脑络康缓释胶囊的制备工艺和体外释放度的研究

以羟丙甲基纤维素作为主要的缓释辅料,采用正交设计方法优化处方研制成脑络康缓释胶囊.以人参皂苷的累积释放量作为考察指标,按照<药典>规定的缓释制剂的释放度进行优选.结果:最佳的处方工艺即羟丙甲基纤维素216 mg,乙基纤维素24 mg,混合稀释剂132 mg,释放曲线符合Higuchi动力学模型.     

Effects of 5-Hydroxytraptamine on Aggregation,Release Reaction and Mobilization of Cytosolic Free Calcium Concentration in Rabbit Normal and Washed Single Platelets

In rabbit platelet rich plasma (PRP), 5-hydroxytraptamine (5-HT,0.03～3μmol/L) induced decrease in light transmission (DLT) dose-de pendently with centralization, as revealed by electron microscopy. However, 5-HT did not induced platelet aggregation and release reaction. 5-HT-induced DLT was inhibited by methysergide (0.3～30μmol/L), indomethacin (0.3～10μmol/L) and PGE_1 (0.01～0.3μmol/L) in a dose-dependent manner, but not EGTA(0.3～3mmol/L). Collagen(Coll), arachidonic acid (AA), adenosine diphosphate (ADP) and a stable thromboxane A2 analoge(STA_2) also induced DLT before aggregation by themselves, which was also inhibited by PGE_1, but not inhibited by EGTA except for Coll However,Coll-, AA-, STA_2-and ADP-induced DLT were reduced by pretreatment of PRP with 5-HT dose-depen-dently. The duration of DLT by Coll and AA were decreased from 151.4±5.93 sec and 15(?)38±0.60sec to 45.44±4.04 sec and 9.00±1.25 sec respectively ((?)±s(?) P<0.01), but not by ADP and STA_2, 3μmol/L of ADP-and 0.3μmol/L of STA_2-induced aggregation which was not accompanied with release reaction were enhanced by 5-HT pretreatment, but in those (Coil 5μg/ml, AA 100～200μmol/L and STA_2 1～3 μmol/L) with release reaction, the amount of adenosine triphosphate(ATP)were suppressed significantly (P<0.001) by 5-HT pretreatment without the effect on the magnitude of aggregation, The mobilization of cytosolic free calcium concentration ([Ca~(2+)]i) was observed after 5-HT treatment in single washed platelet, the results indicated that the basic level of [Ca~(2+)] i was 64.78±3.24nmol/L and this level was increased dose-dependently and significantly at 30 sec after administration of 5-HT and the time of peak value of [Ca~(2+)] i was at 90～100 sec.The similar time courses of suppression of ATP released during aggregation, in cases of Coll(5μg/ml), AA (200μmol/L) and STA_2(3μmol/L), by 5-HT were also found in the present experiment.     

In vitro release of lectins by Phallusia mamillata hemocytes.

-Lactose specific lectins are released from Phallusia mamillata hemocytes during short-term cultures. The molecular weight of the subunits, the immunological cross-reaction and the sugar specificity suggest that the released lectins are similar to those isolated from the sonicated hemocytes. Because lectin release appears to take place independently of active protein synthesis, the possibility exists that lectins are pre-formed, stored in hemocytes and released when in vitro conditions stimulate the cells.     

Indikation, OP-Technik und Ergebnisse des endoskopischen Releases der Plantarfaszie (ERPF)

Zusammenfassung Fragestellung Ziel der vorliegenden Untersuchung ist es, die Indikation, OP-Technik sowie die Ergebnisse des endoskopischen Releases der Plantarfaszie darzustellen. Material und Methode An 5 nicht fixierten Präparaten wurde eine biportale Technik zum endoskopischen Release der Plantarfaszie erprobt. Ziel war es hierbei zum einen, die Relation zwischen Plantarfaszie und plantarem Fersensporn zu evaluieren; zum anderen wurde eine Technik erprobt, bei welcher nur 50–70% der medialen Plantarfaszie vom Kalkaneus abgelöst wurde.Über einen Zeitraum von 5 Jahren wurde diese Technik bei 10 männlichen und 7 weiblichen Patienten mit dem klinischen Bild einer Plantarfasziitis durchgeführt. Das mittlere Alter der Patienten betrug 35 Jahre (24–56 Jahre). Alle Patienten durchliefen zunächst konservative Therapieversuche von zumindest 6 Monaten. Ergebnisse Bei den ersten 5 Patienten wurde der Eingriff unter Bildwandlerkontrolle durchgeführt; bei den weiteren Patienten erfolgte die Resektion ohne intraoperative BV-Kontrolle. Bei allen Patienten konnte der Eingriff wie geplant durchgeführt werden. Die endoskopischen Portale heilten ohne Probleme. Die OP-Zeit ist im Rahmen der Lernkurve mit Zeiten zwischen 21 und 74 Minuten (MW: 41 Minuten) noch länger als in der offenen Technik. Der Nachuntersuchungszeitraum betrug zwischen 4 und 48 Monate (MW: 18,5 Monate). Bei 13 der 17 Patienten kam es zu einer klinischen Verbesserung und sie würden den Eingriff erneut durchführen lassen. 7 Patienten zeigten ein gutes und 6 ein sehr gutes Ergebnis im Ogilvie-Harris-Score. Bei 2 Patienten war das initiale Ergebnis nicht zufriedenstellend. Die Ursache hier lag in einer ossären Übermüdungsreaktion des Kalkaneus. Diese Komplikation wurde durch Entlastung über 6 Wochen symptomastisch behandelt. Bei zwei weiteren Patienten stellten sich sekundäre Überlastungen am lateralen Fußrand ein. Im Rahmen der frühen Rehabilitationsphase war es wichtig, trotz des minimalinvasiven Vorgehens, eine vorsichtige Belastungssteigerung durchzuführen. Schlussfolgerung Die Technik des endoskopischen Releases der Plantarfaszie (ERPF) ist standardisiert und reproduzierbar durchführbar. Sie führt zu guten mittelfristigen Ergebnissen. Ein Stabilitätsverlust der plantaren Verspannung sollte jedoch unbedingt vermieden werden.     

Effect of Carbamazepine on Dopamine Release and Reuptake in Rat Striatal Slices

Carbamazepine has been shown to enhance dopaminergic agonist behavioral effects, but not to displace [3H]spiroperidol binding. To verify if carbamazepine acts presynaptically on dopaminergic neurons, reuptake and release of [3H]dopamine were measured in rat striatal slices in vitro. It was observed that carbamazepine blocked 20% of the reuptake of [3H]dopamine, while cocaine blocked 82% of the reuptake, compared with control. Carbamazepine released 62% and tyramine released 92% of the accumulated [3H]dopamine, compared with control. It was concluded that carbamazepine acts presynaptically on striatal neurons, mainly through enhancement of dopamine release. This finding can be related to some behavioral effects described for carbamazepine; however, the importance of its effects in epileptic and manic-depressive patients remains to be clarified.     

关节镜下松解术治疗冻结肩25例报告

目的探讨关节镜下松解术治疗冻结肩的疗效.方法2001年10月～2003年10月,我院对25例冻结肩在关节镜下行松解术.全麻下肩关节后路进镜,前路进射频电刀烧灼肱二头肌长头肌腱及肩袖间隙部位的滑膜充血炎症区,切割盂肱上韧带、盂肱中韧带、肩胛下肌肌腱关节囊内部分,手法松解剩余挛缩.25例术后3、6个月随访肩关节活动范围及美国肩肘协会评分(ASES).结果手术时间75～98 min,平均85 min.无术中并发症.25例除术后1周肩关节内旋与术前无明显改善外(x2=8.558,P=0.073),术后各个时期肩关节其它活动范围比术前均有明显改善(P＜0.05).术后3个月和6个月比术后1周改善更明显(P＜0.05).25例术后3个月和6个月ASES评分(87.4±4.6,88.1±6.0)均比术前(45.8±10.0)明显改善(q=28.738,29.221;P＜0.05),但3个月与6个月评分相比较无显著性差异(q=0.484,P＞0.05).结论肩关节镜下手术松解冻结肩可以明显缩短病程,取得稳定满意的效果.     

Autoregulation of contractility in the myocardial cell

Summary An investigation was carried out on isolated cat's papillary muscle in order to study displacement effects upon the intensity and the time course of the contractile activity. Displacements occurring before or very early during a contractile cycle produce effects which can be entirely explained on the basis of the cardiac active length-tension relation. Displacements occurring later exhibit additional effects in so far as either stretches or releases induce a drop of contractile activation such that the course of the subsequent tension development is markedly below that of the same displacement applied earlier. In order to separate these effects from those based on the active length-tension correlation experiments were performed in which very short release-stretch or stretch-release operations were applied so that the muscle length was virtually the same at the beginning and at the end of the operation. The results obtained under these conditions can be summarized as follows.The extend to which contractile tension drops after a stretch-release or a release-stretch cycle has been applied depends upon (1) the stimulus intervention interval (2) the length change performed (3) the velocity of displacement during the intervention. It is not dependent on the initial muscle length. Increasing the extracellular Ca-concentration considerably reduces the displacement effects. The results are tentatively explained by assuming an internal feedback loop between a variable of the contractile machinary and the preceding mechanism of activation.This investigation was supported by the Deutsche Forschungsgemeinschaft (grant Ka 287, 1+3).     

Microdialysis: a way to study in vivo release of neurotrophic bioactivity: a critical summary

Microdialysis has been proven to be a valuable tool to study in vivo release of various neurotransmitters in the rat brain. Recently we demonstrated for the first time the release of neurotrophic bioactivity in the brains of awake rats. Neurotrophic factors, however, exist in extremely low concentrations in the brain compared to neurotransmitters, rendering their detection particularly difficult. This review summarizes knowledge about the use of microdialysis for the detection of neurotrophic bioactivity, its limits, and its problems.Abbreviations BDNF Brain-derived neurotrophic factor - EIA Enzyme immunoassay - NGF Nerve growth factor - NT-3 Neurotrophin-3     

The effects of calcium and magnesium on inhibitory junctional transmission in smooth muscle of guinea pig small intestine

Summary The membrane potential of smooth muscle cells in the circular layer of the guinea pig ileum was recorded using intracellular electrodes. Transmural stimulation, in the presence of atropine, caused a transient hyperpolarization, an inhibitory junction potential (IJP). IJP's are thought to result from the action of transmitter released from intramural inhibitory nerves. It has been reported that, in the guinea pig jejunum, the amplitude of the IJP resulting from field stimulation is not altered by changes in the calcium and magnesium ion concentration in the bathing solution. Experiments reported here have shown that the IJP amplitude decreased markedly on reducing the calcium ion concentration and or increasing the magnesium ion concentration. Indirect evidence is presented suggesting that the decrease in amplitude of the IJP is due to a decrease in the amount of transmitter released.     

Ouabain enhances release of acetylcholine in the heart evoked by unilateral vagal stimulation

Summary The aim of the study was to elucidate peripheral effects of ouabain on the parasympathetic innervation of the heart, effects that could contribute to the experimentally and clinically well established vagal effect of cardiac glycosides. The experiments were carried out with ouabain concentrations of 3×10^–7 and 10^–6 mol/l, which were considered therapeutic, as they increased force of contraction and did not elicit arrhythmias in incubated chicken atria.In atrial preparations of chickens and guinea-pigs the negative chronotropic and inotropic effects of acetylcholine (ACh) were not altered by 3×10^–7 mol/l ouabain. Resting efflux of ACh from perfused chicken hearts was increased by ouabain from 10 to a maximum of 30 pmol/g min, whereas release of ACh evoked by bilateral vagal stimulation at 3 or 20 Hz for 1 min was unchanged (resting release subtracted). In contrast, release of ACh caused by unilateral vagal stimulation was augmented by ouabain up to 200% of the control. Release by unilateral stimulation (80 pmol/g; 20 Hz) was calculated for each experiment by averaging the releases evoked by consecutive stimulation of the right and left nerves. Ouabain infused for 90 min did not alter the tissue content of ACh (5.5 nmol/g).Within 2 days after unilateral (left) vagal transsection (denervation of cardiac ganglia) the release of ACh evoked by stimulation of the intact nerve (20 Hz) increased from about 80 to 200 pmol/g, whereas the release from the lesioned nerve markedly declined. One day after denervation, ouabain had lost the ability to facilitate the release of ACh evoked by stimulation of the intact nerve, whereas the release by stimulation of the lesioned nerve was still increased.It is concluded that ouabain at therapeutic concentrations increased resting release of ACh but did not influence the mechanism of action potential-evoked release of ACh. The effect of exogenous ACh on sinus node activity was not enhanced by ouabain. The observation that ouabain increased release of ACh caused by unilateral, but not by bilateral vagal stimulation was explained by an increase in the number of activated postganglionic neurons arising from those (contralateral) ganglia that received a subthreshold input from the stimulated vagus nerve.Supported by the Deutsche ForschungsgemeinschaftSome of the results are part of the M.D. theses of M. Feinauer and B. Ullrich