[Experimental study of preventing emphysema with elastase inhibiting agents].

We have observed the influence of Radix Salviae Miltiorrhizae and Ligustrazini Hydrochloridum on the elastase activity and the protective effects of the two medicines on the elastic fibers. The results showed that Radix Salviae Miltiorrhizae and Ligustrazini Hydrochloridum can inhibit the activity of porcine pancreatic elastase and human sputum elastase. These two drugs can protect arterial and pulmonary elastic fibers from the destruction of elastase. Since these traditional Chinese herbs have little toxic effect and no antigenic character, they can be used in the preventing emphysema. The study suggest that it is useful Radix Salviae Miltiorrhizae and Ligustrazini Hydrochloridum are as favourable elastase inhibiting agents, which may be used in the prevention of emphysema extensively.

[The role of hemorheologic changes in the pathogenesis of acute hemorrhagic necrotizing pancreatitis].

The hemorheologic alterations were studied in experimental acute hemorrhagic necrotizing pancreatitis (AHNP) which was induced by injection of 5% sodium taurocholate into the main pancreatic duct. The results showed that during the early stage of AHNP, all of hemorheologic parameters were significantly elevated, and continually increased at the rest intervals. The authors suggested that the blood viscosity and hematocrit increase, red blood cells tend to aggregate, and erythrocyte deformation decrease are the causation of pancreatic microcirculatory disturbances and promoting pancreatic progressive necrosis. After using low molecular dextran and Salvia miltiorrhizae, the hemorheologic alterations in AHNP were recovered, and the histologic observation improved. Our data indicate the hemorheologic disturbances is one of the key factors in the pathogenesis of AHNP.

[The characteristics of the action of polyphytochol on the course of experimental hepatitis and cholecystitis]. / Osobennosti deistviia polifitokhola na techenie éksperimental'nogo gepatita i kholetsistita.

The effect of polyphytochol representing a combination of vegetable agents was studied on models of acute toxic hepatitis caused by CCl4 and cholecystitis. The efficiency of the drug in pathology of the hepatobiliary system was shown: it decreases cholestasis acting as a choleretic and bile-secreting drug, acts on the main pathogenetic links in hepatitis, exerts a marked membrane-stabilizing effect, influences favourably the processes of synthesis in the liver.

Depth and duration of skin analgesia to needle insertion after topical application of EMLA cream.

We have determined the depth and duration of analgesia to needle insertion after topical application of EMLA cream (Eutectic Mixture of Local Analgesics). EMLA was applied for 30, 60, 90 and 120 min and the sensory and pain threshold depths were determined before analgesia (1.0 and 1.9 mm, respectively) and up to 4 h after the cream was removed from the skin. The maximal depth of analgesia (approx. 5 mm) was observed 30 min after a 90-min application and during the 60-min period after a 120-min application of EMLA cream, for both sensory and pain thresholds. For application times shorter than 120 min, the depth of analgesia increased during the period after removal of the cream. This suggests new guidelines for the use of this topical analgesic.

[Effects of radix Salviae Miltiorrhizae on visceral pain discharges in the posterior nucleus of the thalamus in cats].

Extracellular microelectrode method and stereotaxic technique of brain were used to investigate the effects of Radix Salviae Miltiorrhizae on the discharges of visceral pain in the posterior nucleus of thalamus(po)in cats. Experiments showed that Radix Salvia Miltiorrhizae inhibited the discharges of visceral pain in po, Radix Salviae Miltiorrhizae acts directly on the peripheral nerve trunk and cannot block its exciting conduction. This suggests that the analgesic effect of Radix Salviae Miltiorrhizae is exerted via central nervous system.

[Experimental study on myocardial protection with verapamil and salvia miltiorrhiza Bunge cardioplegia].

Myocardial 45Ca sequestration was studied in dogs during 60 minutes of global ischemia and 30 minutes of reperfusion using cardiopulmonary bypass (CPB) and myocardial function was studied before and after CPB. Group A (n = 5), as a control, received cold hyperkalemic cardioplegic solution, Group B (n = 5) received the same solution plus verapamil (150 micrograms/kg/L) and Group C plus specific activity (TSA = DPM x 10(4)/g) and plasma specific activity (PSA = DPM x 10(4)/ml) were determined by biopsy before and after release of the cross-clamp The results showed that myocardial function in Group B and C were better than that in Group A (P less than 0.01). It is suggested that verapamil and Salvia miltiorrhiza Bunge effectively control myocardial calcium sequestration during early reperfusion and reduce myocardial reperfusion injury As to myocardial protection, cardioplegia with verapamil and Salvia miltiorrhiza Bunge were superior to hyperkalemic alone. Verapamil cardioplegia was still better than Salvia miltiorrhiza Bunge.

Inhibition of clastogenic effect of radiation by Liv. 52 in the bone marrow of mice.

The frequency of micronuclei in bone marrow cells of mice treated or not with Liv. 52 and then exposed to 4.5 Gy of gamma-radiation was evaluated from 6 h to 14 days post irradiation. The frequency of micronuclei increased from 6 h to 24 h post irradiated in both irradiated groups and declined thereafter, the frequency of micronuclei remaining significantly lower in the Liv. 52-treated group. These data demonstrate that Liv. 52 protects the bone marrow of mice against radiation injury.

Effect of antacid treatment on endogenous prostaglandin synthesis in human antral and duodenal mucosa.

Using 14C-labeled arachidonic acid as precursor for in vitro prostaglandin synthesis, the effect of an antacid containing Al (OH)3, Mg(OH)2 and CaCO3 on endogenous prostaglandin synthesis was investigated in antral and duodenal mucosa of healthy volunteers. After three weeks of treatment with a high-dose antacid, there was no detectable change in the total capacity of the mucosa for prostaglandin synthesis, but the prostaglandin profile was markedly altered. The relative amounts of PGE2 and PGF2 alpha synthesized by antral and duodenal mucosa increased at the expense of the prostaglandins A2/B2, thromboxane A2, and prostacyclin. In a short-term study, this change was not observed following a single antacid dose within 1 hr after application. It is concluded that long-term antacid treatment may alter the prostaglandin pattern formed by gastroduodenal mucosa and this may be related to its therapeutic effect.

[Changes in the deformability of erythrocytes and 2,3-DPG in coronary artery stenosis].

The changes of deformability of RBC and 2,3-DPG in RBC in patients with coronary artery stenosis and the influence of some factors on them were studied. The results showed that: (1) the deformability index was inversely proportional to the degree of lesions of coronary vessels (P less than 0.01); (2) the 2,3-DPG was inversely proportional to the degree of lesions of coronary vessels (P less than 0.01); (3) there was a significant decrease in deformability index after using contrast medium; (4) Saliva may increase deformability of RBC and 2,3-DPG; (5) Nifedipine may increase deformability of RBC. These results showed: (1) the possible existence of microcirculatory dysfunction in coronary artery disease and in parallel of impaired deformability of RBC; (2) the possibility of normalization of the decreased deformability of 2,3-DPG in RBC by Salvia; (3) the possibility of increase of velocity of blood flow in microcirculation in coronary artery disease by Salvia.

The mechanism of ceruminolysis.

In a previous study comparing the efficacy of a selection of commonly used ceruminolytics, the authors noted that aqueous-based preparations, and in particular solutions of sodium bicarbonate, were more effective in disintegrating cerumen than most organic-based preparations. In that study, the authors also observed that not only had the wax truly disintegrated following exposure to the aqueous-based preparations, but also that a marked degree of swelling of the wax spheres had occurred with these preparations. In this paper the mechanism of ceruminolysis was investigated by means of a number of commonly available histological techniques. Our findings show that desquamated sheets of corneocytes are the major constituent of cerumen plugs and provide the structural framework of the wax bolus. Ceruminolytics work by hydrating the keratin cells of these sheets of desquamated stratum corneum and subsequently inducing keratolysis, with disintegration of the wax.

[Use of amphotericin B-cells to detect inhibitors of cellular cholesterol biosynthesis].

A new method for detecting inhibitors of cellular cholesterol biosynthesis is reported. It was established according to the principle that amphotericin B binds sterols in the membranes of animal cells to form a complex which kills the cells. The method was simple, reliable and easy to handle. Moreover, the cost was low. Using this method, the authors had screened twenty Chinese herbs and found that Salvia miltiorrhiza and its extracts inhibit cellular cholesterol biosynthesis efficiently.

The effect of radix Salviae miltiorrhizae on vasoactive intestinal peptide in cerebral ischemia: an animal experiment.

The levels of vasoactive intestinal peptide (VIP) in three regions of rat brain were assayed in 62 rats. Bilateral common carotid artery ligation was done in 50 rats. Half an hour before ligation 26 rats were given 10 g/kg of Radix Salviae Miltiorrhizae (RSM); 24 rats were given same volume of normal saline as controls. A sham operation was done in 12 rats. Half an hour (n = 30) and 3 hours (n = 32) after operation, the rats were quickly decapitated. VIP levels were assayed in cerebral cortex, hippocampus and caudate nucleus. In salin-treated animals, VIP levels of cerebral cortex and caudate nucleus at 3 hour group were significantly decreased compared with the sham-operated group. No significant difference was found between RSM-treated and sham-operated groups. The preliminary results suggest that VIP may be involved in the pathophysiological procedures of cerebral ischemia and RSM may attenuate the dysfunction of VIP during cerebral ischemia.

Highly polarized secretion of inhibin by Sertoli cells in vitro.

We have studied the regulation of inhibin secretion by rat Sertoli cells grown on extracellular matrix-impregnated porous filters in a twin chamber assembly. Previous studies have established that rat Sertoli cells cultured under these conditions reproduce the morphological and functional polarization observed in the Sertoli cell in situ. Sertoli cells isolated from 18- to 22-day-old Wistar rats were cultured for up to 8 days with daily changes of fully defined supplemented Eagle's Minimum Essential Medium (MEM). Rat inhibin was measured by RIA and pituitary cell bioassay, and transferrin by RIA. Inhibin measured by immunoassay or bioassay was always readily detectable in the upper, but not the lower, chamber. Inhibin secretion into the upper chamber exhibited a dose-dependent stimulation of up to 3.7-fold by ovine FSH, with a medium effective dose of 2.2 micrograms/liter and a constant bio- to immunoreactive ratio (3.6 +/- 0.4). Apically directed secretion accounted for over 80% of inhibit output under basal conditions and over 94% with FSH stimulation. Insulin also stimulated upper chamber inhibin secretion at a high dose (5 mg/liter) but not at lower doses or in conjunction with FSH exposure of Sertoli cells. Testosterone augmented FSH-induced stimulation of inhibin secretion, but was ineffective without FSH exposure. In contrast to inhibin secretion, for which FSH is the principal regulator, transferrin secretion by Sertoli cells is more evenly bidirectional (overall mean upper to lower chamber ratio of 1.5) and requires exposure to other stimuli (insulin, retinoic acid, and testosterone) in addition to FSH to achieve maximal secretion. Both submaximal and maximal FSH stimulation of inhibin output were augmented by a phosphodiesterase inhibitor, isobutylmethylxanthine, and these effects were fully reproduced by forskolin, which suggests the involvement of cAMP in the vectorial secretion of inhibin. The marked polarization of Sertoli cell inhibin secretion in vitro could not be explained by restricted transmembrane passage of inhibin. It is, therefore, suggested that the bulk of inhibin secretion by the immature rat Sertoli cell in vivo may be directed primarily into the seminiferous tubular lumen. Thus, in addition to its role in endocrine negative feedback signaling to the pituitary, inhibin may also have important functions in seminiferous tubular function and the support of spermatogenesis.

Characterization of de novo folate synthesis in Pneumocystis carinii and Toxoplasma gondii: potential for screening therapeutic agents.

Drug therapy studies imply that Pneumocystis carinii and Toxoplasma gondii possess the enzymes necessary for de novo folate synthesis. To verify this, incorporation of [3H]paraaminobenzoic acid [( 3H]PABA) into reduced folates by P. carinii and T. gondii was investigated. Both organisms synthesized tritiated reduced folates. In P. carinii, 10-formyltetrahydrofolate and tetrahydrofolate, and in T. gondii, 5-formyltetrahydrofolate were the major synthesized folates. P. carinii remained metabolically active in vitro for only a few days. Because current systems for screening antipneumocystis agents are cumbersome, the utility of this assay system for screening therapeutic agents was investigated. Sulfonamides and pentamidine efficiently inhibited de novo folate synthesis in P. carinii. Inhibitors of dihydrofolate reductase such as trimethoprim and trimetrexate were poor inhibitors for P. carinii but efficient inhibitors for T. gondii. This study demonstrates the first unambiguous evidence of metabolic activity in P. carinii, and provides a potential assay for efficiently screening antipneumocystis drugs in vitro.

[Improving venous tone and capillary sealing. Effect of a combination of Ruscus extract and hesperidine methyl chalcone in healthy probands in heat stress]. / Venentonisierung und Kapillarabdichtung. Die Wirkung der Kombination aus Ruscus-Extrakt und Trimethylhesperidinchalkon bei gesunden Probanden unter Wärmebelastung.

The drug combination of Ruscus-extract and hesperidine methyl chalcone (HMC) involves two basic mechanisms in the treatment of venous diseases: increase in venous tonicity and edema protection. This was shown in a double-blind study on 20 healthy volunteers by comparing the effectiveness of the individual substances, the combination and a placebo on the venous hemodynamics and the volume of the foot. Ruscus-extract augments the tonicity of the venous wall. This is expressed by a decrease in venous capacity (p less than 0.01), a reduction in the blood pool in the lower leg under orthostatic conditions, and a decrease in tissue volume of the foot and ankle (p less than 0.01). HMC lowers the capillary filtration rate (p less than 0.01) but augmented the blood pool. The increase in blood volume can be explained by dehydration of the tissue of the lower leg lowering the pressure of tissue on the venous system and increasing the blood pool in the limb. After administration of the combination, the blood volume was between the Ruscus and HMC volumes, while the effects on filtration rate, venous capacity and tissue volume corresponded to the changes seen after administration of HMC and Ruscus extract alone.

[Direct detection of oxygen free radicals produced by myocardial reperfusion using electron spin resonance spectroscopy].

There is a growing evidence for the role of oxygen free radicals (OFR) in mediating myocardial tissue injury during myocardial ischemia and particularly during reperfusion. But almost all of the evidence was indirect, using electron spin resonance (ESR) spectroscopy, we have directly measured OFR generated in ischemic and reperfused isolated rabbit hearts. 17 hearts were rapidly frozen in liquid nitrogen after their arrest by cardioplegic solution and sampled after 150 min of sustained hypothermic global ischemia or after reperfusion. The ESR spectra obtained from experiment have directly demonstrated that OFR is produced in significant amounts in the isolated rabbit hearts during early stage of reperfusion but only small amount during ischemia. The mitochondrial electron transport chain appeared to be the main source of OFR. We found that superoxide dismutase scavenged OFR generated during reperfusion efficiently, but catalase did not. We believe that superoxide anion, not hydroxyl radical, is the main OFR which is responsible for myocardial reperfusion injury. We also found that Salvia, a traditional Chinese medicine, a very efficient OFR scavenger, had the similar effect as superoxide dismutase.

Penile desensitization does not affect postcopulatory genital autogrooming in rats: evidence for central motor patterning.

Postcopulatory genital autogrooming was studied in rats following desensitization of the glans penis due to topical application of an anesthetic ointment or to surgical transection of the dorsal penile nerve. These treatments sharply reduced the number of mounts resulting in intromission, but genital autogrooming was largely unaffected. The probability and duration of genital grooming were sensitive to the mount bout status of the copulatory event. The probability of autogrooming was higher, and the duration longer, after mounts that ended mount bouts and after intromissions, than after mounts that were incorporated within a mount bout. These findings suggest that the apparently compulsive genital autogrooming within a copulatory context is not regulated by afferent impulses from the penis, but may largely reflect central motor programing.

Early treatment of Campylobacter jejuni enteritis.

The bacteriologic and clinical effects of early antibiotic treatment of Campylobacter jejuni enteritis were studied. Erythromycin rapidly eliminated C. jejuni from stools, whereas trimethoprim-sulfamethoxazole did not. Despite its bacteriologic effectiveness, erythromycin did not reduce the duration or severity of diarrhea, abdominal pain, or other symptoms.