Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.

The antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum.

Malarial parasites and antioxidant nutrients.

Susceptibility to oxidative stress is a well-established feature of the malarial parasite. Pharmacologists have taken advantage of this property to design highly effective pro-oxidant antimalarial drugs. Less well appreciated is the fact that nutritional manipulation of host oxidative stress status by dietary means can have a profound effect on the growth of the parasite.

Observations of the time-course of the inflammatory response of rectal mucosa to gliadin challenge in gluten-sensitive subjects.

Expression of endothelial adhesion molecules is a key factor in localizing inflammatory processes. We have evaluated the time-course expression of E-selectin, ICAM-1, and VCAM-1 in rectal mucosae from coeliac patients (CD) with T-lymphocyte sensitization to wheat (gliadin) protein. Ten treated, eight untreated CD patients and five disease controls underwent a dynamic 4 h rectal gluten challenge.

Perception of risk for malaria and schistosomiasis in rural Malawi.

A sample of 120 individuals--representative of the Malawian population in terms of gender and age distribution--were interviewed regarding their perceptions of the diseases malaria and schistosomiasis. Particular attention was paid to judgements regarding the level, seriousness, predictability and controllability of these health risks. Sample sites were lowland marshland areas where both diseases were highly prevalent.

Interactions between interleukin-2-activated lymphocytes and vascular endothelium: binding to and migration across specialized and non-specialized endothelia.

A prerequisite for the successful immunotherapy of solid tumours with interleukin-2 (IL-2)-activated lymphocytes is their ability to home to the tumour tissue. Lymphocyte homing is a complex process which is known to involve at least two independently regulated events: adhesion to the luminal surface of vascular endothelium and the subsequent transendothelial migration of lymphocytes. In this study we have used an in vitro model of lymphocyte homing which employs specialized high endothelium to ask whether IL-2-activated lymphocytes are able to migrate across vascular endothelium in order to leave the blood vessel.

Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides.

Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50's against P.

Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria.

On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7-chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities.

Teaching skills through the enhancement of natural antecedents.

The manipulation of the natural antecedents of a task offers a potentially valuable alternative to teaching strategies requiring the presentation of additional prompting stimuli, particularly in work with individuals with severe learning difficulties. The utility of procedures involving the enhancement of natural antecedents has frequently been demonstrated, but this has generally been with respect to tasks of limited ecological validity. This study reports an attempt to teach coat-buttoning skills to two women with severe learning difficulties using an antecedent enhancement procedure.

Lymphocyte adhesion to high endothelium is mediated by two beta 1 integrin receptors for fibronectin, alpha 4 beta 1 and alpha 5 beta 1.

Using a rat model we have previously proposed a role for fibronectin as an adhesive ligand on high endothelial cells (HEC) for recirculating lymphocytes. Lymphocyte adhesion to high endothelial cells was blocked by CS1 peptide (from the type III connecting segment of fibronectin) and RGD-containing peptides using two different in vitro assays of lymphocyte-HEC recognition, the frozen section assay and cultured HEC. In order to study the receptors utilised by lymphocytes to bind to HEC we have developed a xenogeneic model in which the adhesion of human lymphocytes to HEC cultured from rat lymph nodes is measured.

Allograft rejection in CD4+ T cell-reconstituted athymic nude rats--the nonessential role of host-derived CD8+ cells.

PVG-rnu/rnu nude rats reject fully allogenic renal (DA) and skin (BN, AO) allografts after the adoptive transfer of naive CD4+ T cells alone, but rejection is accompanied by the accumulation of many nude-derived CD8+ leukocytes within the graft. In addition, mononuclear cells infiltrating the rejecting renal grafts in these animals display cytotoxic activity in vitro against specific and third-party alloantigens. In this investigation we have treated CD4+ T cell-restored nude rats bearing renal or skin allografts with the mAb MRC OX8 to deplete the host of CD8+ cells.

ICAM-1-independent lymphocyte transmigration across high endothelium: differential up-regulation by interferon gamma, tumor necrosis factor-alpha and interleukin 1 beta.

The adhesion of lymphocytes to cytokine-treated high endothelium was studied using cultured high endothelial cells (HEC). Pretreatment of the HEC layer with a variety of cytokines caused up-regulation of lymphocyte adhesion with the effects ordered interferon gamma (IFN-gamma) greater than tumor necrosis factor-alpha (TNF-alpha) greater than or equal to interleukin 1 beta (IL 1 beta). Increased lymphocyte adhesion was found to be independent of ICAM-1 as expression by HEC was not increased by cytokines and antibodies against ICAM-1 did not block adhesion.

Transdermal artelinic acid: an effective treatment for Plasmodium berghei-infected mice.

Artelinic acid, a derivative of the naturally occurring antimalarial artemisinin, has been incorporated into a gel suitable for transdermal administration. The formulation was tested for efficacy in Plasmodium berghei-infected mice for both curative and prophylactic properties by application to their partially denuded backs, beginning on days 3 and 0, respectively, after injection of parasitized erythrocytes. In the curative experiments, rapid elimination of the parasitemia and 60-day survival of five of five mice was achieved by dermal application of gel containing 0.

Allospecific recognition of hemic cells in vitro by natural killer cells from athymic rats: evidence that allodeterminants coded for by single major histocompatibility complex haplotypes are recognized.

We have previously shown that large granular lymphocyte (LGL)-enriched cell populations have the capacity to spontaneously recognize and kill allogeneic small lymphocytes and bone marrow cells (BMC) in vitro in certain strain combinations of rats. Here, we have studied the alloreactivity of natural killer (NK) cells from PVG nude (RT1c) rats against a panel of major histocompatibility complex (MHC) incompatible hemic cells. Both lymphocytes and BMC from the AO (RT1u), DA (RT1a), BN (RT1n) as well as the MHC-congenic PVG-RT1u (RT1u) rat strains were efficiently killed in vitro, whereas cells from syngeneic PVG rats were spared.

The relationship of staff:client ratios, interactions, and residential placement.

The behavior of staff and persons with severe handicaps was surveyed in nine settings, including four traditional institutions, three large community-based units, and two groups of small homes. Data were collected that established the relationship among staff:client interactions, client responding, and the size of staff:client groups. The latter showed that the institutions were characterized by larger client and staff groups than the large community units.

Evaluation of Army field sanitation during Blazing Trails '87.

US medical personnel serving in Ecuador analyzed how the field sanitation procedures of troops employed in Blazing Trails '87 had impact on living conditions and overall health of the troops. Such a situation allowed evaluation of USAR troop training and preparedness in field sanitation. Results indicate that field sanitation training needs to be improved at the unit level.

T cell receptor-bearing cells among rat intestinal intraepithelial lymphocytes are mainly alpha/beta+ and are thymus dependent.

Rearrangement of both the beta and gamma chain T cell receptor (TcR) genes was detected in intestinal intraepithelial lymphocytes (IEL) from normal euthymic rats. Flow cytometric analyses showed that about 73% of the IEL were CD3+ (1F4) and that 67% were TcR alpha/beta+ (R73). About 5% of the IEL were found to be CD3+, TcR alpha/beta- in double-labeling experiments suggesting that a small fraction of IEL in the rat express the alternative TcR gamma/delta.

Plasmodium yoelii: comparative antimalarial activities of dietary fish oils and fish oil concentrates in vitamin E-deficient mice.

Feeding vitamin E-deficient diets containing either fish oils such as menhaden, salmon, or anchovy oil or fish oil concentrates based on n-3 ethyl esters or free fatty acids protected mice against Plasmodium yoelii as indicated by decreased parasitemia and improved survival. The fish oil concentrates depressed plasma tocopherol levels more strongly in vitamin E-supplemented mice than the menhaden oil. The free fatty acid concentrate appeared to suppress parasitemia in vitamin E-deficient mice better than the menhaden oil, although ultimate survival was similar in both groups.

The importance of sustainability in the design of culturally appropriate programmes of early intervention.

The need for early intervention with regard to children with developmental disabilities is of increasingly universal relevance. The means adopted in pursuit of this end will, however, vary appropriately across cultures. All intervention programmes will inevitably share many features in common, but to be truly effective, programmes need to take into account circumstances in the locality in which they operate.

Cationic antiprotozoal drugs. Trypanocidal activity of 2-(4'-formylphenyl)imidazo[1,2-a]pyridinium guanylhydrazones and related derivatives of quaternary heteroaromatic compounds.

A series of quaternary 2-phenylimidazo[1,2-a]pyridinum salts has been prepared and evaluated for antiparasitic activity. Primary attention was focused on derivatives with amido, substituted hydrazone, and heterocyclic functionality at the para position of the phenyl substituent. Guanylhydrazones and N-substituted guanylhydrazones of the 4'-formyl-substituted compounds are very active against the blood state Trypanosoma rhodesiense in mice by subcutaneous or oral administration.

Use of synthetic peptides to probe lymphocyte--high endothelial cell interactions. Lymphocytes recognize a ligand on the endothelial surface which contains the CS1 adhesion motif.

The extravasation of recirculating lymphocytes into lymph nodes, which is crucial for immune system function, occurs constitutively from specialized post-capillary venules in the lymph node paracortex. The migration of lymphocytes between the structurally distinct high endothelial cells which line these blood vessels is a rapid process involving highly specific cellular recognition events. Although a number of lymphocyte surface molecules have been identified that mediate adhesion to high endothelial cells (the first step in extravasation), the equally important endothelial molecules which serve as their ligands are still poorly understood.

Menhaden-fish oil in a vitamin E-deficient diet: protection against chloroquine-resistant malaria in mice.

Feeding a vitamin E-deficient diet containing 5% menhaden oil to mice affords significant protection against both a chloroquine-sensitive and a chloroquine-resistant line of the malarial parasite. Nutritional manipulation may offer a new approach to the problem of drug-resistant malaria, a rapidly emerging global threat to public health.

Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii.

Young female mice were fed torula-yeast-based diets deficient in vitamin E or selenium or supplemented with cod-liver oil to determine the effect of host antioxidant status on the therapeutic efficacy of the Chinese traditional antimalarial drug qinghaosu (QHS), a sesquiterpene endoperoxide. Vitamin E deficiency enhanced the antimalarial action of QHS against Plasmodium yoelii, both in terms of decreased parasitemia and improved survival but Se deficiency did not. A vitamin E-deficient diet containing 5% cod-liver oil had such strong antimalarial activity in itself that no additional therapeutic benefit of QHS could be demonstrated.

Major histocompatibility complex control of NK-related allogeneic lymphocyte cytotoxicity in rats. The contributions of strong and medial transplantation antigens.

Allogeneic lymphocyte cytotoxicity (ALC) describes the elimination of allogeneic lymphocytes in vivo by an NK-related activity. There is evidence that ALC is demonstrable between donor and recipient when these are incompatible at MHC gene loci alone. Since ALC is a property of T cell-deficient nude rats, the role of the MHC in this rejection process needs further study.

Interaction between lymphocytes and cultured high endothelial cells: an in vitro model of lymphocyte migration across high endothelial venule endothelium.

The interaction between lymphocytes and cultured high endothelial venule endothelium has been studied using light and electron microscopy. High endothelial cells (HEC) in monolayer culture bound lymphocytes 15-200-fold more efficiently than aortic endothelium, aortic fibroblasts or serum-coated glass. Light microscopy of lymphocytes bound to HEC showed two populations.