Cost-effectiveness of seasonal influenza vaccination in pregnant women,healthcare workers and adults >= 60 years of age in Lao People’s Democratic Republic

BackgroundPregnant women, healthcare workers (HW), and adults >= 60 years have shown an increased vulnerability to seasonal influenza virus infections and/or complications. In 2012, the Lao People's Democratic Republic (Lao PDR) initiated a national influenza vaccination program for these target groups. A cost-effectiveness evaluation of this program was undertaken to inform program sustainability.MethodsWe designed a decision-analytical model and collected influenza-related medical resource utilization and cost data, including indirect costs. Model inputs were obtained from medical record abstraction, interviews of patients and staff at hospitals in the national influenza sentinel surveillance system and/or from literature reviews. We compared the annual disease and economic impact of influenza illnesses in each of the target groups in Lao PDR under scenarios of no vaccination and vaccination, and then estimated the cost-effectiveness of the vaccination program. We performed sensitivity analyses to identify influential variables.ResultsOverall, the vaccination of pregnant women, HWs, and adults >= 60 years could annually save 11,474 doctor visits, 1,961 days of hospitalizations, 43,027 days of work, and 1,416 life-years due to laboratory-confirmed influenza illness. After comparing the total vaccination program costs of 23.4 billion Kip, to the 18.4 billion Kip saved through vaccination, we estimated the vaccination program to incur a net cost of five billion Kip (599,391 USD) annually. The incremental cost per life-year saved (ICER) was 44 million Kip (5,295 USD) and 6.9 million Kip (825 USD) for pregnant women and adults >= 60 years, respectively. However, vaccinating HWs provided societal cost-savings, returning 2.88 Kip for every single Kip invested. Influenza vaccine effectiveness, attack rate and illness duration were the most influential variables to the model.ConclusionProviding influenza vaccination to HWs in Lao PDR is cost-saving while vaccinating pregnant women and adults >= 60 is cost-effective and highly cost-effective, respectively, per WHO standards.     

紫杉醇诱导HL—60细胞凋亡的研究

目的：观察抗微管药紫杉醇对急性白血病细胞株HL－60是否具有凋亡诱导作用,并进一步研究bcl－2基因在此过程中的作用。方法：（1）以紫杉醇处理HL－60细胞,观察细胞生长抑制作用的时间效应和剂量效应,在光镜和电镜下观察细胞形态变化;（2）用流式细胞仪检测药物孵育前后细胞凋亡率（AP）的变化;（3）用RT－PCR法检测药物孵育前后bcl-2基因的表达水平。结果：（1）在一定剂量和时间范围内紫杉醇能抑制HL－60细胞生长;（2）紫杉醇能诱导HL－60细胞凋亡,并显示剂量效应：（3）在紫杉醇诱导HL－609细胞凋亡过程中,bcl－2基因表达水平下调。结论：紫杉醇能诱导HL－60细胞凋亡;bcl-2基因参与了紫杉醇诱导HL－60细胞凋亡的调控。     

Analysis of receptor-G protein interactions in permeabilized cells

Receptor-induced binding of the stable GTP analogue, guanosine 5-[-thio]triphosphate (GTP [S]), to guanine nucleotide-binding regulatory proteins (G proteins) was measured in various permeabilized cells. In myeloid differentiated human leukemia (HL-60) cells, permeabilized with either digitonin, streptolysin O or Staphylococcus aureus -toxin, binding of GTP [S] induced by three distinct chemoattractant receptors was observed. The extent of receptor-stimulated GTP [S] binding (maximally about 2-fold) was independent of the type of permeabilizing agent used. In human erythroleukemia cells permeabilized with digitonin, agonist activation of thrombin and neuropeptide Y receptors increased GTP [S] binding by 1.8- and 1.5-fold, respectively. Finally, in adherently grown human embryonic kidney cells permeabilized with digitonin, activation of the stably expressed human muscarinic m3 receptor increased GTP[S] binding by about 1.6-fold. In digitonin-permeabilized HL-60 cells, a quantitative analysis of formyl peptide receptors and interacting G proteins was performed. About 50,000 formyl peptide receptors per cell were detected. Agonist binding to these receptors was fully sensitive to regulation by guanine nucleotides and pertussis toxin. The number of high-affinity GTP [S] binding sites, most likely representing heterotrimeric G proteins, was calculated to be about 670,000 per cell. Stimulation of formyl peptide receptors led to the activation of about 130,000 of high-affinity GTP [S] binding sites, indicating a ratio of about three activated G proteins per one agonist-activated receptor.Overall, this study indicates that receptor-stimulated GTP [S] binding to G proteins in permeabilized cells is a sensitive and rapid method for analyzing receptor-G protein interactions, which can be applied to a variety of cultured cells and for various receptor systems.     

1,25-Dihydroxyvitamin D3 promotes prostaglandin E1-induced differentiation of HL-60 cells

Human promyelocytic HL-60 cells can be induced by biochemical agents to differentiate in vitro towards divergent types of myelomonocytic cells. It has been reported that prostaglandin E₁ (PGE₁) can induce granulocytic differentiation and that 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) can induce monocytic differentiation. We have now examined the effects of these compounds, both alone and in combination, on HL-60 cell differentiation. PGE₁ (1 g/ml) or 1,25(OH)₂D₃ (10 nM) each inhibited cell proliferation over 48–96 hours of treatment, but combined treatment with both agents was necessary to produce a strong inhibition. The percentage of HL-60 cells that can reduce nitroblue tetrazolium (NBT) (a characteristic index of early monocytic or granulocytic differentiation) increased 13-fold within 72 hours of PGE₁ treatment, and 1,25(OH)₂D₃ produced a fivefold stimulation. However, combined treatment (PGE₁ plus 1,25(OH)₂D₃) produced a dramatic 35-fold increase. HL-60 cells did not produce significant levels of nitric oxide (NO) before 48 hours in culture, and treatment with PGE₁ or 1,25(OH)₂D₃ did not significantly increase cellular NO elaboration over control levels. However, combined treatment produced a striking 12-fold increase over control levels. Similarly, combined treatment was necessary to obtain the maximal time-dependent stimulation of cellular lactate dehydrogenase (LDH) activity (a marker of granulocytic differentiation) as well as acid phosphatase (ACP) activity. During this same period of time, PGE₁, but not 1,25(OH)₂D₃, markedly stimulated cellular claboration of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-, and 1,25(OH)₂D₃ cotreatment strongly augmented these effects. Thus, combined treatment with 1,25(OH)₂D₃ plus PGE₁ generally augmented the apparent conversion of these cells, producing synergistic (multiplicative) or additive effects. Furthermore, PGE₁ induced within 48 hours the more general phenotypic changes classically associated with the differentiation of these cells: increased expression of chloroacetate esterase (ChAE) (a granulocytic marker), decreases in the nuclear/cytoplasmic ratio (characteristic of development beyond the promyelocyte/myelocyte stage), and major alterations in morphology from floating spherical cells to loosely adherent, elliptical polygons. 1,25(OH)₂D₃ had little effect itself on most of these parameters, but augmented the morphological changes induced by PGE₁ treatment. Within 48 hours, the ability of these cells to reduce the tetrazolium salt WST-1, a general measure of cellular metabolic activity, was increased by PGE₁, but not by 1,25(OH)₂D₃; however, the combination of 1,25(OH)₂D₃ and PGE₁ again produced the strongest stimulation. Similarly, only PGE₁ significantly reduced intracellular ATP levels, but combined treatments produced a more pronounced decrease. In summary, our findings suggest that PGE₁, not 1,25(OH)₂D₃, is sufficient to promote rapid in vitro differentiation of HL-60 cells along the granulocytic pathway; however, the PGE₁-induced conversion of these cells is markedly augmented by cotreatment with 1,25(OH)₂D₃. In addition, these converted HL-60 cells preferentially utilize the glycolytic pathway, rather than the citric acid cycle, for production of ATP, a metabolic characteristic that resembles that described for mature granulocytes.     

雷藤甲素和亚硒酸钠对人白现细胞系HL60生长抑制作用的 …

目的针对雷藤甲素治疗宽度窄的缺点,探讨与亚硒酸钠联合用药以减低雷藤甲素剂量的可能性。方法以ＭＴＴ试验观察不同浓度雷藤甲素、亚硒酸钠单独或组合对ＨＬ６０细胞的生长抑制作用,以基于中效原理的药物量效作用分析软件分析协同、相加、拮抗作用。ＣＩ＜１时为协同,＝１时为相加,＞１时为拮抗。结果半数（１８／３６）组合呈现协同效应,其中７个生长抑制率＞７０％。含雷藤甲素１００ｎｍｏｌ·Ｌ－１或含亚硒酸钠１００μｍｏｌ·Ｌ－１的所有组合ＣＩ均＜１。结论提示在该两药联合用药方案中减低雷藤甲素的剂量而仍保持原水平疗效的可能性是存在的,值得进一步研究。     

147Pm诱导血红细胞系对60Coγ射线辐射的适应性反应

目的　研究低剂量１４７Ｐｍ 内照射能否改变相继高剂量６０Ｃｏγ射线引起的ＲＢＣ 损伤的适应性效应。方法　应用外周血ＲＢＣ计数、网织红细胞（ＲＣ）计数、正常染红细胞（ＮＣＥ） 微核和嗜多染红细胞（ＰＣＥ） 微核检测,观察低剂量１４７Ｐｍ 内污染诱导小鼠ＲＢＣ系统的适应性反应。结果　剂量为２ ．０Ｇｙ 的６０Ｃｏ γ射线外照射可引起明显的血ＲＢＣ 系统损伤,与正常对照组比较,ＲＢＣ和ＲＣ计数显著降低（ Ｐ＜ ０．０１） ;ＮＣＥ和ＰＣＥ微核细胞率明显增高（Ｐ＜ ０．０１） 。预先用０．３７、３ ．７ 和３７Ｂｑ／ｇ 体重的１４７Ｐｍ 内污染预处理动物,３ 天后再予２．０Ｇｙ 的高剂量６０Ｃｏ γ射线外照射,ＲＢＣ和ＲＣ计数则显著增高,ＮＣＥ和ＰＣＥ微核细胞率显著降低,与单纯高剂量６０Ｃｏ γ射线外照射组比较有非常显著性差异（Ｐ＜ ０．０１）;并且某些指标与正常对照组比较已无显著性差异（ Ｐ＞ ０．０５） 。结论　预先用低剂量１４７Ｐｍ β射线内照射动物, 可诱导血ＲＢＣ 系统的放射适应性反应,使血ＲＢＣ系统对相继高剂量６０Ｃｏ γ射线外照射引起的损伤效应有了明显的抵抗力。提示外周血ＲＢＣ 系统可作为低剂量辐射细胞生物效应的观察指标之一     

电针对佐剂关节炎大鼠脊髓单胺类递质含量的影响

为观察电针局部取穴对佐剂关节炎大鼠脊髓单胺类递质含量的影响, 将Ｗｉｓｔａｒ 雄性大鼠２１ 只, 随机分为正常对照组、佐剂关节炎模型组和电针局部取穴加模型组, 电针局部取穴组针刺患侧太溪、昆仑穴,接Ｇ－ ６８０５ 电针仪, 频率１５ Ｈｚ, 时间２０ ｍｉｎ , 隔日针刺１ 次。于实验后１４ ｄ 上午取脊髓组织, 测定５－ 羟色胺（５－ ＨＴ） 、多巴胺（ＤＡ）、去甲肾上腺素（ＮＡ） 、５ － 羟吲哚乙酸（５ － ＨＩＡＡ） 的含量。结果： 电针局部取穴组脊髓５ － ＨＴ、５ － ＨＩＡＡ含量均显著升高, 脊髓ＮＡ、ＤＡ含量显著下降。结果表明脊髓单胺类递质参与炎性痛大鼠电针镇痛的调制过程     

Respecting the aesthetic units in the surgery of palpebral malignancy

Summary The authors, based on their own experience in this field suggest their own therapeutical view which can be described as follows: a much more frequent use of plastic procedures using sliding flaps from the cheek, associated usually with chondromucosal free grafts from the septum, will give not only much better aesthetic results but also a better guarantee against neoplastic recurrence due to the possibility of being able to carry out a much larger ablation.     

G protein-mediated receptor-receptor interaction: studies with chemotactic receptors in membranes of human leukemia (HL 60) cells

Summary Differentiated human leukemia (HL 60) cells contain high numbers of receptors for the chemotactic factors, N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) and complement component 5a (C5a), both coupled to pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). Agonist activation of either receptor stimulated binding of the GTP analog, guanosine 5-[-thio]triphosphate (GTP[S]), to membrane G proteins and by a similar extent in a non-additive manner. The possible interaction of the two receptors was studied by measuring agonist binding to one receptor in the presence of the other receptor agonist. fMet-Leu-Phe and C5a had no effects on [¹²⁵I]C5a and fMet-Leu-[³H]Phe receptor binding, respectively, when studied in the absence of regulatory ligands. Similarly, the inhibitory effects of NaCl and GDP on agonist receptor binding were not altered in the presence of the other receptor agonist. In contrast, in the presence of the GTP analogs, GTP[S] and guanosine 5-[,-imino] triphosphate, fMet-Leu-Phe and C5a reduced the binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe, respectively, in a concentration-dependent manner. The potencies of the GTP analogs to inhibit binding of [¹²⁵I]C5a and fMet-Leu-[³H]Phe was increased about 3-fold by fMet-Leu-Phe and C5a, respectively. The data presented suggest that fMet-Leu-Phe and C5a receptors share the same G protein pool in membranes of HL 60 cells and that activation of these G proteins by one of the two receptors decreases the availability of G proteins for the other receptor. Correspondence to T. Wieland at the above address     

C60-AEDP对肿瘤细胞的生物学效应

目的研究富勒烯（fullerene）及其衍生物C60-AEDP 对H22肝癌细胞的影响及作用机制.方法 MTT法观察药物在不同浓度、不同条件和不同时间下,对细胞生长方式的影响,FCM法了解其作用机制.结果光照12h,只有C60-AEDP表现出对H22、S180肿瘤细胞的生长抑制效应,且浓度越大,抑制越明显,但抑制率没有一个超过50%;在非光照条件下,也只有C60-AEDP表现出对H22肿瘤细胞的生长抑制效应,并且浓度越大、作用时间越长,抑制越明显,抑制率也没有超过50%;通过FCM观察,在光照条件下,C60-AEDP可引起G1/S周期阻滞,在非光照条件下,C60-AEDP可引起M/G1周期细胞阻滞,都可引起细胞凋亡增加.结论在体外条件下,C60-AEDP在光照条件下和非光照条件下,均表现出对肿瘤细胞生长的抑制效应.这种抑制效应可能是通过对细胞周期的影响起作用的.