Fetal growth in hypertensive women]

The Authors examine the correlation between hypertensive disorders of pregnancy and fetal growth. The results of a study of 342 pregnancies, confirm a significant correlation between hypertension and fetal growth retardation. These findings, so evident in moderate and severe hypertension, have also been confirmed in cases of mild hypertension. The medical treatment also in the pregnancies with mild hypertension, and a larger utilisation of operative deliveries, determined a decrease in perinatal mortality and morbidity.     

Effects of HDL3 on the expression of matrix-degrading proteases in human endothelial cells

Modified lipoproteins have been suggested to modulate the expression of matrix-degrading proteases in the vascular wall. Since oxidized high density lipoprotein (HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of native and oxidized HDL3 on the expression of 35 proteases and their inhibitors in human endothelial cells using microarray analysis. Matrix metalloproteinase (MMP)-1, -2, -10, -13 and -14, tissue inhibitor of MMP (TIMP)-1, -2 and -3, cathepsin B and D, and cystatin C were expressed under basal conditions, of which MMP-10 and cystatin C expression have not been described before in endothelial cells. Native HDL3 increased MMP-1 and MMP-14 expression and decreased MMP-13 expression, whereas oxidized HDL3 increased PAI-1 and MMP-1 expression. The expression pattern was confirmed by quantitative real-time PCR. In summary, a large repertoire of matrix-degrading proteases is expressed in endothelial cells, an expression that can be modulated by native and oxidized HDL3.     

Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting

Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m²; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.     

Aetiology of preterm labour: bacterial vaginosis

Bacterial vaginosis (BV) is a common condition characterised by a polymicrobial disorder, with an overgrowth of several anaerobic or facultative bacteria and with a reduction or absence of lactobacillus colonisation. The prevalence of BV ranges from 4 to 64%, depending on the racial, geographic and clinical characteristics of the study population. In asymptomatic women, the prevalence varies from 12 to 25%, and similar percentages are observed in pregnant women. Although BV is associated with several adverse outcomes, such as upper genital tract infections, pelvic inflammatory disease, endometritis, preterm birth and low birthweight, many basic questions regarding the pathogenesis of BV remain unanswered. Mucosal immune system activation may represent a critical determinant of adverse consequences associated with BV. An unequal risk for BV acquisition and\or recurrence could derive from different mucosal immune host abilities and\or capability of invading microbes to produce factors that inactivate the local immune response. BV is associated with a two-fold increased risk of preterm birth, with the greatest risk when BV is present before 16 weeks of gestation (odds ratio = 7.55). This may indicate a critical period during early gestation when BV-related organisms can gain access to the upper genital tract and set the stage for spontaneous preterm labour later in gestation. The results of treatment trials for pregnant women with BV have been heterogeneous, with anywhere from an 80% reduction to a two-fold increase in preterm birth among women who received treatment. For this reason, in current clinical practice significant controversy surrounds determining not only who and when to screen but also who and how to treat. Recent evidence shows that individual genetic backgrounds can affect chemokine production. This is an interesting area for future research and could lead to trials of treatment only for women genetically predisposed to preterm birth.     

DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children.

OBJECTIVE: In our study we evaluated the frequency of three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene, in a cohort of 130 HIV-1 infected mothers and their children, collected by the Italian group SIGO in Obstetrics and Gynecology. METHODS: The three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene were genotyped by direct sequencing of PCR products. RESULTS: The C allele at position -44 was shown to be significantly different in both HIV-1 positive mothers and their children when compared to the healthy controls. The odds ratio for -44 C allele in children born to HIV-1 infected mothers is 7.09 (confidence interval 3.38-15.3) while the odds ratio for this allele in HIV-1 infected mothers is 6.42 (confidence interval 3.14-13.4). CONCLUSIONS: Our results evidence a high frequency of the -44 CC allele in HIV-1 infected mothers and their children with augmented potential risk of maternal fetal transmission. This potential vertical transmission risk has been successfully prevented by antiretroviral drug treatment and cesarian section of the HIV-1 positive mothers.     

The effect of lithium on growth factor production in long-term bone marrow cultures

We have previously reported that lithium chloride (LiCl) stimulates the production of granulocyte-macrophage colony-forming cells (GM-CFC), pluripotent stem cells (CFU-S), and differentiated granulocytes, macrophages and megakaryocytes in murine Dexter marrow cultures and that this effect appears to be mediated indirectly by a radioresistant adherent marrow cell. In this study we have established that exposure of murine Dexter cultures to LiCl (4 mEq/L) causes an increase of colony-forming cell megakaryocytes (CFU-meg) over 1 to 6 weeks of culture in both supernatant (188% to 611%) and stromal phases (123% to 246%). Moreover, we have shown that lithium treatment of either irradiated (1,100 rad) or unirradiated stromal cells increased production of activities stimulating formation of megakaryocyte, granulocyte, macrophage, and mixed lineage colonies and proliferation of the factor-dependent cell line, FDC-P1. This FDC-P1 stimulatory activity was completely blocked by an antibody to purified recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF). The baseline or lithium-induced--stromal-derived bone marrow colony stimulating activity was partially blocked by the antibody to rGM-CSF and by an antibody to purified colony stimulating factor I (CSF-1); the two antibodies combined resulted in greater than 90% inhibition of the lithium-induced marrow stimulatory activity. In addition, radioimmunoassay (RIA) showed that although CSF-1 was detectable in supernatants of these cultures, exposure to lithium did not increase CSF-1 levels. These data indicate that Dexter stromal cells produce CSF- 1 and GM-CSF and that lithium appears to exert its stimulatory effects on in vitro myelopoiesis by inducing production of GM-CSF.     

Organic light emitting diode improves diabetic cutaneous wound healing in rats

A major complication for diabetic patients is chronic wounds due to impaired wound healing. It is well documented that visible red wavelengths can accelerate wound healing in diabetic animal models and patients. In vitro and in vivo diabetic models were used to investigate the effects of organic light emitting diode (OLED) irradiation on cellular function and cutaneous wound healing. Human dermal fibroblasts were cultured in hyperglycemic medium (glucose concentration 180 mM) and irradiated with an OLED (623 nm wavelength peak, range from 560 to 770 nm, power density 7 or 10 mW/cm² at 0.2, 1, or 5 J/cm²). The OLED significantly increased total adenosine triphosphate concentration, metabolic activity, and cell proliferation compared with untreated controls in most parameters tested. For the in vivo experiment, OLED and laser (635 ± 5 nm wavelength) treatments (10 mW/cm², 5 J/cm² daily for a total of seven consecutive days) for cutaneous wound healing were compared using a genetic, diabetic rat model. Both treatments had significantly higher percentage of wound closure on day 6 postinjury and higher total histological scores on day 13 postinjury compared with control. No statistical difference was found between the two treatments. OLED irradiation significantly increased fibroblast growth factor‐2 expression at 36‐hour postinjury and enhanced macrophage activation during initial stages of wound healing. In conclusion, the OLED and laser had comparative effects on enhancing diabetic wound healing.