ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewIn the past few years, mitochondria have been carefully studied to ascertain whether and how in patients affected by HIV antiretroviral therapy is able to alter their functionality and exert a toxic effect on immune cells, as well as on cells present in other districts.Recent findingsA variety of in-vivo and ex-vivo models have been developed to investigate the functionality of mitochondria and DNA during a variety of physiopathological situations, including HIV infection and its treatment. Numerous technologies are available to study at the single-cell or at the single-organelle level a variety of parameters, such as membrane potential, the activity of respiratory chain enzymes, and DNA content or its sequence. As far as in-vitro studies are concerned, a substantial homogeneity of data exists, and several changes in different mitochondrial parameters have been described that depend upon the drug used, the cell model and the parameter investigated. On the other hand, different results have been reported on biological material collected from HIV-positive patients and immediately analysed. Ex-vivo studies showed that changes in mitochondrial DNA content or in the functionality of the organelle exist in some tissues or cells, but not in others.SummaryOne of the possible causes of the discrepancies is the technologies used to investigate mitochondria, and this paper summarizes some of the pros and cons of the main methods used to study mitochondrial function or DNA.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewTo review recent clinical data regarding viral fitness and its potential utility in clinical practice.Therapeutic failure of antiretroviral regimens is often due to the development of drug resistance. The viral loads achieved by these drug-resistant variants frequently remain suppressed below pretreatment levels. Furthermore, many patients with virologic failure continue to maintain stable CD4 counts and remain clinically well. One possible explanation for these observations is that the resistant virus that emerges during failure of highly active antiretroviral therapy is less fit than its wild-type counterpart as a result of the requirement to maintain resistance mutations that allow it to replicate in the presence of antiretroviral drugs. Since there are many patients with limited treatment options due to extensive resistance or drug toxicities, or both, there is intense interest in exploring the possibility that viral fitness can be exploited for clinical benefit. This review describes the assays that are used to measure fitness and replication capacity, and investigations of their utility in clinical practice.Recent findingsA number of methods have been developed to measure viral fitness. Replication kinetic and competitive culture assays are accurate, but labour and time intensive. The availability of a rapid, single-cycle recombinant assay that measures viral replication capacity presents the possibility that assessments of viral fitness could be incorporated into clinical management. The replication capacity assay appears to correlate with more standard measures of viral fitness, and recently accumulated data in both wild-type and drug resistant viral populations suggest that replication capacity describes an intrinsic characteristic of HIV-1. A number of investigations of the clinical utility of fitness and replication capacity assays have established correlations between these measurements and virologic and immunologic outcomes.SummaryMuch progress has been made in the past year in our understanding of viral fitness and replication capacity. Assays that measure these viral characteristics have the potential to expand the range of clinical strategies employed against HIV-1. Further investigations are needed to firmly establish the clinical utility of these assays.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewIn this review we will discuss the recent finding that different drug classes/antiretroviral therapy regimens may differ importantly with respect to their effect on the plasma lipid profile. On the basis of this we will illustrate how such differences, together with knowledge of the presence of other classic coronary artery disease risk factors, open the door for individualized treatment based on criteria in addition to the HIV-1 viral load and CD4 cell count.Recent findingsA large proportion of patients using protease inhibitor-based therapy develop insulin resistance and elevated plasma concentrations of LDL-cholesterol, total cholesterol and triglycerides, which has raised the concern that HIV-infected patients treated with antiretroviral therapy may be at an increased risk of developing premature coronary artery disease. Recent findings suggest that the use of non-nucleoside reverse transcriptase inhibitor-based therapy, in particular nevirapine, results in an elevation in HDL-cholesterol, which may be associated with a decreased incidence of coronary artery disease.SummaryIt is becoming increasingly important to carry out an adequate coronary artery disease risk assessment in each patient both before and approximately annually after the initiation of antiretroviral therapy. In patients with an already considerable risk of coronary artery disease based on traditional risk factors, particularly when it is expected to be difficult to modify these, starting with either a triple nucleoside reverse transcriptase inhibitor or a non-nucleoside reverse transcriptase inhibitor-based regimen may be the preferred option, given the propensity of such regimens to have either no effect or potentially even beneficial effects on the lipoprotein profile.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewAlthough the incidence of Kaposi's sarcoma in established market economies has fallen since the introduction of highly active antiretroviral therapy, it remains the most common tumour in individuals with HIV infection. Kaposi's sarcoma-associated herpesvirus is the aetiological agent of Kaposi's sarcoma and its role in the subversion of cellular machinery provides an understanding of the fundamental mechanisms involved in immunobiology and carcinogenesis. The focus of this review will be to discuss articles published from August 2001 to August 2002 that provide advances in our knowledge of this process, and also to review new data concerning the transmission and identification of Kaposi's sarcoma-associated herpesvirus infection in different populations.Recent findingsWe have an improved understanding of the epidemiologies of classic, endemic, post-transplant and AIDS-associated Kaposi's sarcoma. The role of specific genes in tumorigenesis has been further defined, with particular reference to the switch from latent to lytic infection and the involvement of cytokines and angiogenic factors.SummaryKaposi's sarcoma-associated herpesvirus is widespread in immunosuppressed individuals and is associated with significant morbidity and mortality. The study of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus represents an important model of the interplay between the immune system and cancer, and may lead to the development of clinically useful therapies including vaccines.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewTo review the published literature on pelvic inflammatory disease over the past year and put into context the major findings.Recent findingsChlamydia trachomatisremains the commonest identified cause of pelvic inflammatory disease, and yet our understanding of how it causes mucosal damage and the factors explaining why only a subgroup of women develop pelvic inflammatory disease are not known. The increasing evidence for a chlamydial toxin may help to explain how tissue damage occurs and the indolent nature of many chlamydial infections. The evidence forMycoplasma genitaliumas an important sexually transmitted cause of pelvic inflammatory disease is growing, with implications for treatment regimens and diagnostic testing. Power Doppler ultrasound has been reported to be both sensitive and specific in diagnosing pelvic inflammatory disease, although larger studies are needed to confirm these early results. Outpatient treatment with cefoxitin and doxycycline appears to be as effective when given in an outpatient setting compared with inpatient management with the same agents in a large randomized controlled trial with almost 3 years' follow-up.SummaryThere remain many gaps in our knowledge of pelvic inflammatory disease, but the reviewed studies increase our understanding of the pathogenesis of infection, and offer the possibility of better diagnosis and reassurance about the long-term success of antibiotic treatment.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewDespite much interest in the mechanisms of immune protection against sexually transmitted diseases (STDs), little is known about the role of the immune system in the genital tract. A better knowledge is needed to understand not only host protection against STDs, but also how tolerance is established in pregnancy to avoid rejection of the foetus.Recent findingsThe immune system of the genital tract displays characteristic features that are unique, and therefore distinct from those of other mucosal and systemic immune sites. It is functionally separate from the mucosal immune systems of the lung or intestine, and contrary to these systems, antibodies in the genital tract are dominated by IgG and not IgA. Most of the IgA is polymeric and consists of equal proportions IgA1 and IgA2. Polymeric IgA is actively transported via the polymeric immunoglobulin receptor on the basolateral surface of the epithelial cell, whereas it is not known how IgG antibodies are secreted. Antibody levels and isotypes exhibit strong hormonal dependence. Less is known about cell-mediated immune responses in the genital tract. Interest has focused on adhesion molecules, the existence of regulatory T and natural killer cells, and whether innate and early adaptive immune responses may be stimulated by local vaginal, intranasal or intestinal vaccinations. These topics are reviewed here and the most recent developments in these areas are reported.SummaryA greater knowledge of immune activation and the homing of leukocytes to the genital tract is important for future attempts to design vaccines against STDs, as well as in understanding foetal tolerance.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID