Comparison of two strategies for the administration of injectable depot medroxyprogesterone acetate: among women who returned to a family planning clinic at three- or six-month intervals

Objectives: The aim of this study was to compare the clinical performance of depot medroxyprogesterone acetate (DMPA) in women who received injections every 3 months at the Family Planning Clinic, and those who received every other injection at a health care facility near their place of residence, only returning to the clinic every 6 months.

Materials and methods: The medical charts of DMPA users from 2 January 1980 through 31 December 2012 were evaluated for this study. Two cohorts of women were created and compared: those who regularly received DMPA injections every 3 months (3-month group) at the clinic and those who received alternating 3-month injections at a health care facility near their residence house, returning to the clinic every 6 months for an injection (6-month group). In addition, effectiveness rates, reasons for discontinuation, and continuation rates were evaluated.

Results: Overall, 2637 women received all injections at 3-month intervals at the clinic, and 1190 women received every other injection at a health care facility near their residence. The women in the 3-month group had higher pregnancy rates and higher discontinuation rates (with the exception of discontinuation due to the loss of libido).

Conclusion: The women who received alternating injections near their homes were more likely to continue using DMPA as a contraception method and presented lower pregnancy and discontinuation rates (for the majority of reasons), when compared to those women who returned to the clinic every 3 months.     

Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagonist from human blood granulocytes and monocytes: Evidence for the involvement of plasma IgG,complement C3 and β2 integrin

Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads. Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004     

Regulation of membrane excitability by intracellular pH (pHi) changers through Ca2+-activated K+ current (BK channel) in single smooth muscle cells from rabbit basilar artery

Employing microfluorometric system and patch clamp technique in rabbit basilar arterial myocytes, regulation mechanisms of vascular excitability were investigated by applying intracellular pH (pH_i) changers such as sodium acetate (SA) and NH₄Cl. Applications of caffeine produced transient phasic contractions in a reversible manner. These caffeine-induced contractions were significantly enhanced by SA and suppressed by NH₄Cl. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) was monitored in a single isolated myocyte and based the ratio of fluorescence using Fura-2 AM (R _340/380). SA (20 mM) increased and NH₄Cl (20 mM) decreased R _340/380 by 0.2 ± 0.03 and 0.1 ± 0.02, respectively, in a reversible manner. Caffeine (10 mM) transiently increased R _340/380 by 0.9 ± 0.07, and the ratio increment was significantly enhanced by SA and suppressed by NH₄Cl, implying that SA and NH₄Cl may affect [Ca²⁺]_i (p < 0.05). Accordingly, we studied the effects of SA and NH₄Cl on Ca²⁺-activated K⁺ current (IK_Ca) under patch clamp technique. Caffeine produced transient outward current at holding potential (V _h) of 0 mV, caffeine induced transient outward K⁺ current, and the spontaneous transient outward currents were significantly enhanced by SA and suppressed by NH₄Cl. In addition, IK_Ca was significantly increased by acidotic condition when pH_i was lowered by altering the NH₄Cl gradient across the cell membrane. Finally, the effects of SA and NH₄Cl on the membrane excitability and basal tension were studied: Under current clamp mode, resting membrane potential (RMP) was −28 ± 2.3 mV in a single cell level and was depolarized by 13 ± 2.4 mV with 2 mM tetraethylammonium (TEA). SA hyperpolarized and NH₄Cl depolarized RMP by 10 ± 1.9 and 16 ± 4.7 mV, respectively. SA-induced hyperpolarization and relaxation of basal tension was significantly inhibited by TEA. These results suggest that SA and NH₄Cl might regulate vascular tone by altering membrane excitability through modulation of [Ca²⁺]_i and Ca²⁺-activated K channels in rabbit basilar artery.     

Immediate effects of foot orthoses on pain during functional tasks in people with patellofemoral osteoarthritis: A cross-over,proof-of-concept study

Background

The purpose of the study was to determine whether prefabricated foot orthoses immediately reduce pain during functional tasks in people with patellofemoral osteoarthritis, compared to flat insoles and shoes alone.

独蒜兰乙酸乙酯萃取物通过内源性线粒体通路诱导白血病K562细胞和HL-60细胞凋亡

目的:探讨独蒜兰乙酸乙酯萃取物对人慢性粒细胞白血病K562细胞和急性髓性白血病HL-60细胞增殖及凋亡的影响以及诱导凋亡的途径。方法:采用XTT法、台盼蓝拒染法、Annexin V-FITC/PI双染法、PI染色法、4',6-二脒基-2-苯基吲哚(DAPI)染色和Western blot法研究不同浓度独蒜兰乙酸乙酯萃取物对上述2种白血病细胞增殖、凋亡、细胞周期和凋亡相关蛋白表达等方面的影响。结果:独蒜兰正丁醇萃取物对K562细胞活力几乎没有抑制作用,而乙酸乙酯萃取物能显著抑制K562和HL-60细胞的活力和增殖。乙酸乙酯萃取物对于HL-60细胞作用24 h的半数抑制浓度(IC_(50))为(42.14±2.54)mg/L,对于K562细胞的IC_(50)为(51.28±3.12)mg/L。Annexin V-FITC/PI和DAPI染色结果显示,乙酸乙酯萃取物呈剂量依赖性诱导2种细胞凋亡,且50 mg/L的乙酸乙酯萃取物作用后K562细胞的凋亡率为33.1%,而HL-60细胞的凋亡率为63.1%,说明HL-60细胞对乙酸乙酯萃取物更加敏感,伴有典型的细胞核凋亡形态学改变。PI染色结果显示HL-60细胞和K562细胞都被阻滞于G_2期。Western blot结果显示,随着药物浓度的升高,细胞凋亡抑制蛋白Bcl-2的表达降低,而促凋亡蛋白Bax、cleaved caspase-3和活化的多腺苷二磷酸核糖聚合酶的表达逐渐升高,内源性线粒体凋亡的特征胞浆中细胞色素C和凋亡诱导因子表达也逐渐升高。结论:独蒜兰乙酸乙酯萃取物能显著抑制K562和HL-60细胞增殖,并通过触发内源性线粒体凋亡通路诱导这2种细胞凋亡。     

Prevention of unintended pregnancies by using emergency contraception: the differences between levonorgestrel and ulipristal acetate. A theoretical model using data from a survey on the use of emergency contraception in Spain, 2017

Objective: To estimate the differences in unintended pregnancies avoided using either levonorgestrel (LNG) or ulipristal acetate (UPA) emergency contraception (EC).

Design: Cross-sectional study.

Setting: Survey carried out in Spain.

Participants: 1000 Spanish women reporting unprotected sex in 2017.

Main measurements: EC use, reasons for not using EC, calculation of the number of unintended pregnancies avoided.

Results: 39% of Spanish women having had unprotected sex used EC. 61% of those women did not use EC and 11% did not know the existence of this resource. In 2017 the use of EC prevented 101,271 unintended pregnancies. If instead of using LNG every woman had used UPA another 15,979 additional pregnancies could have been prevented.

Conclusions: If all Spanish women having unprotected sex used EC we could expect a significant decrease in the number of unintended pregnancies and abortions. Using UPA instead of LNG would have a greater impact on that reduction with the corresponding benefit for women and society as a whole.     

Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal uterine bleeding?

BACKGROUND: Abnormal uterine bleeding is commonly associated with progestin-only contraceptives, including depot medroxyprogesterone acetate (DMPA), and remains the main reason why these agents are discontinued. Matrix metalloproteinases (MMP), enzymes which degrade specific extracellular matrix components, and leukocytes are implicated in menstruation. Alteration in endometrial MMP-9 and leukocytes has been described in users of other progestin-only contraceptives, suggesting a potential role in the pathogenesis of abnormal uterine bleeding. METHODS: This study describes the immunohistochemical localization of MMP-9, the tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2 and TIMP-3, and leukocytes [CD3+ T lymphocytes, CD68+ macrophages and CD56+ uterine natural killer cells (uNK cells)] in the endometrium of women using DMPA. Comparison is made with perimenstrual endometria from normal cycling women. RESULTS: Similar to the perimenstrual period, an influx of MMP-9 positive cells (identified as neutrophils and CD3+ T cells on the basis of dual immunofluorescence), macrophages and uNK cells was observed in the endometrium of DMPA users. However, significantly more endometrial T lymphocytes were observed in DMPA users. Immunoreactive TIMP, present in all endometrial compartments, demonstrated a significantly decreased immunostaining intensity score in endometrial epithelium (TIMP-1 and TIMP-2), stroma (TIMP-1, TIMP-2 and TIMP-3), endothelium (TIMP-1 and TIMP-2) and vascular smooth muscle (TIMP-1) of DMPA users compared with controls. No correlation was observed between the parameters studied and bleeding patterns reported by subjects. CONCLUSIONS: These findings provide additional evidence for the importance of the MMP/TIMP balance in the loss/maintenance of endometrial integrity and in the complex pathological mechanisms involved in the troubling side-effect of menstrual bleeding disturbance.     

Chain‐Length‐Dependent Termination of Vinyl Acetate and Vinyl Pivalate Bulk Homopolymerizations Studied by SP‐PLP‐EPR

Bulk homopolymerizations of vinyl acetate and vinyl pivalate are studied by EPR experiments between ?65 °C and 60 °C with dicumyl peroxide acting as the photoinitiator. No mid‐chain radicals are seen, which demonstrates that backbiting plays no role. The chain‐length dependence of the termination rate coefficients measured up to 13% monomer conversion is adequately represented by the composite model. The power‐law exponents α_s and α_l for short‐chain and long‐chain radicals are: α_s(VAc) = 0.57 ± 0.05, α_s(VPi) = 0.67 ± 0.15, α_l(VAc) = 0.16 ± 0.07, and α_l(VPi) = 0.16 ± 0.07. The crossover chain lengths differ largely: i_c(VAc) = 20 ± 10 and i_c(VPi) = 110 ± 30. The rate coefficient for termination of two radicals of chain length unity, , which is the fourth composite‐model parameter, depends on temperature, as does the monomer fluidity.

     

醋酸曲安奈德局部注射联合手术切除治疗耳部瘢痕疙瘩

目的总结注射醋酸曲安奈德控制瘢痕疙瘩生长后联合手术切除耳垂瘢痕疙瘩的临床经验。方法采用耳垂瘢痕疙瘩局部注射醋酸曲安奈德治疗3~4次后,手术切除耳垂瘢痕疙瘩,术中保留部分瘢痕疙瘩边缘皮肤并行无张力缝合,术后观察6~24个月。结果本组31只耳手术切口全部一期愈合,随访6~24个月,26只耳治愈,4只耳有效,1只耳无效,有效治愈率约96.8%。结论醋酸曲安奈德局部注射后手术切除能有效治疗耳部瘢痕疙瘩。     

色钉菇乙酸乙酯提取物对脂多糖损伤的多巴胺能神经元的保护作用

目的 探讨不同剂量的色钉菇乙酸乙酯提取物对帕金森病（PD）模型小鼠多巴胺能神经元的保护作用。 方法 以昆明小鼠为实验材料,将脂多糖（LPS）定位注射至黑质内复制PD模型。30只小鼠随机分为假手术对照组、LPS 实验对照组、低剂量实验组（LPS+ 100mg/kg）、中剂量实验组（LPS+ 200mg/kg）和高剂量实验组（LPS+ 400mg/kg）,每组6只。用免疫荧光方法显示多巴胺能神经元和星形胶质细胞,荧光显微镜下观察、计数黑质内的阳性细胞数。结果 LPS实验对照组小鼠的黑质内,多巴胺能神经元数量少于假手术组（P<0.05）,且细胞胞体变圆,突起变短;星形胶质细胞胞体增大, 多呈激活形态。低剂量实验组与中剂量实验组小鼠黑质内的多巴胺能神经元数量多于LPS实验对照组（P<0.05）,星形胶质细胞密度降低;高剂量实验组小鼠黑质内的多巴胺能神经元数量与实验组差异无统计学意义（P>0.05）。 结论 低剂量与中剂量的色钉菇乙酸乙酯提取物能够抑制星形胶质细胞的激活,对LPS导致的多巴胺能神经元损伤有显著保护作用。