银杏叶提取物活血通络作用的药效学研究

目的：观察银杏叶提取物(EGb)的活血通络功效。方法：小鼠耳廓微循环实验、胶原蛋白-肾上腺素诱导的小鼠体内血栓形成实验、大鼠血液流变学实验及离体兔耳灌流实验。结果：银杏叶提取物经口给药．能显著改善小鼠耳廓微循环，抑制胶原蛋白-肾上腺素诱导的小鼠体内血栓形成，降低大鼠血液粘度，并能显著扩张离体兔耳血管。结论：银杏叶提取物有显著的活血化瘀功效。     

The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy on biomechanical stability and cement fill in the metastatic spine

A biomechanical study comparing simulated lytic vertebral metastases treated with laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty alone. To investigate the effect of tumor ablation using LITT prior to vertebroplasty on biomechanical stability and cement fill patterns in a standardized model of spinal metastatic disease. Vertebroplasty in the metastatic spine is aimed at reducing pain, but is associated with risk of cement extravasation in up to 10%. Six pairs of fresh-frozen cadaveric thoracolumbar spinal motion segments were tested in axial compression intact, with simulated metastases and following percutaneous vertebroplasty with or without LITT. Canal narrowing under load, pattern of cement fill, load to failure, and LITT temperature and pressure generation were collected. In all LITT specimens, cement filled the defect without extravasation. The canal extravasation rate was 33% in specimens treated without LITT. LITT and vertebroplasty yielded a trend toward improved posterior wall stability (P = 0.095) as compared to vertebroplasty alone. Moderate rises in temperature and minimal pressure generation was seen during LITT. In this model, elimination of tumor by LITT, facilitates cement fill, enhances biomechanical stability and reduces the risk of cement extravasation.     

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? a prospective cohort study

Background  

The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia.     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Usefulness of contrast material in MR of patients with neurofibromatosis type 1.

PURPOSEOur objective was to determine the usefulness of routine administration of contrast material in brain MR imaging for the evaluation of areas of probable myelin vacuolization and neoplasms in patients with neurofibromatosis type 1 (NF-1).METHODSWe retrospectively reviewed 112 consecutive contrast-enhanced brain MR studies obtained over a period of 7 years in 109 symptomatic and asymptomatic patients compiled from two institutional NF-1 data bases. MR studies were analyzed for areas of probable myelin vacuolization, with attention to degree of enhancement and its impact on lesion detection and characterization. Usefulness of contrast material was graded as 0 = not useful, 1+ = somewhat useful, and 2+ = useful.RESULTSOf 112 studies, 45% (n = 49) were normal. In the remaining 63 studies, 88 regions of probable myelin vacuolization and 52 tumors were identified. Enhancement was not observed in any regions of probable myelin vacuolization. Enhancement was present in 31% of tumors, and, of these, was found to be useful in 44%, somewhat useful in 12%, and not useful in 44%. For enhancing tumors, contrast agent was useful for lesion detection in 19% and for lesion characterization in 25%.CONCLUSIONContrast administration is useful in baseline MR studies to maximize tumor detection and characterization, to add confidence to the diagnosis of benign probable myelin vacuolization, and to document stability of neoplasms on follow-up examinations.     

Anti-tumor effect of tumor necrosis factor and its induction of tumor variant of MBT-2 transitional cell carcinoma of the bladder

The effect of tumor necrosis factor (TNF), a potential anti-tumor agent, was assessed both in vivo and in vitro against MBT-2 transitional cell carcinoma of the bladder in C3H/HeHa mice. Systemic administration of either single or multiple doses of TNF into tumor bearing animals resulted in partial tumor regression and had a consistent but transient anti-tumor effect. Compared to control, untreated tumor bearing animals, TNF-treated tumor bearing mice had significantly smaller tumor volumes and slower tumor growth rates over the period of 12 days following TNF inoculation. No significant difference in tumor volumes and tumor growth rates between controls and TNF-inoculated mice was observed from day 12 to day 21 after TNF treatment. Assessment of TNF cytotoxicity against in vitro MBT-2 cell line using 3[H]-thymidine proliferation assay showed significant sensitivity of MBT-2 cells to treatment with TNF. A "Variant" MBT-2 cell line was derived by sequential culturing of the original MBT-2 cells in the presence of progressively higher concentrations of TNF in culture medium. Although the significant growth suppression on the MBT-2 tumor appears to be transient, further studies are warranted which may elucidate the immunologic and biologic behavior of TNF and this transplantable animal tumor.     

β-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

The use of 15-p-iodophenyl--methyl-pentadecanoic acid (Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioctivity (residue curves) were obtained following bolus injections of both Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, Me-IPPA kinetics were insenstive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significatly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond Me-IPPA-CoA in the oxidative pathway.     

An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype

Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1. The causes of epimutations are unknown, although recently an association with assisted reproductive technologies has been described. To date the only genetic mutations described in BWS are in the CDKN1C gene. In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analyzed for variants. Four single nucleotide polymorphisms (SNPs) were found in DMR0 (T123C, G358A, T382G and A402G) which occurred in three out of 16 possible haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the DMR0 SNPs. There was a significant increase in the frequency of the CAGA haplotype and a significant decrease in the frequency of the CATG haplotype in the patient cohort compared to controls. These associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated with LOM at KvDMR1. This indicates either a genetic predisposition to LOM or interactions between genotype and epigenotype that impinge on the disease phenotype.     

Genome-wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early-onset, major depression.

We previously described the results of a genome-wide linkage survey for genetic loci that influenced the development of unipolar mood disorders in 81 families identified by individuals with Recurrent, Early-Onset, Major Depressive Disorder (RE-MDD) [Zubenko et al. 2003b; Am J Med Genet (Neuropsychiatr Genet) 123B:1-18]. In the current study, we extended this linkage analysis by including the history of a suicide attempt as a covariate to identify chromosomal regions that harbor genes that influence the risk of this behavior in the context of mood disorders. This approach identified six linkage peaks with maximum multipoint DeltaLOD scores that reached genome-wide adjusted levels of significance (2p, 5q, 6q, 8p, 11q, and Xq). Four of these (2p, 6q, 8p, and Xq) exceeded the criterion for "highly-significant linkage" (genome-wide adjusted P < 0.001) recommended by Lander and Kruglyak [1995; Nat Genet 11:241-246]. The strongest evidence for linkage was observed in analyses employing affected relative pairs (ARPs) with the most severe and disabling Mood Disorders: Depression Spectrum Disorder and RE-MDD. The highest DeltaLOD score that emerged from this linkage analysis, 5.08, occurred for ARPs with Depression Spectrum Disorder at D8S1145 (37.0 cM, 18.2 Mbps, P < 0.0001) at cytogenetic location 8p22-p21. Significant linkage results on Xq arose from analyses of ARPs with RE-MDD at DXS1047 (143 cM, 127.8 Mbps, DeltaLOD = 3.87, P < 0.0001), a finding that may contribute to the higher rate of suicide attempts among women than men. These findings provide evidence for suicide risk loci that are independent of susceptibility loci for Mood Disorders, and suggest that the capacity for suicide risk loci to affect the development of suicidal behavior depends on the psychiatric disorder or subtype with which they interact.