Volume 106  ·   Issue 12  ·  1993

The protective effect of improving the microcirculation on the retinal ganglion cells (RGC) and the ultrastructure of the optic nerve after intravenous (i.v.) use of Salviae miltiorrhiza (SMR) was studied in a chronic intraocular hypertension model in 36 rabbits. These rabbits were treated with topical 0.5% timolol, or i.v. SMR or i.v. 0.9% saline for 1, 3, 5 or 8 weeks. The intraocular pressure (IOP) was 19.6±2 mmHg and the RGC density was 1140±121.2/mm2 in control rabbits. After one week of intraocular hypertension (IOP between 30 and 40 mmHg), the RGC densities decreased to between 650 and 820/mm2. Following the use of timolol for 1 to 8 weeks, IOP returned to control level and the RGC density increased to 1015±7/mm2. After treatment with i.v. saline for 8 weeks, the RGC density decreased progressively from 651±1/mm2 at the beginning of treatment to 83±3/mm2. The RGC density of those rabbits treated with i.v. SMR for 8 weeks remained virtually unchanged (658±5/mm2) compared to the RGC density at the beginning of the treatment. Severe ultrastructural damage of optic nerve and collapsed capillaries were found in rabbits treated with saline while these findings were mild in rabbits treated with SMR. During these periods of treatment, the intraocular hypertension did not decrease in rabbits treated with either saline or SMR. From these findings and the fact that SMR improves local microcirculation, it is considered that the compromised microcirculation is one of the mechanisms in the pathogenesis of optic nerve damage in chronic glaucoma.

In acute cerebral ischemia there are severe damages of endothelium which have been recognized as the stimuli to secrete endothelin-1, an endothelium-derived peptide and the most potent vasoconstrictor ever known. This study was to measure plasma endothelin-1 level in patients with cerebral infarction and explore the relationship between endothelin-1 and ischemic stroke. The possible involvement of endothelin-1 in local regulation of cerebral arterioles was also investigated. Plasma levels of endothelin-1 were measured by radioimmunoassay in 21 patients. Using a micro-video system, the endothelin-1 actions were also observed on rat pial arterioles in vivo, and with incomplete cerebral ischemia model (rat), effect of ischemia affects the endothelin-1 action. There was a marked increase in plasma endothelin-1 level in the patients and the elevation persisted during the acute and subacute period of stroke. There was a positive correlation between the peptide concentration and infarct size (r=0.655, P<0.01). In rats, endothelin-1 (dose range: 10-10 mole/L-10-7 mole/L) induced a dose-dependent arteriole contraction after subdural administration. Arteriole calibers were decreased by 27.7%±3.8% (10-9 mole/L), 46.8%±4.9% (10-8 mole/L) and 78.5%±4.7% (10-7 mole/L), respectively. Cerebral ischemia significantly enhanced the action of endothelin-1 (96.4%±7.2% vs 58.2%±6.8%). Endothelin-1 plays an important role in regulating local circulation of ischemic brain. The notable and lasting increase in plasma level of endothelin-1 are associated with cerebral ischemia and infarction. The peptide seems to be involved in the pathophysiology of acute cerebral ischemia and plays a deleterious role in the progress of cerebral infarction.

A three-year prospective study was carried out in 283 postmenopausal women to evaluate the effects of a long-acting estriol derivative-nylestriol. The women were randomly assigned into 3 groups: group A (136 cases, nylestriol 2 mg/2 wk), group B (97, nylestriol 1 mg/2 wk) and group C (50, placebo/2wk). LDL-C decreased and HDL-C increased after 3 months of medication (P<0.05), but TC and TG not significantly changed in any group (P>0.05). No changes of lipids were found in group C (P>0.05). Serum ALP, Ca/Cr and Hpr/Cr in fasting urine decreased in 3 months in both group A and B (P<0.05), but not in group C (P>0.05). Forearm bone mineral content loss was restrained in groups A and B (P>0.05), but decreased markedly in group C (P<0.01). The Kupperman index scores decreased by about 50% after 3 months and 80% in 12 months in groups A and B. Nylestriol induced mild stimulatory effect on the uterine endometrium, and addition of 6 mg of provera daily for 7-10 days every 6 months is recommended. Nylestriol exhibited no obvious effect on the breast. This study demonstrated that nylestriol can be used as an effective and acceptable estrogen replacement therapy for postmenopausal women.

Testis homotransplantation has been carried out in 11 patients since 1986. Of them, 8 suffered from congenital testicular dysplasia and the other 3 from orchiatrophy as a result of orchitis. Preoperatively, manifestations were a small penis, small testes, sexual dysfunction, indistinct secondary sex characteristics and low serum testosterone (1.7-7.35 mmol/L). Three cases had cadaver transplants and 8 had living relatives' transplants. The patients were followed up for 7 months to 4 years. The secondary sex characteristics and sexual function were improved remarkably after transplantation. Serum testosterone increased up to 12.8-18.2 mmol/L. All of 5 married patients resumed sexual intercourse satisfactorily. Three others got married after transplantation and have enjoyed normal sexual functions. Spermatozoa have been found in the semen in 3 of the cases.

The effect of captopril cardioplegia on ischemic and reperfusion myocardium after 3 hours of hypothermic (13±1 C) arrest and 35 minutes of reperfusion was studied in the isolated working rabbit heart. In comparison with the control group, captopril cardioplegia reduced the content of angiotensin II (381±56 vs 507±84 pg/g wt of the control group, P<0.01) and MDA (50.0±9.2 vs 85.1±16.1 pmol/mg pr, P<0.01) in the reperfusion myocardium; augmented the renin activity of ischemic (1050±353 vs 669±301 pg/g wt/h, P<0.05) and reperfusion myocardium (1261±421 vs 498±353 pg/g wt/h, P<0.01) increased the 6-K-PGF1α/TXB2 ratio in the reperfusion myocardium (by 48.1% of the control group). Meanwhile, captopril cardioplegia could also decrease the content of calcium (0.027±0.015 vs 0.045±0.014 microM/mg pr, P<0.05) and sodium (0.54±0.26 vs 0.82±0.15 microM/mg pr, P<0.05) in the reperfusion myocardium, but had no effect on the potassium content. The results show that the protective effect of captopril on hypothermic myocardium may be related to the free radical scavenging action, inhibition of angiotensin II production, improvement of PGI2/TXA2 ratio and decrease of calcium and sodium overload in the myocardium.

Chinese are more sensitive to the beta-blocking and hypotensive effects of propranolol than Caucasians. To determine the contribution of ethnic differences in the plasma binding of propranolol to the differences in sensitivity, 8 Caucasians (22.8±1.5 yr) and 8 Chinese (31.8±2.1 yr) were studied following single doses of 0, 10, 20, 40 and 80 mg propranolol orally. The binding of propranolol in plasma was determined by equilibrium dialysis after addition of 300 mg racemic propranolol to the plasma. The concentrations of free and bound (+) and (-)-propranolol were determined by stereospecific high performance liquid chromatography (HPLC). Dosage had no influence on the plasma binding of either enantiomer. The unbound fractions of both (-)-propranolol (16.06±0.79% vs 12.41±0.93%, P<0.05) and (+)-propranolol (17.73±0.81% vs 14.33±0.89%, P<0.01) were greater in Chinese than Caucasians, respectively. In both groups, the ratio of unbound (-) to (+)-propranolol was less than 1 (P<0.01) and was greater in Chinese (0.91±0.01 vs 0.88±0.01) (P<0.01), implying that in Chinese less isomers of both types were bound and there was a greater unbound proportion of the pharmacologically active (-)-propranolol which may contribute to their increased sensitivity to propranolol. It is demonstrated that ethnic differences in stereoselective protein binding may be an important variable in interindividual determinants of drug response.

Although it has been confirmed that insulin dependent diabetes mellitus (IDDM) is a kind of autoimmune disease, islet cell autoantibodies (ICAs), insulin autoantibodies (IAA) and anti-GAD-glutamic acid decardaxylase antibodies have been found in the sera of patients with IDDM and immunotherapies have been used in some patients with IDDM, yet the manner in which the dysfunctional immunosystem acts on beta cells and causes damage to them remains to be clarified. Recently, possible involvement of the abnormal production of IL-6 in autoimmune symptoms was suggested in patients with cardiac myxomas, Castleman's disease and rheumatoid arthritis. However reports of IL-6 abnormal production in patients with IDDM are rare. In the present study, we examined whether or not an abnormal expression of IL-6 mRNA was present in mononuclear cells (PBMNCs) of the peripheral blood of patients with IDDM. We devised a highly sensitive, specific and semiquantitative protocol, ie, reverse transcription and polymerase chain reaction (RT-PCR). We have used such an assay to measure the relative expression levels of IL-6 mRNA in PBMNCs from 12 early IDDM patients (duration<6 mon, 8.20±3.85 yr), 29 newly-diagnosed NIDDM patients (54.85±9.12 yr), 23 normal children (8.20±3.26 yr) and 12 normal adults (31.92±11.22 yr). In this assay significantly high expression levels of IL-6 mRNA were found in PBMNCs from patients with IDDM (P<0.05). The relative levels were 0.91±0.19; 0.10±0.06; 0.43±0.08; 0.10±0.07, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

It is known that intracellular Ca2+ is overloaded during ischemia as a result of the altered activity of the Na+/Ca2+ exchanger, one of the major pathways of Ca2+ efflux. But the molecular mechanism of the alteration is still unknown. We cloned a -500bp cDNA fragment of rat cerebellar Na+/Ca2+ exchanger gene. Using this cDNA fragment as the probe, we found that the Na+/Ca2+ exchanger mRNA is widely distributed in rat central and peripheral nervous system such as in cerebra, heart, lung and kidney. Using focal cerebral ischemic model, we detected the gene expression of Na+/Ca2+ exchanger in ischemic brain by Northern bolt and in situ hybridization, and found that in ischemic tissues, the mRNA level of Na+/Ca2+ exchanger is lowered.

A new approach called Time-Space Scheme has been recommended for measuring the velocity of moving blood cells in the microvasculature. In each sampling time, the data are put into a row, then rows are integrated in sequential times as sequential rows. The motion of various objects in the field of microcirculation can be analyzed from the time-space image. In the time-space image RBC's flow appears as a diagonal dark stripe and WBC's flow as a bright stripe. The slope at different points on those stripes reflects the local velocity of RBCs and WBCs. Using the time-space image analyzing method, the velocities of erythrocyte and leukocyte in microcirculation are measured simultaneously by a self-designed interactive image processing system. According to characteristic of leukocyte flowing movement, leukocytes in microvasculature are divided into the three kinds: central axial-flowing leukocyte, rolling leukocyte and adhesive leukocyte. On this basis, we introduce the leukocyte-endothelium contact time as a quantitative index for leukocyte-endothelium interaction. During hemorrhagic shock, the phenomenon of leukocyte-endothelium adhesion has been observed by this system, which suggests that the method is effective and useful for the research of microcirculation.