The role of metalloproteinase and hypoxia conditions in endometrial cells and embryo implantation

In the process of implantation, metalloproteinase enzymes play a key role in basement membrane degradation and endometrial extracellular matrix. The activity of these enzymes is impeded by binding Tissue Inhibitors of Metalloproteinase (TIMP). The oxygen concentration in the mammalian uterus at the time of implantation is about 2-5%. It is seen that the imposition of hypoxia on cancer cells increases the expression of metalloproteinase enzymes and reduces the expression of metalloproteinase inhibitors, resulting in increased cell invasion. To know the effect of Hypoxia-Inducible Factor (HIF) and other related factors, we decided to evaluate hypoxic conditions on endometrial epithelial cells of the uterus and roll of matrix metalloproteinases (MMPs) on angiogenesis and invasion of the embryo during implantation. In this study, human and mouse endometrial epithelial cells were incubated for 24-48 hours in hypoxic conditions. Subsequently, the expression level of TIMP-1 was measured in mouse and human epithelial cells by Real-Time PCR technique. The cell viability in hypoxic conditions was evaluated by MTT assay. Our results demonstrated that hypoxia reduced the quantitative gene expression of TIMP-1 in the human and mouse endometrial epithelial cells compared to the control group. It can be concluded that applying hypoxic conditions by reducing the TIMP-1 expression and consequently increasing MMP expression, may improve the embryo implantation rate

Effects of lidocaine incorporation (without epinephrine) on pain and 2-week complications of botulinum toxin: a double-blind randomized placebo-controlled clinical trial

Abstract No study has assessed the effects of the incorporation of isolated lidocaine into botulinum toxin for reducing its pain or complications. Studies on the dilution of botulinum toxin with other materials are as well extremely few, small, and limited methodologically. Therefore, we aimed to evaluate, for the first time, the effects of the incorporation of lidocaine alone into botulinum toxin type A on post-injection pain and complications. In this 2-week prospective, multicenter, double-blind randomized placebo-controlled clinical trial, 729 participants (667 females) were enrolled. They were randomized into placebo and lidocaine dilutions (about 2:1), and then into two brands of toxins (Dysport versus Xeomin). Hence, there were 4 subgroups. In the 2 experimental subgroups, botulinum toxin was diluted with 2% lidocaine without adrenaline; in the 2 control subgroups, botulinum toxin was diluted with normal saline as a placebo. After injection, the pain level was recorded (as an 11-scale numerical rating scale from 0 to 10). After 2 weeks, post-injection complications were assessed based on the participants’ reports and the surgeon’s observations. Data were analyzed using 3-way ANCOVA, multiple binary logistic regression, and bivariable analyses (α = 0.05, β ≤ 0.1). The mean ± SD pain levels in the lidocaine group (n = 263) and the placebo group (n = 466) were 3.51 ± 2.04 and 4.15 ± 2.35, respectively. The mean ± SD pain levels in the subgroups ‘Xeomin-Lidocaine (n = 61), Dysport-Lidocaine (n = 202), Xeomin-Placebo (n = 133), and Dysport-Placebo (n = 333)’ were respectively 3.39 ± 1.86, 3.55 ± 2.09, 4.61 ± 2.49, and 3.97 ± 2.24. Lidocaine incorporation (P = 0.001), Dysport brand (P = 0.030), and younger age (P = 0.032) [but not sex (P = 0.406)] reduced pain. The only significant findings for 2-week complications were for the associations observed between aging with increased asymmetry (P = 0.022, OR = 1.032) and a need for a retouch (P = 0.039, OR = 1.021). Botulinum toxin dilution with lidocaine alone (without adrenaline or other ingredients) can reduce pain without affecting postinjection complications. Toxin brands may cause different extents of pain. Aging, but not sex, may increase pain. Two-week complications were not affected by any factors, except aging in the case of asymmetry and the need for a botulinum toxin retouch