Long-lasting effects of chronic chlorimipramine treatment of rats on exploratory activity on a hole-board, and on immobility in the forced swimming test

The study concerned the effects of acute and chronic clomipramine administration to male rats on exploratory activity in a novel environment (hole-board) and on immobility in the forced swimming test. Acute clomipramine administration did not alter either exploratory activity on a hole-board as measured 3 or 20 h after drug administration, or immobility in the forced swimming test as measured 20 h after drug administration. Approximately 20 h after the last injection of clomipramine, the rats chronically treated with the drug showed reduced exploratory activity on the hole-board. In contrast, chronic clomipramine treatment significantly increased the activity in the forced swimming test. The effects of the drug on exploratory and forced swimming activities persisted for 14 days after the cessation of clomipramine administration. These data indicate that chronic clomipramine administration exerted profound and long-lasting effects on central nervous system function. The long-lasting action of the drug on behaviour in the forced swimming test might explain the long-term beneficial effect of antidepressant drugs in counteracting behavioral depression.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

Platelet 5-hydroxytryptamine increases with platelet age in dogs.

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.     

Prevalence of latex sensitization and allergy in Portuguese children

The prevalence of latex allergy has been increasing not only in risk groups but also in the general population, where it is accepted to average 1%. In children, latex sensitization prevalence studies are scarce and involve different population sampling and allergy testing methods, which makes it difficult to compare across studies. Nevertheless, existing studies point towards a low prevalence of latex allergy in children, which still needs to be confirmed in the Portuguese population. Aiming at studying the prevalence of latex sensitization and allergy in a sample of Portuguese children, we studied 182 children from two different hospital outpatient clinics. A standardized questionnaire focusing on atopic background, previous history and allergic signs or symptoms on exposure to latex or fruits was given to all children and parents. Skin prick testing was performed with a battery of common aeroallergens as well as latex. Serum total IgE, Phadiatop, F x 5E and latex-specific IgE were determined in all children. Specific IgE to latex-crossreacting fruits was determined in latex-sensitized children. Based upon the questionnaire, the prevalence of latex allergy would be 0.5%. The prevalence of latex sensitization would be 3.8%, when based solely upon skin prick testing, and 12.1% (>/=0.35 IU/ml) or 6.6% (>/=0.70 IU/ml) when based singly upon determination of latex-specific IgE. When positive results for either test were considered, the prevalence of latex sensitization was 14.3%. All latex-sensitized children were atopic. Sensitivity to latex-crossreacting foodstuffs was demonstrated in 61.5% of latex-sensitized children (16/26). This study shows that the prevalence of latex allergy and sensitization in Portuguese atopic and non-atopic children, as analysed using various diagnostic methods, is similar to that observed in other countries. In addition, the assessment of latex allergy and sensitization should always include skin prick testing and determination of serum IgE.     

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.