binding affinity. On the other hand, the Hershberger assays of three phthalates were performed at the same dosages, and the results showed androgen antagonistic affinity only in the assay of phthalic acid di-n-amyl ester without receptor binding affinity.     

A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.

We have previously demonstrated that in mice, the decrease in serum thyroxine (T(4)) level by polychlorinated biphenyls (PCBs) occurs without an increase in the UDP-glucuronosyltransferase (T(4)-UDP-GT) for T(4) glucuronidation, although the PCB-induced decrease in rats is generally thought to occur through induction of T(4)-UDP-GT, UGT1A1, and UGT1A6. In the present study, to further clarify the relationship between the decrease in serum T(4) level and the increase in UGT1A activity by PCB in rats, we examined the relationship using Wistar rats and Gunn rats, a mutant strain of Wistar rats deficient in UGT1A isoforms. The serum total T(4) level was markedly decreased not only in the Wistar rats but also in the Gunn rats 4 days after treatment with a PCB, Kanechlor-500 (KC500, 100 mg/kg) or 2,2',4,5,5'-pentachlorobiphenyl (PentaCB, 112 mg/kg), and there was no significant difference in magnitude of the decrease between the two rat strains. At the same time, the level and activity of T(4)-UDP-GT were significantly increased by treatment with either KC500 or PentaCB in Wistar rats but not in Gunn rats. In addition, no significant change in the level of serum total triiodothyronine (T(3)) and thyroid-stimulating hormone by the KC500 treatment was observed in either Wistar or Gunn rats. Furthermore, significant decrease in the activity of hepatic type-I deiodinase, which mediates the deiodization of T(4) and T(3), by treatment with KC500 or PentaCB was observed in both Wistar and Gunn rats. From the serum of KC500- or PentaCB-treated Wistar and Gunn rats, mono- and di-hydroxylated PCB metabolites, which would bind to T(4) binding serum protein (transthyretin), were detected. In conclusion, the present results suggest that the decrease in serum total T(4) level by either KC500 or PentaCB in Gunn rats was not dependent on the increase in hepatic T(4)-UDP-GT activity. The findings further suggest that the PCB-mediated decrease in serum T(4) level might occur, at least in part, through formation of the hydroxylated PCB metabolites. Furthermore, even in Wistar rats, the PCB-mediated decrease in serum T(4) level might occur not only through the increase in hepatic T(4)-UDP-GT but also via formation of hydroxylated PCB metabolites.     

Effect of gonadotropin-releasing hormone antagonist on ovarian and uterine weights in immature female rats

The immature rat uterotrophic assay has been proposed as a screening test method for detecting estrogenic and antiestrogenic chemicals. Although the immature rat uterotrophic assay is advantageous because the test animals are not traumatized by the ovariectomizing process, the effect of endogenous estrogen on ovarian and uterine weight in the immature animals that are used in immature rat uterotrophic assay has not received much attention. In this study, 19-day-old rats were treated with antide, a gonadotropin-releasing hormone antagonist, antide, to block gonadal production of endogenous estrogen. Uterine and ovarian weights of the antide-treated animals were markedly lower than those of control animals. This finding suggests that endogenous gonadal estrogen may already be acting on the uterus and ovaries in immature rats. Blocking endogenous estrogen with a gonadotropin-releasing hormone antagonist may enhance the sensitivity of the immature rat uterotrophic assay; however, the possibility that this protocol may interfere with the ability of the immature rat uterotrophic assay to detect centrally-mediated effects can not be discounted.