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Papers by Maria Antonietta Castaldi

Endometrial cancer in unicornuate uterus: a case report

PubMed, 2015

Purpose of investigation: Miillerian anomalies have not been implicated as a significant risk fac... more Purpose of investigation: Miillerian anomalies have not been implicated as a significant risk factor for the development of cervical, uterine, and ovarian cancers; in the present literature, there are only a few reports of endometrial cancer arising in patients with Miillerian abnormalities. To the best of the authors' knowledge, this is the first reported case of endometrial cancer arising in a patient with unicornuate uterus. Case report: A 69-year-old Caucasian woman underwent clinical examination and office hysteroscopy with endometrial biopsy because of abnormal post-menopausal bleeding. The diagnosis was endometrial cancer in unicornuate uterus, hence the patient underwent total hysterectomy with pelvic lymphadenectomy. Conclusion: Uterine malformations and genetic disorders may cause a delayed diagnosis of gynaecological cancers. Gynaecological examination in asymptomatic patients and differential diagnosis in abnormal uterine bleeding patients should be considered.

Nutrients, 2025

Background: Leptin, a protein predominantly produced by adipocytes, plays a crucial role in regul... more Background: Leptin, a protein predominantly produced by adipocytes, plays a crucial role in regulating energy balance, inflammation, immunity, and fetal growth. During pregnancy, maternal serum leptin levels increase, peaking in the second trimester, with placental production contributing to this rise. Leptin has also been identified in fetal tissues, and its concentration in umbilical cord blood correlates with birth weight. This study aimed to evaluate serum and umbilical cord blood leptin concentrations in rural Burundian women living in marginal nutritional conditions, and investigate potential gender differences in fetal leptin levels. Methods: We analyzed data from 38 healthy singleton pregnancies (20 male and 18 female newborns) delivered at Hôpital Autonome de Ngozi, Burundi. Leptin concentrations were measured in maternal and umbilical cord blood samples. Results: Our results revealed that neonatal leptin levels were significantly higher in female compared to male newborns, consistent with findings in other populations. Leptin concentrations in umbilical cord blood were positively correlated with neonatal birth weight and the Kaup index, while maternal leptin levels did not show such associations. Conclusions: Despite the challenging nutritional environment in this rural African setting, our findings suggest that leptin's role in fetal growth regulation may transcend maternal nutritional status. The gender difference observed in leptin levels could be linked to genetic or epigenetic factors rather than fat content or reproductive hormones. This study supports the notion that leptin may be an important regulator of fetal development, even in malnourished populations, and underscores the need for further research to elucidate its mechanisms in pregnancy.

Clinical and Experimental Medicine, Apr 5, 2024

Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutatio... more Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutations in circulating cell-free DNA (cfDNA). The aim of this study was to investigate feasibility, sensitivity, and specificity of non-invasive prenatal test (NIPT) for identification of chromosomal abnormalities in cfDNA from a total of 77 consecutive patients with non-Hodgkin B-cell lymphomas, Hodgkin lymphoma (HL), or plasma cell dyscrasia. In this case series, half of patients had at least one alteration, more frequently in chromosome 6 (23.1%), chromosome 9 (20.5%), and chromosomes 3 and 18 (16.7%), with losses of chromosome 6 and gains of chromosome 7 negatively impacting on overall survival (OS), with a 5-year OS of 26.9% and a median OS of 14.6 months, respectively (P = 0.0009 and P = 0.0004). Moreover, B-cell lymphomas had the highest NIPT positivity, especially those with aggressive lymphomas, while patients with plasma cell dyscrasia with extramedullary disease had a higher NIPT positivity compared to conventional cytogenetics analysis and a worse outcome. Therefore, we proposed a NIPT-based liquid biopsy a complementary minimally invasive tool for chromosomal abnormality detection in hematological malignancies. However, prospective studies on larger cohorts are needed to validate clinical utility of NIPTbased liquid biopsy in routinely clinical practice.

Journal of leukocyte biology, 2015

Mesenchymal stem cells from the Warton'Jelly of the human umbelical cord: biological properties and therapeutic potential

Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiat... more Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medi...

International Journal of Gynecology & Obstetrics, 2012

Frontiers in Endocrinology

In vivo (Athens, Greece)

During the woman's fertile period, the non-pregnant uterus is subject to constant cyclic chan... more During the woman's fertile period, the non-pregnant uterus is subject to constant cyclic changes. The complex mechanisms that control the balance among proliferation, differentiation, cell death and the structural remodeling of the extracellular matrix can contribute to the benign or malignant endometrial pathological state. The small leucine-rich proteoglycans (SLRPs) are important components of cell surface and extracellular matrices. Using immunohistochemistry, we showed that the distribution patterns of SLRPs were completely modified in the pathological compared to normal endometrium. The expression of SLRPs was low/absent in all endometrial pathologies examined compared to normal endometrium. We observed an increase of lumican from proliferative to secretory phase of the endometrium and a decrease of fibromodulin, biglycan and decorin. In menopause endometrial tissue, the level of expression of fibromodulin, biglycan, decorin and lumican dramatically decreased. The results ...

Clinical and Experimental Obstetrics & Gynecology, 2020

Objective: To evaluate gynaecological features of a group of transfusion dependent beta-thalassem... more Objective: To evaluate gynaecological features of a group of transfusion dependent beta-thalassemic women and to analyze their reproductive function with the morpho-functional features of genital female tract. Materials and Methods: Cross-sectional study in a University Hospital and Tertiary Care Center. Fifty-nine transfusion-dependent beta-thalassemic women in reproductive age, were divided into two groups: to group A were assigned women with spontaneous menarche (n=44), while to group B were allocated patients with inducted menarche. Data on demographic characteristics, iron overload in liver and heart (evaluated with T2* RMN method), chelation therapy, and reproductive function were collected. Difference in demographic characteristics, chelation therapy, iron status, and reproductive function between groups were assessed, together with correlation analysis of iron overload. Results: Patients in group B had a worse reproductive function and a higher myocardial iron overload, than patients in group A. Moreover multivariate logistic regression showed a significant correlation between uterine biometry, FSH, E2, parity and hearth iron T2*HSIV, but not with liver iron. Conclusion: The present data shows that myocardial iron loading could be putative of prolonged and severe iron overload in the female genital tract, impairing fertility and reproductive function in patients affected with beta-thalassemia major under chelation therapy.

Thalassemia and infertility

Human Fertility, 2016

Abstract Beta-thalassemia (BTM) major is the most common haemoglobin disorder in the world, with ... more Abstract Beta-thalassemia (BTM) major is the most common haemoglobin disorder in the world, with high prevalence in people of Mediterranean, Arab or Asian origin. It has been estimated that about 1.5% of the global population (80–90 million people) are carriers of BTM. In patients with BTM, long-term transfusion therapy for the correction of anaemia leads to toxic iron overload, resulting in significant morbidity including liver damage, cardiac complications and endocrine dysfunction. The commonest abnormality is hypogonadotropic hypogonadism, which presents with primary amenorrhoea, delayed puberty or secondary amenorrhoea with consequent infertility. Nevertheless, current improvements in the management of thalassemia disorders offer patients the possibility of having a regularly functioning reproductive system and increased chances of achieving a pregnancy. The aim of the present review is to analyse all aspects of fertility management in BTM women, by examining the main causes of infertility, in order to give practical tools to ensure a complete diagnostic work-up and discuss intervention options to guarantee maximum reproductive health.

Il dolore pelvico cronico e un’entita complessa, la cui natura e tuttora enigmatica e per il qual... more Il dolore pelvico cronico e un’entita complessa, la cui natura e tuttora enigmatica e per il quale esistono poche strategie terapeutiche universalmente efficaci. L’endometriosi e una patologia ginecologica, cronica e benigna, importante causa di dolore pelvico cronico, per la quale sono state sviluppate numerose terapie. L’obiettivo del nostro studio e stato valutare l’efficacia dell’ associazione di nuove molecole, l’ N-palmitoiletanolamide micronizzata e la transpolidatina, nel trattamento del dolore pelvico cronico correlato all’endometriosi. Materiali e metodi. Il presente studio, randomizzato e controllato, in doppio cieco a gruppi paralleli, ha coinvolto 54 pazienti con diagnosi laparoscopica di endometriosi suddivise in 3 gruppi di trattamento della durata di 3 mesi: associazione N-palmitoiletanolamide micronizzata e transpolidatina 200 mg + 20 mg 3 volte al giorno (gruppo A = 18 pz); placebo (gruppo B = 18 pz); singolo corso di Celecoxib 200 mg 2 volte al giorno (gruppo C = ...

Introduzione. La sindrome metabolica contribuisce in maniera rilevante al rischio cardiovascolare... more Introduzione. La sindrome metabolica contribuisce in maniera rilevante al rischio cardiovascolare nella postmenopausa e la disfunzione endoteliale gioca un ruolo rilevante nella patogenesi del danno cardiovascolare. L’influenza dell’HRT sulla funzione endoteliale e’ stata valutata in donne sane e con differenti tipologie di molecole, ma mancano dati sull’impatto di nuovi progestinici in donne affette da sindrome metabolica. Scopo dello studio e valutare gli effetti del drospirenone 2 mg in combinazione con estradiolo emidrato 1 mg su parametri di funzione endoteliale in donne in postmenopausa affette da sindrome metabolica. Materiali e metodi. Ventotto pazienti in postmenopausa di cui 14 sane (gruppo A) e 14 con sindrome metabolica (gruppo B) sono state trattate con drospirenone 2 mg ed estradiolo emidrato 1 mg per sei mesi. La funzione endoteliale nei due gruppi e stata valutata all’arruolamento e a fine terapia attraverso la misurazione della reattivita dell’arteria brachiale e de...

Scopo dello studio. Valutazione della relazione tra dolore ed endometriosi, ed in particolare la ... more Scopo dello studio. Valutazione della relazione tra dolore ed endometriosi, ed in particolare la possibile correlazione tra disturbi vescico-urinari e la quantita di fibre nervose e cellule gangliari resecate con l’intervento chirurgico laparoscopico per endometriosi profonda. Materiali e metodi. Studio retrospettivo su 230 donne con endometriosi severa e sottoposte ad intervento di chirurgia laparoscopica. Sede dello studio: Hopital de Hautpierre, Strasburgo e Seconda Universita di Napoli. Risultati. L’incidenza di ritenzione urinaria e stata del 4.5% (n=10). Assenza di differenze quantitative nel pattern di distribuzione di fibre nervose e cellule gangliari nei campioni resecati di entrambi i gruppi. Netto miglioramento della sintomatologia dolorosa in entrambi i gruppi, con peggioramento della disuria nelle pazienti con ritenzione urinaria post-operatoria. Conclusioni. Con la tecnica chirurgica nerve-sparing si e avuta una bassa incidenza di ritenzione urinaria; tuttavia non sono...

Obiettivi. Il nonilfenolo (NP) e un inquinante ubiquitario sia dell’ambiente acquatico che di que... more Obiettivi. Il nonilfenolo (NP) e un inquinante ubiquitario sia dell’ambiente acquatico che di quello terrestre. Tale composto e considerato un importante interferente endocrino e la sua attivita simil-estrogenica e stata investigata in numerosi studi in vivo e in vitro. Tuttavia, mentre gli effetti citotossici del NP sono conosciuti, i suoi effetti sulla morte cellulare non sono noti. Abbiamo deciso di evidenziare gli effetti del NP su cellule immortalizzate di adenocarcinoma endometriale (Hec1A), e in particolare gli effetti su ciclo cellulare e apoptosi. Materiali e metodi. Il ciclo cellulare e stato analizzato mediante citofluorimetria. Abbiamo evidenziato che il NP e in grado di inibire il ciclo cellulare e favorire l’apoptosi in maniera concentrazione- e tempo-dipendente, raggiungendo gli effetti maggiori alla concentrazione di 10-8 M per 48h. La citofluorimetria ha evidenziato che il NP e in grado di determinare il blocco delle cellule in fase G2/M e di incrementare la percent...

Obiettivi. I distruttori endocrini sono sostanze capaci di interferire con il sistema riproduttiv... more Obiettivi. I distruttori endocrini sono sostanze capaci di interferire con il sistema riproduttivo ed implicate nella patogenesi di patologie ginecologiche come l’endometriosi. I bisfenoli A e B (BPA e BPB) sono utilizzati nella sintesi della plastica ed ampiamente presenti nell’ambiente. L’obiettivo dello studio e valutare la correlazione tra esposizione a BPA e BPB e comparsa di endometriosi. Materiali e metodi. Attraverso analisi di HPLC e spettrometria di massa sono stati identificati e quantificati BPA e BPB nel siero di 51 donne sane e 58 con diagnosi laparoscopica di endometriosi. Risultati. I livelli di bisfenolo sono risultati inferiori al limite di quantificazione (LOQ) in tutte le 51 pazienti sane, mentre nelle pazienti affette da endometriosi il BPA e stato ritrovato in 30 soggetti ed il BPB in 16, sebbene sia stato possibile quantificarli, rispettivamente, solo in 15 e 10 campioni nei quali il livello degli analiti era superiore al LOQ. Conclusioni. Questi risultati sug...

International Journal of Stem Cells, 2019

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiat... more Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.

Journal of Ovarian Research, 2016

In 1963 George Mathé announced to the world that he had cured a patient of leukaemia by means of ... more In 1963 George Mathé announced to the world that he had cured a patient of leukaemia by means of a bone-marrow transplant. Since than much progress has been made and nowadays Hematopoietic Stem Cell Transplantation (HSCT) is considered the most effective treatment of numerous severe haematological diseases. Gynaecological complications in HSCT women represent a serious concern for these patients, but often underestimated by clinicians in the view of Overall Survival. The main gynaecological complications of HSCT are represented by: premature ovarian failure (POF), thrombocytopenia-associated menorrhagia, genital symptoms or sexual problems in course of chronic GVHD (cGVHD), osteoporosis, secondary solid tumours due to immunosuppressive drugs to treat cGVHD and severity of cGVHD, and fertility and pregnancy issues. In particular fertility-related issues are always more relevant for patients, whose life expectation is constantly growing up after HSCT. Thus, taking care of a patient undergoing HSCT should primarily include gynaecological evaluation, even before conditioning regimen or chemotherapy for the underlying malignancy, as, in our opinion, it is of great importance to ensure a complete diagnostic work-up and intervention options to guarantee maximum reproductive health and a better quality of life in HSCT women. The present review aims at describing principal features of the aforementioned gynaecological complications of HSCT, and to define, on the basis of current international literature, a specific protocol for the prevention, diagnosis, management and follow-up of gynaecological complications of both autologous and heterologous transplantation, before and after the procedure.

Triclosan and bisphenol a affect decidualization of human endometrial stromal cells

Molecular and Cellular Endocrinology, 2016

In recent years, impaired fertility and endometrium related diseases are increased. Many evidence... more In recent years, impaired fertility and endometrium related diseases are increased. Many evidences suggest that environmental pollution might be considered a risk factor for endometrial physiopathology. Among environmental pollutants, endocrine disrupting chemicals (EDCs) act on endocrine system, causing hormonal imbalance which, in turn, leads to female and male reproductive dysfunctions. In this work, we studied the effects of triclosan (TCL) and bisphenol A (BPA), two widespread EDCs, on human endometrial stromal cells (ESCs), derived from endometrial biopsies from woman not affected by endometriosis. Cell proliferation, cell cycle, migration and decidualization mechanisms were investigated. Treatments have been performed with both the EDCs separately or in presence and in absence of progesterone used as decidualization stimulus. Both TCL and BPA did not affect cell proliferation, but they arrested ESCs at G2/M phase of cell cycle enhancing cell migration. TCL and BPA also increased gene expression and protein levels of some decidualization markers, such as insulin growth factor binding protein 1 (IGFBP1) and prolactin (PRL), amplifying the effect of progesterone alone. All together, our data strongly suggest that TCL and BPA might alter human endometrium physiology so affecting fertility and pregnancy outcome.

Biomechanical features of bidirectional-barbed suture: a randomized laboratory analysis

Surgical technology international, 2014

The aim of the current prospective study was to evaluate the biomechanical stability of barbed su... more The aim of the current prospective study was to evaluate the biomechanical stability of barbed suture vs. conventional suture. Biomechanical stability of a 14x14-cm PDO/polydioxanone, with a half circle and 36-mm needle, bidirectional barbed 0-Quill suture (Angiotech, Vancouver, British Columbia, Canada) vs. 1-Poliglecaprone 25 (Monocryl, Ethicon, Inc, Somerville, NJ) suture was evaluated on biological specimens. The 1-Monocryl suture was chosen because it is widely used by gynecological surgeons in the repair either of the vaginal cuff or the uterine wall defects. Forty specimens of aponeurotic muscle, obtained from abdominal wall of a lamb, were prepared, and randomly assigned to 1 of 2 repair groups: Group A (n = 20) classic repair with 1-Monocryl suture; Group B (n = 20) 0-Quill barbed suture. Each specimen was transected at the midpoint and then repaired. Biomechanical stability of the repaired specimen was verified on a CMT6000 electromechanical universal testing machine (SANS...