The behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with buserelin

This randomized double-blind placebo-controlled study was initiated to analyze the behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with a low dose (20 g) of a luteinizing hormone-releasing hormone analogue (Buserelin), administered daily, as a nasal spray, for a short period (28 days). Fifty-nine true cryptorchid boys were randomly assigned to 3 groups: buserelin, treatment [22], surgical treatment [18] or placebo control group [19]. The 3 groups of patients were similar before treatment in regard to testicular position, chronological and bone age, height and weight, luteinizing hormone, follicle-stimulating hormone, testosterone, penile size and the volume of the contralateral descended testis. None of the patients had retractile testes. Buserelin significantly induced testicular descent compared to the boys treated with a placebo (P<0.01). A normal epididymis was found more often in boys with successful descent (P<0.003). A closed processus vaginalis was also more frequently observed in the group treated with buserelin than in surgically treated one (P<0.05). In conclusion, buserelin was capable of inducing testicular descent besides provoking further development of the epididymis and closing the processus vaginalis.     

Lactogenic Activity of Rats Stimulated by Gunnera Perpensa L. (Gunneraceae) from South Africa

Gunnera perpensa L. (Gunneraceae) is a medicinal plant used by Zulu traditional healers to stimulate milk production. The effect of an aqueous extract of the rhizome of the plant on milk production in rats was investigated. Female lactating rats that received oral doses of the extract of G.perpensa significantly (p<0.05) produced more milk than controls. The plant extract did not however, significantly influence the levels of prolactin, growth hormone, progesterone, cortisol, ALT, AST and albumin in the blood. The mammary glands of rats treated with the extract showed lobuloalveolar development. The extract (0.8 µg/ml) was also found to stimulate the contraction of the uterus and inhibit (23%) acetylcholinesterase activity. The cytotoxicity of the extract (LC₅₀) to two human cell lines (HEK293 and HepG2) was 279.43 µg/ml and 222.33µg/ml, respectively. It is inferred that the plant extract exerts its activity on milk production and secretion by stimulating lobuloalveolar cell development and the contraction of myoepithelial cells in the alveoli. It is concluded that Gunnera perpensa contains constituents with lactogenic activity that apparently contribute to its effectiveness in folk medicine.     

Dopa-responsive dystonia in British patients: new mutations of the GTP- cyclohydrolase I gene and evidence for genetic heterogeneity

Dopa-responsive dystonia (DRD) was originally described in a series of Japanese patients, but is now increasingly recognized in other countries. Recently the GTP cyclohydrolase I (GTPCH) gene was isolated as the first causative gene for dopa-responsive dystonia (DRD). Mutations were identified in three Japanese families with autosomal dominantly inherited DRD and in one sporadic Japanese patient. Characterisation of the exon-intron boundaries of this gene has now allowed the analysis of mutations at the level of genomic DNA. Amplifying all six exons, we analyzed the GTPCH gene in nine British families with 33 affected family members and in three sporadic cases and found six new mutations. Only point mutations were found, causing a stop codon in one family and an amino acid change in highly conserved regions of the gene in a further four families and in one sporadic case. None of these mutations were detected more than once and none of the mutations previously described were found in our patients. No mutations were identified in four families and in two sporadic cases.      

提高人类精液中圆形细胞数量测定的精确度

本研究的目的是提高用过氧化物酶试验检测精液中的白细胞时所得的圆形细胞数量的精确度。精液样本的圆形细胞浓度在（0．6～6）&#215;10^6／mL之间,降低精液的稀释度,增加被测悬浮液的体积。1＋5（1：6）的稀释度适合于测量过氧化物酶活性,并能为细胞检测提供足够清晰的背景。在该稀释度下,测定Neubauer-改良精子计数板两边所有18个网格中的细胞数量,额定细胞浓度为（1．9～3．3）&#215;10^6／mL的10个样本中只有3个样本的圆形细胞数／〉400个。由于更低浓度的精子稀释液不适合测定圆形细胞或其过氧化物酶反应产物,所以无法精确测量（抽样误差5％）参考下限值（1&#215;10^6／mL）。结果表明,正是由于测定精液中的10个样本中圆形细胞很难精确到1&#215;10^6／mL,所以白细胞精液症临界值的确定一直存在诸多分歧。因此需要建立一些统计学上合理的参考限。     

血小板激活因子对大鼠脑血管通透性的影响及药物的保护作用

颈内动脉注射血小板激活因子(PAF),再给伊文思蓝,可见脑实质染色程度加深,而颈内动脉只注射伊文思蓝,脑实质未见染色。而我们合成的新药SZ-1可剂量依赖性地抑制PAF诱导的脑实质伊文思蓝染色程度的加深。在体外培养的脑微血管平滑肌细胞上,PAF能显著刺激~(14)-花生四烯酸的释放,而SZ-1能剂量依赖性地抑制这种释放,提示PAF在脑内产生的损害除与其他因素相关外,还与其刺激花生四烯酸释放有密切关系,SZ-1对PAF引起的脑部损害有保护作用。     

皮炎消净饮I号冲剂治疗异位性皮炎的实验研究

目的：研究皮炎消净饮I号冲剂（PYXJY1）治疗异位性皮炎（AD）的作用机理。方法：①动物实验：二硝基氯苯（DNCB）所致豚鼠耳肿试验,致敏处真皮内单核细胞和淋巴细胞聚集试验;醋酸所致小鼠腹腔毛细血管通透性增加试验。②实验室检测：单克隆抗体免疫荧光标记法检测AD患有治疗前后的CD4／CD8（TH／Ts）水平。结果：PYXJY1可明显抑制二硝基氯苯所致豚鼠耳肿胀及其真皮内单核细胞和淋巴细胞聚集,抑制醋酸所致小鼠腹腔毛细血管通透性的增加,作用与氢化可的松相似。使AD患者升高的CD4／CD8降低至正常。结论：PYXJY1具有良好的抗炎和迟发变态反应作用,并可调节AD患者CD4／CD8水平,对AD有较好的治疗效果。     

Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

Background

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition.

Materials and methods

We investigated the effect of two dual PI3K/mTOR (both mTORC1 and mTORC2) inhibitors, NVP-BEZ235 and NVP-BGT226, on SQ20B laryngeal and FaDu hypopharyngeal cancer cells characterised by EGFR overexpression, on T24 bladder tumor cell lines with H-Ras mutation and on endothelial cells. Analysis of target protein phosphorylation, clonogenic survival, number of residual ??H2AX foci, cell cycle and apoptosis after radiation was performed in both tumor and endothelial cells. In vitro angiogenesis assays were conducted as well.

Results

Both compounds effectively inhibited phosphorylation of Akt, mTOR and S6 target proteins and reduced clonogenic survival in irradiated tumor cells. Persistence of DNA damage, as evidenced by increased number of ??H2AX foci, was detected after irradiation in the presence of PI3K/mTOR inhibition, together with enhanced G2 cell cycle delay. Treatment with one of the inhibitors, NVP-BEZ235, also resulted in decreased clonogenicity after irradiation of tumor cells under hypoxic conditions. In addition, NVP-BEZ235 blocked VEGF- and IR-induced Akt phosphorylation and increased radiation killing in human umbilical venous endothelial cells (HUVEC) and human dermal microvascular dermal cells (HDMVC). NVP-BEZ235 inhibited VEGF-induced cell migration and capillary tube formation in vitro and enhanced the antivascular effect of irradiation. Treatment with NVP-BEZ235 moderately increased apoptosis in SQ20B and HUVEC cells but not in FaDu cells, and increased necrosis in both tumor and endothelial all cells tumor.

Conclusions

The results of this study demonstrate that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.     

Changes in peripheral blood CD5 (Bla) B-cell populations and autoantibodies following blood transfusion

BACKGROUND: CD5 B cells and the natural autoantibodies they produce play a role in antigen presentation, tolerance induction, and maintenance of an idiotypic immune network. The effects of transfusion on autoantibodies and peripheral blood CD5 B cells were studied. STUDY DESIGN AND METHODS: Eight previously transfused patients with sickle cell anemia and five patients who underwent orthopedic surgical procedures with transfusion were enrolled in the study. Patients in both groups received 1 to 2 units of allogeneic packed red cells. Ten untransfused healthy adults and five patients who underwent orthopedic surgery without transfusion were enrolled as controls. Peripheral blood CD5 B cells, serum levels of IgM, antinuclear antibodies, rheumatoid factor, and anticardiolipin IgM were quantitated either at the beginning of the study (baseline sample), before transfusion, or before surgery and either at 1-, 2-, 4-, 6-, and 8-week intervals after transfusion, after surgery, or after the baseline sample was obtained. RESULTS: IgM levels and the absolute number of B cells that coexpressed CD5 rose to twice pretransfusion levels in six of eight transfused sickle cell anemia patients and in four of five transfused orthopedic surgery patients. No comparable increases in CD5 B cells were noted in untransfused controls. Preexisting rheumatoid factor and antinuclear antibody levels increased in four of five transfused orthopedic surgery patients. One sickle cell anemia patient developed anti-Fya despite receiving Fya-negative blood. Increasing titers of anti-Fya paralleled the increases in IgM and CD5 B cells after transfusion. One patient who developed a positive direct antiglobulin test after transfusion had large increases in serum anticardiolipin IgM. Anticardiolipin IgM was subsequently eluted from direct antiglobulin test-positive red cells obtained after transfusion. Antibodies with anti-Fya-like activity and anticardiolipin IgM were produced in vitro by CD5 B cells and not by conventional CD5-negative B cells. CONCLUSION: An association was found between transfusion-induced increases in CD5 B cells and increased autoantibody production. These data may have implications for immunologic intervention to prevent the induction of red cell antibodies and other changes in the immune system caused by exposure to foreign antigens via blood transfusion.     

Restoration of adenylate cyclase responsiveness in murine myeloid leukemia permits inhibition of proliferation by hormone. Butyrate augments catalytic activity of adenylate cyclase

Mechanisms of leukemic cell clonal dominance may include aberrations of transmembrane signaling. In particular, neoplastic transformation has been associated with reduced capacity for hormone-stimulated adenylate cyclase activity. In the present study, prostaglandin E, a hormonal activator of adenylate cyclase that has antiproliferative activity in myeloid cells, and cholera toxin, an adenylate cyclase agonist that functions at a postreceptor site by activating the adenylate cyclase stimulatory GTP-binding protein (Gs), were studied for antiproliferative activity in two murine myeloid cell lines. FDC-P1, an interleukin 3 (IL 3)-dependent myeloid cell line and a tumorigenic IL 3- independent subline, FI, were resistant to these antiproliferative agents. The in vitro ability of the "differentiation" agent, sodium butyrate, to reverse their resistance to adenylate cyclase agonists was studied. The antiproliferative action of butyrate involved augmentation of transmembrane adenylate cyclase activity. Increased adenylate cyclase catalyst activity was the primary alteration of this transmembrane signaling group leading to the functional inhibitory effects on leukemia cells, although alterations in regulatory G- proteins appear to play a secondary role.