Papers by Michael Koutsilieris
Biomolecules, Dec 19, 2023
Endometriosis is a benign, estrogen-dependent gynecological condition with an uncertain exact pat... more Endometriosis is a benign, estrogen-dependent gynecological condition with an uncertain exact pathogenetic mechanism. The aim of this study was to evaluate the potential differential expression of Insulin Growth Factor 1 (IGF-1) isoforms in deeply infiltrating endometriotic (DIE) lesions, in ovarian endometriomas, and in the eutopic endometrium of the same endometriosis patients and to compare their expression with that in the eutopic endometrium of women without endometriosis. A total of 39 patients were included: 28 with endometriosis, of whom 15 had endometriomas only, 7 had DIE nodules only, and 6 had both DIE and endometriomas, and 11 without endometriosis served as controls. We noticed a similar pattern of expression between IGF-1Ea and IGF-1Ec, which differed from that of the IGF-1Eb isoform, possibly implying differential biological actions of different isoforms in DIE subtypes. We observed a tendency of lower expression of IGF-1Ea and IGF-1Ec in endometriomas without DIE compared to endometriomas with concurrent DIE or in DIE nodules. In conclusion, differential expression of IGF-1 isoforms may indicate that DIE with its associated ovarian lesions and simple ovarian endometriosis should be considered as two forms of the disease developing under different molecular pathways.
PubMed, Jul 1, 1996
We analyzed the expression of plasminogen activator inhibitor 1 (PAI-1) in 16 leiomyomas and adja... more We analyzed the expression of plasminogen activator inhibitor 1 (PAI-1) in 16 leiomyomas and adjacent myometrium of women who underwent a hysterectomy while in the proliferative (n = 8) and secretory phases (n = 8) of the menstrual cycle. We localized the PAI-1 and its mRNA expression in smooth muscle and vessel endothelial cells of uterine tissues using immunocytochemistry and in situ hybridization. The expression of PAI-1 mRNA was higher in 11 (68.75%) of 16 leiomyomas compared with the adjacent myometrium (leiomyoma/myometrium ratio, 1.4-3.0; mean, 2.045). The leiomyoma:myometrium ratio of PAI-1 mRNA expression did not change during the proliferative (Phase I) and secretory (Phase II) phases of the menstrual cycle. In the remaining five samples, the leiomyoma:myometrium ratio of PAI-1 mRNA expression was close to 1 (0.8-1.2; mean, 0.92). Because the locus of the PAI-1 gene is on chromosome 7q22, we screened for loss of heterozygosity (LOH) in these samples using the PAI-1 marker and D7S471, an anonymous marker 12 cM telomeric to PAI-1. Four of five samples with low leiomyoma:myometrium ratio had LOH for the PAI-1 and/or D7S471 markers. The fifth sample demonstrated a noninformative analysis for these markers but had LOH for the D7S515, D7S666, and D7S518 markers, all centromeric to PAI-1. Because del(7)(q22), associated with a relatively low PAI-1 mRNA expression, can deregulate matrix proteinases and growth factors' activity in leiomyomas, it is conceivable that del(7)(q22) results in heterogeneous leiomyoma biology.
PubMed, Feb 3, 2009
Skeletal muscle regeneration is a highly synchronized process involving the activation of various... more Skeletal muscle regeneration is a highly synchronized process involving the activation of various cellular and molecular events, coordinating inflammation and regeneration processes which are crucial for the beneficial outcome of tissue remodeling. Fibrosis, a failure of tissue remodeling, is initiated with muscle regeneration; however, it is the result of an excessive inflammatory response, representing an imbalance between enhanced production and deposition and impaired degradation of extracellular matrix (ECM) components of the muscle. Therefore, factors influencing the relative degree of muscle fiber regeneration as compared to the amount of scar formation have a critical role in functional muscle remodeling. Herein we have focused on the role of urokinase-type plasminogen activator (uPA) and transforming growth factor beta 1 (TGF/1) in ECM degradation and reconstitution in muscles.
Proteinolytic activity against IGF-binding proteins involved in the paracrine interactions between prostate adenocarcinoma cells and osteoblasts
PubMed, May 1, 1992
PA-III rat prostate adenocarcinoma cells are capable of inducing osteoblastic reaction after inoc... more PA-III rat prostate adenocarcinoma cells are capable of inducing osteoblastic reaction after inoculation onto rat skeleton. In this study PA-III cells and osteoblast-derived rat osteosarcoma cells (UMR 106 cells) were employed to characterize the cellular interactions in the PA-III cell-induced bone tumors, in vitro. Insulin-like growth factor-I (IGF-I) and conditioned media (CM) of UMR 106 cells stimlated tritiated-thymidine incorporation into the DNA of PA-III cells growing in serum-free media. This effect was inhibited by monoclonal anti-hIGF-I antibody. In addition PA-III cell CM contained proteinolytic activity for the IGF-binding proteins of UMR 106 cell CM (IGFBP-1 and -2). This proteinase activity hydrolyzed also benzyloxycarbonyl-lysine thiobenzyl ester (BLT) and its action on IGFBPs and BLT was inhibited by benzamidine and aprotinin. Proteinase activity of PA-III cell CM when bound covalently to tritiated-dilsopropylfluoro-phosphate (DFP) and then analyzed on SDS-PAGE gel electrophoresis, revealed the presence of radioactivity linked with a 35 kDa protein band. This proteinase was eluted in the void volume of the G-50 sephadex column and was retained on and eluted from p-benzamidine affinity column. The 35 kDa proteinase was retained on and was eluted from cartridges of the C18 silica by 80% acetonitrile over 0.1% trifuroacetic acid. This partially purified material hydrolyzed BLT substrate and IGFBPs of UMR 106 cell CM and its effect was inhibited by benzamidine and aprotinin. These data indicate that PA-III cell CM contains a 35 kDa proteinase capable of digesting the IGFBPs and thus increases the bioavailability of osteoblast-derived IGFs. This mechanism may participate in the pathophysiology of the PA-III cell-induced bone tumor and its subsequent osteoblastic reaction.
Cell Transplantation, Jul 4, 2019
Since the introduction of autologous platelet-rich plasma (PRP) in medical practice, various stud... more Since the introduction of autologous platelet-rich plasma (PRP) in medical practice, various studies have documented that implementing PRP can enhance healing and the anti-aging process, employing angiogenesis regeneration due to the multiple growth factors and cytokines involved. Numerous reports have shown promising results with the use of PRP in ovarian treatment, regarding ovarian regeneration and reactivation of folliculogenesis. This case series reports on two women with premature ovarian failure (POF) aged 40 and 27 years, respectively, and one menopausal woman aged 46 years. All patients presented with lack of menstrual cycle for over a year. The women reported previous failed in vitro fertilization (IVF) attempts, and, after rejecting the option of oocyte donation, they opted for the approach of autologous ovarian PRP treatment. Following PRP treatment, the three patients were invited to conceive naturally. The primary outcome was the restoration of menstruation following autologous ovarian PRP treatment, as well as an improvement in hormonal profile, a decrease in follicle-stimulating hormone (FSH) levels, and a concurrent increase in anti-Mu ¨llerian hormone (AMH) levels. Further to that, our patients achieved pregnancy through natural conception within 2-6 months following PRP treatment, resulting in currently ongoing complication-free clinical pregnancies -a first report in the literature for menopausal and POF patients. Implementation of PRP should be further investigated through randomized controlled trials (RCTs), as it may hold the key to successful treatment for a certain cohort of patients exploring reproductive treatment options following menopause.
Mediterranean Journal of Rheumatology, 2022
Since its discovery, vitamin D was shown to have both immunostimulatory and immunomodulatory effe... more Since its discovery, vitamin D was shown to have both immunostimulatory and immunomodulatory effects on the immune system. A growing body of evidence so far linked vitamin D deficiency with the development and severity of several systemic and organ specific autoimmune/inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In the present report, the multiple and diverse effects of vitamin D on the immune system are reviewed.
Journal of Assisted Reproduction and Genetics, May 20, 2019
Purpose The present systematic review and network meta-analysis aims to uniquely bring to literat... more Purpose The present systematic review and network meta-analysis aims to uniquely bring to literature data supporting the true place of the alternative practice of day-4 embryo transfer (D4 ET) in an IVF laboratory, beyond the one-dimensional option of facilitating a highly demanding program. Methods A systematic search was conducted in the databases of PubMed/Medline, Embase, and Cochrane Central Library, resulting to six prospective along with nine retrospective cohort studies meeting eligibility criteria for inclusion. A comparison of D4 ET with day-2 (D2), day-3 (D3), and day-5 (D5) ET, respectively, was performed employing R statistics. The sourced results indicate no statistically significant difference regarding clinical pregnancy rates, and ongoing pregnancy/live birth rates stemming from the comparison of D4 with D2, D4 with D3, and D4 with D5 ET, respectively. Additionally, no statistically significant difference could be established in respect to cancelation, and miscarriage rates, following the comparison of D4 with D3 and D4 with D5 ET. Interestingly, we report statistically significant lower preterm birth rates associated with D4 ET, in contrast with D5 ET (RR, 0.19; 95% CI, 0.05-0.67; p value = 0.01). Conclusions The aforementioned results may serve as advocates buttressing the option of D4 ET as a valid candidate in the ET decision-making process. Possible limitations of the current study are the publication bias stemming from the retrospective nature of certain included studies, along with various deviations among studies' design, referring to number and quality of transferred embryos, or different culture conditions referring to studies of previous decades.
European Respiratory Journal, Sep 1, 2012
Body: Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes... more Body: Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep, which leads to the presence of excessive daytime sleepiness. Regarding the psychological comorbidity in patients diagnosed with OSAS, previous studies focused mainly on depressive and, secondarily, to anxiety symptoms. Aims and Objectives: To record the prevalence of anxiety and depressive symptoms and of alexithymic characteristics in a sample of OSAS patients and to investigate their relation to respiratory parameter (Apnea -Hypopnea Index, AHI) of polysomnography. Methods: The study was conducted in a certified sleep laboratory. 35 randomly selected patients were examined for anxiety, depression and alexithymia using the Spielberger Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI) and the Toronto Alexithymia Scale (TAS-20), respectively. Results: A high prevalence of anxiety (41.4%) and depressive symptoms (55.2%) and of alexithymic characteristics (41.4%) was observed in OSAS patients. Although the control group showed a higher prevalence of anxiety (66.7%) and depressive (83.3%) symptoms, there were no differences between the two groups (t-test p> 0.05). With regard to severity, no differences were observed between subgroups (mild, moderate and severe OSAS, ANOVA p> 0.05). Women showed higher scores in BDI and STAI compared to men (t-test p <0.05). Finally, no correlation was observed between psychometric scores and AHI (Pearson correlation p> 0.05). Conclusions: This study supports the presence of a high degree of psychological burden on patients diagnosed with OSAS, regardless of the severity, as determined by the AHI.
Purpose The aim of this study was to investigate whether the presence of benign or malignant nodu... more Purpose The aim of this study was to investigate whether the presence of benign or malignant nodular thyroid disease affects levels of circulating angiogenesis cytokines. Methods In this study we investigated levels of angiopoietin – 1 and − 2 (Ang-1 and Ang-2 respectively), vascular endothelial growth factor –A (VEGF-A), galectin-3 (Gal-3), urokinase plasminogen activator receptor (uPAR) and plasminogen activation inhibitor – 1 (PAI-1) in 40 patients with differentiated thyroid cancer (DTC), 45 with thyroid papillary microcarcinoma (mPTC), 53 patients with multinodular goiter (MNG) and 58 controls. Six months after surgery 28 patients resubmitted blood samples. Results: Statistically significant lower levels of Ang-1 were observed in DTC, mPTC and MNG patients compared to controls (p < .05, p < .05 and p < .001 respectively). No significant differences were observed in the levels of the other factors. A significant increase in Ang-1 levels (p < .05) was documented in th...
Scientific Reports
The aim of this study is the development of a prediction model indicating successful application ... more The aim of this study is the development of a prediction model indicating successful application of Oocyte Retrieval performed during the Luteal Phase (LuPOR) in poor responders, as defined by the retrieval of at least one MII oocyte. Recruitment included 1688 poor responders diagnosed as per Bologna Criteria, undergoing natural cycle ICSI between 2012 and 2020. Oocyte collections were performed during the follicular phase and during the luteal phase similarly. Antral Follicle Count (AFC), Estradiol (E2) levels evaluated on both trigger days prior to Follicular Phase Oocyte Retrieval (FoPOR) and LuPOR, and the number of small follicles 8–12 mm that were not aspirated during FoPOR were identified as predictive factors indicative of an efficient LuPOR practice with an Area Under the Curve (AUC) of 0.86, 0.86, 0.89 as well as 0.82 respectively. The combination of the above-mentioned characteristics into a prediction model provided an AUC of 0.88, specificity and a sensitivity of 0.73 a...
Mediterranean Journal of Rheumatology
Vitamin D is an agent involved in bone and mineral homeostasis. It has been recognized as a poten... more Vitamin D is an agent involved in bone and mineral homeostasis. It has been recognized as a potent immunomodulator. It has immune-enhancing properties, and it induces immune tolerance. Vitamin D deficiency has been shown to be related to the development of autoimmune disorders. Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and it has been shown to be related with disease activity. Vitamin D deficiency has also been found in patients with systemic lupus erythematosus (SLE) and it was shown to be related to disease activity and renal involvement. Vitamin D deficiency has also been observed in multiple sclerosis. Vitamin D has been found to act as a supplemental therapeutic agent in multiple sclerosis. Sjögren's syndrome is a systemic autoimmune disease affecting the exocrine glands, known as an autoimmune epithelitis. The disease has a complex pathogenesis, requiring a genetic background, immune cell activation, and autoantibody production. The disease affects the exocrine glands, lacrimal, and salivary glands leading to ocular and oral dryness. Vitamin D levels have been measured in patients with Sjögren's syndrome and an association was observed between low vitamin D levels, peripheral neuropathy and the presence of lymphoma. In other cohorts, such as a Turkish cohort, vitamin D deficiency was observed in patients with Sjögren's syndrome. The aim is to measure serum vitamin D levels in consecutive patients with primary Sjögren's syndrome and investigate the relationship between vitamin D levels and the presence of immunologic markers, clinical, serological, and histopathological characteristics.
European Respiratory Journal, 2012
Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of up... more Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep, which leads to the presence of excessive daytime sleepiness. Regarding the psychological comorbidity in patients diagnosed with OSAS, previous studies focused mainly on depressive and, secondarily, to anxiety symptoms. Aims and Objectives: To record the prevalence of anxiety and depressive symptoms and of alexithymic characteristics in a sample of OSAS patients and to investigate their relation to respiratory parameter (Apnea - Hypopnea Index, AHI) of polysomnography. Methods: The study was conducted in a certified sleep laboratory. 35 randomly selected patients were examined for anxiety, depression and alexithymia using the Spielberger Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI) and the Toronto Alexithymia Scale (TAS-20), respectively. Results: A high prevalence of anxiety (41.4%) and depressive symptoms (55.2%) and of alexith...
Resilience of the hellenic navy SEALs assessed by heart rate variability during cognitve tasks
European Heart Journal, 2021
Background The interaction between high physical performance under extreme conditions and simulta... more Background The interaction between high physical performance under extreme conditions and simultaneous control of the cognitive executive functioning has been a subject of research in literature for the past few decades. Stroop test and Heart-rate variability (HRV), have been verified clinical tools for the assessment of cerebral and autonomic/ cardiovascular stress responses respectively. Purpose The investigation of HRV adaptive response to stress and cognitive stress resilience under extremely strenuous conditions. Methods 34 consecutive subjects were enrolled. Of them, 18 were candidates under intense preparation for their enlistment in the Hellenic Navy SEALs (HNS) and 16 were healthy controls (HC). All subjects underwent stroop tasks, along with mental state and personality examination. HRV variables in time and frequency domains recordings were acquired, during each aforementioned cognitive testing procedure. Results HNS's performance on both cognitive and emotion stroop ...
Progressive Day-to-Day Dehydration Of Elite Soldiers During SEAL School Training
Medicine & Science in Sports & Exercise, 2021
Frontiers in Cell and Developmental Biology, 2021
Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impair... more Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impairing fertility dynamics. The three distinct classifications of ovarian insufficiency are poor ovarian response, premature ovarian insufficiency/failure, and advanced maternal age, sharing the common denominator of deteriorated ovarian reserve. Despite efforts to define clear lines among the three, the vast heterogeneity and overlap of clinical characteristics renders their diagnosis and management challenging. Lack of a consensus has prompted an empirically based management coupled by uncertainty from the clinicians’ perspective. Profiling of patients in the era of precision medicine seems to be the way forward, while the necessity for a novel approach is underlined. Implicating miRNAs in the quest for patient profiling is promising in light of their fundamental role in cellular and gene expression regulation. To this end, the current study sets out to explore and compare the three pathop...
Poster presentations, 2020
BioMed Research International, 2018
Surrogacy is an assisted reproduction-based approach in which the intended parents assign the ges... more Surrogacy is an assisted reproduction-based approach in which the intended parents assign the gestation and birth to another woman called the surrogate mother. The drivers of surrogacy refer largely to infertility, medical conditions, same-sex couples’ parenting, and cases of diversity regarding sexual identity and orientation. Surrogacy consists of a valid option for a variety of conditions or circumstances ranging from medical to social reasons. However, surrogacy may be associated with risks during the preimplantation, prenatal, and neonatal period. It became obvious during the exhaustive literature research that data on surrogacy and its association with factors specific to the IVF practice and the options available were not fully represented. Could it be that surrogacy management adds another level of complexity to the process from the ovarian stimulation, the subsequent IVF cycle, and the techniques employed within the IVF and the Genetic Laboratory to the fetal, perinatal, an...
Scientific Reports, 2020
The aim of this study is to assess the value of laparoscopy for couples diagnosed with mild male ... more The aim of this study is to assess the value of laparoscopy for couples diagnosed with mild male factor infertility and at least three previous failed In-Vitro Fertilization (IVF) attempts. A total of 169 couples were included in this prospective cohort study. Patients were presented with the option of being subjected to laparoscopic investigation for correction of previously unidentified endometriosis or pelvic adhesions. The outcome measures were Live Birth/Ongoing Pregnancy, clinical pregnancy and positive hCG rate. One-hundred and one of them opted for, whereas 68 opted against laparoscopic investigation. All patients proceeded with a single ICSI cycle. Following laparoscopic investigation, 43 patients were diagnosed with endometriosis, 22 with adhesions, while for 36 patients laparoscopic investigation provided no further diagnosis. No statistically significant differences were observed regarding baseline hormonal levels and other characteristics between the two groups and the ...
Abstracts Accepted for Publication, 2019
The corresponding ORs [95%CI] in the dominant model were 0.38 [0.17-0.82] and 0.48 [0.25-0.92], r... more The corresponding ORs [95%CI] in the dominant model were 0.38 [0.17-0.82] and 0.48 [0.25-0.92], respectively. No statistically significant associations between fatigue status and other SNPs tested were detected. We report novel associations between genetic makeup and primary SS-associated fatigue with the rs9514828 and rs1224141 BAFF T/T genotypes decreasing the likelihood of fatigue development among these patients. These findings need to be validated in multi-center studies.
In Vivo, 2019
Background/Aim: Patients diagnosed with chronic endometritis (CE) may fail to respond to standard... more Background/Aim: Patients diagnosed with chronic endometritis (CE) may fail to respond to standard antibiotic treatment. The driver behind the approach reported here was the imperative need for alternative therapeutic solutions. Case Report: This case report presents a woman with CE and premature ovarian insufficiency having experienced repeated implantation failures following donated embryo transfers. The patient was diagnosed with CE through hysteroscopy, microbiological analysis and scanning electron microscopy. Following the suggested antibiotic treatment, she underwent a new embryo transfer, but with subsequent pregnancy loss. Following a second antibiotic scheme, all diagnostic procedures certified the persistence of CE. The patient underwent autologous, intrauterine platelet-rich plasma treatment and a subsequent embryo transfer. The diagnostic procedures indicated no signs of CE, while the embryo transfer resulted in a twin pregnancy and birth. Conclusion: Platelet-rich plasma may be employed as a first-line CE treatment, especially for patients who fail to respond to conventional antibiotic schemes. Chronic endometritis (CE) is a persistent inflammatory condition of the inner lining of the uterine cavity. It is characterized by infiltration of plasma cells and lymphocytes present in the endometrial stroma, increased cell density of the stroma, asynchronous maturation of epithelial cells and stromal fibroblasts, as well as by superficial mucosal oedema. The inflammation is often asymptomatic or oligosymptomatic with abnormal uterine bleeding and vaginal discharge, lower abdominal pain, fever, leukorrhea and menstrual dysfunction (1). A growing body of evidence points to patients with endometriosis presenting more frequently with CE further associated with infertility of unknown aetiology, unexplained repeat pregnancy losses and repeat embryo implantation failures following in vitro fertilization (IVF) treatments (2-5). Endometrial receptivity in CE can be defined as dysfunctional, since the local expression of numerous genes encoding cytokines, chemokines, apoptotic proteins and adhesion molecules is dysregulated (6-8). On the subject of CE and implantation failure, decidualization and the mechanism of its modification may provide an explanation. The process of decidualization takes place in endometrial stromal cells. Decidua differentiates to maintain pregnancy, while it produces growth factors, hormones and cytokines (9). Its role may be pivotal in regulating trophoblast invasion and the challenge presented by the maternal immune system . Therefore, the association between CE and implantation failure may be provided given the role of the decidua on implantation and the fact that CE appears to modify the process of decidualization (9). CE is considered to be attributed to ascending infection caused by organisms of the indigenous vaginal flora, sexually-transmitted infections, and tuberculosis, as well as through medical procedures that enable a pathway for bacteria to enter the uterus through the cervix. In the 515 This article is freely accessible online.
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Papers by Michael Koutsilieris