Artemisinin enhances heme-catalysed oxidation of lipid membranes.

Artemisinin, a sesquiterpene endoperoxide derived from a traditional Chinese herbal remedy for fevers, is a promising new antimalarial drug, particularly useful against multidrug resistant strains of P. falciparum. Despite widespread clinical use, its mode of action remains uncertain.

A phantom study: evaluation of renal artery stenosis using helical CT and 3D reconstructions.

Purpose: We studied which set of CT parameters and modeling parameters yielded accurate measurements of three graded artificial renal artery stenoses.

Method: An acrylic phantom resembling the abdominal aorta and renal arteries was constructed. Stenotic segments had diameters of 1.

Evaluating health care management programs and schools of public health: some experiences in Europe.

The European Healthcare Management Association (EHMA) has built upon the ACEHSA model of accreditation to develop a European version-- program review--which takes account of the variety of health systems, cultures, and languages in Europe. This article describes the manner in which EHMA's ¿program review¿ evolved, and the distinctive features of the process. It then analyzes some of the lessons that have emerged from the twenty-two evaluations completed in nine countries, distinguishing between issues of effectiveness (needs, objectives, and outcomes) and efficiency (inputs, processes, and outputs).

Development of a single-shot subunit vaccine for HIV-1. 2. Defining optimal autoboost characteristics to maximize the humoral immune response.

The design of a single-shot subunit vaccine for HIV-1 with polylactic-coglycolic acid (PLGA) sustained-release technology to effect an autoboost of antigen (MN gp120) at a given time after the primary immunization requires in-depth knowledge about the timing, the duration, and the need for coadjuvant in the autoboost. These questions cannot be answered unambiguously with PLGA microspheres, so we have conducted studies using Alzet minipumps to release antigen at prescribed times to mimic a PLGA autoboost. The results show that a discrete autoboost is preferred over continuous release of antigen, that the time profile of the autoboost (whether pulsatile or a 2-week continuous release) does not affect the booster immune response, and that only antigen is required in the booster immunization (a coadjuvant in the boost does not give higher titers).

Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1.

Lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is involved in leukocyte adhesion during cellular interactions essential for immunologic responses and inflammation. mAbs against LFA-1 have been shown to inhibit several T cell-dependent immune functions in vitro and prevent graft failure after bone marrow transplantation in vivo. A murine anti-human CD11a mAb, MHM24, has been humanized and shown to prevent adhesion of human T cells to human keratinocytes and the proliferation of T cells in response to nonautologous leukocytes in the mixed lymphocyte response assay.

Salivary binding antibodies induced by human immunodeficiency virus type 1 recombinant gp120 vaccine. The NIAID AIDS Vaccine Evaluation Group.

Salivary binding antibodies induced by candidate human immunodeficiency virus type 1 (HIV-1) vaccines in healthy, HIV-1 uninfected volunteers were assessed in a clinical trial evaluating intramuscularly injected HIV-1MN recombinant gp120 (rgp120) vaccine alone or with HIV-1IIIB rgp120 vaccine. The two rgp120 vaccines induced envelope glycoprotein-specific immunoglobulin G (IgG) and IgA antibodies in whole saliva and serum.

Age bias, but no gender bias, in the intra-household resource allocation for health care in rural Burkina Faso.

Household survey data, time allocation data, and qualitative interviews were used to examine whether households allocate their resources for health care differently between age and gender groups. Households allocated significantly fewer resources to the health care of sick children compared to that of sick adults. In contrast there were no such differences with regard to gender.

Antibody to native human immunodeficiency virus type 1 envelope glycoproteins induced by IIIB and MN recombinant gp120 vaccines. The NIAID AIDS Vaccine Evaluation Group.

The ability of antibody induced by MN and IIIB recombinant gp120 (rgp120) human immunodeficiency virus type 1 (HIV-1) vaccines the bind to oligomeric native and monomeric recombinant HIV-1 envelope glycoproteins (rgp 120) was measured in 25 uninfected, healthy adult volunteers. A major focus was to evaluate the effect of simultaneous and sequential immunization with vaccines representing different strains of HIV-1 on the ability to broaden cross-reactivity of antibodies against these and other HIV-1 strains. A flow cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced antibody to envelope glycoprotein expressed by infected and rgp120-coated target cells was used, MN rgp120 HIV-1 vaccine given alone and coadministered with IIIB rgp120 HIV-1 vaccine elicited antibody which bound to cells infected with HIV-1MN, HIV-IIIB, HIV-1RF, and HIV-1-SF2.

The iron environment in heme and heme-antimalarial complexes of pharmacological interest.

Mössbauer spectroscopy has been utilized to probe the electronic environment of iron in a number of Ferriprotoporphyrin IX complexes of relevance to malaria. The markedly different iron environments found for the complexes of hemin with quinine, chloroquine, and the Chinese herbal antimalarial artesunate suggest that these compounds act by protecting the heme from polymerization to insoluble hemozoin, and by facilitating the transport of the protected heme to the food vacuole membrane where it is able to exercise its cytotoxic redox catalytic activity. Mössbauer parameters determined here for purified malaria pigment and synthetic beta-hematin confirm the chemical identical-ness of these species.

The role of private providers in maternal and child health and family planning services in developing countries.

This paper uses data from the Demographic and Health Surveys program (DHS) in 11 countries in Asia, Africa, and Latin America to explore the contribution of private health care providers to population coverage with a variety of maternal and child health and family planning services. The choice of countries and services assessed was mainly determined by the availability of data in the different surveys. Private providers contribute significantly to family planning services and treatment of children's infectious diseases in a number of the countries studied.

Antibodies that selectively inhibit leukocyte function-associated antigen 1 binding to intercellular adhesion molecule-3 recognize a unique epitope within the CD11a I domain.

Several studies indicate that the I domain located in the alpha chain (CD11a) of leukocyte function-associated antigen-1 (LFA-1; CD11a/CD18) plays an essential role in ligand recognition. We recently identified three distinct epitopes (IdeA, IdeB, and IdeC) within the CD11a I domain, recognized by antibodies that block binding of LFA-1 to intercellular adhesion molecules (ICAM) 1, 2, and 3. In the present study, we used a series of human/murine CD11a I domain chimeras, to localize a fourth I domain epitope (IdeD), recognized by three independently derived anti-CD11a antibodies that selectively block the binding of LFA-1 to ICAM-3, but not to ICAM-1.

Retail pharmacies in developing countries: a behavior and intervention framework.

Retail pharmacies in developing countries are one of the most important sources of advice on pharmaceuticals. Among the reasons the clients give are ease of access; availability of medicines; quality of service (no waiting and convenient hours of operation); and cheaper products, availability of credit, or the option to buy drugs in small amounts. However, the appropriateness of prescribing by retail pharmacy staff has been found to be far from acceptable.

Critical amino acids in the lymphocyte function-associated antigen-1 I domain mediate intercellular adhesion molecule 3 binding and immune function.

We have identified amino acid residues within the evolutionarily conserved I domain of the alpha-chain (CD11a) of the leukocyte integrin leukocyte function-associated antigen (LFA) 1 that are critical for intercellular adhesion molecule (ICAM) 3 (CD50) binding. ICAM-3, a ligand of LFA-1, is thought to mediate intercellular adhesion essential for the initiation of immune responses. Using a panel of human/murine I domain chimeras and point mutants, we observed that the Ile-Lys-Gly-Asn motif, located in the NH2-terminal part of the CD11a I domain, is required for ICAM-3 but not ICAM-1 binding.

Reaction between ferriprotoporphyrin IX and the antimalarial endoperoxide artesunate gives an intermediate species with enhanced redox catalytic activity.

The kinetics of the reaction between ferri(Fe(III) protoporphyrin IX (haemin) and the potent sesquiterpene endoperoxide antimalarial artesunate are shown to be consistent with a three-step, two-intermediate mechanism, with the final product possessing a degraded tetrapyrrole ring system. Microscopic rate constants for the mechanism have been evaluated. The redox catalytic capability of the haem artesunate complex is shown to be approximately fourfold that of haemin alone, suggesting a possible mechanism of action of the drug.

Experiences in paying for health care in India's voluntary sector.

This article summarizes the results of four in-depth case studies on the financing and costs of the health care programmes of well-known non-government organizations (NGOs) in India. These organizations have shown a high degree of creativity and innovation in developing varied sources of financing to reduce dependency and enable them to sustain their programmes. Government funds play a major role in supporting these voluntary health activities, with less significant roles played by foreign donations, user charges, pre-paid memberships, and public fund raising.

Comparison of rehabilitation practice on hospital wards for stroke patients.

Background And Purpose: The aim of the study was to observe patients on a stroke unit and to compare their activity with that of patients on conventional hospital wards to identify aspects of rehabilitation practice that might account for differences in outcome.

Methods: Stroke patients admitted to the hospital were observed on three 8-hour shifts over 3 consecutive days. An observer recorded, at 10-minute intervals, where patients were, what they were doing, and whether their positioning was as recommended by rehabilitation therapists.

Protection of MN-rgp120-immunized chimpanzees from heterologous infection with a primary isolate of human immunodeficiency virus type 1.

Three chimpanzees immunized with recombinant gp120 from human immunodeficiency virus type 1 (HIV-1) strain MN and 1 control animal were challenged intravenously with a primary isolate of HIV-1SF2. Viral infection was detected in the control animal by viral culture, polymerase chain reaction, and multiple serologic assays beginning 2 weeks after infection. Markers of HIV-1 infection were not detected in any of the gp120-vaccinated animals during 12 months of follow-up.