Effects of deoxynivalenol consumption on body weight and adiposity in the diet-induced obese mouse.

The potential for the obese state to alter sensitivity to toxic chemicals is poorly understood. In this study, dose-response effects of the trichothecene deoxynivalenol (DON), a common food-borne mycotoxin, were determined on body weight of diet-induced obese mice. In study 1, the effects of feeding adult female B6C3F1 mice a high-fat diet (HFD; 60% kcal from fat) containing 0, 2, 5, or 10 ppm DON for 10 wk on body weight and adiposity were compared. Mice consuming 5 or 10 ppm DON exhibited a 15 and 24% decrease in weight gain and a 50 and 83% reduction in periuterine fat, respectively. In study 2, mice were fed HFD for 8 wk to induce obesity and the effects of consuming HFD + 0, 2, 5, or 10 ppm DON for 8 wk were then determined. Mice fed 5 or 10 ppm DON exhibited a 16 and 23% weight reduction and a 0 and 40% periuterine fat reduction, respectively. In a follow-up experiment, food consumption was measured prior to and after the transition from HFD to HFD + 10 ppm DON. Exposure to DON was found to lower HFD consumption within 1 d, with significant weight loss in DON-fed mice evident after 6 d. In both studies 1 and 2, consumption of 5 or 10 ppm DON diminished circulating levels of insulin-like growth factor acid-labile subunit. Taken together, DON consumption lowered weight gain and produced weight loss in diet-induced obese mice at higher thresholds than that observed previously in normal B6C3F1 mice.

Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain: potential mechanisms for HIV dementia.

The CXC chemokine receptor CXCR4 was the first molecule identified as a coreceptor working in conjunction with CD4 to mediate cellular entry for the human immunodeficiency virus (HIV-1). Since that original discovery, 11 other seven-mtransmembrane domain molecules, many of which are chemokine receptors, have been shown to facilitate HIV entry into cells. These include CCR5, CCR3, CCR2, CCR1, CCR8, CX3CR1, STRL33 (BONZO), GPR15 (BOB), GPR1, US28, and APJ. In studies done by this and other labs, CCR3, CCR5, and CXCR4 have been identified in CNS microglia and several laboratories, including ours, have shown that CXCR4 is expressed in neurons. Neuronal expression of CCR2, CCR3, and CCR5 has been less consistent. We performed a semiquantitative immunohistochemical analysis of the expression of CCR2, CCR3, CCR5, and CXCR4 in 23 regions of the brain and in two sections of the spinal cord. Hippocampal neurons were positive for CCR2, CCR3, and CXCR4, but not for CCR5. In other regions of the brain, neurons, and glial cells reacted with anti-CCR2, anti-CCR3, and anti-CXCR4 antibodies, whereas only glial cells (primarily microglia) were positive for CCR5. The areas of highest expression, however, seem to be subcortical regions and the limbic system. The limbic system plays a key role in memory, and the presence of CXCR4-which can bind the viral envelope protein gp120-min a subset of neurons from this system may play a role in the development of HIV-related dementia.

Chemokine receptors in the human brain and their relationship to HIV infection.

Chemokine receptors have been recently identified as the important co-factors which in conjunction with CD4, mediate entry of HIV into its target cells. The brain is one of the most prominent targets of HIV infection, where it leads to HIV encephalitis (HIVE) and HIV-associated dementia. Knowledge of the distribution, physiology, and pathology of chemokines and chemokine receptors in the human brain is fundamental for understanding the pathogenesis of the interaction between HIV and the central nervous system (CNS). There is also increasing evidence that chemokine receptors expression in the CNS increases during pathological, especially inflammatory, conditions. The major co-factors for HIV infection, CCR5, CCR3, and CXCR4 have been detected in the human brain in a variety of cell types including microglia, astrocytes, neurons, and vascular endothelial cells. Furthermore, antibodies to chemokine receptors can also block HIV infectivity in cultured CNS cells. This indicates that chemokine receptors are likely to have a functional role in the pathogenesis of HIVE.

CXCR-4 (Fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons.

Entry of the type 1 human immunodeficiency virus into most cells requires the presence of the CD4 protein in combination with one of several recently described co-receptors. CXCR-4 (fusin) was the first identified, and it serves as co-receptor for T-cell-line tropic (T-tropic) HIV-1 isolates. To determine the expression of CXCR-4 in the brain, a major target of HIV pathology, we used immunohistochemistry and reverse transcriptase polymerase chain reaction with CXCR-4-specific antibodies and probes. We found that CXCR-4 was expressed in several cell types in brain, but notably in neurons and microglia, a finding that was replicated in tissue culture. The study of the expression of CXCR-4 in the brain, which may be one of many chemokine receptors in the central nervous system, may provide further insight into the interactions between brain cells, pathogens, and the immune system, and help understand the pathogenesis of HIV dementia.

Defensin stimulates the binding of lipoprotein (a) to human vascular endothelial and smooth muscle cells.

There is evidence to suggest that elevated plasma levels of lipoprotein (a) [Lp(a)] represent a risk factor for the development of atherosclerotic vascular disease, but the mechanism by which this lipoprotein localizes to involved vessels is only partially understood. In view of studies suggesting a link between inflammation and atherosclerosis and our previous finding that leukocyte defensin modulates the interaction of plasminogen and tissue-type plasminogen activator with cultured human endothelial cells, we examined the effect of this peptide on the binding of Lp(a) to cultured vascular endothelium and vascular smooth muscle cells. Defensin increased the binding of Lp(a) to endothelial cells approximately fourfold and to smooth muscle cells approximately sixfold. Defensin caused a comparable increase in the amount of Lp(a) internalized by each cell type, but Lp(a) internalized as a consequence of defensin being present was not degraded, resulting in a marked increase in the total amount of cell-associated lipoprotein. Abundant defensin was found in endothelium and in intimal smooth muscle cells of atherosclerotic human cerebral arteries, regions also invested with Lp(a). These studies suggest that defensin released from activated or senescent neutrophils may contribute to the localization and persistence of Lp(a) in human vessels and thereby predispose to the development of atherosclerosis.

The prevalence and distribution of schistosomiasis in Zambia.

PIP: This paper attempts to approach an accurate report of prevalence of schistosomiasis in Zambia by bringing together several reports. A review of some early prevalence studies in Zambia shows the prevalence of S. hematobium infection to be (14-40%) and that for S. mansoni to range from (0-7%), in the Northern and Luapula Provinces. The areas around Lakes Kariba in the south, and Bangweulu in the north had prevalence rates of (3-35%) for S. hematobium and (2-6%) for S. mansoni. A nationwide survey found the overall prevalence of S. hematobium to be about 16%. The Gwembe Valley in the South had the highest prevalence of 57.9% for S. hematobium; S. mansoni with a prevalence of (45-77%) in the Northern Province from more recent studies is not very widespread. A comprehensive study performed between 1969-73 covered almost the entire rural population and found an overall prevalence of 16.8%, varying greatly between ecozones. The 5-14 year age group showed the highest prevalence. A 1976-82 study of rural primary school children in several provinces found high prevalence rates. Specimen gathering and analysis is described for most studies analyzed, revealing some inconsistencies threatening the reliability of data. Available data do show the spotty and local nature of the prevalence rates between areas. There have not been many studies of S. mansoni prevalence, possibly due to the difficulties involved with the collection of stool specimens, but prevalence (especially seasonal) has been shown to be high in certain areas (although low generally). The areas around the 2 major lakes show considerable prevalence of both parasites, and further study is needed on the health impact of man-made lakes in Zambia and elsewhere.^ieng

A national study of fluoride mouthrinse adoption: implications for school health personnel.

The ongoing adoption of school-based fluoride mouthrinse programs in the U.S. has provided the opportunity to study the issues surrounding the adoption and implementation of a health technology by public schools. Findings from a National Study on the Diffusion of Preventive Health Measures to Schools have been selected for analysis with regard to the role of school health personnel in the adoption and delivery of the service. A more visible role for school health personnel as on-site health experts is discussed, as well as the potential ways for increasing their involvement through facilitating initial program adoption, relaying accurate and up-to-date implementation information to decision-makers, developing a constituency for long-term program support and ensuring program accuracy through monitoring and continuing education.

A double-blind comparative clinical trial of mefloquine and chloroquine in symptomatic falciparum malaria.

A total of 99 male Zambian patients with symptomatic falciparum malaria were treated in a double-blind randomized manner with either mefloquine (1000 mg given in one day) or chloroquine (1500 mg given over 3 days). An S-type response was seen in all the chloroquine patients and 98% of the mefloquine group; one patient in the latter group (2%) showed an RI-type response, but the parasites obtained during the recrudescence were sensitive to both chloroquine and mefloquine in the in vitro microtest, and the patient responded satisfactorily to oral chloroquine. The rate of clearance of parasitaemia was marginally faster in the chloroquine-treated group. The rate of clearance of fever was similar in the two groups. Both drugs were well tolerated and side-effects such as nausea, vomiting, dizziness, loose stools, and pruritus were mild and transient. Pruritus was more common after chloroquine administration and dizziness more common in the mefloquine group. There were no drug-induced alterations in the haematological and biochemical profiles.

Initial experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium.

Initial studies of the tolerance and efficacy of praziquantel in the treatment of human infections due to Schistosoma haematobium were conducted at the WHO Tropical Diseases Research Centre, Ndola, Zambia. The first stage of the trial was a double-blind assessment against placebo of the tolerance and efficacy of oral doses of 1x20, 2x20, or 3x20 mg/kg in patients with a minimum schistosome egg excretion of 50 per random 10-ml sample of urine. Later a single-blind trial was carried out of the efficacy of three oral doses, each of 20 mg/kg, given at 4-hour intervals, or of a single oral dose of 50 mg/kg.In 79 young Zambians with S. haematobium infections (and often other parasitic infections), patient tolerance to the drug was very good, only minor post-treatment symptoms of intermittent epigastric pain, anorexia, and headache being noted, all of short duration.No changes of clinical relevance were detected in the results of a battery of haematological and biochemical tests. Post-treatment eosinophilia occurred in 42% of drug-treated patients but also in 30% of those given placebo. Serial electrocardiograms revealed no changes of significance.At six months after treatment, of 73 patients followed up, only 1 case of parasitological failure was detected. At one year, 66 (83.5%) of 79 patients with S. haematobium infection were followed up and 2 (2.5%) parasitological failures were detected.Two years after treatment, 45 (57%) of 79 patients with S. haematobium showed negative urines, 7 (9%) had positive hatching tests, and 27 (34%) were absent.