Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease

Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events.     

DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells

Human contact with fungi does not usually lead to pathological consequences, as the immune system manages to defeat the invader pathogens. Nevertheless, under immune suppression, fungi overcome immune defenses and cause diseases that range from nonserious colonizations of keratinizated tissue (Dermatophytosis) to life threatening disseminated infections (Aspergillosis). Host defenses against fungi rely on innate and adaptative responses, with dendritic cell (DC) and macrophage surface receptors having a major role in the recognition of fungal pathogens and in the orchestration of an effective immune response. DC-SIGN is a C-type lectin involved in the recognition of bacterial, viral and parasitic pathogens, as well as in interactions between cells of the immune system. Its expression is restricted to DCs and subsets of macrophages. Here we show that DC-SIGN mediates the binding and capture of Aspergillus fumigatus and keratinophylic fungi, including Chrysosporium tropicum, by human DCs, describe the requirements of these interactions and discuss their potential involvement in the onset and persistence of pulmonary fungal infections.     

Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).     

Decreased anti-donor major histocompatibility complex class I and increased class II alloantibody response in allograft tolerance in adult rats

Permanent tolerance to allografts can be induced in adult rats by donor-specific transfusions (DST) prior to transplantation. We have previously reported, in a model of heart allograft, the presence of a heavy leukocyte infiltrate, in the allograft which displayed a strong allospecific cytotoxicity when tested in vitro against donor cells, and a strong accumulation of mRNA for granzyme A and perforin in vivo. In contrast, there was a major decrease in the accumulation of mRNA for interleukin-2 and interferon-γ. These results suggested that the DST-induced tolerance was associated with a decrease in type-1 T helper (Th1) cell function. The major role of preformed antibodies in xeno and allorejection is clearly established. Nevertheless, the consequences of alloantibody production in acute rejection and tolerance induction remains to be elucidated. We here analyze the alloantibody response in rejecting and DST-treated recipients. We show that, after transplantation, tolerant recipients, in contrast to rejecting ones, mount a low IgM alloresponse that switches to low IgG production. Detailed analysis of IgG alloantibodies in DST-treated recipients revealed that their production decrease was not equally distributed. Whereas rejecting animals mounted a strong anti-class I and II IgG alloantibody response, DST-treated recipients produced anti-class II and low titers of anti-class I IgG alloantibodies. Furthermore, among IgG subclasses, tolerant recipients predominantly produced IgG2a, a profile which, in the rat, is compatible with a Th2-controlled response. Finally, the passive transfer of immune serum from rejecting animals to DST-treated recipients could abrogate the tolerance. We suggest that the absence of anti-class I alloantibodies combined with preserved and/or increased anti-class II production plays a major role in graft tolerance in this model. These results reinforced the role of alloantibodies in rejection and in induction of tolerance.     

Orofacial evaluation of individuals with temporomandibular disorder after LED therapy associated or not of occlusal splint: a randomized double-blind controlled clinical study

Lasers in Medical Science - This study compared the effects of LED therapy associated with occlusal splint (OS) on the signs and symptoms of temporomandibular disorder (TMD). In this randomized,...     

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review

Neurosurgical Review - Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after...