Suppression of dendritic cell differentiation through cytokines released by Primary Effusion Lymphoma cells

Functional impairment of dendritic cells (DC) appears to be one of the mechanisms responsible for tumor escape from the control of the immune system. DC isolated from tumor-bearing animals and cancer patients with solid or with hematological malignancies have phenotypic and functional abnormalities. In addition, supernatants from in vitro cultured tumor cells have been shown to interfere with DC differentiation from CD34+ and monocyte precursors. Primary effusion lymphoma (PEL) is a Human Herpesvirus-8 (HHV-8)-associated tumor, which releases several cytokines such as IL-6, IL-10 and VEGF and its growth seems to be dependent on them in vitro or in vivo. In the present study, we found that these cytokines released by PELs have also an important role in interfering with the in vitro differentiation of immature DC (iDC) from CD14+ monocytes. The iDC obtained in the presence of PEL supernatants showed reduction of FITC-dextran uptake, reduction of MLR allostimulatory activity and altered expression of surface molecules, suggesting that cytokines released by PEL adversely affect DC differentiation.     

PCB and other organochlorine compounds in blood of women with or without miscarriage: a hypothesis of correlation

Polychlorobiphenyls (PCBs) have been shown to affect reproduction in experimental animals and in human beings following intoxication. The concentrations of PCBs and other organochlorine compounds were determined in blood samples from 120 women hospitalized for miscarriages and 120 full-term pregnancy controls. The average PCB hematic level (reported as Fenclor 54) was higher in women with miscarriages than in control women. No differences were detected as far as the hematic concentrations of hexachlorobenzene and DDT compounds were concerned. The reproductive history of each woman was assessed together with confounding variables on the phenomenon of miscarriage and the factors regarding environmental exposure and food intake. Food consumption did not indicate diet as the main source of PCB intake.     

Temperature-Induced Surface Effects on Drug Nanosuspensions

Purpose

The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even though such interface effects can be of pharmaceutical relevance. Such potential effects in drug nanosuspensions were to be studied for temperatures of 25 and 37°C by using complementary surface analytical methods.

Methods

Atomic force microscopy, inverse gas chromatography and UV surface dissolution imaging were used together for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Fenofibrate and bezafibrate were selected as model drugs in presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively.

Results

It was demonstrated that in case of bezafibrate nanosuspension, a surface modification occurred at 37°C compared to 25°C, which notably affected dissolution rate. By contrast, no similar effect was observed in case of fenofibrate nanoparticles.

Conclusions

The combined usage of analytical surface methods provides the basis for a better understanding of phenomena that take place on drug surfaces. Such understanding is of importance for pharmaceutical development to achieve desirable quality attributes of nanosuspensions.

     

Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated.     

Medium term treatment and prophylaxis of dysfunctional metrorrhagia in adolescence

The authors compared the therapeutic effectiveness of these different pharmacological methods of preventing dysfunctional menometrorrhagia in adolescents, which were: 1) chorionic gonadotropin, 2) cyclofenil, 3) ovariostatics. Therapy was given during 2 menstrual cycles, and effects were evaluated both during the treatment and for the succeeding 2 cycles. Parameters followed were: a) clinical recovery, b) persistence of spotting, c) effectiveness in inducing ovulation. The results were equally good both in treatment with ovariostatics and ovulation inducers. The latter proved however, more effective during follow-up. Side-effects were very rare, so much so that, in no case was it necessary to suspend treatment.     

Spontaneous abortion in relation to the presence of hexachlorobenzene in the Italian environment

This study determined hexachlorobenzene (HCB) levels in the blood of women who had suffered spontaneous abortions (120 cases) and women with healthy reproductive functions (120 controls). Samples were collected in 1984 during an epidemiological investigation into the relation between polychlorobiphenyl levels in the blood and spontaneous abortion in the women. Evaluation of the HCB data showed no significant differences between the groups, the blood of the group with spontaneous abortion containing 1.6 +/- 1.6 ppb HCB compared with 1.5 +/- 1.1 ppb for the control group.     

Prenatal diagnosis of congenital diaphragmatic hernia: an update

Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1:4000 live births. Most frequently the diaphragmatic defect is a left and posterolateral (Bochdalek) one. Prenatal diagnosis is made at ultrasonography; the relevant sonographic features will be described in the paper. Cystic adenomatoid malformation of the lung (CAML), pulmonary sequestration, bronchogenic cysts, pulmonary hypoplasia/agenesia need to be considered in differential diagnosis. In some cases, diagnosis of CDH is not possible "in utero": in such cases, herniation of abdominal viscera into the thorax takes place presumably just at delivery through a small diaphragmatic defect. CDH may be associated with intrauterine growth retardation (IUGR), chromosomal abnormalities (3%) and/or other malformations (10-50%): such as Central Nervous System, digestive, cardiac and urogenital anomalies. Therefore, search of associated malformations and amniocentesis with analysis of fetal karyotype are mandatory, whenever a CDH is diagnosed. CDH is still at present characterised by a high mortality (reportedly, about 45%). Many prognostic factors have been correlated to postnatal outcome of CDH: some of them are valuable prenatally by ultrasonography. However, the role of sonography in the prediction of neonatal outcome is still controversial: in particular, although many ultrasonographic parameters have been proposed, prenatal evaluation of pulmonary hypoplasia (a crucial factor related to postnatal survival) has not proved to be very accurate so far. Nevertheless, it is undisputable that prenatal diagnosis itself represents a crucial prognostic factor for CDH, since it allows birth of the affected fetuses in 3d level Perinatologic Centres provided with a Neonatal Intensive Care Unit and Neonatal Surgery.     

Sequential Gn-RH superagonist and medroxyprogesterone acetate treatment of uterine leiomyomata

A group of 48 women with symptomatic leiomyomata were treated during 6 months with the short-acting Gn-RH superagonist analog buserelin. The first (group C) was followed up for an additional six months of no medication. The second (group M) was treated for 6 additional months with medroxyprogesterone acetate (MPA) at doses decreasing from 200 to 25 mg/day. Buserelin therapy significantly decreased uterine size (P less than 0.001) in all patients, the average final volume being 48.5% of the original (from 262 +/- 147 ml to 127 +/- 85.4 ml). In group C there was a significant (P less than 0.001) re-growth during the post-treatment observation period (from 120 +/- 81.0 ml to 198 +/- 77.2 ml); a significant (P less than 0.01) re-growth was also observed in group M during MPA medication (from 132 +/- 77.2 ml to 170 +/- 96.0 ml). The agonist had also a marked effect on fibroids: on average they decreased from 75.1 +/- 74.3 ml to 24.7 +/- 23.3 ml (P less than 0.025). In group C during the post-buserelin period of observation without treatment, there was a significant re-growth from 23.7 +/- 21.6 ml to 47.7 +/- 27.5 ml (P less than 0.001), whereas in group M treatment with MPA prevented any significant re-growth (from 25.6 +/- 24.8 to 30.6 +/- 32.9 ml; P greater than 0.3).     

The impact of the factor V Leiden mutation on pregnancy

A resistance to the anticoagulant activity of activated protein C (APC), most frequently due to a point mutation in the Factor V gene (the Leiden mutation), represents the most common genetic cause of thrombophilia. The Leiden mutation has been significantly related to pregnancy complications associated with hypercoagulation, e.g. deep vein thrombosis during pregnancy (8-fold increased risk), pre-eclampsia (prevalence of the mutation up to 26%), placental infarction extending to > 10% of the placenta (10-fold increased risk), abruptio placentae (prevalence of the mutation up to 29.6%), and second- and third-trimester pregnancy failure (prevalence of the mutation up to 31.3%). An association of the maternal mutation with recurrent first-trimester miscarriage does not emerge from the literature, although fetal mutation (frequency higher than twice compared with that of the general population) has been related to early spontaneous miscarriage. Although some evidence suggests an association between APC resistance and intrauterine growth retardation, no significant relationship emerges currently from the literature. Screening for the Leiden mutation would seem advisable in women with previous pregnancy complications amongst those associated with APC resistance. Carriers of the mutation should be given appropriate counselling. The screening of asymptomatic women is not recommended at present.