CHARACTERISTICS OF THE MACULAR MICROVASCULATURE IN IDIOPATHIC EPIRETINAL MEMBRANE PATIENTS WITH AN ECTOPIC INNER FOVEAL LAYER.

PURPOSE: To identify the characteristics of the retinal microvasculature in epiretinal membrane patients with ectopic inner foveal layer (EIFL). METHODS: Patients were classified into two groups: those without EIFL (Group 1) and those with EIFL (Group 2). The vessel density (VD), perfusion density (PD), and the foveal avascular zone (FAZ) parameters were compared using optical coherence tomography angiography. Linear regression analysis was performed to identify the optical coherence tomography angiography parameters associated with best-corrected visual acuity. RESULTS: The VD of the central area in Group 1 and Group 2 was 11.6 ± 3.3 and 17.2 ± 2.8 mm -1 , respectively ( P < 0.001), the PD of the central area was 21.7 ± 6.2 and 32.0 ± 5.5%, respectively ( P < 0.001), and the FAZ area was 0.24 ± 0.11 and 0.09 ± 0.08 mm 2 , respectively ( P < 0.001). Based on the linear regression analysis, the VD of the central area (B = 0.018, P = 0.003), the PD of the central area (B = 0.009, P = 0.004), and FAZ area (B = -0.489, P = 0.013) were significantly associated with best-corrected visual acuity in patients with epiretinal membrane. CONCLUSION: The VD and PD of the foveal area were significantly higher in patients with EIFL, and the FAZ area was lower in patients with EIFL than in those without EIFL. In addition, the VD and PD of the foveal area were negatively associated with best-corrected visual acuity, and the FAZ area was positively associated with best-corrected visual acuity in patients with epiretinal membrane.

Di-(2-ethylhexyl) Phthalate Triggers Proliferation, Migration, Stemness, and Epithelial-Mesenchymal Transition in Human Endometrial and Endometriotic Epithelial Cells via the Transforming Growth Factor-ß/Smad Signaling Pathway.

Di-(2-ethylhexyl) phthalate (DEHP) is a frequently used plasticizer that may be linked to the development of endometriosis, a common gynecological disorder with a profound impact on quality of life. Despite its prevalence, vital access to treatment has often been hampered by a lack of understanding of its pathogenesis as well as reliable disease models. Recently, epithelial-mesenchymal transition (EMT) has been suggested to have a significant role in endometriosis pathophysiology. In this study, we found that DEHP treatment enhanced proliferation, migration, and inflammatory responses, along with EMT and stemness induction in human endometrial and endometriotic cells. The selective transforming growth factor-ß (TGF-ß) receptor type 1/2 inhibitor LY2109761 reversed the DEHP-induced cell proliferation and migration enhancement as well as the increased expression of crucial molecules involved in inflammation, EMT, and stemness, indicating that DEHP-triggered phenomena occur via the TGF-ß/Smad signaling pathway. Our study clearly defines the role of DEHP in the etiology and pathophysiological mechanisms of endometriosis and establishes an efficient disease model for endometriosis using a biomimetic 3D cell culture technique. Altogether, our data provide novel etiological and mechanistic insights into the role of DEHP in endometriosis pathogenesis, opening avenues for developing novel preventive and therapeutic strategies for endometriosis.

A Marine Collagen-Based Biomimetic Hydrogel Recapitulates Cancer Stem Cell Niche and Enhances Progression and Chemoresistance in Human Ovarian Cancer.

Recent attention has focused on the development of an effective three-dimensional (3D) cell culture system enabling the rapid enrichment of cancer stem cells (CSCs) that are resistant to therapies and serving as a useful in vitro tumor model that accurately reflects in vivo behaviors of cancer cells. Presently, an effective 3D in vitro model of ovarian cancer (OC) was developed using a marine collagen-based hydrogel. Advantages of the model include simplicity, efficiency, bioactivity, and low cost. Remarkably, OC cells grown in this hydrogel exhibited biochemical and physiological features, including (1) enhanced cell proliferation, migration and invasion, colony formation, and chemoresistance; (2) suppressed apoptosis with altered expression levels of apoptosis-regulating molecules; (3) upregulated expression of crucial multidrug resistance-related genes; (4) accentuated expression of key molecules associated with malignant progression, such as epithelial-mesenchymal transition transcription factors, Notch, and pluripotency biomarkers; and (5) robust enrichment of ovarian CSCs. The findings indicate the potential of our 3D in vitro OC model as an in vitro research platform to study OC and ovarian CSC biology and to screen novel therapies targeting OC and ovarian CSCs.

Simple-structured, subfemtosecond-resolution optical-microwave phase detector.

We demonstrate a simple all-fiber photonic phase detector that can measure the phase (timing) difference between an optical pulse train and a microwave signal with subfemtosecond resolution and -60 dB-level amplitude-to-phase conversion coefficient. It is based on passive phase biasing of a Sagnac loop by the intrinsic phase shift of a symmetric 3×3 fiber coupler. By eliminating the necessity of magneto-optic components or complex radio frequency (RF) electronics for phase biasing of the Sagnac loop, this phase detector has potential to be implemented as an integrated photonic device as well. When using this device for synchronization between a 250 MHz mode-locked Er-fiber laser and an 8 GHz microwave oscillator, the minimum residual phase noise floor reaches <-154 dBc/Hz (at 8 GHz carrier) with integrated root mean square (rms) timing jitter of 0.97 fs [1 Hz-1 MHz]. The long-term rms timing drift and frequency instability are 0.92 fs (over 5000 s) and 4×10-19 (at 10,000 s averaging time), respectively.

Impact of high myopia on inner retinal layer thickness in type 2 diabetes patients.

To investigate the impact of the combination of type 2 diabetes (DM) and high myopia on inner retinal layer thickness of the macular area. The patients were divided into four groups: control (group 1), patients with DM without high myopia (group 2), patients with high myopia without DM (group 3), and patients with DM and high myopia (group 4). Ganglion cell complex (GCC) thickness was compared among the groups. Linear regression analysis was performed to identify factors associated with GCC thickness. A total of 194 eyes were enrolled: 59 in group 1, 52 in group 2, 49 in group 3, and 34 in group 4. The average parafovea GCC thicknesses were 113.9 ± 10.4, 112.4 ± 11.2, 112.2 ± 7.8, and 102.6 ± 15.1 µm (P < 0.001), and the average perifovea GCC thicknesses were 104.8 ± 13.2, 103.5 ± 10.8, 103.6 ± 8.8, and 93.9 ± 15.5 µm in groups 1, 2, 3 and 4, respectively (P = 0.001). In multivariate analyses, age (ß = - 0.20, P = 0.007), DM duration (ß = - 0.34, P = 0.023), and axial length (ß = - 1.64, P < 0.001) were significantly associated with parafoveal GCC thickness. The GCC was significantly thinner when high myopia and DM were combined, compared to either condition alone. Additionally, age, DM duration, and axial length were significant factors associated with GCC thickness. The combination of mechanical stretching and neurodegeneration would accelerate neural damage to the retina, resulting in greater inner retinal layer thinning.

Reproducibility of each retinal layer thickness measurement in epiretinal membrane patients with ectopic inner foveal layers.

BACKGROUND: To identify the reliability of each retinal layer thickness measurement in epiretinal membrane (ERM) patients with ectopic inner foveal layers (EIFLs). METHODS: Subjects were divided into two groups: ERM patients with EIFLs (Group 1) and without EIFLs (Group 2). The retinal layer thickness was measured twice, and intraclass correlation coefficient (ICC) and coefficient of variation (CV) values were calculated. RESULTS: In Group 1, the CVs of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were 22.39%, 13.12%, 13.37%, 13.21%, 15.09%, and 11.94%, while the ICCs were 0.431, 0.550, 0.440, 0.286, 0.279, and 0.503, respectively. In Group 2, the CVs were 18.20%, 10.59%, 10.65%, 13.27%, 14.75%, and 10.37%, while the ICCs were 0.788, 0.834, 0.830, 0.715, 0.226, and 0.439, respectively. The average central macular thickness (CMT) was significantly correlated with the CVs of NFL (coefficient = 0.317; P < 0.001), GCL (coefficient = 0.328; P < 0.001), and IPL (coefficient = 0.186; P = 0.042) in Group 1. CONCLUSIONS: The reproducibility of the inner retinal layer thickness measurements in ERM patients with EIFLs was low compared to those without EIFLs. The reproducibility of the outer retinal layer thickness measurements, including OPL and ONL, was poor regardless of the presence of EIFLs in ERM patients. Additionally, the thicker the CMT in patients with EIFLs, the lower the reproducibility of the inner retinal layer thickness measurements.

Effects of long-term intermittent pharmacological therapy with ulipristal acetate on reducing the volume of uterine fibroids and relieving symptoms.

BACKGROUND: The aim of this study was to compare the effects of a 12-week course and four repeated 12-week courses of daily 5 mg ulipristal acetate (UPA) on reducing the volume and relieving symptoms of uterine fibroids. METHODS: From 2016 to 2019, 287 female patients with uterine fibroids diagnosed using ultrasonography were recruited. The patients received four 12-week course treatments of daily UPA administration in the first and fourth sessions, respectively. During the first and fourth courses of UPA, we measured the volume of the fibroids using ultrasonography to study the effect on volume reduction. The measured outcomes included symptomatic relief and adverse effects. RESULTS: After the first UPA treatment course, menorrhagia was improved in 82.2% of patients. A total of 59.5% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 160.9 cm3 to 104.6 cm3. After the fourth treatment course, 87.4% of patients reported decreased bleeding. A total of 67.2% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 171.7 cm3 to 106.5 cm3. In 64 (38.1%) patients in group A and 36 (30.3%) in group B, the fibroid volume increased. Among them, 72% of patients showed improved symptoms. CONCLUSIONS: Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.

Analyses of the ratio of ganglion cell-inner plexiform layer thickness to vessel density according to age in healthy eyes.

PURPOSE: To identify how the inner retinal layer and microvasculature change with age by analyzing the relationships of ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD), and the ratio of these measurements with age in healthy eyes. METHODS: Participants were divided into five groups according to age. The GC-IPL thickness, VD, and GC-IPL/VD ratio were compared among the groups. Linear regression analyses were performed to identify relationships of GC-IPL/VD ratio with age. RESULTS: The average GC-IPL thicknesses were 84.84 ± 5.28, 84.22 ± 5.30, 85.20 ± 6.29, 83.29 ± 7.06, and 82.26 ± 5.62 µm in the 20s, 30s, 40s, 50s, and 60s age groups, respectively. The VDs were 20.94 ± 1.50, 21.06 ± 1.50, 20.99 ± 1.03, 20.71 ± 0.93, and 19.74 ± 1.73 mm-1 in the 20s, 30s, 40s, 50s, and 60s age groups, respectively. The GC-IPL/VD ratio was 4.05, 4.00, 4.06, 4.02, and 4.17 in each group, respectively, and the ratio of the 60s age group was significantly higher than that of other groups. In linear regression analyses, the GC-IPL/VD ratio was significantly associated with age in the participants aged ≥ 50 years (B = 0.014, P = 0.013), whereas it was not in the participants aged < 50 years (B = 0.003, P = 0.434). CONCLUSIONS: GC-IPL thickness and macular VD showed a tendency to decrease beginning in the 50s age group and the GC-IPL/VD ratio was significantly increased in the 60s age group. Additionally, the GC-IPL/VD ratio was positively associated with age in subjects aged ≥ 50 years, which implies a more pronounced decline over time in VD rather than GC-IPL thickness.

Massively parallel electro-optic sampling of space-encoded optical pulses for ultrafast multi-dimensional imaging.

High-speed and high-resolution imaging of surface profiles is critical for the investigation of various structures and mechanical dynamics of micro- and nano-scale devices. In particular, recent emergence of various nonlinear, transient and complex mechanical dynamics, such as anharmonic vibrations in mechanical resonators, has necessitated real-time surface deformation imaging with higher axial and lateral resolutions, speed, and dynamic range. However, real-time capturing of fast and complex mechanical dynamics has been challenging, and direct time-domain imaging of displacements and mechanical motions has been a missing element in studying full-field structural and dynamic behaviours. Here, by exploiting the electro-optic sampling with a frequency comb, we demonstrate a line-scan time-of-flight (TOF) camera that can simultaneously measure the TOF changes of more than 1000 spatial coordinates with hundreds megapixels/s pixel-rate and sub-nanometre axial resolution over several millimetres field-of-view. This unique combination of performances enables fast and precise imaging of both complex structures and dynamics in three-dimensional devices and mechanical resonators.

The impairment of the deep vascular complex in prolonged type 2 diabetes patients without clinical diabetic retinopathy.

PURPOSE: To identify the effects of prolonged type 2 diabetes (T2DM) on the retinal microvasculature of each retinal capillary plexus in patients without clinical diabetic retinopathy (DR). METHODS: Subjects were divided into three groups: the control group (98 eyes), patients with T2DM < 10 years (DM group 1, 84 eyes), and patients with T2DM ≥ 10 years (DM group 2, 55 eyes). The vessel densities (VD) of the superficial and deep capillary plexus (SCP and DCP) were compared. Linear regression analyses were performed to identify factors associated with the VD. RESULTS: The mean VDs of the SCP in the control group, DM group 1, and DM group 2 were 35.9 ± 4.2, 34.9 ± 3.9, and 34.6 ± 5.1, respectively (P = 0.042). The mean VDs of the DCP in the three groups were 36.1 ± 3.1, 35.9 ± 3.0, and 34.0 ± 3.3, respectively (P < 0.001). In multivariate analyses, the BCVA was a significant factor associated with both the superficial VD (B = -7.10, P = 0.019) and deep VD (B = -5.70, P = 0.039). Hypertension (B = -1.22, P = 0.021) and DM duration (B = -0.20, P < 0.001) were significant factors associated with deep VD. CONCLUSIONS: T2DM patients without DR showed decreased VD in the SCP and DCP. The microvascular impairment of the DCP in patients with T2DM ≥ 10 years was in particular, more severe. Additionally, ischemia caused by hypertension and accumulated impairment of microvasculature due to prolonged T2DM would affect the DCP.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

PURPOSE: Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. METHODS: Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. RESULTS: There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. CONCLUSIONS: These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Attosecond electronic timing with rising edges of photocurrent pulses.

There has been remarkable progress in generating ultralow-noise microwaves from optical frequency combs in the last decade. While a combination of techniques has enabled tens to hundreds of attoseconds residual jitter in microwave extraction, so far most of research efforts have been focused on extracting single-tone microwaves from combs; there has been no study on the noise properties of photocurrent pulses directly extracted from the photodiode. Here, we reveal that the residual jitter between optical pulses and rising edges of photocurrent pulses can be in the tens of attoseconds regime. The rising-edge jitter is much lower than the falling-edge jitter, and further, this ultralow rising-edge jitter could be obtained by both p-i-n and (modified-)uni-travelling-carrier photodiodes. This finding can be directly used for various edge-sensitive timing applications, and further shows the potential for ultrahigh-precision timing using silicon-photonic-integrable on-chip p-i-n photodiodes.

Peritoneal fluid from endometriosis patients switches differentiation of monocytes from dendritic cells to macrophages.

Immunological abnormalities of cell-mediated and humoral immunity might be associated with the pathogenesis of endometriosis. This study has examined the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the phenotypic characteristics of macrophages and dendritic cells (DCs) derived from monocytes. Monocytes were obtained from healthy young volunteers and cultured with ePF (n=12) or a control PF (cPF) (n=5) in the presence or absence of macrophage-colony stimulating factor (M-CSF) or IL-4 plus granulocyte macrophage-colony stimulating factor (GM-CSF). The ePF was demonstrated to increase expression levels of CD14 and CD64 on isolated monocytes in the presence or absence of M-CSF. Compared with cPF, addition of 10% ePF to GM-CSF plus IL-4-treated monocytes significantly down-regulated CD1a expression and up-regulated CD64 expression, but did not enhance expression levels of class II MHC. ePF had no effect, however, on tumor necrosis factor-alpha-induced maturation of DC. Levels of IL-6, IL-10 and M-CSF production were higher in ePF-treated than cPF-treated monocytes for both cell culture conditions with GM-CSF plus IL-4 and M-CSF. A neutralizing IL-6 antibody, but not an IL-10 antibody, abrogated the ePF-induced down-regulation of CD1a, up-regulation of CD64 and secretion of M-CSF. These results suggest that ePF favorably induces monocyte differentiation toward macrophages rather than DCs, and that this effect is mediated by IL-6. A reciprocal mode of cell differentiation between macrophages and DCs in response to ePF may be related to the pathogenesis of endometriosis.

Nerve growth factor stimulates proliferation, adhesion and thymopoietic cytokine expression in mouse thymic epithelial cells in vitro.

Thymic epithelial cells, which constitute a major component of the thymic microenvironment, provide a crucial signal for intrathymic T cell development and selection. Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. NGF is increasingly recognized as a potent immunomodulator, promoting "cross-talk" between various types of immune system cells. The present study clearly shows that NGF stimulates mouse thymic epithelial cell activities in vitro including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7, GM-CSF, SDF-1, TARC and TECK. Thus, our data are of considerable clinical importance showing that trophic NGF activity could be used to enhance the thymus regeneration and develop methods to improve host immunity when the immune function is depressed due to thymic involution.

Effects of menopausal hormone therapy on uterine myoma in menopausal women.

OBJECTIVES: The aim of the present study is to evaluate the long term effects of estrogen-progestogen therapy (EPT) on uterine myomas volume in postmenopausal women. METHODS: We performed a retrospective analysis on postmenopausal women with asymptomatic uterine myoma during the period between April, 2008 and September, 2012. Postmenopause was defined as amenorrhea for longer than a year or serum follicle stimulating hormone levels higher than 40 IU/L. The volume of the myoma was assessed by transvaginal ultrasonography for every 6 months after administration of EPT. RESULTS: Thirty-eight women were included in the study, with 32 in the EPT group and 6 in the control group. Overall, uterine myoma volume (mean ± standard deviation, cm(3)) in the EPT group was 19.5 ± 24.6 at baseline, and those at 6 and 12 months were 24.7 ± 35.1 and 28.5 ± 56.4, respectively. Myoma volume did not change significantly with EPT, and these changes were not significantly different from the control group. Myoma volume changes were not significantly different in the subgroups according to the route of estrogen administrations and the method of progestogen administrations. Clinically significant volume increases during one year of EPT was noted in 28.1% (9/32), however, only one showed transient increases. CONCLUSION: Our results suggest that treating postmenopausal woman with EPT on a long-term basis does not increase the volume of uterine myomas.

The Relationship between Uterine Myoma Growth and the Endocrine Disruptor in Postmenopausal Women.

OBJECTIVES: To investigate the number of leiomyoma patients-exposed to bisphenol A (BPA) and to observe whether the serum concentration of BPA is related to leiomyoma growth. METHODS: A total of 158 patients were recruited for this study. Leiomyoma patients were divided into three groups, mild (n = 48), moderate (n = 32) and severe (n = 28), according to the size of leiomyomas. The control (n = 30) group was defined as having no leiomyomas. Transvaginal ultrasonography was used to identify and measure the leiomyomas. Serum BPA concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: BPA was detected in 87.0% out of a total of 158 samples, and in 86.0% out of 108 leiomyoma patients. In detail, the detection rates of serum BPA were 88.0% in the control group, 77.2% in the mild group, 90.0% in the moderate group and 96.0% in the severe group. The mean BPA concentration in the control group was 0.558 ± 0.097 ng/mL, the leiomyoma groups, the mean BPA concentrations were 0.274 ± 0.063 ng/mL (mild), 0.346 ± 0.064 ng/mL (moderate) and 0.647 ± 0.039 ng/mL (severe) (P = 0.0003). Values represent the mean ± standard error. CONCLUSION: The detection rates of serum BPA in the control and leiomyoma groups were 88.0% and 86.0%, respectively. However, there was no significant difference in the serum BPA concentrations between the control and leiomyoma groups. To verify the effect of BPA on leiomyoma growth, a close and sequential monitoring is recommended for people who are at risk for uterine leiomyoma.

Prediction of multiple pregnancies by the number of early cleaving embryos.

AIM: The aim of the present study was to investigate the number of early cleaving embryos as an effective predictor for multiple pregnancies in human in vitro fertilization (IVF). METHODS: The study analyzed early cleavage (EC) in 190 cycles of IVF. The EC of embryos to the two-cell stage was assessed at two time points, namely 25 and 27 h after insemination. Embryos that had cleaved at each time point were designated EC-1 and EC-2, respectively, whereas other embryos were designated as non-EC (NEC). The number of cycles with EC-1 embryos was not included in the results for the EC-2 group. RESULTS: Clinical pregnancy rates were significantly higher in the EC-1 group compared with the EC-2 and NEC groups (58.2%, 31.8% and 22.9%, respectively; P < 0.05). The pregnancy outcome was positively related to the number of EC-1 embryos. Multiple pregnancy rates were significantly increased up to 41.4% when the number of EC-1 embryos was two or more. CONCLUSIONS: The results confirm that 25 h after insemination is a more effective critical time point for the selection of EC embryos and that the number of EC embryos could be a useful parameter for the prediction of multiple pregnancies.

Effects of peritoneal fluid from endometriosis patients on the release of vascular endothelial growth factor by neutrophils and monocytes.

BACKGROUND: An increase in the level of the vascular endothelial growth factor (VEGF) production has been reported in the peritoneal fluid (PF) of endometriosis patients. This suggests that changes in the vascular permeability and angiogenesis play an important role in the pathophysiology of this disease. This study examined the effects of the PF obtained from endometriosis patients on the release of VEGF by neutrophils and monocytes. METHODS: Neutrophils and monocytes were obtained from young healthy volunteers and cultured with the PF obtained from either endometriosis patients (EPF) (n=18) or a control group (CPF) (n=4). A human monocyte/macrophage cell line, THP-1, was cultured with either 10% EPF or 10% CPF. The PF and culture supernatants were assayed for VEGF using ELISA. Real-time PCR and Western blotting were used to measure the VEGF mRNA and protein expression level, respectively. RESULTS: The VEGF levels were higher in the EPF than in the CPF (591+/-75 versus 185+/-31 pg/ml, P<0.05). However, the level of VEGF released by THP-1 cells in CPF and EPF was similar. The EPF induced the release of VEGF by neutrophils, but no VEGF was released by monocytes. The VEGF mRNA expression levels in the neutrophils were higher in the EPF, which was abrogated by cycloheximide, suggesting that the EPF induces the production of VEGF in neutrophils. Neutralizing antibodies against IL-8 and TNF-alpha did not completely prevent the EPF-induced release of VEGF by the neutrophils, even though these growth factors stimulated the release of VEGF by neutrophils. There was a positive correlation between the VEGF and IL-10 concentrations in the EPF (correlation coefficient=0.549, P=0.012, n=18), but the neutralizing antibody of IL-10 did not affect the release of VEGF by the EPF-treated neutrophils. CONCLUSION: The EPF induced the production and release of VEGF by neutrophils, suggesting that neutrophils may be a source of peritoneal VEGF. In addition, neutrophil-derived VEGF might be a marker for diagnosing endometriosis.

Modulation of neutrophil apoptosis by plasma and peritoneal fluid from patients with advanced endometriosis.

BACKGROUND: The increased production of pro-inflammatory chemoattractant cytokines for neutrophils in endometriosis suggests that changes in the immune system play an important role in the pathophysiology of endometriosis. The effects of plasma and peritoneal fluid from patients with advanced endometriosis on the apoptosis of neutrophils were investigated. METHODS: Apoptotic changes of neutrophils were evaluated by morphological changes using Giemsa staining. Apoptosis was confirmed by DNA electrophoretic analysis. RESULTS: Compared with the plasma (n = 20) and peritoneal fluid (n = 5) of healthy controls, the addition of 10% plasma (n = 20) and peritoneal fluid (n = 10) from patients with endometriosis to an in-vitro culture of neutrophils from healthy subjects reduced the percentage of apoptotic cells from 65.3 +/- 6.6 to 27.2 +/- 4.6% (P < 0.001) and from 45.3 +/- 4.8 to 10.5 +/- 4.3% (P < 0.001) respectively. Neutralizing interleukin-8 antibody abrogated the delay of neutrophil apoptosis induced by peritoneal fluid, but not in the plasma of endometriosis patients. CONCLUSIONS: These findings show that interleukin-8 is one of the neutrophil survival factors in the peritoneal fluid of endometriosis patients and that an unidentified survival factor is also present in the plasma of patients with endometriosis.