取代四氢异喹啉衍生物的合成及其生物活性

粉防己碱有钙拮抗作用,临床试用于治疗高血压,其裂解产物钙拮抗作用降低,但有α-肾上腺素能受体拮抗作用,本文以裂解物为先导化合物设计合成了两类取代的四氢异喹啉衍生物Ⅲ及Ⅳ。初步药理试验表明:大部分化合物有α-肾上腺素能受体拮抗作用,少数化合物钙拮抗活性有所增强,其中Ⅲ_15,19对正常麻醉大鼠有一定的降压作用、Ⅳ_17,19对实验性动物心律失常有明显的保护作用。部分化合物量化计算表明:化合物与α₁-受体作用方式可能是形成电荷转移复合物。     

Efficacy of the dorsal pedal bypass for limb salvage in diabetic patients: short-term observations

Limbs of diabetic patients with distal tibial disease are frequently considered unreconstructible; however, when studied with intraarterial digital subtraction angiography, the dorsal pedal artery is frequently found to be patent. We have reviewed our recent experience with 96 patients, 94% of whom had diabetes and had 97 bypasses placed to the dorsal pedal artery. All procedures were for limb salvage. Superimposed infection was present in 42.3%. In 92 instances where intraarterial digital subtraction angiography successfully visualized the dorsal pedal artery, 91 bypasses were placed. In 12 other cases where the dorsal pedal artery was not visualized by intraarterial digital subtraction angiography but audible with the continuous-wave Doppler, bypasses were completed successfully in six. All procedures were performed with vein. Inflow was taken from the femoral artery in 48, popliteal artery in 45, tibial artery in 2, and from a femoral tibial graft in 2. Perioperative mortality was 1.92%. Actuarial graft patency, limb salvage, and patient survival were 82%, 87%, and 80%, respectively at 18 months. We conclude that bypass grafting to the dorsal pedal artery can be reliably performed with acceptable short-term results. An attempt should always be made to visualize the foot vessels angiographically, especially in diabetic patients, so that this valuable option in arterial reconstruction will not be overlooked.     

Executive and compensatory memory retraining in traumatic brain injury

A controlled treatment outcome study was conducted comparing the efficacy of memory remediation treatment with no treatment on traumatic brain-injury patients. The memory remediation treatment consisted of both compensatory and executive training skills and was delivered 6 hours weekly over a 2 1/2-week period. Six subjects in the treatment group and 6 subjects in the control group were matched on WAIS-R FSIQ scores, pre-test memory scores and age. Pre-and post-test measures were obtained for both groups on a paragraph memory task. A significant difference was demonstrated between the treatment and control post-test memory scores. The experimental group significantly improved memory scores beyond that of the control group, suggesting that memory remediation is effective for head-injury patients with memory deficits. Discussion of findings and suggestions for further investigation are presented.     

Antisense-mediated specific inhibition of P120 protein expression prevents G1- to S-phase transition.

A pentadecadeoxyribonucleotide (5'-AAAGCCCCCCACCAC), complementary to a splice junction site of mRNA for human proliferation-associated nucleolar protein P120, inhibited expression of the P120 gene and the mitogen-induced proliferation of human lymphocytes. The inhibition of P120 gene expression and proliferation was concentration dependent and reached 90% at 200 microM, as measured by [3H]thymidine uptake and by densitometric scanning of Northern (mRNA) and Western (protein) blots of P120. Inhibition was not observed in cells treated with the correspondent nonsense oligomer. P120 antisense oligomer treatment prevented S-phase entry of mitogen-stimulated lymphocytes, as determined by flow cytometric analysis, but did not block G0-G1 transition assessed by morphological blast transformation and induction of [3H]uridine incorporation. Results of this study suggest that P120 expression may be required for the upregulation of nucleolar function necessary for cell proliferation.     

The iron uptake mechanisms of enteropathogenic Escherichia coli: the use of haem and haemoglobin during growth in an iron-limited environment.

The iron uptake mechanisms of enteropathogenic Escherichia coli (EPEC) were examined and compared with those of control E. coli strains. The incidence of aerobactin production was similar (39% and 37% respectively) in the two groups. The quantities of enterochelin produced by aerobactin-negative EPEC and control strains were similar, as were the quantities of enterochelin produced by aerobactin-positive EPEC and control strains. The ability to use haem or haemoglobin as an iron source in an iron-restricted environment was found in 80.4% and 60.8% of EPEC strains respectively, and in 76.6% and 56.6% of control E. coli strains. The ability of E. coli strains to use these compounds was not related to the production of enterochelin or aerobactin or to the production of haemolysins, and may be an important characteristic of bowel organisms. When growing in an iron-limited environment, the iron contained in haemoglobin was used in preference to ovotransferrin-bound iron. During periods of haemoglobin-stimulated growth, the enterochelin uptake system was shown to be fully expressed and may be involved in transport of haemoglobin-derived iron into the cell. Uptake of ovotransferrin-bound iron took place immediately upon exhaustion of haemoglobin-derived iron. The ability to use iron derived from haem compounds represents an alternative iron uptake mechanism for organisms growing in an iron-limited environment and allows greater flexibility during growth in vivo.     

Malignant histiocytosis. Complete remission in two pediatric patients

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients.