盐酸维拉帕米脉冲控释片人体内的药代动力学及生物利用度研究

目的：比较盐酸维拉帕米脉冲释放片与其片芯在人体的药代动力学特征及生物利用度。方法：采用拉丁方设计,将志愿者８人随机分为３组,交叉口服Ⅲ,Ⅳ型脉冲片和片芯,以片芯为对照制剂,考察体内脉冲控释效果。结果：Ⅲ型脉冲片在体内的时滞为４ｈ,而ｃｍａｘ,ＡＵＣ等与片芯无明显差异,达到设计要求。结论：该研究制备的脉冲释放制剂为防治心血管疾病的凌晨发作提供了一个良好的剂型选择。     

Antifungal Activity of a New Triterpenoid Glycoside from Pithecellobium racemosum (M.)

Purpose. In a continuation of our search for novel antifungal compounds from higher plants, the standard extract of the bark of Pithecellobium racemosum was found to have good activity against important AIDS-related opportunistic yeasts. Methods. The extract was subjected to bioguided fractionation using silica gel column chromatography which led to purification of triterpene glycosides. The structures of these compounds were determined by a combination of spectroscopic (IR, NMR, HRMS) and chemical methods. Results. Compound 1 is a new glycoside, 3-O[-L-arabinopyranosyl (1 -2)][-L arabinopyranosyl (1 -6)]2-acetoamido-2-deoxy--D-gluco-pyranosyl oleanolic acid and Compound 2 was identified as the known compound 3-O-[-L-arabinopyranosyl (l-2)]-L-arabinopyranosyl (1-6)] 2-acetamido-2-deoxy--D-glucopyranosyl echinocystic acid. Conclusions. Compound 1 is a new glycoside, 3-O-[-L-arabinopyranosyl (1-2)]-L-arabinopyranosyl (l-6)]-2-acetoamido-2-deoxy--D-glucopyranosyl oleanolic acid and exhibits moderate antifungal activity against T. mentogrophytes, C. albicans and S. cerevisiae with MIC values of 6.25, 12.5 and 12.5 g/ml respectively.     

Change in process: bringing about change in health care through action research

• ? A 2-year action-research project aiming to facilitate the management of change was carried out in a district general hospital.
• ? Hospital managers and senior ward nurses had very different views concerning the source of challenges and problems within the hospital organization.
• ? A case-study of nurses' experience of change at ward level was produced as part of the diagnostic phase of the action research.
• ? The results of the case-study indicated that general managers and professionals had different agendas for change hut that there is common ground between them.

     

Modulation of action potential duration by inhibition of the transient outward current in sheep cardiac Purkinje fibers

In sheep cardiac Purkinje fibers concentration-dependent inhibition of transient outward current (i_to) by 4-aminopyridine (4-AP, 3-1000 mol/l) was recorded with the two-microelectrode voltage-clamp technique, and correlated effects on action potential duration measured at — 70 mV (APD-70) were investigatigated.Half-maximal inhibition of i_to-amplitude occurred at 15 mol/l 4-AP. The drug exhibited no major effect on voltage-dependent control of inactivation but reduced the maximally available i_to-current. At different activation frequencies (0.05 Hz, 0.25 Hz, 1 Hz) an equal amount of i_to-current, measured as percentage of the respective control, was inhibited by 4-AP. The APD-70 was on the average increased by 4-AP (3–500 mol/l) in a concentration-dependont manner up to 151 % of control. The drug-induced prolongation, measured as percentage of the respective control, was independent of stimulation frequency (0.05 Hz, 0.25 Hz, 1 Hz). Prolongation of APD-70 was on the average more pronounced for short action potentials (APD-70<150 ms: 169 % of reference) than for longer ones (APD-70 150–300 ms: prolongation to 117 % of reference; 500 mol/l 4-AP; 0.25 Hz stimulation rate). Few long control signals (APD-70 >300 ms) were shortened by 4-AP. These results indicate that inhibition of i_to-current by appropriate drugs will result in a reduction of inhomogeneity of action potential duration.     

Preparation and local anaesthetic activity of benzotriazinone and benzoyltriazole derivatives

Two sets of benzotriazinone and benzoyltriazole derivatives were prepared and tested for local anaesthetic activity in comparison with lidocaine. Several of the prepared compounds exhibited a fairly good activity comparable or superior to that of lidocaine. The presence of a benzotriazinone or a benzoyltriazole moiety as an aromatic system was quite profitable for both the intensity and duration of activity. The acute toxicity in mice of the four most potent compounds of the series was also assessed. Compound 1b, which has an anaesthetic activity comparable to that of lidocaine, was also characterized by a more favourable therapeutic index. All compounds were tested in vitro to evaluate their negative chronotropic action in isolated rat right atria.     

创建爱婴市 强化爱婴行动

深圳市从１９９３年开展创建爱婴医院、争创爱婴市活动。主要做法：提高认识,加强领导,全面推进爱婴行动;部门协作,齐抓共管,形成社会系统工程;儿童优先,母亲安全,促进医院产科改革;建章立制,规范管理,巩固和发展－创建成果;进入社区,进入家庭,促进妇幼保健工作。到１９９６年底,全市有１０张以上产科床位的医疗保健机构３５间已全部通过市、省和国家爱婴医院三级评审;住院期间和４个月的母乳喂养率分别提高到９６．２％和５２．６％;孕产妇和婴儿死亡率分别降至１２．９／１０万和１３．４‰。     

Synthesis and analgesic and anti-inflammatory activities of 1,2-benzothiazine derivatives

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/anti-inflammatory efficacy and their effects on gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent analgesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.     

Relaxation kinetics of formoterol and salmeterol in the guinea pig trachea in vitro

The mechanisms producing long duration of action for formoterol and salmeterol are not fully understood. The aim of the current study was to examine how the concentration of long and short acting ₂-adrenoceptor agonists affects their relaxation kinetics in airway smooth muscle. Onset (time to peak relaxation) and offset of action (reassertion of reversible relaxation following repeated -adrenoceptor blockade and washout) were measured in the guinea pig trachea precontracted postjunctionally by carbachol 0.3 M in vitro. At 10–1,000% (C _1O–C _1,000) of the maximally effective concentration (C ₁₀₀: 150 nM formoterol, 10 M salbutamol, 30 M salmeterol), salbutamol had a shorter time to peak relaxation than did salmeterol. Formoterol and salmeterol had a similar time to peak relaxation at C ₁₀, but, in contrast to salmeterol, formoterol's time to peak relaxation became markedly shorter and similar to that of salbutamol as the concentration was increased up to C _1,000. Significant reversible reasserted relaxation was demonstrated for salmeterol alone at C ₁₀. At C ₃₀–C _1,000, however, salmeterol produced irreversible relaxation only, in spite of repeated -adrenoceptor blockade by sotalol 10 M followed by washout. In contrast, formoterol produced an increasing reversible reasserted relaxation at C ₃₀–C _1,000. Salbutamol produced significant, reversible reasserted relaxation at C _1,000 only. In conclusion, the concentration determines the onset and offset of action for formoterol and to a lesser extent for salbutamol, but not for salmeterol. To cause sustained action, a submaximally effective concentration is sufficient for salmeterol, whereas formoterol requires a maximally effective concentration. The rank order of concentration dependence for the relaxation kinetics is not paralleled by the rank order of lipophilicity for formoterol, salbutamol, and salmeterol. Therefore, factors other than lipophilicity may also play a role in determining the relationship between concentration and relaxation kinetics for the investigated ₂-agonists. Offprint requests to: Anders Linden, MD, PhD     

Closing the theory—practice gap: a model of nursing praxis

Summary

• ? Despite the efforts of nursing theorists, educationalists and practitioners, the theory-practice gap continues to defy resolution. This paper argues that only by reconsidering the relation between theory and practice can the gap be closed.
• ? Drawing upon ideas from teaching and other practice-based disciplines, including nursing, the article suggests that the current model of viewing theory as informing and controlling practice should give way to a mutually enhancing model in which theory is derived from practice, and in turn influences future practice.
• ? This coming together of theory and practice is referred to as nursing praxis, and suggests that informal theory should be unique to each individual encounter with each patient.
• ? The clinical nurse is thus not only a practitioner, but a theorist and researcher, who responds to patients not according to some grand, inflexible theory, but by the process of reflection-in-action, drawing upon their expertise and a repertoire of past experiences and encounters.

     

Ischaemia induced alternans of action potential duration in the intact-heart: dependence on coronary flow, preload and cycle length

Clinical and experimental evidence relate action potential duration(APD) alternans to ischaemic heart disease and ventricular arrhythmias.The present investigation was performed to study the quantitativerelationship between APD alternans and the degree ofischaemia,loading conditions and cycle length (CL) in an intact heart. Monophasic action potentials (MAP) were simultaneously recordedby contact electrodes from two left (LV) undone right ventricular(RV) sites in 20 Langendorff-perfused rabbit hearts. The preparationswere subjected to global ischaemia at flow rates ranging from40% of normal flow to complete cessation of flow. Pacing wasperformed at either constant or regularly changing CL. The magnitudeof APD alternans was expressed as beat-to-beat differences inaction potential duration of two consecutive MAPs. During normalper fusion, neither very fast pacing at a CL of 200 ms nor periodicalrate switches resulted in persistent APD alternans. Pacing ata constant CL of 800 ms did not induce A PD alternans at completecessation of flow for 6 min. However, alternans developed progressivelyat a constant CL of 400 ms after 2.8±0.3 min of completeischaemia at the pre-loaded LV, andafter 4.6±0.4 minat the unloaded RV (P<0.01). The reduction of preload atthe LV from 15 to 5 mmftg end-diastolic pressure delayed developmentof APD alternans from 2.8±0.3 min to 4.3±0.4 min(P < 0.05) at 400 ms CL. Following graded under per fusionof 40%, 20% and 10% of initial flow, persistent APD alternansdeveloped in relation to the degree of flow reduction and increasedprogressively with duration ofischaemia. APD alternans at theLV always preceded the onset of APD alternans at the RV. Inexperiments with identical flow rates the shortest CL of 200ms resulted in the greatest and earliest initiation of APD alternanscompared to the longer CL (P<0.01, P<0.001). An increasein CL from 400 to 800 ms immediately abolished APD alternans,generated by the shorter CL, at any time during the 6 min periodof complete ischaemia. Similarly, increasing the cycle lengthfrom 200 or 400 to 600 ms eliminated APD alternans up to 6 minof ischaemia and significantly reduced its magnitude between7 and 10 min within a few beats. We conclude that persistent APD alternans is a characteristicfinding in the rabbit heart during global ischaemia. It is asensitive parameter of the severity of ischaemia and dependson the degree and duration of ischaemia as well as on the preload.The CL appears to have an independent effect on the generationof APD alternans, which is functionally separate from the effectof CL on the ischaemic burden. An eventual impact of these observationscould be the application of APD alternans as a diagnostic toolin electrophysiological examinations of myocardial ischaemiain experimental and clinical settings.