Hydroxychloroquine is much less active than chloroquine against chloroquine-resistant Plasmodium falciparum, in agreement with its physicochemical properties.

The 4-aminoquinoline drug hydroxychloroquine (HCQ) is reported to be as active as chloroquine (CQ) against falciparum malaria, and less toxic. Existing prophylactic regimens for areas where there is CQ-resistant malaria recommend CQ with proguanil as an alternative where none of the three preferred regimens (atovaquone-proguanil, doxycycline or mefloquine) is thought suitable. In such cases, toxicity is likely when CQ-proguanil is administered to persons being treated for autoimmune disease with daily HCQ. The question therefore arises whether in such circumstances HCQ could effectively replace the CQ component of the prophylactic combination. We confirmed similar activity of CQ and HCQ against CQ-sensitive Plasmodium falciparum, but found that whereas HCQ in vitro was 1.6 times less active than CQ in a CQ-sensitive isolate, it was 8.8 times less active in a CQ-resistant isolate. The result can also be predicted from an analysis of the physicochemical properties of CQ and HCQ. To give limited protective effect similar to 300 mg CQ base weekly against CQ-resistant P. falciparum would demand daily doses of HCQ above the recommended safe level. These observations contraindicate the use of HCQ in prophylaxis or treatment of CQ-resistant falciparum malaria. Where CQ-proguanil prophylaxis is the only option available in a patient on high-dose HCQ treatment, visiting a CQ-resistant area, replacement of the anti-inflammatory regimen by a daily CQ course at a suitable dose should be considered

Caracterização das explorações agrícolas no Ribatejo

Face à importância da adopção de incentivos à reestruturação fundiária no nosso país, é continuamente vital a análise do tipo de investimento que se vem a realizar desde a nossa entrada na Comunidade. Este trabalho constitui um primeiro estudo referente à caracterização das explorações agrícolas que beneficiaram de apoios, no Ribatejo. Numa segunda e terceira fases pretende-se relacionar os investimentos realizados com a estrutura física da exploração e uma posterior caracterização do beneficiário-tipo

Cognitive mechanisms of treatment in depression

Cognitive abnormalities are a core feature of depression, and biases toward negatively toned emotional information are common, but are they a cause or a consequence of depressive symptoms? Here, we propose a ‘cognitive neuropsychological' model of depression, suggesting that negative information processing biases have a central causal role in the development of symptoms of depression, and that treatments exert their beneficial effects by abolishing these biases. We review the evidence pertaining to this model: briefly with respect to currently depressed patients, and in more detail with respect to individuals at risk for depression and the effects of antidepressant treatments. As well as being present in currently depressed individuals, negative biases are detectable in those vulnerable for depression due to neuroticism, genetic risk, or previous depressive illness. Recent evidence provides strong support for the notion that both antidepressant drugs and psychological therapies modify negative biases, providing a common mechanism for understanding treatments for depression. Intriguingly, it may even be possible to predict which patients will benefit most from which treatments on the basis of neural responses to negative stimuli. However, further research is required to ascertain whether negative processing biases will be useful in predicting, detecting, and treating depression, and hence in preventing a chronic, relapsing course of illness