吗啡增强谷氨酸单钠神经毒性及其作用机制

用皮层神经细胞体外培养、形态学观察、单个神经细胞内游离钙检测及乳酸脱氢酶(LDH)测定等方法,观察了吗啡对谷氨酸单钠(MSG)神经毒性增强作用以及纳洛酮对吗啡作用的逆转,分析了其可能的作用机制。结果表明:吗啡能显著增强的MSG的细胞毒作用.纳络酮可逆转这种增强作用,细胞内Ca²⁺超载可能是兴奋性神经毒素引起神经元死亡的共同病理学机制。     

In vivo and in vitro suppression of primary B lymphocytopoiesis by tumor-derived and recombinant granulocyte colony-stimulating factor

Transplantation of a granulocytosis-inducing murine CE mammary carcinoma into mice suppresses primary B lymphopoiesis in the marrow. The mechanisms of this tumor-induced B-cell suppression were investigated using Whitlock-Witte-type lymphoid cultures. When seeded with normal marrow progenitors, stromal cells of tumor-bearing mice supported the production of B220+ cells as well as did either stomal cells derived from control mice or the stromal cell line S17. Cultured over normal stroma, marrow cells of tumor-bearing mice depleted of adherent cells and B220+ cells generated B220+ cells as effectively as a similar cell population from control mice. However, interleukin-7- responsive progenitors, were completely depleted from the marrow of tumor-bearing mice. When conditioned medium (CM) of cloned CE tumor cells known to produce granulocyte colony-stimulating factor (G-CSF) and macrophage-CSF, or recombinant murine G-CSF was added to the cultures established with S17 cells, B220+ cell production was significantly diminished. Antiserum to murine G-CSF blocked these effects. These in vitro observations were corroborated by the elimination of marrow B220+ cells in mice injected with G-CSF. These in vitro and in vivo studies suggest that G-CSF plays an inhibitory role in primary B lymphopoiesis by blocking stromal cell-mediated differentiation of early B-cell progenitors into phenotypically recognizable B220+ pre-B cells.     

Does Diet‐Induced Weight Loss Lead to Bone Loss in Overweight or Obese Adults? A Systematic Review and Meta‐Analysis of Clinical Trials

Diet‐induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta‐analysis (using a random‐effects model) to quantify the effect of diet‐induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight‐loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual‐energy X‐ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet‐induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm² in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], –0.014 to –0.005, –0.021 to –0.008, and –0.024 to –0.000 g/cm², at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet‐induced weight loss on lumbar spine or whole‐body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (–0.011 g/cm²; 95% CI, –0.018 to –0.003 g/cm²) after 6 months. Although no statistically significant changes occurred in serum concentrations of N‐terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C‐terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N‐terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet‐induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet‐induced weight‐loss intervention induces a small decrease in total hip BMD, but not lumbar spine BMD. This decrease is small in comparison to known metabolic benefits of losing excess weight. © 2015 American Society for Bone and Mineral Research     

Analysis of interphase cells for the Philadelphia translocation using painting probe made by inter-Alu-polymerase chain reaction from a radiation hybrid

Fluorescence in situ hybridization (FISH) probe for the identification of the Philadelphia (Ph) translocation [t(9;22) (q34;q11)] in chronic myelogenous leukemia cells was developed by inter-Alu-polymerase chain reaction of DNA from an interspecific somatic cell hybrid containing approximately 5 Mb of human DNA covering the ABL gene region on human chromosome 9q34. This probe was large enough to be effective in identifying the genomic domains yet small enough to resolve them in more than 90% of bone marrow interphase cells. Combination of the probe with a cosmid contig probe for the BCR region of chromosome 22 in two- color FISH reduced the frequency of false-positive identification of the Ph chromosome to less than 1%. The procedure allows detection of as few as 1% Ph+ cells independent of the cycling status or BCR/ABL expression level of cells, and the quantitation of non-Ph chromosome- containing interphase nuclei in the marrow of patients judged 100% Ph+ by standard cytogenetics.     

Mechanism of lower genotoxicity of toremifene compared with tamoxifen

An increased incidence of endometrial cancer has been reported in breast cancer patients taking tamoxifen (TAM) and in healthy women participating in the TAM chemoprevention trials. Because TAM-DNA adducts are mutagenic and detected in the endometrium of women treated with TAM, TAM adducts are suspected to initiate the development of endometrial cancer. Treatment with TAM has been known to promote hepatocarcinoma in rats, but toremifene (TOR), a chlorinated TAM analogue, did not. TAM adducts are primarily formed via sulfonation of the alpha-hydroxylated TAM metabolites. To explore the mechanism of the lower genotoxicity of TOR, the formation of DNA adducts induced by TOR metabolites was measured using (32)P-postlabeling/ high-performance liquid chromatography analysis and compared with that of TAM metabolites. When alpha-hydroxytoremifene was incubated with DNA, 3'-phosphoadenosine 5'-phosphosulfate, and either rat or human hydroxysteroid sulfotransferase, the formation of DNA adducts was two orders of magnitude lower than that of alpha-hydroxytamoxifen. alpha-hydroxytoremifene was a poor substrate for rat and human hydroxysteroid sulfotransferases. In addition, the reactivity of alpha-acetoxytoremifene, a model activated form of TOR, with DNA was much lower than that of alpha-acetoxytamoxifen. Thus, TOR is likely to have lower genotoxicity than TAM. TOR may be a safer alternative by avoiding the development of endometrial cancer.     

Elevated basal FSH and embryo quality: lessons from extended culture embryos

Background  The relationship between elevated basal FSH and embryo quality remains a topic of heated discussion among practitioners of ART. Some authors suggest a negative effect of raised FSH on the quality of embryos and therefore on IVF treatment outcome. We postulate that women with elevated FSH who respond well to ovarian stimulation and have embryos to transfer, have the same chance of conceiving like women of a similar age with normal FSH. To test this hypothesis, we studied women with elevated basal FSH who made enough embryos to qualify for blastocyst culture and day 5 embryo transfer. Methods  Analysis of data collected prospectively, on women age 25–43 years, who underwent IVF between January 2005 and December 2006. The women were divided into: those with high FSH (≥10 IU/L) and women with normal FSH (<10 IU/L). We analysed data to show treatment outcome in the two groups, following embryo transfer on day 3 and after transfer on day 5. Outcome measures include number of oocytes retrieved, number of embryos available, implantation rate, pregnancy and live birth rate. Results  Among the 1,858 women who under-went a day 3 transfer, 1,368 had basal FSH ≤ 10 IU/L, and in 492 basal FSH was above 10 IU/L. The average number of oocytes retrieved was lower among women with elevated FSH (10.12 ± 5.6 Vs 6.16 ± 3.9). Women with a normal FSH, had a higher pregnant and live birth rate than those with elevated FSH (43.3% vs 27.9% p = 0.021) and (30.8% vs 17.6% p = 0.028) respectively. 398 women made enough embryos to qualify for extended embryo culture to blastocysts. Of these 366 had an FSH ≤ 10 IU/L and 32 had FSH > 10 IU/L. In this group, there was no significant difference in the pregnancy and live birth rates between women with elevated and those with normal FSH, (67.2% vs 65.6%) and (51.9% vs 43.8%) respectively. In this selected group of women where quantity is not an issue, the quality of embryos was same irrespective of whether the basal FSH was low or high. Conclusion  Women with elevated basal FSH who respond well to stimulation and generate a good number of oocytes / embryos have a chance of becoming pregnant and having a live birth similar to that of women of their age. Women should therefore not be denied the benefits of IVF based solely on the basal FSH level as a subset may respond well and therefore have a good chance of taking home a baby.     

Serum cardiac troponin T levels as an indicator of myocardial injury in ischemic and hemorrhagic stroke patients

Many studies in the literature have clearly shown the increase in creatine kinase-myocardial subfraction (CK-MB) levels and changes in electrocardiography (ECG) after stroke. However, the studies on cardiac troponin T (cTnT) which is more sensitive and specific to myocardium after stroke are relatively scarce. Moreover, its associations with volume of stroke lesions and type of stroke have not been investigated thoroughly. Thus, the aims of this study were to investigate a predictive value of cTnT in assessing myocardial injury and cardiac dysfunction in different types of stroke (hemorrhagic or ischemic stroke) and its relationship with stroke size and volume. This study included 62 patients (30 males and 32 females) with acute stroke confirmed by computed tomography (CT). Blood samples were obtained within 24 hours of stroke onset to measure the serum levels of creatin kinase (CK), CK-MB, lactate dehydrogenate (LDH), and cTnT. ECG and echocardiography were performed to assess myocardial function and left ventricular ejection fraction (LVEF). Of all patients included in the study, 20 patients (32%) demonstrated elevations in cTnT, while 28 patients (45%) had increased CK-MB levels. Serum levels of cTnT were positively correlated with stroke volume (r = 0.65, p < 0.0001), while inversely correlated with LVEF (r = -0.53, p < 0001). Serum levels of both CK-MB and cTnT were higher in patients with hemorrhagic stroke than those with ischemic stroke but this difference was not significant (p > 0.05). As a conclusion, cTnT has a higher specificity and sensitivity in detecting myocardial injury after stroke of both ischemic and hemorrhagic origins. Measurement of the serum levels of cTnT is of clinical importance in evaluating myocardial injury and provides a useful aid in estimating the volume of stroke lesions.     

静脉内平滑肌瘤病伴细胞不典型

患者，女性，54岁，中国籍，因急性左下肢水肿就诊。既往有子宫肌瘤史2年。腹部及盆腔凹显示左髂总静脉血栓及子宫左下部肌瘤(直径6cm)。考虑静脉血栓系肌瘤压迫髂静脉所致，予抗凝治疗，为缩小子宫体积以减轻其对髂静脉的压力，皮下注射促性腺激素释放激素类似物(GnRHa)3个月。患者对GnRHa冶疗无不良反应，治疗后闭经。4月后复查腹部及盆腔CT显示子宫明显缩小，