Efficacy and tolerance of mefloquine in the treatment of infants and children with Plasmodium falciparum malaria]

Only a limited number of treatments are available for use in young children with malaria. OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerance of mefloquine treatment in children, especially in infants of less than 15 kg, in an endemic area of malaria (French Guiana). METHOD: This five-years (1996-2000) retrospective study included 61 children aged six months to 16 years who have been treated with mefloquine for acute P. falciparum malaria. Twenty-six of these children weighted less than 15 kg. The efficiency of the treatment was evaluated using clinical and parasitic data that had been validated according to the criteria of the World Health Organization (WHO). Tolerance was compared with the data in the medical literature. RESULTS: None of the 59 patients who were given the treatment correctly presented signs of early therapeutic failure as defined by the WHO. Apyrexia was obtained in 47.8 h on average (CI 95%: 39-57; median: 36 h). The mean time required to obtain negative parasitism was 90.8 h (CI 95%: 80-101; median: 96 h) among the 51 patients in whom this was measured. Mild side effects were observed in 27.8% of the cases affecting mainly the digestive system. No differences were observed regarding efficacy or tolerance for children who weighed less than 15 kg. CONCLUSION: Mefloquine represents an efficient treatment for acute uncomplicated P. falciparum malaria in children and is well tolerated even in infants.     

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.     

Population-based study of emergency department admissions and deaths from injuries in Barcelona,Spain: Incidence,causes and severity

The aim of this study was to estimate the incidence of morbidity and mortality due to injuries in the population over the age of 14 years in Barcelona, Spain. Injury distribution according to sex, age, external cause, place of occurrence of the injury and severity was also obtained. A one-year survey was conducted in the emergency departments of the six main hospitals in Barcelona, based on a multistage sampling. Information was collected prospectively in emergency services by specially trained non-staff interviewers. Mortality data were drawn from death certificates. The incidence rate was 74.7 injury cases per 1,000 person-years over 14 years of age, higher in males than in females. Injury rates were highest in the youngest age-group and progressively lower until people over 75 years of age. Main external causes of injury were falls, being struck or caught by objects, and traffic-related injuries. The leading specific causes of injury mortality were traffic injuries, suicides and poisonings. While the overall admission incidence was 3.34 cases per 1,000 inhabitants, the proportion of hospitalized cases was 45.0 per 1,000 injury cases admitted to emergency rooms, higher for females, for traffic injuries and in the elderly population. Ninety-six percent of injury cases had an ISS value of 8 or less, mean ISS being highest for traffic injuries and falls. Injury morbidity and mortality amongst residents of Barcelona follow sex, age and cause of injury patterns which are, overall, comparable to those observed in other industrialized countries, suggesting that similar etiologic factors might be operating in those areas. The results should enable the orientation of injury prevention policies in the urban environment targeted on the young and the elderly population.     

Ischemic preconditioning increases the tolerance of Fatty liver to hepatic ischemia-reperfusion injury in the rat

Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation.     

Effects of Cannabinoids on the Immune System and Central Nervous System

This review aims to improve understanding of the modulatory effects that cannabinoids exert on the immune system and CNS. Cannabinoids possess immunomodulatory activity, are neuroprotective in vivo and in vitro and can modify the production of inflammatory mediators, such as nitric oxide, prostanoids and cytokines, that are expressed by, and act on, the immune system and the brain. The mechanisms of cannabinoid actions are not fully understood, but appear to involve complex interactions between cannabinoid receptors and a number of signal transduction pathways. Endogenous cannabinoid ligands appear to act as local modulators of immune/inflammatory reactions. Cannabinoid-induced immunosuppression may have implications for the treatment of neurological disorders that are associated with excess immunological activity, such as multiple sclerosis and Alzheimer's disease. There is anecdotal evidence that cannabis use improves the symptoms of multiple sclerosis, and studies with animal models are beginning to provide evidence for the mechanism of such effects. The development of nonpsychotropic cannabinoid analogues and modulators of the metabolism of endogenous cannabinoid ligands may lead to novel approaches to the treatment of neurodegenerative disorders.     

Protein C deficiency: identification of a novel two-base pair insertion and two point mutations in exon 7 of the protein C gene in Spanish families.

We have applied single-strand conformation polymorphism (SSCP) to the analysis of exon 7 of the anticoagulant protein C (PC) gene, in 13 PC-deficient Spanish families. Abnormal patterns were visualized in three samples from type I or quantitative PC deficient proposita. A previously undescribed mutation due to a TT insertion after nucleotide 6139, between codons Gly-142 and Arg-143 was found in one family. The mutation (6139,ins TT) should result in a frameshift with a stop at codon 156, which agrees with the presence of a type I or quantitative PC deficiency in the affected members of the family. The second mutation identified was a C to T transition at nucleotide 6274, 9 base pairs into intron G. This mutation (6274,C-->T), found for the first time in a Spanish family, is identical to the previously characterized PC Sant Louis. The third mutation was a G to A transition that replaces arginine 178 with glutamine (178,R-->Q). This is the third case of 178,R-->Q mutation in 17 apparently unrelated Spanish families with type I PC deficiency. Furthermore, SSCP analysis allowed the detection of another previously described mutation in a PC-deficient Spanish family (178,R-->W).