黄参方剂诱导胃癌癌前病变细胞凋亡和影响BCL—2蛋白表达的研究

目的：探讨黄参方剂对胃癌癌前病变细胞凋亡及相关基因表达的影响。方法：将７２例胃癌癌前变患者随机分为２组,治疗组３７例,口服黄参方剂６０ｍｌ／ｄ;对照组３５例,口服维酶素片１２片／天,疗程２月。治疗后胃镜同一部位取材,检测治疗前后细胞凋亡指数和ＢＣＬ－２蛋白的表达。采用原位末端标记法（ＴＵＮＥＬ）检测细胞凋亡,采用免疫组化检测ＢＣＬ－２蛋白的表达。结果：黄参方剂组服药前后细胞凋亡指数分别为（１９．８     

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.     

Effects of adenosine on electrical activity of isolated guinea pig hearts

Summary Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated.Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff.Adenosine in concentrations of 3 and 10 M reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636±109 and 111±35 (mean±SE) beats, respectively.During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 M, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed.These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias.     

GABA-mediated synaptic transmission in neuroendocrine cells: a patch-clamp study in a pituitary slice preparation

Patch-clamp recording techniques were applied to thin slices of the rat pituitary gland in order to study synaptic transmission between hypothalamic nerve terminals and neuroendocrine cells of the intermediate lobe. Inhibitory postsynaptic currents (IPSCs) could be evoked by electrical stimulation of afferent neuronal fibres in the surrounding tissue of the slice. The IPSCs could be evoked in an all-or-nothing mode depending on the stimulus intensity, suggesting that single afferent fibres were stimulated. They had a chloride-dependent reversal potential and were blocked by bicuculline (K _d=0.1 M), indicating that they were mediated by -aminobutyric acid A (GABA_A) receptors. In symmetrical chloride solutions the current/voltage relation of the IPSC peak amplitudes was linear. The IPSCs were characterized by a fast (1–2 ms) rise time and a biexponential decay, with time constants of 21±4 ms and 58±14 ms at a holding potential of –60 mV (n=6 cells). Both decay time constants increased with depolarization in an exponential manner. Spontaneously occurring IPSCs had a time course that was similar to that of evoked IPSCs. These miniature IPSCs, recorded in 1 M tetrodotoxin, displayed an amplitude distribution that was well fitted by single Gaussian functions, with a mean value of its maxima of 18.1±2.3 pA (n=4 cells). Amplitude histograms of evoked IPSCs were characterized by multiple peaks with a modal amplitude of about 18 pA (n=6 cells). These findings indicate the quantal nature of GABAergic synaptic transmission in this system, with a quantal conductance step of about 280 pS. Single-channel currents underlying the IPSCs were studied by bath application of GABA to outside-out patches excised from intermediate lobe cells. Such GABA-induced currents revealed two conductance levels of 14 pS and 26 pS. In conclusion, GABAergic synaptic transmission in neuroendocrine cells of the pituitary has properties that are quite similar to those observed in neurones of the central nervous system.     

Cytologic diagnosis of cavernous hemangioma of the liver with fine-needle biopsy.

We present the cytopathologic findings in seven cases of cavernous hemangiomas of the liver diagnosed by direct "squash" smears made on tissue obtained through image-guided fine-needle biopsy. The diagnosis in each case was confirmed histologically. Utilizing this simple cytologic technique, the morphologic findings in these common hepatic lesions are as accurate and diagnostic as histologic examination.     

Effects of prostacyclin analogue,OP-2507, on function and metabolism in the ischemic working rat heart

We examined the effects of a new stable prostacyclin analogue, OP-2507, on myocardial function and metabolism in the ischemic working rat heart preparation. The hearts were perfused with Krebs-Henseleit bicarbonate (KHB) buffer, and whole heart ischemia was induced by one-way aortic valve for 15min follows by reperfusion for 30min. In the treated hearts, OP-2507, 20ng·ml^–1, was administered to KHB buffer from the beginning to the end of experiment. During ischemia, coronary flow in the OP-2507 group increased significantly more than that in the control group. The mechanical performance of both groups was impaired after ischemia. However, the recovery of coronary flow, cardiac output, peak systolic pressure and LV dP/dT_max was significantly higher in the treated group than in the control group. The incidence of ventricular fibrillation during reperfusion was 100% and 25% in the control and the OP-2507 groups, respectively. Myocardial ATP content was significantly higher in the treated hearts than that in the control hearts. These results indicate that this stable prostacyclin analogue is beneficial in myocardial ischemia, even without its well known action of preventing platelet aggregation.(Oguchi T, Kashimoto S, Nakamura T, et al.: Effects of prostacyclin analogue, OP-2507, on function and metabolism in the ischemic working rat heart. J Anesth 6: 446–454, 1992)     

Monosynaptic Interjoint Reflexes and their Central Modulation During Fictive Locomotion in Crayfish

An in vitro preparation of the crayfish nervous system has been utilized to study an interjoint reflex pathway and its variability during rhythmic locomotor activity. The coxo-basal chordotonal organ (CBCO) is a joint stretch receptor spanning the second joint of walking legs in crayfish, where it encodes joint movements and position. Mechanical stimulation (stretch and release) of the CBCO and electrical stimulation of the CBCO nerve elicits reflex responses in promotor and remotor motor neurons innervating muscles moving the basal thoraco-coxal (TC) leg joint. Promotor and remotor motor neurons receive monosynaptic excitatory inputs from at least four CBCO afferents, including both stretch- and release-sensitive CBCO afferents. In a tonic preparation, in which there is no tendency to produce alternating bursts of activity in antagonistic motor neurons, the reflex responses were evoked during each cycle of imposed movement. However, when the preparation became rhythmic and produced bouts of fictive locomotion, the reflex responses were unstable and their gain was phasically modulated. Paired recordings indicate that such a modulation of the monosynaptic interjoint reflex could be due to both a phasic change in the excitability of the motor neurons and presynaptic inhibition that reduces the excitatory input from CBCO primary afferents.     

GABA-Mediated Presynaptic Inhibition in Crayfish Primary Afferents by Non-A,Non-B GABA Receptors

GABAergic presynaptic inhibition has been investigated in primary afferents using an in vitro preparation of the crayfish, Procambarus clarkii. Presynaptic terminals of a leg proprioceptor, the coxo-basal (CB) chordotonal organ, were impaled in the neuorpil of the 5th thoracic ganglion. Pressure ejection of small volumes of the GABAA or GABAB receptor agonists, muscimol and 3-aminopropylphosphinic acid (3-APA), both induce depolarizing responses in the impaled CB sensory terminal. These depolarizations are not blocked by the specific GABAA and GABAB receptor antagonists, SR-95531 and phaclofen, but they are abolished by picrotoxin. Both muscimol- and 3-APA-induced depolarizations are carried by an increase in conductance to Cl-. The presynaptic increase in conductance to Cl- by GABA receptor activation leads to a depression of sensory synaptic transmission through a shunting of the incoming spikes. Monosynaptic EPSPs elicited in motor neurons by CB sensory nerve stimulation are depressed by muscimol and 3-APA. GABA-mediated presynaptic modulation occurs in crayfish primary afferents which can adjust the gain of reflexes. These results show that GABA-activated Cl- channels can induce a modulation of synaptic transmission, but also that the distinction between GABAA and GABAB receptors, as in vertebrates, is not applicable to the crustacean primary afferents.     

中药载体制剂的研究进展

总结近年来中药载体制剂的研究工作和文献报道，综述了有关脂质体、微粒、毫微粒、乳剂等作为载体在中药制剂中的应用。     

中药和天然药靶向制剂的研究进展

靶向制剂可以提高靶组织的药理作用强度和降低全身的不良反应 ,是一种比较理想的给药方式 ,为第四代的药物剂型。采用脂质体作为药物载体是研究的重点 ,磁靶向 ,酶靶向制剂也是研究热点。此外 ,口服结肠靶向给药系统 (OCDDS)也是靶向制剂的一个重要部分 ,其是经口服将药物运送到回盲肠后释放并发挥局部或全身的治疗作用。中药靶向制剂的研究在我国还仅处于试探阶段 ,目前中药和天然药物的靶向制剂的研究大多数是以天然单一有效成分为原料药物 ,而用中药有效部位研制的靶向制剂屈指可数 ,这与制定中药有效部位的质量标准及制剂工艺难度大有关。中药新剂型和新技术的开展是中药国际化的关键 ,需要有组织地开展多学科合作 ,靶向制剂是中药今后发展的一个重要课题。