潘生丁增强5-氟脲嘧啶抗肿瘤作用的体外实验研究

通过检测 MKN45人胃癌细胞株3~H-TDR 掺入情况,在体外实验研究潘生丁和抗癌药物5-氟脲嘧啶之间的协同作用。结果表明二者间有显著的协同效应(P<0.01),为下一步的动物实验和临床应用提供了理论依据。     

The effect of intrauterine devices (stainless steel ring, copper-T220 and levonorgestrel) on the DNA content in isolated human endometrial cells

The effect of three different intrauterine devices on the DNA content in human endometrial cells has been studied in 29 women before and after the insertion of an IUD; a stainless steel ring (9 subjects), Copper-T220 (11 subjects) and a medicated IUD releasing levonorgestrel at a rate of 2 micrograms/day (9 subjects). The material was grouped into "bleeders" (having more than 8 days of bleeding and spotting per month) and "non-bleeders" (having less than 8 days of bleeding and spotting per month). The DNA content was assessed on isolated endometrial cells smeared from thin biopsies and the amount of DNA per cell nucleus was measured by means of a Feulgen microspectrophotometric method. No significant difference was found between the "bleeders" and the "non-bleeders" as to the DNA content. Nevertheless, when the total number of subjects were pooled together, a significant increase in the DNA content was found in the post-insertion specimens in the groups of women using the SS and the T-Cu IUDs. Furthermore, a significant decrease in the DNA content was also found when the specimens obtained after the insertion of the LNG IUD were compared with those obtained after 24 months' use of the stainless steel ring and the Copper-T220 device (p less than 0.01 and p less than 0.002, respectively). It is concluded that the insertion of an inert IUD or an T-Cu IUD, induces significant alterations in the DNA content of the human endometrium adjacent to the device, whereas the use of the LNG device does not significantly modify the DNA synthesis when used for 3-10 months. No correlation was found between the DNA content per cell and the number of days of bleeding and spotting.     

雷丸多糖的抗炎及免疫刺激作用

Lei Wan, Poliporus mylittae Cook et Mass(Omphalia lapidescena Scbraet) is a kind of fungus used in traditional Chinese medicine, as an antheiminthie From Lei Wan, an "active component designated as. S-4001 had been isolated.Preliminary results indicate that S-4001 belongs to D, β, 1-3 glucan with some 1-6 linkages.After administration of S-4001, significant antiinflammatory activity was found in various experimental animal models, including croton oil induced ear edema in mice and agar or yeast induced ankle swelling in rats. An inhibitory action on leucocyte migration inducced by intraperitoneal injection of CMC in rats was also observed. The plasma content of corticosterone was significantly increased, but the content of ascorbic acid in the adrenals did not change in rats given S-4001. Apart from these actions, S-4001 showed a number of immunostimulating actions such as increasing the clearance of Congo red from mice blood and potentiating the immunohemolysis reaction in 615 mice.     

Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology.     

用细胞酶联免疫吸附法筛选分泌抗人B细胞分化抗原单抗的杂交瘤

用活化的人Ｂ细胞株３Ｄ５细胞免疫ＢＡＬＢ／Ｃ小鼠，取小鼠脾脏细胞与ＳＰ２／０细胞融合，融合后细胞置甲基纤维素半固体培养基生长。以０．５％甲醛处理的３Ｄ５细胞和ＣＥＭ细胞包被酶细胞反应阳性而与ＣＥＭ细胞反应阴性的克隆。再经间接免疫荧光染色后，用流式细胞仪复测以上所得３３个阳性克隆，结果３Ｄ５阳性ＣＥＭ阴性者２７例，占８１．８２％，表明ＣＥＬＩＳＡ法是一个粗筛抗人Ｂ细胞分化抗原的简便有效方法。     

Responses of reticulospinal neurons in the lateral reticular nucleus area of the rat to cutaneous noxious and non-noxious stimulation

Response properties of reticulospinal neurons in the lateral reticular nucleus (LRN) area to natural cutaneous stimulation were investigated systematically in 45 urethane-anesthetized rats by using extracellular recording techniques. A total of 64 neurons were tested with peripheral stimuli, of which 19 were responsive only to noxious stimuli; 7 responsive to both noxious and non-noxious stimuli; 4 responsive only to non-noxious stimuli; and 34 not responsive to any cutaneous stimuli. Both the noxious and non-noxious receptive fields were large and bilateral. Among the neurons responding to noxious stimuli, the majority (72%) was excited. This study provides evidence that some reticulospinal neurons in the rat LRN area are involved in the mechanisms of nociception.     

含生长抑素mRNA神经元在移植视网膜发育中的表达

将６０例鼠龄１４ｄＳＤ大鼠视网膜移植到出生后１ｄ大鼠中脑偏左侧处，同时摘除新生鼠的右眼。术后１０ｄ至２２ｄ分别取移植视网膜及其中脑，在相应的年龄取正常视网膜作对照，应用原位杂交组化技术──地高辛标记的生长抑素的ｃＲＮＡ探针检测移植和正常视网膜中含生长抑素ｍＲＮＡ神经元出现时间、发育规律及定位分布。同时用免疫组化方法显示生长抑素免疫反应神经元的形态，以作对照和补充。原位杂交组化实验结果表明：在出生当天的移植视网膜节细胞层已出现阳性表达，出生后４ｄ，外核层也出现小的含生长抑素ｍＲＮＡ神经元，此种神经元随后减少、消失；与此同时内核层及节细胞层内含生长抑素ｍＲＮＡ神经元逐渐增多，至生后１２ｄ接近成年水平。通过对非移植大鼠视网膜进行正常对照观察，移植视网膜与非移植的正常视网膜生后发育的结果相似。生长抑素免疫反应神经元与原位杂交含生长抑素ｍＲＮＡ神经元的表达部位是一致的，但生长抑素免疫反应神经元可见其突起。     

实验性糖尿病对小鼠肝脏酶组织化学和超微结构的影响

实验用四氧嘧啶建造糖尿病动物模型，８周后取肝作组织学、酶组织化学和超微结构的观察，以探讨实验性糖尿病对肝组织结构和功能的影响。表明在糖尿病状态下，肝细胞的结构和功能均受到一定的损害。     

Glibenclamide treatment in a Cantú syndrome patient with a pathogenic ABCC9 gain‐of‐function variant: Initial experience

Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain‐of‐function mutations in the regulatory (SUR2) and pore‐forming (Kir6.1) subunits of K_ATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg^–1 kg^–1 day^–1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg^?1 kg^?1day^?1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS.     

Spontaneous waves in the dentate gyrus of slices from the ventral hippocampus

Spontaneous negative-going potentials occurring at an average frequency of 0.7 Hz were recorded from the dentate gyrus of slices prepared from the temporal hippocampus of young adult rats. These events (here termed "dentate waves") in several respects resembled the dentate spikes described for freely moving rats during immobile behaviors and slow-wave sleep. Action potentials were observed on the descending portion of the in vitro waves and, as expected from this, whole cell recordings established that the waves were composed of depolarizing currents. Dentate waves appeared to be locally generated within the granule cell layer and were greatly reduced by antagonists of AMPA-type glutamate receptors or by lesions to the entorhinal cortex. Simultaneous recordings indicated that the waves were often synchronized in the inner and outer blades of the dentate gyrus. Knife cuts through the perforant path and the commissural/associational system did not eliminate synchronization, leaving electrotonic propagation via gap junctions as its probable cause. In accord with this, cuts that separated the two blades of the dentate eliminated synchronization between them, and a compound that inhibits gap junctions reduced wave activity. Dentate waves were regularly accompanied by sharp waves in field CA3 and were reduced in size by the acetylcholinesterase inhibitor, physostigmine. It is hypothesized that dentate waves occur when spontaneous glutamate release from dentate afferents produces action potentials in neighboring granule cells that then summate electrotonically into a population event; once initiated, the waves propagate, again electrotonically, and thereby engage a significant portion of the granule cell population.