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1.
Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno
−, m−, p− isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain
mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed
for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data
of ring-substituted compounds. The best correlated QSAR equations are as follows: pI50=0.804 Π2 Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI50=1.815 π-0.825 Π2 R+0.900 Es2+0.869 Es3+0.796 Es4−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference
between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of
MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group,
a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position,
and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries,
hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site
near ortho position constitute active sites of MAO-B. 相似文献
2.
Suk Hee Heo Yong Yeon Jeong Sang Soo Shin Tae Woong Chung Heoung Keun Kang 《Korean journal of radiology》2007,8(2):180-183
We report an uncommon case of solitary, small hepatic angiosarcoma that was initially considered as a hemangioma. We present the imaging findings, with an emphasis on the initial and follow-up CT and MR findings, as well as report on the more suggestive findings of angiosarcoma than those of a hemangioma. 相似文献
3.
Mi Sook Gwak Kwang-Woong Lee Shi Yeon Kim Jihyun Lee Jae Won Joh Sung Joo Kim Hwan Hyo Lee Jean Wan Park Gaab Soo Kim Suk-Koo Lee 《Liver transplantation》2005,11(3):331-335
During liver transplantation for hepatocellular carcinoma (HCC) patients, HCC could theoretically be introduced into the systemic circulation when salvaged blood is used with an autotransfusion device. Several reports have shown that some types of leukocyte depletion filters (LDFs) could completely reduce the risk for reintroducing some types of tumor cells. In this study, we tested the ability of the LDF (RCEZ1T, Pall Biomedical Co, NY, USA) to reduce the risk for reintroducing HCC cells in vitro by using a very sensitive detection method. We divided the test group into 6 groups: group I was 10 cells, group II was 20 cells, group III was 2 x 10(3) cells, group IV was 2 x 10(5) cells, group V was 2 x 10(6) cells, and group VI was 2 x 10(7) cells. The counted cells in 200 mL saline were passed through the RCEZ1T using the force of gravity. To identify the presence of cells, the pellet was resuspended, and polymerase chain reaction (PCR) was performed. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene, was used as a primer. In groups I and II, the HCC cells were completely filtered in all experiments. However, in groups III, IV, and V, the HCC cells were not completely filtered in a few of the repeated experiments, with the unfiltered rate of tumor cells being between 8% and 20%. In group VI, the HCC cells were not completely filtered in all the repeated experiments. In conclusion, the RCEZ1T filter markedly reduced the risk for reintroduction of HCC cells. However, at high HCC cell load the filter cannot completely remove all the tumor cells. Further studies are required to assess the impact in clinical settings. 相似文献
4.
Guk-Hee Suh Hyun Gyun Son Young-Su Ju Kyeong Hyeong Jcho Byeong Kil Yeon Young Min Shin Baik Seok Kee Sung-Ku Choi 《The American journal of geriatric psychiatry》2004,12(5):509-516
OBJECTIVE: Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. METHODS: This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5-1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. RESULTS: Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. CONCLUSION: Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population. 相似文献
5.
Howard B. Yeon Jacob Weinberg Vincent Arlet Jean A. Ouelett Kirkham B. Wood 《European spine journal》2007,16(9):1379-1385
Fifteen skeletally immature patients with double major adolescent idiopathic scoliosis with large lumbar curves and notable L4 and L5 coronal plane obliquity were retrospectively studied. Seven patients who underwent anterior release and fusion of the lumbar curve with segmental anterior instrumentation and subsequent posterior instrumentation ending at L3 were compared with eight patients treated with anterior release and fusion without anterior instrumentation followed by posterior instrumentation to L3 or L4. At 4.5 years follow-up (range 2.5-7 years), curve correction, coronal balance and fusion rate were not statistically different between the two groups; however, the group with anterior instrumentation had improved coronal plane, near normalangulation in the distal unfused segment compared with the group without anterior instrumentation. In cases involving severe lumbar curvatures in the context of double major scoliosis, when as a first stage anterior release is chosen, the addition of instrumentation appears to restore normal coronal alignment of the distal unfused lumbar segment, and may in certain cases save a level compared with traditional fusions to L4. 相似文献
6.
7.
Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treatingt-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate andt-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate withp-toluenesulfonic acid in CH3CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at bothin vitro andex vivo levels. It was found fromin vitro measurements that(E)-p-NTCP at 6.0×10?5M elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast,(E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with IC50 values, 2.5×10?7M and 1.4×10?6M, respectively. It was also noted from(E)-m-NTCP thatm-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According toex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by(E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas,(E)-p-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between(E)-m-NTCP and(E)-p-NTCP were sought in relation to differing electron withdrawing effects ofm-andp-substituents which will influence electron density of the side chain amino functions and the partitions. 相似文献
8.
Kouda K Nakamura H Kohno H Ha-Kawa SK Tokunaga R Sawada S 《Mechanisms of ageing and development》2004,125(5):375-380
Dietary restriction (DR) is known to prolong life in laboratory animals. Intermittent (alternate-day) fasting or short-term repeated fasting has also been reported to increase the life span of animals. In the present study, we investigated the changes or induction of abnormalities of protein metabolism in rats during fasting, and measured asialoglycoprotein uptake and cell death/proliferation in the liver of rats receiving fasting and refeeding. In the results, liver weight decreased significantly after 48 h of fasting and increased during the refeeding period, returning to the pre-fasting level by 12 h of refeeding. Cell death, determined by single stranded DNA (ssDNA) staining method, increased during the fasting period, and returned to the pre-fasting level during the refeeding period. Cell proliferation, determined using antibodies (Ab) against proliferating cell nuclear antigen, decreased during the fasting period, and increased during the refeeding period. Changes in cell death and cell proliferation were inversely related. However, there was no significant difference in asialoglycoprotein uptake by the whole liver between the ad libitum (AL)-fed rats and 48 h fasted rats. Thus, neither the changes in liver weight nor cell death/proliferation affected asialoglycoprotein uptake on a living body. These results suggest that episodes of 48 h fasting do not induce protein metabolism abnormalities in the liver. 相似文献
9.
Transmissible spongiform encephalopathies (TSE) are attributed to the conversion of the cellular prion protein (PrP(c)) into an abnormal isoform (PrP(sc)). This can be caused by the invasion of living organisms by infectious particles, or be inherited due to mutations on the PrP(c) gene. One of the most intriguing problems of prion biology is the inability to generate the infectious agent in vitro. This argues strongly that other cellular proteins besides those added in test tubes or found in cellular preparations are necessary for infection. Despite recent progress in the understanding of prion pathology, the subcellular compartments in which the interaction and conversion of PrP(c) into PrP(sc) take place are still controversial. PrP(c) interacts with various macromolecules at the cell membrane, in endocytic compartments and in the secretory pathway, all of which may play specific roles in the internalisation of PrP(sc) and conversion of PrP(c). A specific interacting protein required for the propagation of prions was originally proposed as a prion receptor, and later referred to as a ligand, a cofactor, protein X, or a partner. However, current studies indicate that PrP(c) associates with multi-molecular complexes, which mediate a variety of functions in distinct cellular compartments. It is proposed that a deeper understanding of the mechanics of such interactions, coupled to a better knowledge of the corresponding signalling pathways and ensuing cellular responses, will have a major impact on the prevention and treatment of TSE. 相似文献
10.
Gyeol Seong Seungbaek Lee Yang Won Min Yeon Sil Jang Hong Seog Kim Eui-Joong Kim So-Young Park Cheol-Hyun Kim Dong Kyung Chang 《Nutrients》2021,13(2)
Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment. 相似文献