Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

End-stage renal disease in both husband and wife in Taiwan.

AIM: The incidence and prevalence of end-stage renal disease (ESRD) are extremely high in Taiwan. It is an interesting fact that both the husband and wife in some families of Taiwan suffer from ESRD. Therefore, we attempted to identify the potential risk factors of such couples. METHODS: This is a retrospective observational study. Six couples receiving maintenance dialysis in our hospital from 1996 to 2006 were enrolled in this study. Detailed medical history; drugs history including over-the-counter drugs (OCD), analgesics and herbal remedies; occupational history and onset of transitional cell carcinoma (TCC) were recorded. These data are correlated with pre-dialysis laboratory findings. The outcomes of dialysis and TCC were also recorded and analyzed. RESULTS: Two males were Chinese herbal medicine practitioners. All the patients (12/12) had taken Chinese herbs and most of them (10/12) had also taken OCD (especially cold remedies and analgesics). We found all of them had bilateral contracted kidneys, mild proteinuria and trace glucosuria. One patient's renal biopsy revealed Chinese herb nephropathy. Four patients (33%) suffered from TCC. Three patients expired during follow up due to hyperkalemia, extensive TCC and suicide, respectively. CONCLUSIONS: The prevalence of Chinese herbs or compound analgesics abuse is high in couples with ESRD. The clinical features and high incidence of TCC are compatible with drug related chronic tubulointerstitial nephritis. Abuse of offending agents should be considered as a risk factor in family members with ESRD.

Calcium bioavailability of nanonized pearl powder for adults.

The present study was aimed to evaluate the calcium bioavailability of pearl powder for humans. Both the nanonized pearl powder (NPP) and the micronized pearl powder (MPP) prepared by a dry grinder were tested. A group of healthy adults free from hyperthyroidism, hypercalcemia, and hypocalcemia were recruited as the subjects for oral administration with the pearl powder. The bioavailability was evaluated by the serum total calcium increment, the serum intact parathyroid hormone (iPTH) reduction, and the urine calcium/creatinine ratio increment in 6 h after administration. The results show better absorption and retention of calcium from NPP, as reflected with the shorter time elapsed before the maximum concentration of calcium appeared in the serum, higher iPTH reduction, more calcium absorption, and higher maximum calcium concentration (C(max)) in serum after ingestion, than that from MPP. We conclude that pearl powder is a beneficial source of calcium for adults and that nanonization improves its calcium bioavailability.

Two new indole alkaloids from Nauclea officinalis.

Two new indole alkaloids, naucleactonin A and B, along with two known compounds, naucleficine and nauclefidine, were isolated from the bark and wood of Naucleaofficinalis, which has been used as an anti-inflammatory and anti-bacterial agent in folk medicine. Their chemical structures were elucidated by the spectral data, especially 1D and 2D NMR experiments.

Two new xanthones from Hypericum japonicum.

Two new xanthones, 1,6-dihydroxyisojacereubin-5-O-beta-D-glucoside (1) and 3,6,7-tri-hydroxy-1-methoxy-xanthone (2), were isolated from Hypericum japonicum. The structural elucidation of the isolated compounds were primarily based on HREIMS, EIMS, UV, IR, 1D-, and 2D-NMR analyses, including COSY, HMQC, HMBC, and NOESY correlations.

The pharmacology of aminoadamantane nitrates.

Memantine, an aminodamantane, has recently been approved to treat moderate-to-severe Alzheimer's disease in the US after over 20 years on the market in Europe for treatment of Parkinson's disease. The unique properties of Memantine allow for its selective inhibition of abnormally active NMDA receptor channels while preserving normal glutamate activity and healthy neuronal function. Recently, it has been shown that compounds such as nitroglycerin, used for years for ischemic coronary disease, can also regulate the NMDA receptor channel. Novel compounds have been synthesized in an attempt to combine these activities, in an attempt to synergistically improve upon the activities of both nitrates and aminoadamantanes. We have subjected these compounds to several laboratory tests to compare their ability to affect the function of the NMDA receptor and to dilate blood vessels. These tests provide an initial indication of which of the compounds may have enhanced activity relative to memantine. The results also provide guidance for the synthesis of additional compounds that are likely to have the properties that are being sought.

New flavonol glycosides and new xanthone from Polygala japonica.

Three new flavonol glycosides and a new xanthone were isolated from Polygala japonica HOUTT. with eight known compounds. Their structures were identified as 1,7-dihydroxy-3,4-dimethoxy-xanthone (1), kaempferol-7,4'-dimethyl ether (2), physcion (3), guazijinxanthone (4), rhamnetin (5), polygalin A (6), 3,5,7-trihydroxy-4'-methoxy-flavone-3-O-beta-d-galactopyranoside (7), 3,5,3'-trihydoxy-7,4'-dimethoxy-flavone-3-O-beta-d-galactopyranoside (8), 3,5,3',4'-tetrahydroxy-7-methoxy-flavone-3-O-beta-d-galactopyranoside (9), 3,5,3',4'-tetrahydroxy-7-methoxy-flavone-3-O-beta-d-glucopyranoside (10), polygalin B (11), polygalin C (12). Among them, compound 4 is a new xanthone, and 6, 11 and 12 are new flavonol glycosides. Compounds 1, 4, 7 and 8 were tested for cytotoxic activity with MTT assays on five human tumor cell lines, K562, A549, PC-3M, HCT-8 and SHG-44. Compound 4 showed cytotoxic activity against all the five cell lines.

Paradigm shift in NMDA receptor drug development.

Low-affinity, uncompetitive antagonists with rapid 'off-rates', such as memantine offer protection from dementia and other neurological disorders, but break all the old rules of screening for new drugs by high-affinity binding.

Three new saponins from Tribulus terrestris.

Three new steroidal saponins 1-3, together with five known steroidal saponins, L-mannitol and an inorganic salt were isolated from Tribulus terrestris L. (Zygophyllaceae). The structures of the new steroidal saponins were elucidated as hecogenin 3-O-beta-xylopyranosyl(1-->3)-beta-glucopyranosyl(1-->4)-beta-galactopyr anoside (1), hecogenin 3-O-beta-glucopyranosyl(1-->2)-beta-glucopyranosyl(1-->4)- beta-galactopyranoside (2) and 3-O-[beta-xylopyranosyl(1-->2)-[beta-xylopyranosyl(1-->3)]-beta- glucopyranosyl(1-->4)-[alpha-rhamnopyranosyl(1-->2)]-beta-galactopyranos yl]- 26-O-beta-glucopyranosyl-22-methoxy-(3 beta,5 alpha,25R)-furostan-3,26-diol (3). Structure elucidation was accomplished by 1D and 2D NMR spectra (13C-1H COSY, HMQC, HMBC, 1H-1H COSY, TOCSY, and NOESY), mass spectrometry (FABMS, ESIMS) and chemical methods.

Synchronous and "early" metachronous colorectal adenocarcinoma: analysis of prognosis and current trends.

PURPOSE: We evaluated the accuracy of preoperative diagnostic examinations and determined whether patients with synchronous colorectal cancers differ from patients with a single colorectal malignancy in clinicopathologic factors, the possibility of early metachronous colorectal cancer, and postoperative outcome. METHODS: A retrospective evaluation of 1,780 patients with primary colorectal adenocarcinoma from 1987 to 1993 was performed. We divided patients into three groups: Group 1, single colorectal adenocarcinoma; Group 2, synchronous colorectal adenocarcinoma; and Group 3, early metachronous colorectal adenocarcinoma. RESULTS: There were 52 cases (3 percent) in Group 2 and 13 cases (1 percent) in Group 3 (<3 years from the index colorectal cancer operation). Differences in age, gender, and cancer-free rate among the three groups did not reached statistical significance. Compared with cancers in Group 1, significantly more proximal tumor locations and early cancer stage were noted for the second and third cancers in Group 2. In Group 3 a significantly more proximal tumor site was noted for the index colorectal cancer but cancer stage showed no significant difference from cancers in Group 1. Better histologic type was also noted in the index and second cancers in Group 2 than in cancers in Group 1. There was a higher incidence of associated benign adenoma in Group 2 (35 vs. 15 percent in Group 1). The positivity rate of Group 2 was significantly higher by preoperative colonoscopy (71 percent) and incidental findings at surgery (58 percent) than barium enema examination (30 percent). CONCLUSION: Preoperative barium enema examination was an unsatisfactory tool for detecting synchronous tumors. Preoperative colonoscopy demonstrated a higher positivity rate, but it still failed to detect nearly 30 percent of cases with synchronous tumors. Intraoperative palpation of the whole colorectum could detect nearly 60 percent of unexpected synchronous tumors. We believe both colonoscopy and intraoperative palpation of the whole colorectum are crucial to the early detection of synchronous colorectal cancer.

Effects of MCI-154, a calcium sensitizer, on cardiac dysfunction in endotoxic shock in rabbits.

This study was designed to observe the effects of MCI-154, a calcium sensitizer, on cardiac dysfunction after endotoxic shock in rabbits. Ten hours after the rabbits were given injection of 1.0 mg/kg endotoxin (Escherichia coli, O111:B4) via marginal ear veins, 0.1 mg/kg MCI-154 was injected intravenously and then 50 mL/kg normal saline (NS) + 0.1 mg/kg MCI-154 was infused continuously at a rate of 0.7 mL/min. During this process, the parameters of cardiac function were measured. It was found that 10 h after the endotoxin injection, heart rate (HR) was increased significantly while the mean arterial blood pressure (MAP), left ventricular systolic pressure (LVSP), isovolumetric pressure (IP), myocardial contractility (MC), and the area of p-dp/dt(max) vector loop (Lo) all were markedly decreased. Treatment with 50 mL/kg NS alone had slight effects on these parameters. On the contrary, LVSP, IP, MC, and Lo all were increased significantly while HR was not obviously changed and left ventricular end-diastolic pressure (LVEDP) was reduced remarkably following MCI-154 administration in endotoxic shock rabbits. The parameters of myocardial contractility were improved nearly to the values in sham shock group and were markedly higher than that in NS alone-treated group. It can be concluded that MCI-154 can exert significant therapeutic effects on cardiac dysfunction after endotoxic shock, for it improves cardiac function, dilates peripheral blood vessels, and slightly affects HR.

Contralateral heat hyperalgesia induced by unilaterally intraplantar bee venom injection is produced by central changes: a behavioral study in the conscious rat.

In a previous study, we found that subcutaneous (s.c.) intraplantar injection of bee venom unilaterally could produce bilateral heat hyperalgesia. However, the bee venom-induced heat hyperalgesia identified in the injection site was presumed to be different from that identified in the contralateral hindpaw, since the former co-existed with the mechanical hyperalgesia while the latter did not. The aim of the present study was to testify whether the contralateral heat hyperalgesia identified in the bee venom model was a consequence of central changes. The radiant heat and von Frey-type filaments were applied to both the injection site and the contralateral pawpad of conscious rats prior to and 4 h after s.c. bee venom injection. After confirmation of the development of primary heat and mechanical hyperalgesia and contralateral heat hyperalgesia following s.c. bee venom, the sciatic nerve of the injection side was transected. After axotomy, the bee venom-induced heat hyperalgesia in the non-injected hindpaw was not altered at all compared with that prior to axotomy. Moreover, intrathecal pre-treatment with either N-methyl-D-aspartate (NMDA) or non-NMDA receptor antagonist could prevent the development of the contralateral heat hyperalgesia. The present results suggest that central sensitization contributes to development of the bee venom-induced contralateral heat hyperalgesia and activation of both NMDA and non-NMDA receptors in the spinal cord is involved in the processing.

[A new fatty ketone of Radix Polygoni Multiflori Preparata].

OBJECTIVE: Investigating the chemical constituents of Radix Polygoni Multiflori Preparata. METHODS: Compounds were isolated from the CHCl3 extract with column chromatography on silica gel, and identified on the basis of spectral analysis(IR, EI-MS, 1H-NMR, 13C-NMR) and phytochemical properties. RESULTS: Two compounds were isolated and identified as 1,2-dihydroxynonadecone-3(I) and gallic acid(II). CONCLUSION: Compound I is a new compound.

[Structural elucidation of a new tetrahydroxystilbene of Radix Polygoni Multiflori Preparata and study on its cardiovascular activity].

AIM: To investigate the cardiovascular active constituents of Radix Polygoni multiflori Preparata. METHODS: Compounds were isolated from the water soluble extract with column chromatography of Sephadex, ODS and HPLC. The compounds were identified on the basis of spectral analysis (IR, EI-MS, FAB-MS, 1HNMR, 13CNMR, 2D-NMR) and phytochemical properties. Its inhibitory effect on the proliferation of bovine vascular smooth muscle cells were bioassayed in vitro. RESULTS: One compound was isolated and identified as: 2,3,5,4'-tetrahydroxystilbene-2-O-(6"-O-alpha-D- glucopyranosyl)-beta-D-glucopyranoside. CONCLUSION: Compound I is a new compound with cardiovascular activity.

[Isolation and identification of two new secoiridoids of water-soluble chemical constituents from the fruits of Ligustrum lucidum Ait].

Two new secoiridoids named as specnuezhenide (I) and nuezhengalaside (II) were isolated from the water-soluble part of dry fruits of Ligustrum lucidum Ait. Their structures were established on the basis of chemical analysis and spectral data (UV, IR, 1H-NMR, NOEDS, HOMO-DEC, 13C-NMR, DEPT and MS).

[Clinical observation on aplastic anemia treated by Spatholobus suberectus Composita].

OBJECTIVE: To investigate the pharmaceutical effect of Spatholobus Suberectus Composita (SEC) on bone marrow hematopoiesis and microenvironment of aplastic anemia. METHODS: One hundred and six cases of aplastic anemia patients were treated by SEC and the pathological change of bone marrow were observed before and after treatment for 24 months, and compared with 17 cases of normal volunteers as control. RESULTS: The total effective rate was 77.4%. The degree of marrow hyperplasia (15.7 +/- 10.2 vol% vs 39.2 +/- 13.9 vol%), the percentage of the granulocytes (31.4 +/- 12.4% vs 39.9 +/- 10.4%), the erythroblastes (19.8 +/- 15.9% vs 36.7 +/- 13.5%), megakaryocytes (1.4 +/- 2.3 cell/section vs 24.0 +/- 24.6 cells/section), and the microvessel number (40.0 +/- 23.4 ves/100 mm2 vs 201.0 +/- 141.0 ves/100 mm2) ascended significantly (P < 0.01 or P < 0.05). CONCLUSION: SEC could not only irritate the hematopoiesis, but also exert reconstructive action to marrow microenvironment.

A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells.

Translocations involving chromosomal band 11q23 are associated with leukemias. These translocations fuse the MLL, a gene with sequence homology to the Drosophila trithorax, to genes from a number of other chromosomal loci. We have characterized two t(1;11)(q21;q23) translocations that fuse the MLL gene to a novel gene, AF1q on chromosomal band 1q21, in two infants with acute myelomonocytic leukemia (AMMOL). In one of these patients, der(11) represents an inframe fusion of the N-terminal portion of MLL gene to the complete AF1q open reading frame, whereas der(1) does not give rise to an open reading frame. This observation suggests that the N-terminal portion of MLL gene is critical for leukemogenesis in translocations involving band 11q23. The predicted wild-type AF-1q product is a 9-kD protein with no similarity to any other protein in the data banks. The AF1q mRNA is highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, AF1q was expressed in all leukemic cell lines tested.

Effects of Phytolacca acinosa polysaccharides I combined with interleukin-2 on the cytotoxicity of murine splenocytes against tumor cells.

Phytolacca acinosa polysaccharides I (PAP-I), a kind of purified polysaccharides, isolated from Phytolacca acinosa Roxb was found to significantly augment the cytotoxicity of murine splenocytes and interleukin-2 (IL-2) activated splenocytes against P815 tumor cells in vitro. The optimal concentration of PAP-I was 1 microgram.ml-1 and the peak level of the cytotoxicity against P815 tumor cells was reached on d 3-5. The supernatants collected from splenocytes cultured with PAP-I alone or in combination with IL-2 showed no effect on the cytotoxicity against P815 tumor cells. Splenocytes from mice injected ip with PAP-I, 5, 10 and 50 mg.kg-1, thrice a week produced more cytotoxicity against P815 and L929 tumor cells compared with the control group. PAP-I ip was shown to significantly increase IL-2 activated killer cell activity (LAK) against P815 tumor cells. The higher the dosage of PAP-I, the more potent the LAK activity was observed. These results confirmed that PAP-I can augment the cytotoxicity of murine splenocyte against tumor cells and LAK activity and warranted further evaluation of its clinical usefulness.

The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene.

The Long-Evans Cinnamon (LEC) rat shows similarity to Wilson disease in many clinical and biochemical features. We have cloned cDNAs for the rat gene (Atp7b) homologous to the human Wilson disease gene (ATP7B) and have used them to identify a partial deletion in the Atp7b gene in the LEC rat. The deletion removes at least 900 bp of the coding region at the 3' end, includes the crucial ATP binding domain and extends downstream of the gene. Our results provide convincing evidence for defining the LEC rat as an animal model for Wilson disease. This model will be important for studying liver pathophysiology, for developing therapy for Wilson disease and for studying the pathway of copper transport and its possible interaction with other heavy metals.

cDNA cloning of human kidney pyruvate carboxylase.

cDNA clones covering a total of 4017 bp were isolated corresponding to the full length of the message for human pyruvate carboxylase. The coding sequence consisted of a stretch of 3534 bp flanked by a 5' untranslated sequence of 82 bp and a 3' untranslated region of 389 bp excluding the poly-A tail. The translated amino acid sequence of 1178 residues contained consensus sequences for the covalent attachment for biotin, the binding of ATP and the binding of the substrate, pyruvate.