Reduced use of emergency care and hospitalization in patients with post-stroke cognitive impairment treated with traditional Chinese medicine.

BACKGROUND: The effect of traditional Chinese medicine (TCM) on the outcomes of dementia remains unclear. Our purpose is to compare the use of emergency care and hospitalization in patients with post-stroke cognitive impairment (PSCI) with or without treatment of TCM. METHODS: In a stroke cohort of 67 521 patients with PSCI aged over 40 years obtained from the 23 million people in Taiwan's national health insurance between 2000 and 2007, we identified 6661 newly diagnosed PSCI patients who were treated with TCM and 6661 propensity score-matched PSCI patients who were not treated with TCM. Under the control of immortal time bias, we calculated the adjusted rate ratios (RRs) and 95% CIs of the 1-year use of emergency care and hospitalization associated with TCM. RESULTS: The means of the emergency care medical visits (0.40 ± 0.98 vs. 0.47 ± 1.01, P = 0.0001) and hospitalization (0.72 ± 1.29 vs. 0.96 ± 1.49, P < 0.0001) were lower in the PSCI patients treated with TCM than in those without the TCM treatment. The RRs of emergency care and hospitalization associated with TCM were 0.87 (95% CI = 0.82-0.92) and 0.81 (95% CI = 0.78-0.84), respectively. The PSCI patients treated with a combination of acupuncture and herbal medicine had the lowest risk of emergency care visits and hospitalization. CONCLUSIONS: Our study raises the possibility that TCM use was associated with reduced use of emergency care and hospitalization after PSCI. However, further randomized clinical trials are needed to provide solid evidence of this benefit and identify the underlying mechanism.

Prognostic factors for ovarian metastases from primary gastric cancer.

The purpose of this study was to analyze prognostic factors for ovarian metastases from primary gastric cancer, helping establish optimal strategy in ameliorating survival for this entity. Clinical data of 68 consecutive patients histologically diagnosed with ovarian metastases from primary gastric cancer were accrued from 1096 cases with female gastric cancer. Metachronous surgery was performed on 36 patients and 32 received synchronous surgery. There were 14 patients treated with surgery alone and 54 with combined modality therapy. After the median follow-up time of 9.1 months, the median survival time (MST) of 12.4 months was observed for all patients. Patients treated with synchronous surgery tended to have an inferior survival compared with those treated with metachronous surgery (MST: 10.9 vs 14.3 months; P = 0.100). Combined modality showed a significantly better MST compared with surgery alone (13.6 vs 7.9 months; P = 0.004). Chemotherapy cycles (more than four or less than or equal to four) were found to have an impact on survival (MST: 14.3 vs 9.4 months; P = 0.031). Peritoneal metastases, lymphovascular involvement, and unilateral ovarian metastasectomy were independent unfavorable prognostic factors. Combined modality therapy as primary therapy resulted in good outcome, and more aggressive chemotherapy (more than four cycles) was accompanied by an improvement in survival. Innovative systemic treatments need to be explored in treatment of peritoneal metastases and lymphovascular involvement. Bilateral oophorectomy was considered when ovarian metastases were histologically diagnosed.

Response of a calcium sulfate bone graft substitute in a confined cancellous defect.

Calcium sulfate, plaster of Paris, has a long clinical history for use as a bone graft substitute in various skeletal sites. The current authors examined the in vivo response of calcium sulfate pellets alone or in combination with autogenous bone graft in a bilateral critical-size distal femoral cancellous defect in an adult sheep model. New thick bone formation was seen in defects filled with calcium sulfate pellets alone. Increased immunostaining for bone morphogenetic protein-2, bone morphogenetic protein-7, transforming growth factor-beta, and platelet derived growth factor was seen in defects filled with calcium sulfate pellets alone and in combination with autograft. The local acidity during calcium sulfate resorption is proposed as a possible in vivo mechanism for this type of material.

Effect of nifedipine in metastatic colon cancer with DNA mismatch repair gene defect.

Cancer cells that have DNA mismatch repair deficiency are resistant to many cytotoxic drugs. Calcium channel blockers may inhibit the pathways that cause such resistance. We report a patient with hereditary non-polyposis coli and metastatic colon cancer who had a complete response after treatment with a high dose of nifedipine, a calcium channel blocker. Our findings suggest that drugs that interfere with signal transduction could have a clinical role and deserve further study in selected patients.

An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides.

Four macrocyclic cystine-knot peptides of 29-31 residues, kalata, circulin A and B (CirA and CirB), and cyclopsychotride, have been isolated from coffee plants but have undetermined physiological functions. These macrocycles and 10 of their analogs prepared by chemical synthesis were tested against nine strains of microbes. Kalata and CirA were specific for the Gram-positive Staphylococcus aureus with a minimum inhibition concentration of approximately 0.2 microM. They were relatively ineffective against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. However, CirB and cyclopsychotride were active against both Gram-positive and Gram-negative bacteria. In particular, CirB showed potent activity against E. coli with a minimum inhibitory concentration of 0.41 microM. All four cyclic peptides were moderately active against two strains of fungi, Candida kefyr and Candida tropicalis, but were inactive against Candida albicans. These macrocycles are cytotoxic and lysed human red blood cell with a lethal dose 50% of 400 microM. Modifying the Arg residue in kalata with a keto aldehyde significantly reduced its activity against S. aureus whereas blocking the arg in CirA produced no significant effect. The two-disulfide variants and their scrambled disulfide isomers exhibited antimicrobial profiles and potency similar to their native peptides. However, in high-salt assays (100 mM NaCl), few of these macrocyclic peptides, natives or analogs, retained antimicrobial activity. These results show that the macrocyclic peptides possess specific and potent antimicrobial activity that is salt-dependent and that their initial interactions with the microbial surfaces may be electrostatic, an effect commonly found in defensin antimicrobial peptides. Furthermore, their end-to-end cyclic structure with a cystine-knot motif represents a molecular structure of antimicrobials and may provide a useful template for the design of novel peptide antibiotics.

Mutagenicity and specific mutation spectrum induced by 8-methoxypsoralen plus a low dose of UVA in the hprt gene in diploid human fibroblasts.

Exposure of cells to 8-methoxypsoralen plus a low dosage of UVA (365 nm) generates mainly monoadducts (PUVA-I treatment), while further irradiation of PUVA-I treated cells after removal of 8-methoxypsoralen (PUVA-II treatment) converts a high frequency of monoadducts to crosslinks. In this study, a comparison was made of the cytotoxicity and mutagenicity of PUVA-I-treated cells obtained here with those induced by PUVA-II treatment in our previous report. PUVA-I treatment slightly affected the colony-forming ability of cells. However, the 6-thioguanine-resistant cells were markedly increased from 3/10(6) clonable cells in UVA-irradiated populations to 47/10(6) clonable cells in PUVA-I-treated populations. Those results indicated that PUVA-I was more mutagenic than PUVA-II at equal cytotoxic doses, implying that psoralen monoadducts are less cytotoxic and as mutagenic as crosslinks. Mutations in the hypoxanthine (guanine) phosphoribosyltransferase gene of independent PUVA-I mutants were characterized by direct sequencing of cDNA and/or genomic DNA that were amplified by polymerase chain reaction. All the 30 sequenced mutants had single base substitutions. Of those mutations, 21 occurred in the coding region and the others were in the consensus sequences at exon-intron boundaries, thereby resulting in aberrant cDNA. The majority of base substitutions were T to A transversions (23/30); 22 were located at the thymine of 5'TA sites. All of the 24 T.A base pair substitutions (including one T to C) had thymine located on the non-transcribed strand. Five of the six G.C base substitutions were located at the 5' TG or 5' CA sites on the non-transcribed strand. The frequencies of mutations at 5'TA and 5'TG/5'CA sites were similar in PUVA-I- and PUVA-II-induced mutants. However, the specific kind of T.A base pair substitutions induced by PUVA-I is strikingly different from that induced by PUVA-II. While the transient misalignment-realignment model could account for PUVA-II-induced T.A base substitutions, the low cytotoxic effect and the specific T to A substitutions of PUVA-I treatment might be a result of rapid incorporation of nucleotides after insertion of an adenine or a thymine opposite the psoralen monoadducts on the template by DNA polymerases.

Mutation specificity of 8-methoxypsoralen plus two doses of UVA irradiation in the hprt gene in diploid human fibroblasts.

To investigate which specific kinds of base changes are induced by psoralen adducts in the genomic DNA of diploid human fibroblasts, cells were exposed to 8-methoxypsoralen (8-MOP) at 2-12 microM followed by one dose of UVA (365 nm) irradiation (PUVA-I treatment) or two doses of UVA (PUVA-II treatment). While PUVA-I treatment produced little effect on the induction of cytotoxicity, PUVA-II treatment significantly reduced the fibroblasts' colony-forming ability and resulted in about 10-fold increases in mutation frequency at the D0 dose. Mutations in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene of 36 independent PUVA-II mutants were characterized by direct sequencing of cDNA amplified by the polymerase chain reaction (PCR). Seventeen mutants contained single base substitutions and the other 19 mutants either lacked one or more exons, or had deleted or gained nucleotides in the exon boundaries in their cDNA. The intron--exon boundaries of 10 of these 19 putative splicing mutants were further characterized by direct sequencing of the PCR-amplified hprt gene. The results showed that nine contained single base substitutions at the consensus splicing donor and acceptor sites. One splicing mutant possessed two base substitutions located at exon 8, whereas its splicing sites were intact. Most of the base substitutions occurred at T-A base pairs (24/29). The majority of T.A changes occurred at thymine of 5'TA and 5'ATA on the non-transcribed strand. Four of the five G.C base substitutions were located at guanines of 5'TG sites adjacent 3' to AT or TA sequences. In addition, the occurrence of a specific type of mutation was highly correlated to the 5' flanking bases of TA sites. The mutagenesis of 13 of the 16 mutational events at 5'TA sites on the non-transcribed strand can be explained by the preferential incisions of the photoadducts on the transcribed strand followed by misalignment--realignment during translesion repair synthesis of the bulky lesions on the non-transcribed strand.

Mutations induced by 1-nitrosopyrene and related compounds during DNA replication in human cells and induction of homologous recombination by these compounds.

The transformation of normal human cells into cancer cells is a multistep process. Evidence suggests that a minimum of five independent steps (changes) are required for the development of certain kinds of human cancer, as well as for malignant transformation of human cells in culture. Mutations are one of the mechanisms involved in bringing about such changes. A single DNA base substitution mutation can activate an oncogene or inactivate a tumor suppressor gene. Because the action of tumor suppressor genes is to prevent cells from becoming malignant, the activity of both copies of such genes must be eliminated before suppression is lifted. Homologous mitotic recombination between a mutant tumor suppressor gene allele and its non-mutant allele is one mechanism for accomplishing this. The present study was designed to investigate the mechanisms by which certain carcinogenic compounds found in diesel exhaust particles and structurally-related N-substituted aryl carcinogens induce such base substitution mutations and homologous recombination events in mammalian cells in culture, including human cells. The system we employed to determine rapidly the kinds of mutations induced by these compounds, as well as the location of the point mutations in the target gene, involved a circular DNA molecule (plasmid) carrying a small target gene, supF. The target gene was exposed in vitro to radiolabeled compounds and then was allowed to replicate in human cells where the mutations were formed. The sites of mutation induction were compared with the sites of stable binding of the carcinogens to the DNA (adducts). The system used to determine whether these agents could induce homologous recombination consisted of a thymidine kinase-deficient mouse L cell line with a recombination substrate stably integrated into the genome. To determine whether or not excision repair was involved in the mechanism by which carcinogens induced recombination, the recombination substrate was introduced into an excision repair-proficient human cell line and two repair-deficient human cell lines. These cell lines were then compared for the frequency of recombination induced by the agents. All four N-substituted aryl compounds tested in the supF mutagenesis assay produced mainly base substitutions involving guanosine-cytosine (G.C)* base pairs, primarily G.C-->thymidine-adenine (T.A) transversions. However, 1,6-dinitropyrene adducts, formed by exposing the plasmids to 1-nitro-6-nitrosopyrene in the presence of a reducing agent, also induced a significant proportion (17%) of single G.C base-pair deletions.(ABSTRACT TRUNCATED AT 400 WORDS)

[Evaluation of the quality of the crude drug of Panax quinquefolium linn. cultivated in Heilongjiang Province].

A comparison has been made between the Panax quinquefolium introduced and cultivated in Heilongjiang province and the wild one imported from the U.S. in terms of properties, structures and principal chemical constituents. The result shows that the two kinds are very similar or close to each other, though in properties and structures they are slightly different, and in the contents of total saponins, ginsenosides Rb 1 and Re, the cultivated one is lower.