Preventing adverse obstetric outcomes in women with genetic thrombophilia

OBJECTIVE: To improve fetomaternal outcomes in women with obstetric complications and inherited causes of thrombophilia. DESIGN: Clinical trial. SETTING: Thrombophilic women with previous unexplained adverse outcomes. PATIENT(S): Twenty-five women with previous severe obstetric complications were treated during and after pregnancy. INTERVENTION(S): Low fixed dose of heparin or aspirin. MAIN OUTCOME MEASURE(S): Fetomaternal outcome. RESULT(S): Low fixed dose of heparin were administered to 24 pregnant women, aspirin to 7. Overall, among 31 treated pregnant women, 28 (90.3%) compared to 4 of 58 (6.9%) in previous pregnancies had a good obstetric outcome. Two fetal losses <14 weeks gestation and a fetal growth restriction were registered. All newborns, except one, were in the tenth centile or above. All babies were discharged in good clinical status. In the treated pregnancies, no thrombosis or pharmacological side effect was recorded. CONCLUSION(S): Heparin prophylaxis at fixed low doses and possibly aspirin could be efficacious in preventing adverse outcomes in women carrying inherited thrombophilia with previous poor obstetric outcomes.     

Activity against Plasmodium falciparum of cycloperoxide compounds obtained from the sponge Plakortis simplex

There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs. In the last few years, artemisinin, the endoperoxide sesquiterpene lactone derived from Artemisia annua, and its derivatives proved to be very active against Plasmodium falciparum. These compounds are characterized by an endoperoxide pharmacophore that is critical for their antimalarial activity. There are several reports, from our group and others, that marine organisms can be another natural source of stable cyclic peroxides, with selective antifungal or antibacterial activity. With the aim of identifying new bioactive molecules, we evaluated in vitro the antimalarial activity of the major cycloperoxides extracted from the sponge Plakortis simplex. The six-membered endoperoxide compounds plakortin and dihydroplakortin, but not the five-membered cycloperoxide plakortide E, inhibited the growth of cultured P. falciparum parasites, both chloroquine-sensitive D10 strain and chloroquine-resistant W2 strain. The IC50 values were similar for both compounds and in the range of 1263-1117 nM against D10, and 735-760 nM against W2, using the colorimetric parasite lactate dehydrogenase assay. The activity of plakortin and dihydroplakortin was significantly higher against chloroquine-resistant than chloroquine-susceptible parasites, following a pattern similar to that of artemisinin, although they were 50-fold less active. Moreover, plakortin and dihydroplakortin showed an additive effect when used in combination with chloroquine. These results support further studies on cycloperoxides of marine origin to characterize their mechanism of action and identify/synthesize new compounds with stronger antimalarial activity.     

Thrombomodulin expression in endothelial cells after contact with bone cement

The expression of thrombomodulin after contact with CMW 1 bone cement extracts was studied in human umbilical vein endothelial cells. Cement extracts after 1 h and 7-day curing induced no significant variations in thrombomodulin antigen levels and in mRNA expression. Significant increase of thrombomodulin was observed when endothelial cells were treated with all-trans retinoic acid (ATRA). ATRA induced the increase of thrombomodulin also in cells incubated with cement extracts. These results suggest that CMW 1 bone cement does not impair the expression of thrombomodulin in endothelial cells.     

The ultrastructure of nasal mucosa in children with asthma

Nasal brushing has sometimes been used to characterize some affections of the respiratory tract, but seldom employed in chronic diseases such as asthma, for the possible presence of cellular inflammation in the small specimens used for electron microscopy. The present study evaluated the ultrastructure of epithelial cells obtained by nasal brushing in 11 allergic children with asthma, before and after staying in an environment free of allergens, usually implicated in the genesis of inflammatory events. The ultrastructural alterations of the nasal mucosa have been graded on the basis of their severity. Grade I lesions were characterized by well-differentiated mucous and ciliated cells. The ciliated cells appeared usually well preserved but decreased in number. In grade II lesions, most of the epithelial surface was covered by mucous cells. A further phenotype composed of poorly differentiated ciliated or mucous cells was detected. Grade III lesions showed aspects of depletion of the ciliated and mucous cells. The epithelium was largely composed of undifferentiated cells. Furthermore, the comparison of specimens at 2 different times of sampling did not differ. The data demonstrate that in allergic children with asthma, the nasal mucosa showed ultrastructural changes, which appeared to be unmodifiable during a prolonged stay in an environment free of allergens. Moreover, the nasal epithelium may provide a convenient sampling site, allowing grade of mucosal damage, with the benefit that the brush method is minimally invasive and avoids complications related to bronchoscopic examination.     

Immunological changes in patients with primary osteoarthritis of the hip after total joint replacement

We aimed to assess whether the immunological abnormalities which have been observed in patients with loose total hip replacements (THRs) are present in patients with a well-fixed prosthesis. We examined blood samples from 39 healthy donors, 22 patients before THR and 41 with well-fixed THRs of different types (15 metal-on-metal, 13 metal-on-polyethylene, 13 ceramic-on-ceramic). Before THR, the patients showed a decrease in leukocytes and myeloid cells in comparison with healthy donors, and a prevalence of type-1 T lymphocytes, which was confirmed by the increase in ratio of interferon-gamma to interleukin 4. Moreover, patients with metal-on-metal or metal-on-polyethylene implants showed a significant decrease in the number of T lymphocytes and a significant increase in the serum level of chromium and cobalt, although no significant correlation was observed with the immunological changes. In the ceramic-on-ceramic group, leukocytes and lymphocyte subsets were not significantly changed, but a significant increase in type-2 cytokines restored the ratio of interferon-gamma to interleukin 4 to normal values. We conclude that abnormalities of the cell-mediated immune response may be present in patients with a well-fixed THR, and that the immunological changes are more evident in those who have at least one metal component in the articular coupling.     

Kleptomania in impulse control disorders,obsessive-compulsive disorder,and bipolar spectrum disorder: Clinical and therapeutic implications

This paper aims to critically review currently available data on kleptomania and to analyze the possible future evolution of clinical research and therapeutic strategies.     

Hyperthermia inhibits angiogenesis by a plasminogen activator inhibitor 1-dependent mechanism

Hyperthermia (HT) associated with radiotherapy or chemotherapy is a promising method for cancer treatment, although the molecular mechanisms of this process are not well understood. HT exhibits various antitumor effects, including damage of tumor vasculature. Here, we investigate the effect of HT on in vitro and in vivo angiogenesis. We show that heat treatment of endothelial cells (ECs) affect their differentiation into capillary-like structures in two models of in vitro angiogenesis. Furthermore, the formation of new vessels promoted by angiogenic inducers in the chick embryo chorioallantoic membrane assay is impaired after heat treatment. These effects cannot be explained by direct cytotoxicity but are dependent on modulation of angiogenesis-involved genes. Gene expression profile of ECs subjected to heat shock demonstrates that plasminogen activator inhibitor 1 (PAI-1), a protein involved in the control of extracellular matrix degradation, is specifically up-regulated. The use of anti-PAI-1-neutralizing antibodies reverts the effect of HT on the in vitro EC morphogenesis and in vivo vessel formation. Moreover, microvessel outgrowth from PAI-1(-/-) aortic rings was not affected by HT compared with aortic rings from PAI-1(+/+) mice. Heat treatment of murine mammary adenocarcinomas results in inhibition of tumor growth, associated with a reduction of microvessel number and an increase of PAI-1 expression. These results indicate that heat-mediated PAI-1 induction is an important pathway by which HT exerts its antitumor activity and may represent a rationale for a combined cancer therapy based on HT associated with antiangiogenic molecules.     

Malaria clusters among illegal Chinese immigrants to Europe through Africa

Between November 2002 and March 2003, 17 cases of malaria (1 fatal) were observed in illegal Chinese immigrants who traveled to Italy through Africa. A further cluster of 12 was reported in August, 2002. Several immigrants traveled by air, making the risk of introducing sudden acute respiratory syndrome a possibility should such illegal immigrations continue.