CD163 is a member of the scavenger receptor cysteine-rich superfamily restricted to the monocyte/macrophage lineage and is thought to be a useful marker for anti-inflammatory or alternatively activated macrophages. In this study we used mass spectrometric analysis to determine that the antigen recognized by the antibody AM-3K, which we previously generated as a tissue macrophage-specific monoclonal antibody, was CD163. An anti-inflammatory subtype of macrophages stimulated by dexamethasone or interleukin-10 showed strong reactivity for AM-3K and increased expression of CD163 mRNA. Immunohistochemical staining of routinely processed pathological specimens revealed that AM-3K recognized a specialized subpopulation of macrophages. In granulomatous diseases such as tuberculosis, sarcoidosis, or foreign body reactions, tissue macrophages around granulomas, but not component cells of the granulomas such as epithelioid cells and multinucleated giant cells, showed positive staining for AM-3K. In atherosclerotic lesions, scattered macrophages in diffuse intimal lesions were strongly positive for AM-3K, whereas foamy macrophages in atheromatous plaques demonstrated only weak staining. We therefore suggest that, in routine pathological specimens, AM-3K is a useful marker for anti-inflammatory macrophages because these cells can be distinguished from inflammatory or classically activated macrophages. Because AM-3K cross-reacts with macrophage subpopulations in different animal species including rats, guinea pigs, rabbits, cats, dogs, goats, pigs, bovine species, horses, monkeys, and cetaceans, it will have wide application for detection of CD163 in various animals.

Background The aim of this study is to evaluate the relationship between chronic endometritis (CE) and a personalized window of implantation (WOI), identified by results of endometrial receptivity analysis (ERA), and pregnancy outcomes following embryo transfer (ET) based on the ERA outcomes. Methods The single‐center, cross‐sectional study was designed. The study population consisted of 101 infertile women who underwent endometrial sampling between June 2018 and February 2020. We recruited 88 patients who underwent ERA testing and immunohistochemistry of the plasma cell marker CD138 to diagnose CE within 3 months of testing. Subjects were divided into three groups as follows: 33 without CE (non‐CE group); 19 with untreated CE at ERA testing (CE group); and 36 successfully treated for CE before ERA testing (cured‐CE group). CE diagnosis was defined as ≥5 CD138‐positive plasma cells per 10 random stromal areas at ×400 magnification. Results In non‐CE, CE, and cured‐CE groups, the numbers of CD138‐positive cells were 0.7 ± 1.0, 28.5 ± 30.4, and 1.3 ± 1.3, respectively (p < .001). The rates of “receptive” endometrium in non‐CE and cured‐CE groups were 57.6% (19 women) and 50.0% (18 women), respectively; however, in the CE group, this rate was significantly lower than the other two groups (p = .009) at only 15.8% (3 women). After CE were treated prior or posterior to the ERA test in cured‐CE or CE groups, the clinical pregnancy rates at the first ET in non‐CE, CE, and cured‐CE groups were 77.8% (21/27 cycles), 22.2% (4/18 cycles), and 51.7% (15/29 cycles), respectively (p < 0.001). Conclusion CE had detrimental effects on the individual WOI, leading to embryo–endometrial asynchrony; therefore, diagnosis and treatment of CE should be done before ERA testing.

Laparoscopy should be strongly considered for examining women with unexplained infertility.

The object of this study was to enhance the solubility, dissolution rate, and oral bioavailability of rutin by complexation with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The interaction of rutin with cyclodextrins (CyDs) was evaluated by the solubility, and ultraviolet (UV) and circular dichroism (CD) spectrophotometries. The chemical and enzymatic stability of rutin was examined in an alkaline buffer solution and in rat small intestinal homogenates, respectively. Dissolution rates of rutin and its CyD complexes were measured by the dispersed amount method. In vivo absorption studies of rutin after oral administration via conventional tablet containing rutin alone or its beta-CyD complexes was performed on beagle dogs. The stability constants calculated from the phase solubility method increased in the order of HP-gamma-CyD < G2-beta-CyD < beta-CyD < HP-beta-CyD. Spectroscopic studies also revealed that HP-beta-CyD and beta-CyD formed a relatively more stable inclusion complex with rutin. The dissolution rates of rutin increased by the complexation with CyDs in the order of rutin alone < HP-beta-CyD < or = beta-CyD. HP-beta-CyD inhibited the hydrolysis of rutin in the alkaline buffer solution and the small intestinal homogenates of rats, suggesting that HP-beta-CyD may stabilize rutin in a gastrointestinal tract after oral administration. When the tablet containing rutin or its beta-CyD complexes was administered to beagle dogs, the plasma levels of homovanillic acid (HVA) (a major stable metabolite of rutin) after oral administration of HP-beta-CyD complex were much higher than in either that of rutin alone or in its beta-CyD complex. The in vivo absorption study suggests that HP-beta-CyD increased the oral bioavailability of rutin from the gastrointestinal tracts of beagle dogs because of the increase in solubility, faster dissolution rate, and gastrointestinal stability. HP-beta-CyD has a significant advantage with respect to providing high aqueous solubility while maintaining a lack of toxicity in oral pharmaceutical preparations of rutin.

Purpose The purpose of the present study was to use arthroscopy to evaluate the effect of distal tuberosity osteotomy (DTO) in open‐wedge high tibial osteotomy (OW‐HTO) on patellofemoral (PF) cartilage degradation. Methods Between 2012 and 2017, 46 knees underwent DTO in OW‐HTO, and 65 knees underwent conventional OW‐HTO (cOW‐HTO). To assess changes in patellar height, the Blackburne–Peel (BP) ratio and the Caton–Deschamps (CD) index were measured. Arthroscopic evaluation on the PF joint was performed at the initial osteotomy and at the second‐look procedure 1 year later. Statistical analyses were performed to compare difference between the DTO and the cOW‐HTO group. Results In the cOW‐HTO group, the mean BP ratio and CD index decreased significantly from 0.81 and 0.89 preoperatively, respectively, to 0.69 and 0.76 postoperatively, respectively (p < 0.001). In contrast, the DTO group maintained a consistent patellar height; the mean BP ratio and CD index were 0.77 and 0.83 preoperatively, respectively, and 0.73 and 0.80 postoperatively, respectively. Upon arthroscopic evaluation, 39 of 46 patients (84.8%) in the DTO group showed no progression of PF cartilage degradation at the second look; indeed, five of 46 patients (10.9%) even demonstrated improvement. In contrast, 21 of 65 patients (32.3%) in the cOW‐HTO group exhibited increased PF cartilage degradation. There was a significant difference in progression of PF cartilage degradation between DTO and cOW‐HTO (p < 0.001). Conclusion DTO in OW‐HTO maintained the preoperative patellar height, which could help prevent progression of cartilage degeneration in the PF joint after surgery. In respect of the biplanar osteotomy direction in OW‐HTO, the DTO, rather than cOWHTO, is the preferred technique for the treatment of varus knee osteoarthritis to avoid progression of PF cartilage degradation. Level of evidence III.

No abstract

The small intestine plays an important role in all aspects of pharmacokinetics, but there is no system for the comprehensive evaluation of small-intestinal pharmacokinetics, including drug metabolism and absorption. In this study, we aimed to construct an intestinal pharmacokinetics evaluation system and to generate pharmacokinetically functional enterocytes from human induced pluripotent stem cells. Using activin A and fibroblast growth factor 2, we differentiated these stem cells into intestinal stem cell-like cells, and the resulting cells were differentiated into enterocytes in a medium containing epidermal growth factor and small-molecule compounds. The differentiated cells expressed intestinal marker genes and drug transporters. The expression of sucrase-isomaltase, an intestine-specific marker, was markedly increased by small-molecule compounds. The cells exhibited activities of drug-metabolizing enzymes expressed in enterocytes, including CYP1A1/2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, UGT, and sulfotransferase. Fluorescence-labeled dipeptide uptake into the cells was observed and was inhibited by ibuprofen, an inhibitor of the intestinal oligopeptide transporter solute carrier 15A1/PEPT1. CYP3A4 mRNA expression level was increased by these compounds and induced by the addition of 1a,25-dihydroxyvitamin D 3 . CYP3A4/5 activity was also induced by 1a,25-dihydroxyvitamin D 3 in cells differentiated in the presence of the compounds. All these results show that we have generated enterocyte-like cells that have pharmacokinetic functions, and we have identified small-molecule compounds that are effective for promoting intestinal differentiation and the gain of pharmacokinetic functions. Our enterocyte-like cells would be useful material for developing a novel evaluation system to predict human intestinal pharmacokinetics.

Purpose To evaluate the cystectomy-induced damage on the follicular growth and ovulation of an affected ovary during natural cycles. Methods Twenty-eight infertile patients with unilateral ovarian endometriomas who underwent laparoscopic cystectomy were retrospectively evaluated. The ovulation rate of an affected ovary during natural cycles was compared before and after cystectomy in each patient, and it was also determined if ovulation from the affected ovaries resulted in pregnancy.Results After surgery, the ovulation rate was significantly lower than that before cystectomy (16.9±4.5% vs. 34.4± 6.6%, P= 0.013). After surgery, 14 pregnancies were achieved without IVF treatment, and only 2 of them (14.3%) were achieved from an operated-side ovary. However, the pregnancy rate per ovulatory cycle of the operated-side ovary was not different from that of the intact ovary (8.8% vs. 5.8%, P=0.750). Conclusions Laparoscopic cystectomy is an invasive treatment in that it reduces the frequency of ovulation; however the pregnancy rate per ovulation did not deteriorate.