Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.

Mast cells are multifunctional bone marrow-derived cells found in mucosal and connective tissues and in the nervous system, where they play important roles in tissue inflammation and in neuroimmune interactions. Very little is known about endogenous molecules and mechanisms capable of modulating mast cell activation. Palmitoylethanolamide, found in peripheral tissues, has been proposed to behave as a local autacoid capable of downregulating mast cell activation and inflammation. A cognate N-acylamide, anandamide, the ethanolamide of arachidonic acid, occurs in brain and is a candidate endogenous agonist for the central cannabinoid receptor (CB1). As a second cannabinoid receptor (CB2) has been found in peripheral tissues, the possible presence of CB2 receptors on mast cells and their interaction with N-acylamides was investigated. Here we report that mast cells express both the gene and a functional CB2 receptor protein with negative regulatory effects on mast cell activation. Although both palmitoylethanolamide and anandamide bind to the CB2 receptor, only the former downmodulates mast cell activation in vitro. Further, the functional effect of palmitoylethanolamide, as well as that of the active cannabinoids, was efficiently antagonized by anandamide. The results suggest that (i) peripheral cannabinoid CB2 receptors control, upon agonist binding, mast cell activation and therefore inflammation; (ii) palmitoylethanolamide, unlike anandamide, behaves as an endogenous agonist for the CB2 receptor on mast cells; (iii) modulatory activities on mast cells exerted by the naturally occurring molecule strengthen a proposed autacoid local inflammation antagonism (ALIA) mechanism; and (iv) palmitoylethanolamide and its derivatives may provide antiinflammatory therapeutic strategies specifically targeted to mast cells ("ALIAmides").     

Age-related changes in brain: II. Positron emission tomography of frontal and temporal lobe glucose metabolism in normal subjects

While many neuropsychological studies have demonstrated age-related performance alterations in tests thought to reflect frontal and temporal lobe function, there is little direct observation and comparison of these hypothesized brain changesin vivo. The cerebral glucose metabolism of frontal, temporal, and cerebellar regions was examined in 40 young ( =27.5±4.9) and 31 elderly ( =67.6 ± 8.8) normal males using PET-FDG. Univariate analysis showed age-related metabolic reductions in all frontal and temporal lobe regions. The reductions ranged from 13%–24% with the greatest changes in the frontal lobes. Multiple regression analyses showed a stronger age relationship with frontal lobe than with temporal lobe metabolism. The dorsal lateral frontal lobe was the region that appears to change most within the frontal lobes. Examination of the temporal lobe showed that age contributed equally to the metabolic variance of both the lateral temporal lobe and hippocampus. These results suggest that age-related metabolic changes exist in both frontal and temporal lobes and that the frontal lobe change is greater.     

Selecting a pharmacy computer system for the future

Major advances are occurring in the field of computer science that have placed us at the threshold of a significant revolution in the management and application of clinical data. These advances will have a profound effect on the practice of pharmacy and are occurring at a time when many hospital pharmacies are deciding whether to enhance or replace their current systems. To best position your department for the future, it is essential that you are knowledgeable of the advances being made, have a vision for how they will affect your practice, and undergo a well-organized and thorough selection process.     

Xanthogranulomatous pyelonephritis

A four years-old boy with Xanthogranulomatous pyelonephritis was surgically treated at the Pediatric Surgery Unit of the Santa Casa de Misericórdia of Maceió. Comments are made upon pathology, pre-operative diagnostic difficulties, differential diagnosis, and the rare occurrence in children.     

Acute attacks in the extremities of persons living in an area endemic for bancroftian filariasis: differentiation of two syndromes

The natural history of lymphatic disease in human filariasis remains unclear, but recurrent episodes of acute lymphangitis are believed to constitute a major risk factor for the development of chronic lymphoedema and elephantiasis. Prospective analysis of 600 patients referred to the filariasis clinic of the Centro de Pesquisas Aggeu Magalh?es/FIOCRUZ in Recife, Brazil, indicated that 2 distinct acute syndromes accompanied by lymphangitis occur in residents of this filariasis-endemic area. One syndrome, which we call acute filarial lymphangitis (AFL), is caused by the death of adult worms. It is relatively uncommon in untreated persons, usually is asymptomatic or has a mild clinical course, and rarely causes residual lymphoedema. The second syndrome, of acute dermatolymphangioadenitis (ADLA), is not caused by filarial worms per se, but probably results from secondary bacterial infections. ADLA is a common cause of chronic lymphoedema and elephantiasis in Recife as well as in other areas of Brazil where lymphatic filariasis is not present. The syndromes of AFL and ADLA can be readily distinguished from each other by simple clinical criteria.     

Short-term associations between emergency hospital admissions for respiratory and cardiovascular disease and outdoor air pollution in London

There are concerns about the possible short-term effects of outdoor air pollution on health in the United Kingdom. In a study conducted during the time period between 1987 and 1992, investigators determined that ozone had small, but significant effects on emergency respiratory admissions. In the current study, the authors investigated associations between emergency admissions and outdoor air pollution for the time period from 1992 to 1994, inclusive, and compared the results with those obtained in the earlier study. The authors also examined particulate matter less than 10 microm in diameter (PM10) and carbon monoxide in the current study. Appropriate confounding factors, such as seasonal patterns, temperature, and humidity, were controlled for, and the authors used Poisson regression to estimate the association between daily emergency admissions for respiratory and cardiovascular diseases and ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particles measured as Black Smoke, and PM10. Significant positive associations were found between emergency hospital admissions for respiratory disease and PM10 and sulfur dioxide, but such an association did not exist for ozone. The results were not significantly different from earlier results from London and were comparable with those determined in North America and Europe. Cardiovascular disease was associated with carbon monoxide and Black Smoke, but weaker associations existed with the other pollutants studied.     

Maternal zinc supplementation does not affect size at birth or pregnancy duration in Peru.

To estimate the effect of maternal zinc deficiency on pregnancy outcomes, we conducted a zinc supplementation trial in an urban shantytown in Lima, Peru, a population with habitual low zinc intakes. Beginning at 10-24 wk gestation, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg iron and 250 (g folate, with or without 15 mg zinc. Women were followed up monthly during pregnancy. At birth, newborn weight was recorded, and crownheel length, head circumference and other circumferences and skinfold thicknesses were assessed on d 1. At delivery, 1016 remained in the study; duration of pregnancy was known for all women, and birth weight information was available for 957 newborns. No differences were noted in duration of pregnancy (39.4 +/- 2.2 vs. 39. 5 +/- 2.0 wk) or birth weight (3267 +/- 461 vs. 3300 +/- 498 g) by prenatal supplement type (iron + folate + zinc vs. iron + folate; P > 0.05), and there were no differences in the rates of preterm (<37 wk) or post-term (>42 wk) delivery, low birth weight (<2500 g) or high birth weight (>4000 g). Finally, there were no differences by prenatal supplement type in newborn head circumference, crownheel length, chest circumference, mid-upper arm circumference, calf circumference or skinfold thickness at any of three sites. Adjustment for covariates and confounding factors did not alter these results. Adding zinc to prenatal iron and folate tablets did not affect duration of pregnancy or size at birth in this population.     

Tuberculosis treatment adherence in Pelotas, Brazil, from the patient's perspective

This study deals with adherence to tuberculosis treatment among men and women as well as the disease's links and consequences vis-à-vis life styles and treatment outcomes. The ethnographic study was a component of the Tuberculosis Epidemiological Control Project in the city of Pelotas and aimed to identify the reasons patients failed to complete treatment. Direct ethnographic observations and semi-structured interviews were used. Use of the term "adherence" is justified by the concern for extending to other fundamental factors in addition to the patient's own individual responsibility. This approach fostered an understanding of views towards disease, social dynamics among the various protagonists involved in the disease process, and treatment. Some of the factors considered in adherence to treatment were: socio-demographic characteristics, cultural factors, popular beliefs, the cost-benefit relationship, physical and chemical aspects of the drugs, the physician-patient relationship, and level of family participation in treatment.     

Pregnancy outcomes and outdoor air pollution: an ecological study in districts of the Czech Republic 1986-8

OBJECTIVES: Outdoor air pollution has consistently been shown to predict mortality. The finding that this association is stronger in infants than in children or adults raises the question whether air pollution could also be related to pregnancy outcomes--such as birthweight and stillbirth. The association between outdoor air pollution and stillbirths and low birthweight in the Czech Republic, where air pollution was high, was examined. METHODS: An ecological study was conducted, with routinely collected data on stillbirths and low birthweight (< 2500 g), air pollution (total suspended particulates, sulphur dioxide (SO2), and nitrogen oxides (NOx)), and socioeconomic factors (mean income, car ownership, divorce rate, etc). The analyses were restricted to 45 districts on which data on air pollution were available for the period 1986-8. The effects of exposure variables on frequency of pregnancy outcomes were estimated by logistic regression with district-years as the units of analysis. RESULTS: Stillbirth rate (4.2/1000 births in monitored districts) was not significantly associated with any indicator of air pollution, and was weakly related to mean income and proportion of births outside marriage. Crude prevalence of low birthweight (prevalence 5.5%) showed highly significant associations with several socioeconomic factors; after controlling for these, odds ratios (ORs)/50 micrograms/m3 increase in pollutant were: 1.04 (95% confidence interval (95% CI) 0.96 to 1.12) for total suspended particles, 1.10 (1.02 to 1.17) for SO2, and 1.07 (0.98 to 1.16) for NOx. When all pollutants were included in one model, SO2 remained related to low birthweight (OR 1.10 (1.01 to 1.20), p = 0.033). CONCLUSION: These results are consistent with a recent study in China where birthweight was also associated with total suspended particles and SO2 but ecological studies must be interpreted cautiously. Residual confounding by socioeconomic factors cannot be ruled out. The association between air pollution and birthweight requires further investigation.

 

     

Genetic analysis of three patients with an 18p- syndrome and dystonia

Some patients with an 18p- syndrome show dystonia, and a focal dystonia gene has been mapped to chromosome 18p. The authors evaluated the extent of the deletion in three patients with an 18p- syndrome and dystonia using 14 DNA markers on 18p. A common deleted area, covering the DYT7 locus, places the putative dystonia gene between the telomere of 18p and D18S1104 (49.6 cM). Dystonia in these patients may be caused by haploinsufficiency of the DYT7 gene, a new dystonia gene on 18p, or may result from developmental brain anomalies.