A plea for justice for jailed medical workers.
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Child↗
Biomedical subjects
Robin Shattock
Publications and source records attributed to Robin Shattock.
Microbicides 2006 conference.
Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23-26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.
Journal Article↗
Selective transmission of CCR5-utilizing HIV-1: the 'gatekeeper' problem resolved?
Understanding the mechanisms of HIV-1 transmission is crucial for the development of effective preventive microbicides and vaccine strategies, and remains one of the main goals of HIV research. Over the past decade, many studies have focused on trying to identify the 'gatekeeping' mechanism that restricts the transmission of CXCR4-utilizing HIV-1 more efficiently than CCR5-utilizing HIV-1. However, to date, no study has explained the almost perfect negative selection of the former in vivo. Here, we propose that there is no single gatekeeper and that, instead, the selective transmission of R5 HIV-1 depends on the superimposition of multiple imperfect gatekeepers.
HIV Infections↗
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. CAP blocked infection by cell-free and cell-associated HIV-1 in cervical explants. It inhibited infection by cell-free primary HIV-1 isolates (clades A to G and group O) in PBMCs, MDMs, and CEMx174 5.25M7 cells and blocked transmissions of the cell-associated primary HIV-1 isolates from dendritic cells (DCs) to PBMCs, from MDMs to PBMCs, and from PBMCs to CEMx174 5.25M7 cells. The inhibitory activity of CAP on infection by the cell-free and cell-associated primary HIV-1 isolates is independent of viral subtypes and coreceptor usage. These data suggest that CAP is a good microbicide candidate that can be further developed for preventing sexual transmission of HIV-1.
Anti-HIV Agents↗
Interleukin-8 levels in seminal plasma in chronic prostatitis/chronic pelvic pain syndrome and nonspecific urethritis.
OBJECTIVE: To investigate whether a range of cytokines were detectable in the seminal plasma and urine of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and nonspecific urethritis (NSU), and whether cytokine levels correlated with symptom severity in CP/CPPS. PATIENTS AND METHODS: In all, 87 men participated, 33 with CP/CPPS, 31 with NSU, and 23 controls. Interleukin (IL)-1beta, IL-2, IL-6, IL-8 and IL-10 were measured in seminal plasma and first pass urine, and the results were correlated with scores for pain, urinary symptoms and quality-of-life impact using a validated symptom index, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). RESULTS: Seminal plasma levels of IL-8 were higher in men with CP/CPPS and NSU than in controls (P < 0.001), and the levels correlated with NIH-CPSI symptom scores in men with CP/CPPS. There were no significant differences in urinary IL-8 levels in the three groups, and no significant differences in levels of the other cytokines in either semen or urine. CONCLUSION: Semen IL-8 levels correlate with subjective symptoms in men with CP/CPPS. IL-8 might contribute to the pathophysiology of CP/CPPS and NSU, and elevated levels might be a useful marker of the condition.
Adult↗
In vitro and in vivo: the story of nonoxynol 9.
There is an urgent need to expand the range of interventions to prevent HIV transmission and acquisition, especially those that can be controlled by women. Microbicides, defined as antimicrobial products that can be applied topically for the prevention of HIV and other sexually transmitted infections, may offer one of the most promising preventive interventions, because they could be inexpensive, readily available, and widely acceptable. The first microbial product to be clinically evaluated contained Nonoxynol-9 (nonylpenoxypolyethoxyethanol [N-9]), a nonionic surfactant, as the active agent. This article presents a review of the in vitro, ex vivo, and animal model data on the safety of N-9 and a critical analysis of their predictive power based on the results of multiple safety and efficacy trials.
Acquired Immunodeficiency Syndrome↗
IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis.
In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-gamma, TNF-alpha, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-alpha, IFN-gamma, and IL-6 levels and baseline cryptococcal CFU. Log IFN-gamma, G-CSF, TNF-alpha, and IL-6 were correlated positively with the rate of fall in log CFU/ml CSF/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-gamma remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-gamma secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-gamma in the treatment of refractory HIV-associated cryptococcosis.
Cryptococcus neoformans↗
The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells.
Heterosexual transmission of human immunodeficiency virus remains the major route of transmission worldwide; thus, there is an urgent need for additional prevention strategies, particularly those that could be controlled by women. Using cellular and tissue explant models, we have evaluated the potential activity of thiocarboxanilide nonnucleoside analogue reverse transcriptase inhibitor UC-781 as a vaginal microbicide. We were able to demonstrate a potent dose-dependent effect against R5 and X4 infections of T cells. In human cervical explant cultures, UC-781 was not only able to inhibit direct infection of mucosal tissue but was able to prevent dissemination of virus by migratory cells. UC-781 formulated into a carbopol gel (0.1%) retained significant activity against both direct tissue infection and transinfection mediated by migratory cells. Furthermore, UC-781 demonstrated prolonged inhibitory effects able to prevent both localized and disseminated infections up to 6 days post compound treatment. Additional studies were carried out to determine the concentration of compound that might be required to block a primary infection within draining lymph nodes. While a greater dose of compound was required to inhibit both X4 and R5 infections of lymphoid versus cervical explants, this was equivalent to a 1:3,000 dilution of the 0.1% formulation. Furthermore, a 2-h exposure to the compound prevented infection of lymphoid tissue when challenged up to 2 days later. The prolonged protection observed following pretreatment of both genital and lymphoid tissues with UC-781 suggests that this class of inhibitors may have unique advantages over other classes of potential microbicide candidates.
Acrylic Resins↗
Microbicides--aids to safer sex.
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Administration, Intravaginal↗