Development and psychometric testing of an instrument for measuring social participation of adolescents: study protocol of a prospective mixed-methods study.

Introduction: Social participation is an important part of a young person's life. It influences the social experience, social-emotional development and dimensions of competence experience. This applies to people with or without physical disabilities or chronic diseases.

Human immunodeficiency virus type 1 nucleocapsid inhibitors impede trans infection in cellular and explant models and protect nonhuman primates from infection.

Here, we report that the S-acyl-2-mercaptobenzamide thioester (SAMT) class of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NCp7) inhibitors was able to prevent transmission of HIV-1 from infected cells, including primary cells. Furthermore, when SAMTs were introduced during an HIV-1 challenge of cervical explant tissue, inhibition of dissemination of infectious virus by cells emigrating from the tissue explants was observed. Preliminary studies using a rhesus macaque vaginal challenge model with mixed R5 and X4 simian-human immunodeficiency virus infection found that five of six monkeys were completely protected, with the remaining animal being partially protected, infected only by the R5 virus.

Development of a gel permeation chromatographic assay to achieve mass balance in cellulose acetate phthalate stability studies.

Cellulose acetate phthalate (CAP, cellulose acetate 1,2-benzenedicarboxylate) is a common polymeric oral tablet coating. CAP is also a vaginal microbicide candidate that potently inhibits HIV-1 proliferation. This paper describes the development of a precise, stability-indicating gel permeation chromatography (GPC) assay for CAP.

Anti-HIV-1 activity of poly(mandelic acid) derivatives.

Homo- and heterochiral poly(mandelic acid)s (PMDAs) were synthesized under strongly acidic, mildly acidic, and nonacidic conditions. The water-soluble fractions of these polymers were evaluated with respect to their inhibitory activity against the human immunodeficiency virus (HIV-1). Polymers were prepared via a step-growth mechanism, yielding linear polyesters.

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides.

Background: Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined.

Cellulose acetate 1,2-benzenedicarboxylate inhibits infection by cell-free and cell-associated primary HIV-1 isolates.

Cellulose acetate 1,2-benzenedicarboxylate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was previously shown to have potent inhibitory activity against infection by human immunodeficiency virus type 1 (HIV-1) T cell line-adapted (TCLA) strains. In the present study, we determined the inhibitory activity of CAP against infection by cell-free and cell-associated primary HIV-1 isolates with distinct genotypes and biotypes in cervical explants, peripheral blood mononuclear cells (PBMCs), monocytederived macrophages (MDMs), and CEMx174 5.25M7 cells.

Punica granatum (pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide.

For approximately 24 years the AIDS pandemic has claimed approximately 30 million lives, causing approximately 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic.

Safety and distribution of cellulose acetate 1,2-benzenedicarboxylate (CAP), a candidate anti-HIV microbicide in rhesus macaques.

Objectives: To assess the safety and distribution of a cellulose acetate 1,2-benzenedicarboxylate (CAP) gel formulation in rhesus macaques as part of the development process for its use as a vaginally administered product in humans.

Design: The similarities between the reproductive physiology, anatomy and vaginal microflora of human and non-human primates makes non-human primates a relevant animal model to assess the safety and distribution of candidate anti-HIV microbicides.

Methods: CAP gel was instilled once or once daily for 4 days into the vaginal vault of rhesus macaques.

Cellulose acetate 1,2-benzenedicarboxylate protects against challenge with pathogenic X4 and R5 simian/human immunodeficiency virus.

Objectives: To evaluate the protective efficacy of cellulose acetate 1,2-benzenedicarboxylate (CAP) formulated in a glycerol-based gel against infection with CXCR4 (X4) and CCR5 (R5) viruses in the simian/human immunodeficiency virus (SHIV)/rhesus macaque model of HIV-1 transmission.

Design: Mucosal infection of non-human primates is a reasonable model for use in the investigation of HIV-1 intervention strategies.

Methods: Rhesus macaques treated with Depo-Provera 5 weeks prior to challenge were inoculated intravaginally twice, over a period of 6 h with mixed inocula of pathogenic X4- and R5-SHIV in the presence or absence of CAP.

Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic and complementary effects against human immunodeficiency virus type 1 infection.

The combination of two candidate microbicides, cellulose acetate 1,2-benzenedicarboxylate (CAP), a polymer that blocks human immunodeficiency virus type 1 (HIV-1) entry by targeting gp120 and gp41, and UC781, a tight-binding HIV-1 reverse transcriptase inhibitor (RTI), resulted in effective synergy for inhibition of MT-2 cell infection by HIV-1(IIIB), a laboratory-adapted virus strain. The 95% effective concentration values for the combination were reduced about 15- to 20-fold compared with those corresponding to the single compounds. The combination of CAP and UC781 is also synergistic in inhibiting infection of peripheral blood mononuclear cells by a primary HIV-1 isolate, 92US657.

Anti-human immunodeficiency virus type 1 microbicide cellulose acetate 1,2-benzenedicarboxylate in a human in vitro model of vaginal inflammation.

The sexual transmission of human immunodeficiency virus type 1 (HIV-1) is facilitated by inflammation and related epithelial barrier perturbation. Microbicides for vaginal applications are currently being developed to reduce the risk of HIV-1 transmission. However, little is known about their interference with epithelial immune function.

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide.

Background: For approximately 24 years the AIDS pandemic has claimed approximately 30 million lives, causing approximately 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic.

Water dispersible microbicidal cellulose acetate phthalate film.

Background: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS).

Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides.

Background: Cellulose acetate phthalate (CAP) in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH < 5.5, normal for microbicide target sites.

Anti-HIV-1 activity of cellulose acetate phthalate: synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles.

Background: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles.

Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants.

Naturally occurring deletions within the human hepatitis B virus (HBV) preS2 region have frequently been identified in patients with hepatocellular carcinoma (HCC), while chronic carriers without cirrhosis and HCC contain no detectable preS2 deletion variants. We have characterized two different preS2 internal deletion variants from two patients. In addition to several weak phenotypes, our study revealed three unexpected strong phenotypes: (1) a paradoxical "hypermodification" phenomenon was observed with significantly increased size heterogeneity and molecular weights of the secreted middle (M) envelope proteins containing a preS2 internal deletion.

Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120.

Background: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus.

Methods: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope.

Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants.

Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1(Ba-L) infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.

Effect of a cellulose acetate phthalate topical cream on vaginal transmission of simian immunodeficiency virus in rhesus monkeys.

Human immunodeficiency virus type 1 (HIV-1) infection continues to spread in developing countries, mostly through heterosexual transmission. The development of a safe and cost-effective topical microbicide, effective against a range of STDs including HIV-1, would greatly impact the ongoing epidemic. When formulated in a vehicle, a micronized form of cellulose acetate phthalate (CAP), which is an inactive pharmaceutical excipient, has been shown to inactivate HIV-1, herpes simplex virus types 1 and 2, cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi, and Chlamydia trachomatis in vitro.

Microbicide for prevention of sexually transmitted diseases using a pharmaceutical excipient.

Preferred microbicides are expected to inactivate most sexually transmitted viral and nonviral pathogens, including HIV-1, without affecting lactobacilli, components of the natural defense system against sexually transmitted diseases (STDs), be widely available, be inexpensive, and have an established safety record for human use. We show here that cellulose acetate phthalate [C-A-P enteric coating polymer (Eastman)], a compound used for coating of enteric tablets, meets all these criteria.

Cellulose acetate phthalate (CAP): an 'inactive' pharmaceutical excipient with antiviral activity in the mouse model of genital herpesvirus infection.

The spread of sexually transmitted infections caused by herpes simplex virus type 2 (HSV-2) has continued unabated. At least 20% of the United States population has been infected with HSV-2 and there is a high probability of further virus transmission by asymptomatic carriers. Given the absence of effective vaccines, this indicates the need to develop prophylactic measures such as topical microbicides that have antiviral activity.

Kinetics of interaction between 3-hydroxyphthaloyl-beta-lactoglobulin and CD4 molecules.

Kinetics of 3-hydroxyphthaloyl-beta-lactoglobulin-CD4 interaction were evaluated using a biosensor instrument based on surface plasmon resonance. A very fast association (k(a)=2.4+/-0.