Molecular characterization of a new excitatory insect neurotoxin with an analgesic effect on mice from the scorpion Buthus martensi Karsch.

Besides the neurotoxins active on mammals, a new excitatory insect selective toxin with a mice analgesic activity was found and purified from the venom of the scorpion Buthus martensi Karsch (BmK) (Ji, Y.H., Mansuelle, P., Terakawa, S., Kopeyan, C., Yanaihara, N., Hsu, K., Rochat, H., 1996. Toxicon 34, 987; Luo, M.J., Xiong, Y.M., Wang, M., Wang, D.C., Chi, C.W., 1997. Toxicon 35, 723.). This peptide (designated as BmK IT-AP) is composed of 72 amino acid residues. Its primary structure was determined by automated Edman degradation of the N-terminal part of the reduced and S-carboxamidemethylated protein and its lysylendopeptidase degraded fragments. Based on the determined sequence, the gene specific primers were designed and synthesized for 3' and 5' RACE (rapid amplification of cDNA ends). Their partial cDNA fragments obtained by 3' and 5' RACEwere cloned and sequenced and the full length cDNA sequence of BmK IT-AP was then completed by overlapping their two partial cDNA sequences. It encodes a precursor of 90 amino acid residues: a signal peptide of 18 residues and a mature peptide of 72 residues which are consistent with the determined protein sequence of BmK IT-AP. The genomic DNA of the peptide was also amplified by PCR from the scorpion genomic DNA and sequenced, which is a first report on the genomic structure of a scorpion toxin specific for insects. Its sequence revealed an intron of 590 bp inserted in the end part of the signal peptide. The peptide caused a fast excitatory contraction paralysis on house fly larvae. Furthermore, the peptide also showed an obvious analgesic effect on mice, as assayed by using a twisting test model. This effect of BmK IT-AP well characterized at molecular level is first reported among the known scorpion insect neurotoxins.     

Tissue potassium,selenium, and iron levels associated with gastric cancer progression

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe -spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.     

Tedisamil Attenuates Ventricular Fibrillation in a Conscious Canine Model of Sudden Cardiac Death

BACKGROUND: The electrophysiologic and antifibrillatory properties of tedisamil (KC-8857;3,7-di-(cyclopropylmethyl)-9,9-tetramethylene-3,7-diazabicyclo[3.3.1]-nonane dihydrochloride) were studied in a conscious canine model of sudden cardiac death. METHODS AND RESULTS: Three to five days after surgically induced myocardial infarction (2-hour occlusion of the left anterior descending coronary artery), animals were subjected to programmed electrical stimulation to identify those at risk for ischemia-induced ventricular fibrillation. Sixty minutes after tedisamil (10 mg/kg, administered orally) PES was repeated. Tedisamil increased the ventricular effective refractory period from 106 +/- 6 to 134 +/- 7 ms (P <.05) compared to placebo treatment, which did not alter the ERP (123 +/- 6 to 116 +/- 5 ms). Tedisamil prolonged the QTc interval, from a predrug value of 308 +/- 14 to 327 +/- 14 ms, postdrug. The extent of the surgically induced anterior wall myocardial infarct did not differ between groups, tedisamil, 29 +/- 2%, and placebo, 28 +/- 2% of the left ventricle. CONCLUSIONS: Tedisamil conferred protection against ischemia induced ventricular fibrillation; 7 of 10 tedisamil-treated dogs survived, compared to 4 of 14 surviving in the vehicle treated group (P <.05). Although we observed instances of vomiting and/or diarrhea in several dogs after a single oral administration of tedisamil, the data indicate that oral administration of tedisamil provides protection from ischemia-induced ventricular fibrillation in the postinfarcted conscious canine. The mechanism by which tedisamil achieves its antifibrillatory effect may be related to its ability to prolong the ERP of the ventricular myocardium without altering ventricular conduction velocity.     

Primary intramedullary spinal cord primitive neuroectodermal tumor with intracranial seeding in an infant

Primary spinal cord primitive neuroectodermal tumor (PNET) is a rare entity. In all, 13 cases have been reported in the literature, including 3 with intracranial seeding. A 3-month-old girl with involvement of the spinal cord below the mid-thoracic level is described. The brain MRI revealed findings indicative of seeding along the intracranial subarachnoid space. Biopsy, duraplasty and removal of laminotomy flap were done. In spite of a good response to the first cycle of postoperative 8-drugs-in-a-day chemotherapy, further treatment was refused. She died 21 days after the onset of leg weakness, which reveals the rapid progression of untreated cases. To our knowledge, this is the first case of spinal cord PNET with parenchymal involvement that has been described in an infant.     

Central core disease--a case report.

Central core disease is a rare congenital myopathy characterized by the formation of "cores" that consist of abnormal arrangement of myofibrils inside the myofibers. We report a 5-year-old Korean girl who showed a fairly typical clinical course of non-progressive muscle weakness. Electrodiagnostic studies showed low-amplitude polyphasic electromyograph and normal nerve conduction velocity. Gastrocnemius muscle biopsy showed central cores in over 80% of the fibers on H&E section. Histochemistry revealed deficient or absent mitochondrial enzyme in the cores and type I predominance. Ultrastructurally both structured and non-structured cores were found separately or simultaneously in one fiber. This case is the first report in the Korean literature.     

Studies on corneal penetration ofp-hydroxybenzoic acid esters

Corneal permeability of variousn-alkylp-hydroxybenzoates (parabens) was studiedin vitro using excised rabbit corneas, and the effect of lipophilicity of parabens on the corneal permeability was also investigated. Permeability coefficients were obtained from the least-square linear regression after the steady state had been reached. Lipophilicity of parabens was calculated by distribution coefficients determined in octanol-S \(12_\phi [\kern-0.15em[ \) rensen’s buffer solution (pH 5.0). The relationship between lipophilicity and corneal permeability of parabens was not linear, but the optimum lipophilicity for the maximum permeation was found. The influence of tween 80 on corneal permeability of methyl and butylparaben was not significant.     

Studies on the luminescence of channels in rats and its law of changes with "syndromes" and treatment of acupuncture and moxibustion.

We previously reported the discovery of 14 channels in the human body, which possessed the biophysical property of high emission of light. In this study we found the same property on the Ren and Du channels in healthy rats. Additionally, we discovered that the luminance of the related channels in rat models with different "syndromes" varied greatly. For instance, a markedly low luminance appeared on the Du channel in animals with experimental syndrome of Yang deficiency induced by hydrocortisone; while in animals with experimental syndrome of blood deficiency caused by bleeding, an apparently low luminance occurred on the Ren channel. The intensity of the emitted light on Du and Ren channels increased after acupuncture treatment, but not significantly. This phenomenon conforms to the theory in traditional Chinese medicine that the Du channel is the "sea of Yang channels", while the Ren channel is the "sea of Yin channels".     

Characterization and distribution of [3H]ohmefentanyl binding sites in the human brain

Binding properties and localization of [3H]ohmefentanyl, a new ligand for mu opioid receptors, were investigated on normal human brain sections. Binding assays performed at the level of the basal ganglia revealed: (1) a steady-state binding reached after 60 min incubation at room temperature, (2) the presence, in saturation experiments, of an apparent single class of binding sites with a Kd = 1.68 +/- 0.45 nM and a Bmax = 162 +/- 9 fmol/mg protein, (3) an order of potency to inhibit [3H]ohmefentanyl binding as follows: ohmefentanyl greater than [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) greater than ethylketocyclazocine (EKC) much greater than Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu) (BUBU) and U-50,488H. Quantitative autoradiography showed an heterogeneous distribution of [3H]ohmefentanyl binding sites with the highest densities in amygdala, medical geniculate body, thalamus, and caudate nucleus. Binding characteristics and anatomical distribution also show that [3H]ohmefentanyl may bind to a small proportion of additional sites called "DAGO-inaccessible [3H]ohmefentanyl specific binding sites." [3H]Ohmefentanyl binding to these sites can be partly inhibited by sigma ligands such as 1,3-di-o-tolylguanidine (DTG) and haloperidol. However, unlabeled DAGO inhibited more than 80% of [3H]ohmefentanyl specific binding in most of the human brain regions studied, suggesting that the major population of sites labeled by [3H]ohmefentanyl represented mu opioid receptors.     

康莱特联合化学药物动脉灌注治疗转移性肝癌的临床研究

目的：观察康莱特联合化学药物动脉灌注治疗转移性肝癌的疗效。方法：152例转移性肝癌患者随机分为治疗组(康莱特联合化学药物动脉灌注)79例、对照组(化学药物动脉灌注)73例。结果：治疗组的稳定率为87．3％，1年生存率为73．4％，2年生存率为50．6％，均明显高于对照组；并可减低血液高凝状态，提高患者的细胞免疫功能，缓解化疗药物的毒副反应，改善患者的生活质量。结论：康莱特联合化学药物动脉灌注治疗转移性肝癌有较好的疗效。     

不同类型苷类在大孔吸附树脂上的吸附纯化特性研究

目的 :研究黄芩苷等 3种具有不同类型母核的苷类中药成分在大孔吸附树脂上的吸附纯化特性。方法 :以黄芩、栀子和白芍为样本考察它们在D101等 6种不同树脂上的吸附纯化特性。结果 :6种非极性树脂对 3种苷类总体静态吸附能力为黄芩苷 >芍药苷 >栀子苷 ,其洗脱溶剂分别为 75% ,25% ,45%的乙醇 ,洗脱率分别为60% ,93% ,93%。结论 :具有相似母核结构的苷类分子在同一树脂上吸附能力不一定相似 ,但吸附力的大小与分子结构有关 ,对苯乙烯型树脂而言 ,被吸附的分子母核双键数目越多 ,分子与树脂吸附作用力越大。