Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.     

Acute haemodynamic effects of dopexamine in patients with coronary arterial disease

We assessed the acute haemodynamic effects of dopexamine 1 microgram/kg/min and 3 micrograms/kg/min in 21 patients with coronary arterial disease following routine catheterisation. Patients were aged 38 to 72 years and left ventricular ejection fraction ranged from 23 to 79%. Dopexamine was well tolerated in all patients except one in whom transient ventricular arrhythmias occurred with 3 micrograms/kg/min. No patient developed angina. Dopexamine increased cardiac index (2.6 +/- 0.4 to 3.2 +/- 0.1 (P less than 0.001) and 4.0 +/- 1.0 1/min/m2 (P less than 0.001), control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively) and decreased systemic vascular resistance index (3356 +/- 1506 to 2318 +/- 809 (P less than 0.001) and 2252 +/- 1973 dyne.sec.cm-5/m2 (P less than 0.001], but did not affect systemic arterial, pulmonary arterial or right atrial pressure. Maximum positive dP/dt was increased (1294 +/- 324 to 1597 +/- 505 (P less than 0.001) and 2199 +/- 819 mmHg/sec (P less than 0.001] as was left ventricular stroke work index (44 +/- 20 to 51 +/- 21 (P less than 0.05) and 56 +/- 27 g.m/m2 (P less than 0.001) control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively). Left ventricular end diastolic pressure fell with 3 micrograms/kg/min from 19.8 +/- 6.9 to 12.4 +/- 4.6 mmHg (P less than 0.05) in patients with preserved left ventricular ejection fraction (greater than 50%, n = 6), but not in those with impaired left ventricular ejection fraction (less than 50%, n = 15), otherwise the effects in these two subgroups were similar. We conclude that dopexamine has both inotropic and vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiology and control of dengue virus infections in Thai villages in 1987

A severe epidemic of dengue hemorrhagic fever (DHF) in Nakhon Ratchasima, Thailand in August of 1987 prompted a field investigation. DHF rates of 0.4-6.5 cases per 1,000 residents in subdistricts and 2-15 cases per 1,000 residents in 10 villages investigated were reported. Epidemics peaked in neighboring villages at different times; in June and July, and in August before the rainy season began late in the month. In 4 primary schools representing 6 villages, sera from groups of randomly selected children were tested for dengue IgM with the antibody capture ELISA test. Rates of recent dengue infection were 10-65% in the schools and correlated closely with reported rates of DHF. In an effort to control vectors, malathion fog and temephos (1% abate sand granules) were applied. Villagers were educated in prevention and were urged to cover water receptacles. The percentage of houses with larvae dropped from 67 to 20, the percentage of containers with larvae decreased from 30 to 5, and the number of containers with larvae per 100 households decreased from 221 to 33. This was a serious epidemic in which conventional control measures were only moderately effective.     

Visceral fat and prevalence of hypertension among African Americans and Hispanic Americans: findings from the IRAS family study

BackgroundWe examined the relationship between visceral adipose tissue (VAT), independent of overall adiposity, and prevalent hypertension among adults enrolled in the Insulin Resistance Atherosclerosis (IRAS) Family Study. We also examined the role of insulin sensitivity (S(I)) upon hypertension. This was a cross-sectional epidemiological study in which African-American and Hispanic-American families were recruited from three clinical sites. The main outcome measure was prevalent hypertension, as defined by standardized protocol.MethodsThe relationship between VAT and prevalent hypertension was examined in adjusted marginal models among 1,582 participants. All continuous variables were standardized.ResultsA significant VAT by gender interaction prompted separate analyses for VAT according to gender. Further adjustment for S(I) was performed to determine its potential roles in the VAT-hypertension relationship. The mean age (s.d.) of the sample was 41.3 (13.8) years, with a mean body mass index (BMI) (s.d.) of 28.7 (6.0) kg/m(2). Women comprised 58.5% of the sample (N = 925), and Hispanic Americans comprised 69.2% of the sample (N = 1,095). One in five participants (21.2%) had prevalent hypertension. In women, VAT was significantly associated with hypertension, independent of BMI (odds ratio (OR) = 1.49, P = 0.006). African-American women demonstrated increased odds of prevalent hypertension compared to Hispanic-American women (OR = 3.08, P < 0.001). Among men, VAT was not associated with hypertension independent of BMI, and BMI explained a significant amount of the variation in hypertension.ConclusionsA significant relationship may exist between VAT and hypertension among women, but not among men. The relationship between VAT and hypertension in women was not associated with insulin resistance.American Journal of Hypertension (2008). doi:10.1038/ajh.2008.213American Journal of Hypertension (2008); 21, 8, 910-916. doi:10.1038/ajh.2008.213.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Background

Down’s syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer’s disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case–control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population.

Method

Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts).

Results

AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD.

Conclusions

DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less ‘cognitive reserve’.