冠心病重型室性早搏的昼夜节律变化及与心率变异的关系

通过动态心电监测下心率变异分析,研究心脏自主神经功能失调在冠心病重型室性早搏发生机制中的作用。我们对冠心病重型室性早搏组24例、无室性早搏组16例、正常对照组20例,进行24小时心率变异时域指标与室性早搏昼夜发作频次对比分析。结果显示连续RR间期标准差(SDNN)、平均5分钟RR间期标准差(SDANN)、RR间期标准差均值(MSD)三项指标在冠心病组明显低于正常组(P<0.001及P<0.02);SDNN、SDANN在冠心病重型室性早搏组明显小于冠心病无室性早搏组;SDNN与冠心病室性早搏频次在明显的昼夜节律变化和相关性。冠心病室性早搏发生与交感神经活性增强有关,通过24小时心率变异分析,能对此做出客观评价。     

股骨头缺血坏死的CT诊断

本文总结分析股骨间缺血坏死(ANFH)CT表现及CT诊断价值。在35例47个ANFH中,CT发现4例X线平片阴性的ANFH。CT较好的显示ANFH“星状征”异常。以及骨质增生硬化、囊变、碎裂和股骨头变形。CT在发现ANFH和表现其病变程度优于X线平片。     

The role of 5-HT in the impairment of thermoregulation observed in rats administered MDMA (‘ecstasy’) when housed at high ambient temperature

Rationale Administration to rats of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an impairment in thermoregulation which is reflected in a prolonged hyperthermic response to a subsequent dose of MDMA given to rats housed at high ambient temperature.Objective We wished to examine whether the impaired thermoregulation was associated with decreased cerebral 5-HT content produced by the prior neurotoxic dose of MDMA.Methods Rats were injected with drugs decreasing 5-HT function [the tryptophan hydroxlase inhibitor p-chlorophenylalanine (PCPA), and 5-HT receptor antagonists] and rectal temperature was measured after administering MDMA to rats housed at 30°C.Results PCPA pretreatment decreased 5-HT and 5-HIAA concentrations in cortex, hippocampus and striatum by >80% and prolonged the hyperthermia induced in rats housed at 30°C by administering MDMA (5 mg/kg i.p.). A similar prolongation of the hyperthermic response to MDMA was seen when rats were pretreated with methysergide (10 mg/kg i.p.) or the 5-HT_1A antagonist WAY100635 (0.5 mg/kg s.c.).Conclusions Decreasing 5-HT function in diverse ways enhanced the hyperthermic response to MDMA given to rats housed at high ambient temperature. This suggests that loss of 5-HT acting on 5-HT_1A receptors leads to impaired thermoregulation in rats and suggests that the impairment seen in MDMA pretreated rats housed at high ambient temperature is due to a loss in 5-HT function. These data could have implications for recreational users of MDMA, who may have damaged serotoninergic neurons because of prior heavy or frequent use of the drug, when taking further doses of MDMA in hot environments such as dance clubs.     

Helix I of beta-arrestin is involved in postendocytic trafficking but is not required for membrane translocation, receptor binding, and internalization

beta-Arrestins bind to phosphorylated, seven-transmembrane-spanning, G protein-coupled receptors (GPCRs), including the type 1 angiotensin II receptor (AT(1)R), to promote receptor desensitization and internalization. The AT(1) R is a class B GPCR that recruits both beta-arrestin1 and beta-arrestin2, forming stable complexes that cotraffic to deep-core endocytic vesicles. beta-Arrestins contain one amphipathic and potentially amphitropic (membrane-targeting) alpha-helix (helix I) that may promote translocation to the membrane or influence receptor internalization or trafficking. Here, we investigated the trafficking and function of beta-arrestin1 and beta-arrestin2 mutants bearing substitutions in both the hydrophobic and positively charged faces of helix I. The level of expression of these mutants and their cytoplasmic localization (in the absence of receptor activation) was similar to wild-type beta-arrestins. After angiotensin II stimulation, both wild-type and beta-arrestin mutants translocated to the cell membrane, although recruitment was weaker for mutants of the hydrophobic face of helix I. For all beta-arrestin mutants, the formation of deep-core vesicles was less observed compared with wild-type beta-arrestins. Furthermore, helix I conjugated to green fluorescent protein is not membrane-localized, suggesting that helix I, in isolation, is not amphitropic. Bioluminescence resonance energy transfer analysis revealed that both wild-type and beta-arrestin mutants retained a capacity to interact with the AT(1)R, although the interaction with the mutants was less stable. Finally, wild-type and mutant beta-arrestins fully supported receptor internalization in human embryonic kidney cells and mouse embryonic fibroblasts deficient in beta-arrestin1 and -2. Thus, helix I is implicated in postmembrane trafficking but is not strongly amphitropic.     

Novel [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2" -dioxide) derivatives with anti-HIV-1 and anti-human-cytomegalovirus activity

New [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-d-ribofuranosyl]-3'-spiro-5' '-(4'-amino-1',2'-oxathiole-2',2'-dioxide) (TSAO) derivatives substituted at the 4' '-amino group of the spiro moiety with different carbonyl functionalities have been designed and synthesized. Various synthetic procedures, on the scarcely studied reactivity of the 3'-spiroaminooxathioledioxide moiety, have been explored. The compounds were evaluated for their inhibitory effect on both wild-type and TSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl ester (10) or amide groups (12) at the 4'-position conferred the highest anti-HIV-1 activity, while the free oxalyl acid derivative (11) was 10- to 20-fold less active against the virus. In contrast, the presence at this position of (un)substituted ureido or acyl groups markedly diminished or annihilated the anti-HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition of human cytomegalovirus (HCMV) replication at subtoxic concentrations. This has never been observed previously for TSAO derivatives. In particular, compound 26 represents the first TSAO derivative with dual anti-HIV-1 and -HCMV activity.     

A new technique for preparing precision-cut slices from small intestine and colon for drug biotransformation studies

INTRODUCTION: A new technique was developed to prepare precision-cut slices from small intestine and colon with the object of studying the biotransformation of drugs in these organs. METHODS: Rat intestinal slices were prepared in two different ways. In the first method, slices were punched out of the small intestine. In the second method, precision-cut slices were made from agarose-filled and -embedded intestines, using the Krumdieck tissue slicer. This method was also applied to colon tissue. Viability of the slices was determined by analysis of intracellular ATP and RNA levels and morphology. Drug metabolizing activity was studied using lidocaine, testosterone, and 7-ethoxycoumarin (7-EC) as phase I substrates, and 7-hydroxycoumarin (7-HC) as a phase II substrate. RESULTS: Precision-cut slices made from agarose-filled and -embedded intestine better preserved ATP levels than tissue that was punched out of the intestinal wall. After 24 h of incubation, morphology in precision cut-slices showed was quite well preserved while punched out tissue was almost completely autolytic after incubation. In addition, total RNA amount and quality was much better maintained in precision-cut slices, when compared to punched out tissue. Both intestinal slices and punched-out tissue showed high, and comparable, phase I and phase II biotransformation activities. DISCUSSION: It is concluded that preparing precision-cut 0.25 mm slices out of agarose-filled and -embedded intestine provides an improvement, compared with punched-out tissue, and that both intestinal and colon slices are useful preparations for in vitro biotransformation studies.     

Analysis of the toxic potential of venom from Loxosceles adelaida, a Brazilian brown spider from karstic areas.

Loxosceles adelaida spiders (Araneae, Sicariidae) are found near and inside the caves in the Parque Estadual Turistico do Alto Ribeira (PETAR), Sao Paulo, Brazil, which are visited by thousands of tourists every year. Several Loxosceles species are a public health problem in many regions of the world, by causing severe dermonecrosis and/or complement dependent haemolysis upon envenomation. The aim of this study was to characterize the biochemical and biological properties of L. adelaida venom and evaluate the toxic potential of envenomation by this non-synanthropic Loxosceles species. The biological activities of the L. adelaida venom was compared to that of Loxosceles gaucho, a synanthropic species of medical importance in Brazil. L. adelaida venom showed a similar potential to induce haemolysis, dermonecrosis and lethality as L. gaucho venom. L. adelaida crude venom was purified, yielding a 31 kDa component endowed with haemolytic and dermonecrotic activities. In conclusion, we show here that the troglophile Loxosceles species, L. adelaida, commonly found in the complex of caves from PETAR, is potentially able to cause envenomation with the same gravity of those produced by synanthropic species.     

Influence of a ward-based pharmacist on the medication quality of geriatric inpatients: a before–after study

Background Despite several international studies demonstrating that ward-based pharmacists improve medication quality, ward pharmacists are not generally established in German hospitals. Aim We assessed the effect of a ward-based clinical pharmacist on the medication quality of geriatric inpatients in a German university hospital. Method The before-after study with a historic control group was conducted on the geriatric ward. During the control phase, patients received standard care without the involvement of a pharmacist. The intervention consisted of a clinical pharmacist providing pharmaceutical care from admission to discharge. Medication quality was measured on admission and discharge using the Medication Appropriateness Index (MAI). A linear regression analysis was conducted to calculate the influence of the intervention on the MAI. Results Patients in the intervention group (n?=?152, mean 83 years) were older and took more drugs at admission compared to the control group (n?=?159, 81 years). For both groups, the MAI per patient improved significantly from admission to discharge. Although the intervention did not influence the summated MAI score per patient, the intervention significantly reduced the MAI criteria Dosage (p?=?0.006), Correct Directions (p?=?0.016) and Practical Directions (p?=?0.004) as well as the proportion of overall inappropriate MAI ratings (at least 1 of 9 criteria inappropriate) (p?=?0.015). Conclusion Although medication quality was already high in the control group, a ward-based clinical pharmacist could contribute meaningfully to the medication quality on an acute geriatric ward.

     

强化医院适度管理的几点思考

为适应军队面临的发展机遇期和建设转型期,作者结合医院实际较详尽地引进“适度管理”的新观念,提出医院适度管理的六大原则,并指出目前医院管理强调实施适度管理必将会产生的重要意义。     

Retymicin, galtamycin B, saquayamycin Z and ribofuranosyllumichrome, novel secondary metabolites from Micromonospora sp. Tü 6368. II. Structure elucidation

A detailed screening of the secondary metabolite pattern from Micromonospora sp. strain Tü 6368 resulted in the isolation of ten compounds belonging to five different structural families. The structures of the novel compounds 1-(alpha-ribofuranosyl)-lumichrome (3), retymicin (7), galtamycin B (11) and saquayamycin Z (14) were assigned by spectroscopic methods and chemical transformations. This strain fits our hypothesis that the metabolite analysis of biosynthetically talented strains leads readily to novel compounds.