庆大霉素/α半水硫酸钙载药体系的体外释药研究

对硫酸庆大霉素/α半水硫酸钙载药体系进行了模拟条件下体外释药研究，并对其晶体结构进行了分析。X-射线衍射分析结果表明，载药体系中一定含量的硫酸庆大霉素不会影响α半水硫酸钙的水化；模拟条件下体外释药研究表明，各种药物含量的载药体系均表现出了良好的缓释性能，持续释放时间超过了360h；随着试样中载药量的增加，其药物释放速率加快；另外，构制了均一分散和核壳结构两种载药体系，研究结果表明，均一分散型在前期释放速度要大于核壳结构型，而后期核壳结构型则比均一分散型要高。     

Cholinergic responsiveness of neurons in the ventroposterior thalamus of the anesthetized rat

Acetylcholine has been implicated as an important neurotransmitter in the mechanisms of thalamic activation. Cholinergic mechanisms are thought to directly underlie the high level of excitability observed in thalamic relay neurons during waking and rapid eye movement sleep. We sought to determine if the cholinergic responsiveness of neurons in the ventroposterior nuclei of the thalamus in rat is consistent with this view. Neurons in the chloral hydrate-anesthetized rat were studied with extracellular recording and microiontophoretic application of cholinergic agents. In most cases (63% of 63 cells), the ejection of the agonist, carbachol, had no observable effect on spontaneous activity. Facilitation (25%), inhibition (8%) and inhibition followed by facilitation (3%) were also observed. Carbachol ejections that by themselves were ineffective in altering spontaneous activity proved capable, in 93% of 28 cells, of antagonizing the uniformly facilitatory responses produced by glutamate ejection. The putative M1-selective, cholinergic agonist, McN-A-343, was also ineffective alone in altering spontaneous activity in the majority of cases (74% of 27 cells) and produced only inhibitory responses in the remaining seven neurons studied. Interacting applications of McN-A-343 and glutamate resulted, in all cases, in antagonism of glutamate facilitation (N = 12). The various responses to applied cholinergic agonists were all capable of being antagonized by muscarinic receptor-blocking agents. Both the high proportion of inhibitory responses and the antagonism of glutamate facilitatory responses suggest that ventroposterior neurons in the rat differ from other thalamocortical relay neurons in the rat and cat with regard to cholinergic responsiveness. Additionally, the lack of predominantly facilitatory responding renders it unlikely that cholinergic mechanisms directly underlie increases in excitability of ventroposterior neurons observed during waking and rapid eye movement sleep.     

直流高速真空断路器灭弧方案的仿真研究

对直流断路器研制的关键问题——直流高速真空断路器灭弧方案,介绍了几种典型的直流断路器灭弧方案的工作原理。在此基础上,结合具体实例,对采用电流转移原理,实现灭弧进行理论与Matlab仿真建模。仿真结果表明,采用电流转移原理灭弧的直流高速真空断路器具有可行性。     

当前我国城市历史保护区环境整治研究

针对我国城下历史保护区环境整治存在的建设失控、忽视交通和绿地,重建轻管等问题, 指出环境整治与经济发展的相关性, 并结合国外环境整治实践经验,探讨我国城市公共空间环境整治的理论与对策。     

Hepatitis C virus infection among cryoglobulinemic and non-cryoglobulinemic B-cell non-Hodgkin's lymphomas

BACKGROUND AND OBJECTIVE: Since hepatitis C virus (HCV) infection has been associated with different histotypes of B-cell non-Hodgkin's lymphoma (NHL), with or without concomitant production of cryoglobulins (cryolg), we have investigated the prevalence of the infection among NHL with the aim of defining its relationship with the histotype and with the production of cryolg. METHODS: Four-hundred and seventy unselected, consecutive patients with a diagnosis of B-cell NHL were investigated. Anti-HCV antibodies (Ab) and cryolg were sought in all while HCV RNA and rheumatoid factor were detected on HCV-Ab positive samples. RESULTS: Overall, the prevalence of HCV infection was 8.9% (42/470). It was 95.4% (#21) among the 22 patients with, and 4.6% (#21) among the 448 without production of cryoIg. The most common histotype among the HCV-positive, cryoIg-producing cases, was the immunocytoma (16/21, 76%). Among the HCV-positive, non cryoIg-producing cases, the marginal zone and the follicle center lymphomas were the commonest. INTERPRETATION AND CONCLUSIONS: Close association between HCV infection and cryoIg production, already described in mixed cryoglobulinemia, is confirmed also among B-cell NHL. Nevertheless, 50% of HCV-related lymphomas are non-cryoIg producers. Low-grade lymphomas (in particular the immunocytoma) are the most frequent HCV-related lymphomas. Since new therapeutic strategies might be necessary if the virus is detected, screening for cryoIg and for HCV-Ab among B-cell NHL at diagnosis is mandatory.     

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.     

A paradigm of experimentally induced mild hyperthyroidism: effects on nitrogen balance, body composition, and energy expenditure in healthy young men

OBJECTIVE: To conceptualize, with fine needle aspiration cytology (FNAC), the early cellular events occurring in and around fresh autogenous and allogenic bone grafts during the first 40 postimplantation days. STUDY DESIGN: Forty-eight cases of bone grafts were studied by FNAC at serial intervals of 10, 20, 30 and 40 postimplantation days. Twenty patients were recipients of autogenous grafts, 16 received 0.6N HCI partially decalcified allogenic bone implants, and 4 received combined autogenous and allogenic bone grafts (included in the allograft group). There were eight control cases of closed fracture shaft femur, which were managed conservatively. RESULTS: The initial cellular responses in autogenous grafts, allografts and controls appear to be a part of the nonspecific reparative process followed by a more specific phase, with a steady increase in relative lymphocyte count from the 20th day onwards. Osteogenesis, as judged by osteoblasts and osteoclasts, was also comparable. CONCLUSION: Partially decalcified allografts appear to be a good substitute for autogenous bone grafts in clinical practice when adequate autogenous material is not available. FNAC is a good technique for studying bone graft responses without interfering with graft uptake. It is helpful in the early detection of subclinical infection or any other pathology at the graft site.     

A T42A Ran mutation: differential interactions with effectors and regulators, and defect in nuclear protein import

Ran, the small, predominantly nuclear GTPase, has been implicated in the regulation of a variety of cellular processes including cell cycle progression, nuclear-cytoplasmic trafficking of RNA and protein, nuclear structure, and DNA synthesis. It is not known whether Ran functions directly in each process or whether many of its roles may be secondary to a direct role in only one, for example, nuclear protein import. To identify biochemical links between Ran and its functional target(s), we have generated and examined the properties of a putative Ran effector mutation, T42A-Ran. T42A-Ran binds guanine nucleotides as well as wild-type Ran and responds as well as wild-type Ran to GTP or GDP exchange stimulated by the Ran-specific guanine nucleotide exchange factor, RCC1. T42A-Ran.GDP also retains the ability to bind p10/NTF2, a component of the nuclear import pathway. In contrast to wild-type Ran, T42A-Ran.GTP binds very weakly or not detectably to three proposed Ran effectors, Ran-binding protein 1 (RanBP1), Ran-binding protein 2 (RanBP2, a nucleoporin), and karyopherin beta (a component of the nuclear protein import pathway), and is not stimulated to hydrolyze bound GTP by Ran GTPase-activating protein, RanGAP1. Also in contrast to wild-type Ran, T42A-Ran does not stimulate nuclear protein import in a digitonin permeabilized cell assay and also inhibits wild-type Ran function in this system. However, the T42A mutation does not block the docking of karyophilic substrates at the nuclear pore. These properties of T42A-Ran are consistent with its classification as an effector mutant and define the exposed region of Ran containing the mutation as a probable effector loop.     

Characteristics of multicellular spheroids formed by primary cultures of human thyroid tumor cells

Features of multicellular tumor spheroids (MCTS) differed depending on their types of cells. MCTS formed by 4000 human thyroid primary culture epithelial tumor cells displayed diameters between 0.31 and 0.33 mm within 2 days regardless of the stage of malignancy of the originating tumors. Their cellular composition reflected that of the originating tumor in regard to DNA content and the expression of cytokeratin, vimentin, as well as thyroglobulin. During the following 3 weeks, their sizes increased up to diameters of 0.42 mm when their cells had been derived from carcinomas, and MCTS originating from adenomas stopped growing within the next 2 days. After 8 days of incubation, proliferating cells were only found in carcinoma MCTS. The cells were randomly distributed over the total volume of the spheroids, which displayed irregular cell arrangements but not concentric cell layers and did not form necrotic centers.