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Biomedical subjects

Michel Fournier

Publications and source records attributed to Michel Fournier.

At least 55 records · Page 3Linked to original sources
PubMed2003

Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis.

OBJECTIVE: Although lung transplantation is viewed as an acceptable option for patients with end-stage idiopathic pulmonary fibrosis, the survival benefit of this approach is still debated. This study examined whether there was a survival benefit of lung transplantation in a cohort of patients referred to our transplant center with a diagnosis of idiopathic pulmonary fibrosis according to American Thoracic Society criteria. METHODS: Forty-six patients accepted for lung transplantation during a 12-year period with a diagnosis of idiopathic pulmonary fibrosis form the basis of this study. Survival benefit offered by lung transplantation was assessed using Cox proportional-hazards modeling, with patients on a waiting list as the control group. RESULTS: Twenty-eight patients underwent lung transplantation (27 single and 1 double), 16 patients died while waiting, and 2 patients remained on the active waiting list. Diagnosis of idiopathic pulmonary fibrosis was made on histologic examination of the explanted lung or lung biopsy before lung transplantation. There was a pattern of usual interstitial pneumonia in 31 cases (67%). The 15 remaining patients fulfilled all American Thoracic Society criteria for idiopathic pulmonary fibrosis. The median waiting time for organs was 51 days. Survival after lung transplantation was 79.4% at 1 year, 63.5% at 2 years, and 39% at 5 years. The multivariable analysis showed that lung transplantation reduced the risk of death by 75% (95% confidence interval, 8%-86%; P =.03) after adjustment on potential confounding variables. CONCLUSIONS: Lung transplantation is effective in improving the survival of selected patients affected by idiopathic pulmonary fibrosis.

Adult↗
PubMed2003

Immune response of earthworms (Lumbricus terrestris, Eisenia andrei and Aporrectodea tuberculata) following in situ soil exposure to atmospheric deposition from a cement factory.

In order to reduce their energy costs, many cement plants use fuel product substitutes (old tyres and used oil). The combustion of these products generates a metal increase (e.g. Cu, Cd, Pb and Zn) in the atmospheric emissions. After their release, these elements are deposited into the environment and could eventually accumulate up to concentrations of concern. At the Saint-Laurent cement factory (Joliette, QC, Canada), maximum deposition of these elements occurs in the direction of prevailing winds (North-East). We evaluated the potential impact of these depositions upon the immune system of three earthworm species (Lumbricus terrestris, Eisenia andrei and Aporrectodea tuberculata) exposed in a natural environment. The exposure sites were 0.5, 1.0, and 2.0 km downwind from the cement factory, along with an upwind reference site. The immune parameters studied were the cell viability and phagocytic potential of the immune cells (coelomocytes). For both L. terrestris and E. andrei, after 7 d exposure, none of the measured parameters showed significant differences among the sites. On the other hand, for the indigenous worm A. tuberculata, in the most exposed zone (at 0.5 km), we observed an increase in cell viability and phagocytic potential. This increase could possibly be attributed to physicochemical effects such as the alkaline pH of the soil, or alternatively, it could result from beneficial effects induced by an increased calcium supply.

Air Pollutants↗
PubMed2003

Effects of agricultural pesticides on the immune system of Rana pipiens and on its resistance to parasitic infection.

In the past 30 years, many amphibian species have suffered population declines throughout the world. Mass mortality have been frequently reported, and in several instances, infectious diseases appear to be the cause of death. The role that contaminants could play in these die-offs through immunotoxic effects has been poorly investigated. In this study, juvenile leopard frogs (Rana pipiens) were exposed for 21 d to a mixture of six pesticides (atrazine, metribuzin, aldicarb, endosulfane, lindane, and dieldrin) and subsequently challenged with a parasitic nematode, Rhabdias ranae. Exposure to the mixture at environmentally realistic concentrations significantly reduced lymphocyte proliferation. Three weeks after the end of the exposure, lymphocyte proliferation had recovered and was stimulated in frogs challenged with parasites with the exception of those previously exposed to the highest concentration. No pesticide effects on phagocytosis and splenocyte numbers were detectable at the end of the exposure period, but these two parameters were diminished 21 d after the infection challenge in frogs previously exposed to the highest levels of pesticides. In these animals, the prevalence of lung infection by R. ranae also tended to be higher. These results suggest that agricultural pesticides can alter the immune response of frogs and affect their ability to deal with parasitic infection.

Agriculture↗
PubMed2002

Presence and regulation of metallothioneins in peripheral blood leukocytes of grey seals.

Heavy metal residues have been reported at high levels in marine mammals. Although the immunotoxicity of these contaminants has been demonstrated in laboratory models, evaluation of their potential immunotoxicity for human and wildlife species is complicated by variables that modulate the immune response and the immunotoxic effects of xenobiotics under field conditions. Metallothioneins (MT) modulate the bioavaibility of physiological cations and the toxicity of heavy metals. Moreover, these proteins have been demonstrated to modulate immune functions. In the present study, we demonstrated a rapid and sustained increase of transcripts of the two major isoforms of MT (MT-1 and MT-2) in grey seal peripheral blood leukocytes (PBL) exposed in vitro to Zn. This increase in mRNA corresponds to an increase of MT proteins in PBL. However, we demonstrated a high heterogeneity among the three major PBL subpopulations (granulocytes, lymphocytes and monocytes). Monocytes appear to be the most sensitive cells to Zn or Cd exposure. Intracellular MT levels in PBL subpopulations were dependent not only on the duration of exposure and the concentration, but also on the metal species. Cd was more potent than Zn as an inducer of MT in lymphocytes but not in monocytes. Moreover, grey seal peripheral blood lymphocytes are less sensitive to Cd exposure than human lymphocytes. This noninvasive approach helps to better assess the risk of heavy metal exposure by considering the potential role of MT as modulators of immune response.

Animals↗
PubMed2002

Thrombolytic therapy of pulmonary embolism: a meta-analysis.

OBJECTIVES: We sought to assess the efficacy and safety of thrombolytic therapy in patients with an acute pulmonary embolism (PE). BACKGROUND: Thrombolytic therapy is approved for the treatment of acute PE; however, the safety and efficacy of this therapy remain debated. METHODS: A meta-analysis of randomized, controlled trials comparing thrombolytic agents with intravenous heparin in patients with acute PE was performed. Trials were identified through a combined search of the MEDLINE, EMBASE, and Current Contents databases. Three outcome measures were assessed: 1) mortality, 2) recurrence of PE, and 3) major hemorrhage. RESULTS: Nine trials including 461 patients were identified. Compared with intravenous heparin, thrombolytic therapy had no significant effect on mortality (relative risk [RR] 0.63, 95% confidence interval [CI] 0.32 to 1.23) or the recurrence of PE (RR 0.59, 95% CI 0.30 to 1.18), but was associated with an increased risk of major hemorrhage (RR 1.76, 95% CI 1.04 to 2.98). These results were homogeneous and largely unaffected by the formulation of thrombolytic agent, the clinical severity of PE, the extent of vascular obstruction determined radiologically, or the methodologic quality of the included trials. CONCLUSIONS: Compared with intravenous heparin, thrombolytic therapy does not appear to have therapeutic benefit in unselected patients with acute PE, but it is associated with an increased risk of major hemorrhage. Given the small number of patients included in the randomized trials thus far, the negative results in terms of the efficacy outcomes should be interpreted with caution. Definitive evidence of the utility of thrombolytic therapy in this setting requires a large, randomized, controlled trial.

Fibrinolytic Agents↗
PubMed2002

Effects of volatile aromatics, aldehydes, and phenols in tobacco smoke on viability and proliferation of mouse lymphocytes.

Thirteen chemicals present in tobacco smoke were assessed for their effect on viability and proliferation of mouse lymphocytes in vitro. Acetaldehyde, benzene, butyraldehyde, isoprene, styrene, and toluene produced no effect on either viability or proliferation after 3 h of exposure. Formaldehyde, catechol, acrylonitrile, propionaldehyde, and hydroquinone significantly inhibited T-lymphocyte and B-lymphocyte proliferation with IC50 values ranging from 1.19 x 10(-5) M to 8.20 x 10(-4) M after 3 h of exposure. Acrolein and crotonaldehyde not only inhibited T-cell and B-cell proliferation, but also acted on viability with IC50 values ranging from 2.06 x 10(5) M to 4.26 x 10(-5) M. Mixtures of acrolein, formaldehyde, and propionaldehyde or crotonaldehyde were tested and interactive effects at 0.5 and 1 x IC50 were observed. Two mixtures significantly inhibited T-cell proliferation when compared to the control at 0.1 x IC50 concentration. The present study shows that some chemicals known to be present in tobacco smoke exert an effect on lymphocyte viability and proliferation in vitro.

Aldehydes↗
PubMed2002

HIV-1 integrase interacts with yeast microtubule-associated proteins.

The human immunodeficiency virus type 1 (HIV-1) integrase (IN) mediates the insertion of viral DNA into the human genome. In addition to IN, cellular and viral proteins are associated to proviral DNA in the so-called preintegration complex (PIC). We previously reported that the expression of HIV-1 IN in yeast leads to the emergence of a lethal phenotype. This effect may be linked to the IN activity on infected human cells where integration requires the cleavage of genomic DNA. To isolate and characterize potential cellular partners of HIV-1 IN, we used it as a bait in a two-hybrid system with a yeast genomic library. IN interacted with proteins belonging to the microtubule network, or involved in the protein synthesis apparatus. We focused our interest on one of the selected inserts, L2, which corresponds to the C-end half of the yeast STU2p, a microtubule-associated protein (MAP). STU2p is an essential component of the yeast spindle pole body (SPB), which is able to bind microtubules in vitro. After expressing and purifying L2 as a recombinant protein, we showed its binding to IN by ELISA immunodetection. L2 was also able to inhibit IN activity in vitro. In addition, the effect of L2 was tested using the "lethal yeast phenotype". The coexpression of IN and the L2 peptide abolished the lethal phenotype, thus showing important in vivo interactions between IN and L2. The identification of components of the microtubule network associated with IN suggest a role of this complex in the transport of HIV-1 IN present in the PIC to the nucleus, as already described for other human viruses.

Binding Sites↗
PubMed2002

A novel short peptide is a specific inhibitor of the human immunodeficiency virus type 1 integrase.

The retroviral encoded protein integrase (IN) is required for the insertion of the human immunodeficiency virus type 1 (HIV-1) proviral DNA into the host genome. In spite of the crucial role played by IN in the retroviral life cycle, which makes this enzyme an attractive target for the development of new anti-AIDS agents, very few inhibitors have been described and none seems to have a potential use in anti-HIV therapy. To obtain potent and specific IN inhibitors, we used the two-hybrid system to isolate short peptides. Using HIV-1 IN as a bait and a yeast genomic library as the source of inhibitory peptides (prey), we isolated a 33-mer peptide (I33) that bound tightly to the enzyme. I33 inhibited both in vitro IN activities, i.e. 3' end processing and strand transfer. Further analysis led us to select a shorter peptide, EBR28, corresponding to the N-terminal region of I33. Truncated variants showed that EBR28 interacted with the catalytic domain of IN interfering with the binding of the DNA substrate. Alanine single substitution of each EBR28 residue (alanine scanning) allowed the identification of essential amino acids involved in the inhibition. The EBR28 NMR structure shows that this peptide adopts an alpha-helical conformation with amphipathic properties. Additionally, EBR28 showed a significant antiviral effect when assayed on HIV-1 infected human cells. Thus, this potentially important short lead peptide may not only be helpful to design new anti-HIV agents, but also could prove very useful in further studies of the structural and functional characteristics of HIV-1 IN.

Alanine↗
PubMed2002

Isomerization of n-hexane over silica-supported heteropoly acids promoted by the reduced Ce-Ni oxides.

The structure and catalytic properties of silica-supported heteropoly acids promoted by the reduced Ce-Ni oxides are first studied by using chemical analysis XRD, FT-Raman, XPS, EPR, TG, surface area measurements, and microreactor test. It is found that silica-supported heteropoly acids have isomerization activity, but are very easy to deactivate by coke deposition. With the promotion of the reduced Ce-Ni oxides, however, the better activity and the higher selectivity to isomers could be obtained, suggesting that the reduced Ce-Ni oxides really have hydrogenating/dehydrogenating functions. Moreover, it is found that the presence of the reduced Ce-Ni oxides is not only beneficial for eliminating the coke deposition, but also effective for maintaining the structure of silica-supported heteropoly acids during reaction. The effect of the composition of the mechanical mixtures of silica-supported heteropoly acids and the Ce-Ni oxides on the catalytic properties has been explored.

Acids↗
PubMed2002

Prolongation of human neutrophil survival by low-level mercury via inhibition of spontaneous apoptosis.

Low levels of organic and inorganic mercury compounds have been reported previously to induce cell death by apoptosis in human peripheral blood mononuclear cells (MNC). but little is known about their potential effects on the viability and death of polymorphonuclear neutrophils (PMN). In contrast to MNC, PMN are known to undergo readily spontaneous apoptosis both in vivo and in vitro. Therefore, it was hypothesized that PMN may differ from MNC in their reactions to low mercury levels. The effects of methylmercuric chloride (MeHgCl) and mercuric chloride (HgCl2) were evaluated in concentration-response and time-course studies on human PMN viability and on their modes of cell death after in vitro incubation at 37 degrees C. Cell death by apoptosis or necrosis was assessed by annexin V-fluorescein isothiocyanate binding to externalized phosphatidylserine in conjunction with propidium iodide, and flow cytometry analysis. Morphologic counting of pyknotic nuclei and the fluorescence properties of the DNA-binding dye Hoechst 33342 in combination with propidium iodide were used to further confirm apoptotic cell death and to characterize the sequence of Hg-induced cell death. Results show that low concentrations of MeHgCl (1-7.5 microM) that were cytotoxic to MNC actually inhibited PMN spontaneous apoptosis. Low-level HgCl, reproduced the anti-apoptotic effects of MeHgCl on PMN, but to a lower extent. Higher concentrations of MeHgCl and HgCl2 were necrogenic to PMN, but MeHgCl was about an order of magnitude more toxic, and discrete differences were observed in the modalities of cell death induced by both species. These data reveal for the first time that (1) low levels of organic and inorganic mercury species protect human PMN from cell death via inhibition of spontaneous apoptosis, and (2) PMN are more resistant than MNC to mercury-induced cytotoxicity. Since delayed apoptosis and increased resistance to toxicant-induced cell death may lead to excessive accumulation of senescent PMN, evidence indicates that findings of this study may have implications for mercury-induced autoimmunity and inflammation.

Adult↗
PubMed2002

Acute respiratory failure due to diaphragmatic weakness revealing a polymyositis.

Of the different respiratory disorders that complicate the course of polymyositis, diaphragmatic weakness is one that is seldom described and most often suspected rather than confirmed. We report a case of severe diaphragmatic weakness as a cause of acute respiratory failure revealing a polymyositis. The diaphragmatic involvement was proven by a very low esophageal pressure in response to cervical magnetic stimulation of the phrenic nerve. Corticosteroids and intravenous gammaglobulin, combined with mechanical ventilation, achieved a progressive recovery of diaphragmatic weakness.

Journal Article↗
PubMed2002

Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects.

Human populations throughout the world are exposed daily to low levels of environmental contaminants. The consequences of potential interactions of these compounds to human endocrine, reproductive, and immune function remain unknown. The current study examines the effects of subchronic oral exposure to a complex mixture of ubiquitous persistent environmental contaminants that have been quantified in human reproductive tissues. The dosing solution used in this study contained organochlorines (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], polychlorinated biphenyls [PCBs],p,p'-dichlorodiphenoxydichloroethylene [p,p'-DDE],p,p-dichlorodiphenoxytrichloroethane [p,p'-DDT], dieldrin, endosulfan, methoxychlor, hexachlorobenzene, and other chlorinated benzenes, hexachlorocyclohexane, mirex and heptachlor) as well as metals (lead and cadmium). Each chemical was included in the mixture at the minimum risk level (MRL) or tolerable daily intake (TDI) as determined by the U.S. EPA or ATSDR or, for TCDD, at the no observable effect level (NOEL) used to calculate the TDI. Sexually mature male rats were exposed to this complex mixture at 1, 10, 100, and 1000 times the estimated safe levels daily for 70 days. On day 71, all animals were sacrificed and a variety of physiological systems assessed for toxic effects. Evidence of hepatotoxicity was seen in the significant enlargement of the liver in the 1000x group, reduced serum LDH activity (100x), and increased serum cholesterol and protein levels (both 1000x). Hepatic EROD activities were elevated in animals exposed to10x and above. The mixture caused decreased proliferation of splenic T cells at the highest dose and had a biphasic effect on natural killer cell lytic activity with an initial increase in activity at 1x followed by a decrease to below control levels in response to 1000x. No treatment-related effects were seen on bone marrow micronuclei, daily sperm production, serum LH, FSH, or prolactin levels or weights of most organs of the reproductive tract. The weights of the whole epididymis and of the caput epididymis were significantly decreased at 10x and higher doses, although no effect was seen on cauda epididymal weight. The sperm content of the cauda epididymis was increased at the 1x level but not significantly different from control at higher dose levels. A slight, but significant, increase in the relative numbers of spermatids was seen in the animals from the 1000x group with a trend towards reduced proportion of diploid cells at the same dose. Only minor, nondose related changes were seen in parameters related to condensation of chromatin, as determined by flow cytometry, in epididymal sperm. We conclude that the mixture induced effects on the liver and kidney and on general metabolism at high doses but caused only minor effects on immune function, reproductive hormone levels, or general indices of reproductive function measures. These data suggest that additive or synergistic effects of exposure to contaminants resulting in residue levels representative of contemporary human tissue levels are unlikely to result in adverse effects on immune function or reproductive physiology in male rats.

Animals↗
PubMed2002

Differential role of neutrophils and alveolar macrophages in hepatocyte growth factor production in pulmonary fibrosis.

Neutrophils may participate in the development of lung fibrosis. Hepatocyte growth factor (HGF), a growth factor for type II pneumocytes, is produced by neutrophils. We measured the production of HGF by blood and alveolar neutrophils from patients with either idiopathic pulmonary fibrosis (n = 11) or connective tissue disease-associated pulmonary fibrosis (n = 10) and from control patients (n = 10). HGF secretion by alveolar macrophages and the expression of the HGF receptor by alveolar epithelial cells in pulmonary fibrosis were also evaluated. HGF was not detected in bronchoalveolar lavage fluid from controls. HGF concentration in the epithelial lining fluid from patients was 4-fold higher than in plasma, suggesting a local production within the alveolar space. Alveolar neutrophils secreted HGF in vitro. Basal HGF secretion by alveolar neutrophils positively correlated with HGF in the epithelial lining fluid (p = 0.05, rho = 0.582). HGF secretion by alveolar neutrophils could not be further stimulated with lipopolysaccharide, whereas HGF secretion by blood neutrophils doubled with lipopolysaccharide. Alveolar macrophages did not secrete HGF in vitro. The expression of the HGF receptor was greatly increased in the fibrotic lung, supporting the local function of HGF secreted by neutrophils. We conclude that neutrophils are a source of HGF in patients with pulmonary fibrosis.

Hepatocyte Growth Factor↗
PubMed2002

Primary graft failure following lung transplantation: predictive factors of mortality.

STUDY OBJECTIVES: To assess incidence, outcome, and early predictors of mortality for patients with primary graft failure (PGF) following lung transplantation (LTx), and to develop an injury severity score able to accurately predict ICU mortality for these patients. DESIGN: Retrospective cohort analysis. SETTING: Two LTx centers in Paris. PATIENTS: Two hundred fifty-nine patients who underwent LTx over a 12-year period. MEASUREMENTS AND RESULTS: One hundred thirty-one patients (50.6%) met PGF criteria: radiographic graft infiltrate within the first 3 days following LTx associated with gas exchange impairment (PaO(2)/fraction of inspired oxygen ratio < 300 mm Hg). This syndrome was associated with an increased duration of mechanical ventilation (9.1 +/- 1 days vs 3.1 +/- 0.6 days, mean +/- SD; p < 0.001) and ICU mortality (29% vs 10.9%; p < 0.01). The patients with PGF were randomly assigned to developmental (n = 85) and validation (n = 46) samples. Using logistic regression analysis, four variables were found associated with ICU mortality in these patients: age, degree of gas exchange impairment, graft ischemic time, and severe early hemodynamic failure. An ischemia/reperfusion injury severity score was derived using these four variables. Model calibration was good in the developmental and validation samples, as was model discrimination (area under receiver operating characteristic curves, 0.93 and 0.85, respectively). CONCLUSION: PGF following LTx is a frequent event, with significant ICU morbidity and mortality. We demonstrate that four simple factors allow prediction of ICU mortality with good accuracy.

Adult↗
PubMed2002

Bronchiolitis obliterans syndrome after single-lung transplantation: impact of time to onset on functional pattern and survival.

INTRODUCTION: Among risk factors for the progression of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LT), the influence of time to BOS onset is not known. The aim of the study was to assess if BOS occurring earlier after LT is associated with worse functional prognosis and worse graft survival. METHOD: We retrospectively compared functional outcome and survival of all single-LT (SLT) recipients who had BOS develop during follow-up in our center according to time to onset of BOS (< 3 years or > or = 3 years after transplantation). RESULTS: Among the 29 SLT recipients with BOS identified during the study period, 20 patients had early-onset BOS and 9 patients had late-onset BOS. The mean decline of FEV(1) over time during the first 9 months in patients with early-onset BOS was significantly greater than in patients with of late-onset BOS (p = 0.04). At last follow-up, patients with early-onset BOS had a lower mean FEV(1) value (25% vs 39% of predicted, p = 0.004), a lower mean PaO(2) value (54 mm Hg vs 73 mm Hg, p = 0.0005), a lower 6-min walk test distance (241 m vs 414 m, p = 0.001), a higher Medical Research Council index value (3.6 vs 1.6, p = 0.0001), and a higher percentage of oxygen dependency (90% vs 11%, p = 0.001) compared with patients with late-onset BOS. In addition, graft survival of patients with early-onset BOS was significantly lower than that of patients with late-onset BOS (log-rank test, p = 0.04). There were 18 of 20 graft failures (90%) in the early-onset BOS group, directly attributable to BOS in all cases (deaths [n = 10] or retransplantation [n = 8]). In the late-onset BOS group, graft failure occurred in four of nine patients due to death from extrapulmonary causes in three of four cases. The median duration of follow-up after occurrence of BOS was not statistically different between patients with early-onset BOS and patients with late-onset BOS (31 +/- 28 months and 37 +/- 26 months, respectively; p = not significant). CONCLUSION: The subgroup of patients who had BOS develop > or = 3 years after SLT are less likely to have worrisome functional impairment develop in long-term follow-up. Considering the balance between the advantages and risks, enhancement of immunosuppression should be regarded with more caution in this subgroup than in patients with early-onset BOS.

Adult↗
PubMed2002

Response of the amphibian tadpole (Xenopus laevis) to atrazine during sexual differentiation of the testis.

Xenopus laevis tadpoles were exposed for 48 h during sexual differentiation to atrazine at 21 microg/L under static laboratory conditions at 21+/-0.5 degrees C. After this exposure period, tadpoles were fixed and the kidney-gonad complex was microdissected. Quantitative histological analysis of the gonad revealed a 57% reduction in testicular volume among atrazine-exposed tadpoles. In addition, primary spermatogonial cell nests that represent germ cells for the life of the organism were reduced by 70%. Nursing cells, which provide nutritive support for the developing germ cells, had declined by 74%. Testicular resorption was observed among 70% and aplasia or failure of full development of the testis was recorded in 10% of the atrazine-exposed tadpoles. Because cell nests represent the pool of primordial germ cells for the reproductive life of the organism, the combined reduction in spermatogonial cell nests and nursing cells suggest that a pulse exposure to 21 microg/L of atrazine during sexual differentiation could significantly reduce reproduction during the reproductive life of these animals.

Animals↗
PubMed2002

Inhibitors of HIV-1 reverse transcriptase and integrase: classical and emerging therapeutical approaches.

The rapid spread of the AIDS epidemic has stimulated the search for new agents able to arrest the replication of the causative virus, HIV. The best strategy for AIDS treatment involves a combination therapy using inhibitors of reverse transcriptase and protease. However, the emergence of HIV-1 strains resistant to these drugs and their cytotoxicity requires the synthesis and the biochemical and cellular characterization of new antiviral drugs, as well as the development of newer strategies and viral targets. In addition to reverse transcriptase and protease, other retroviral enzymes acting in the replicative cycle of HIV-1 are potential targets for chemotherapeutic intervention. Like all retroviruses, HIV-1 requires the integration of the proviral double-stranded DNA, arising from the reverse transcription step, into the host chromosome for its efficient replication, maintenance of a stably infected state and productive infection. DNA integration is carried out by integrase so this enzyme represents a key area in developing new anti-retroviral therapy. Another novel enzymatic target concerns the RNase H activity associated with the retroviral reverse transcriptase, since a functional RNase H is essential for retroviral replication. Inhibitors against HIV-1 integrase and RNase H having potential therapeutical propeties have not yet been described. We focus this review on the properties of inhibitors of reverse transcriptase and integrase. Some of these antiviral agents have been known for several years while others are emerging as new promising strategies based on the use of oligonucleotides with special emphasis on the SELEX approach, peptides and retrovirucides.

Acquired Immunodeficiency Syndrome↗