Carlo Ticconi

Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe.

Objective: To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. Methods: Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. Results: The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7%, respectively. HIVinfected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96, 95% confidence interval (CI): 2.42‐6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74, 95% CI: 1.34‐16.78) and preterm delivery (OR = 4.10, 95% CI: 2.17‐7.75), respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09, 95% CI: 6.50‐15.65; HIV: OR = 3.16, 95% CI: 1.80‐5.54) and very low birth weight (malaria: OR = 5.04, 95% CI: 1.00‐25.43; HIV: OR = 10.74, 95% CI: 2.1254.41), low Apgar score (malaria: OR = 4.45, 95% CI: 1.42‐13.94; HIV: OR = 5.94, 95% CI: 1.66‐21.30), and fetal growth restriction (malaria: OR = 3.98, 95% CI: 2.51‐6.30; HIV: OR = 4.07, 95% CI: 2.40‐6.92). Dual infection with malaria and HIV was associated with increased risk of maternal, perinatal, and early infant death. Conclusions: Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist.

Macrophage Migration Inhibitory Factor in Human Pregnancy and Labor

PROBLEM: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in reproduction. Presently there is no information on the possible involvement of MIF in the onset of labor.

Antinuclear Autoantibodies in Women with Recurrent Pregnancy Loss

Citation Ticconi C, Rotondi F, Veglia M, Pietropolli A, Bernardini S, Ria F, Caruso A, Di Simone N. Antinuclear autoantibodies in women with recurrent pregnancy loss. Am J Reprod Immunol 2010; 64: 384–392

Thyroid autoimmunity and recurrent miscarriage

Citation Ticconi C, Giuliani E, Veglia M, Pietropolli A, Piccione E, Di Simone N. Thyroid autoimmunity and recurrent miscarriage. Am J Reprod Immunol 2011; 66: 452–459

Role of type I collagen C telopeptide, bone-specific alkaline phosphatase and osteocalcin in the assessment of bone status in postmenopausal women.

Aim:  To investigate the clinical role of the bone turnover markers type I collagen C telopeptide (CTX), osteocalcin (OC) and bone‐specific alkaline phosphatase (BAP) in the assessment of bone status in women with postmenopausal osteoporosis.

Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor-α and transforming growth factor-β 1 output

Inflammatory cytokines can play an important role in the biomolecular processes leading to labour by regulating prostaglandin production in intrauterine tissues. In the setting of intrauterine infection, an increased production of these cytokines by placenta, decidua and fetal membranes occurs and is responsible for the onset and maintenance of preterm labour. However, the factors involved in the control of cytokine release by these tissues in normal pregnancy at term are still largely unknown. We investigated the possibility that the synthesis and release of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) by human fetal membranes at term gestation is regulated by several hormones potentially involved either in the maintenance of pregnancy or in the parturitional process. In the present study, the effects of hydrocortisone, progesterone and oxytocin on TNF-alpha and TGF-beta1 release by explants of fetal membranes at term gestation were evaluated. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the effect of the above hormones on mRNA expression; TNF-alpha and TGF-beta1 release in culture medium was quantitifed by ELISA assays. Results show that both tissue mRNA expression for TNF-alpha and TNF-alpha release in culture medium were significantly increased by oxytocin, but not by hydrocortisone and progesterone. On the contrary, all the hormones tested increased both tissue TGF-beta1 mRNA expression and release in culture medium. These findings suggest that TNF-alpha and TGF-beta1 production by human fetal membranes in uncomplicated pregnancy at term is selectively modulated by oxytocin, hydrocortisone and progesterone.

Thrombin-activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.

OBJECTIVE To investigate the possible association between selected thrombin-activatable fibrinolysis inhibitor (TAFI) single nucleotide polymorphisms (SNPs) and recurrent pregnancy loss (RPL). DESIGN Case-control study. SETTING University hospital. PATIENT(S) One hundred fifty-eight women (86 cases and 72 controls). INTERVENTION(S) Determination of TAFI SNPs -438A/G, +505A/G, +1040T/C, +1542C/G, and +1583A/T by polymerase chain reaction (PCR) reactions and sequencing analysis performed on peripheral blood samples. MAIN OUTCOME MEASURE(S) Analysis of the genotype and allele frequencies of TAFI SNPs -438A/G, +505A/G, +1040T/C, +1542C/G, and +1583A/T in women with and without RPL. RESULT(S) Genotype and allele frequencies of TAFI +505 and +1583 SNPs were significantly different in women with RPL compared with control women. The frequencies of the +505A/A and +505G/G genotypes were 1.2% and 61.6% in women with RPL and 13.9% and 43.1% in control women, respectively. The frequencies of the +1583A/A and +1583T/T genotypes were 1.2% and 61.6% in women with RPL and 13.9% and 45.8% in control women, respectively. The genotype and allele frequencies at TAFI position -438, +1040, and +1542 were not significantly different between RPL and control women. CONCLUSION(S) The SNPs leading to increased TAFI levels are associated with a reduced risk of RPL. It is possible that TAFI is involved in RPL.

Regulation of phosphodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin

Objectives: This study has a twofold aim: 1) to investigate whether protein expression and enzyme activity of phosphodiesterase 4 (PDE5) can be detected in human myometrium and undergo changes in relation to the presence of pregnancy and/or labor; 2) to evaluate whether PDE 5 expression and activity in myometrial cells can be influenced by human chorionic gonadotropin (HCG). Methods: Primary cultures of myometrial cells, obtained from non-pregnant women and from pregnant women at tem, either before or during labor, were carried out in the presence of HCG or dibutyryl-cyclic AMP (ad-cAMP), the non-hydrolizable analogue of cAMP. PDE5 expression in cultures of myometrial cells was detected by immunocytochemistry and western blot. PDE5 activity was detected in cell extracts by enzyme assay. Results: PDE5 is expressed and is functionally active in smooth myscle cells. Treatment of cell cultures with HCG and db-cAMP results in a reduction of PDE5 expression and activity. The effects of HCG and db-cAMP are exerted irrespective of the functional status of the myometrium (n0n-pregnant, pregnant not in labor, pregnant in labor). Conclusions: PDE5 protein is expressed in human non-pregnant and pregnant myometrium. HCG reduces PDE5 expression and enzyme activity in smooth muscle cells, possibly through a pathway involving cAMP

Preoperative Administration of Recombinant Human Erythropoietin in Patients Undergoing Gynecologic Surgery

The effect of preoperative recombinant human erythropoietin (r-HuEPO) in anemic women undergoing gynecologic surgery for benign diseases was evaluated in this prospective, not randomized study. One hundred and twenty women were included in the study. Sixty women were treated preoperatively with r-HuEPO at three different cumulative doses: 80,000, 120,000 and 160,000 IU. Sixty nonanemic women were not treated. Baseline hemoglobin (Hb) levels were measured. Hb levels were also measured on the day of the surgery before starting the procedure, on postoperative day 1 and on the day of discharge from the hospital. Treatment with r-HuEPO significantly increased both preoperative Hb levels and Hb levels at discharge. Conversely, Hb levels at discharge were lower than baseline levels in untreated women. The effect of r-HuEPO on Hb levels was exerted in a dose-dependent fashion. No adverse and/or side effects of treatment were observed. Preoperative treatment with r-HuEPO in selected anemic patients undergoing gynecologic surgery for benign diseases seems to be a safe and useful tool to reduce the need for red blood cell transfusions.

Estrogen Replacement Therapy and asthma

A growing body of clinical and experimental evidence indicates that female sex hormones, particularly estrogen, have significant effects on normal airway function as well as on respiratory disorders, such as asthma. These effects are very complex and are exerted at several levels, directly on airway reactivity or indirectly through regulation of the immune and inflammatory responses in the lung. They can have relevant clinical implications not only according to the phases of the reproductive life in women, but also in relation to the therapeutical administration of estrogen, as in the case of menopausal hormone therapy. Clinical evidence suggests that administration of estrogen to menopausal women is associated with increased rates of newly diagnosed asthma. Conversely, functional studies show that estrogen can improve objective indexes of respiratory functionality.