References of "Moutschen, Michel"
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See detailGHRH-deleted Mice Are Severely Deficient in Vaccine And Immunological Responses Against Streptococcus Pneumoniae
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Desmet, Christophe ULiege et al

Conference (2018, March 20)

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions ... [more ▼]

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions, thymus and T-cell development are not severely affected but a marked spleen atrophy and B-cell lymphopenia were constantly observed (3). Therefore, we investigated vaccinal and anti-infectious responses of Ghrh-/- mice against S.pneumoniae, a T-independent pathogen. Results. Transgenic mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, Pnx23) or protein-PPS conjugate (Prev13). GH treatment of Ghrh-/- mice restored IgM response to Pnx23 vaccine but not to Prev13 suggesting that GH exerts a significant impact on the spleen marginal zone that is strongly implicated in T-independent immunological response to pneumococcal polysaccharides. After intranasal instillation of a non-lethal dose of S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility with a time-dependent increase in lung bacterial load, a bacteremia already after 24h, and a survival limit of 48-72h. In marked contrast, WT and heterozygote mice completely cleared S.pneumoniae infection after 24h. Lungs of infected Ghrh-/- mice were massively infiltrated by inflammatory macrophages, while lung B cells were markedly decreased. Transcription of Ifng, Il10, Cd40, and Cxcl9 was highly increased in the lungs of infected Ghrh-/- mice, whereas Tgfb and Iggj transcripts were unchanged. Resistance of Ghrh-/- mice to infection by influenzavirus H1N1 (a T-dependent antigen) was normal or slightly decreased. Conclusion. This animal model shows that the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in the vaccine and immunological defense against S.pneumoniae. [less ▲]

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See detailWild-type HIV infection despite PrEP: a lot to learn from a case report.
DARCIS, Gilles ULiege; Moutschen, Michel ULiege

in The lancet. HIV (2018), 5(1), 10

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See detailImmunosenescence and infectious diseases
Moutschen, Michel ULiege; Martens, Henri ULiege; Geenen, Vincent ULiege

in Michel, Jean-Pierre; Beattie, B. Lynn; Martin, Finbarr C. (Eds.) et al Oxford Textbook of Geriatric Medicine - 3rd Edition (2017)

In this chapter, we will briefly review the principal modes of interactions taking place between the host’s immune system and the principal groups of microorganisms. We will focus on the way these modes ... [more ▼]

In this chapter, we will briefly review the principal modes of interactions taking place between the host’s immune system and the principal groups of microorganisms. We will focus on the way these modes of interactions are modified by intrinsic and extrinsic factors associated with ageing. As described in Chapter 45, one of the principal features of immunosenescence is linked to thymus involution with subsequent loss of diversity of the repertoire of naïve T-cells. This has a major impact on the adaptative immune responses developed against newly encountered pathogens. Interestingly, more ubiquitous mechanisms associated with the ageing process itself could also have an impact on innate immunity. Defective autophagy impairs the clearance of intracellular pathogens and age-related defects of the ubiquitination-proteasome pathway concur to blunt antiviral responses. In summary, healthy ageing is associated with subtle impairments of innate and adaptive immunity directed against all groups of pathogens. The presence of comorbid states often exerts a synergistic effect on the susceptibility to infectious diseases. [less ▲]

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See detailExploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium
DE VOEGHT, Adrien ULiege; Martens, Henri ULiege; RENARD, Jeanne de Chantal ULiege et al

in PLoS ONE (2017)

Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease ... [more ▼]

Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14). T-cell receptor excision circles (sjTRECs and dβTRECs) were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC) and sCD14 level (p = 0.004). These results suggest a link between thymic function failure, microbial translocation and innate immune activation. [less ▲]

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See detailDusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner
Vandereyken, Maud; Jacques, Sophie; Van Overmeire, Eva et al

in PLoS ONE (2017)

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion ... [more ▼]

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel out- growth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice devel- oped larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour- promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the pres- ence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demon- strates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs. [less ▲]

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See detailRecurrence of visceral and muco-cutaneous leishmaniasis in a patient under immunosuppressive therapy
DARCIS, Gilles ULiege; Van der Auwera, Gert; GIOT, Jean-Baptiste ULiege et al

in BMC Infectious Diseases (2017), 17

Background: Leishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many ... [more ▼]

Background: Leishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many other infectious or alignant diseases. The disease can present in three ways: cutaneous, mucocutaneous, or visceral leishmaniasis, which rarely occur together or consecutively. Case presentation: The patient was a 52 years old immunosuppressed Belgian woman with a long history of severe rheumatoid arthritis. She underwent bone marrow biopsy to explore thrombocytopenia. Diagnosis of visceral leishmaniasis was made by identification of Leishman Donovan (LD) bodies in macrophages. Treatment with liposomal amphotericin B was successful. She later developed cutaneous leishmaniasis treated with amphotericin B lipid complex. She next presented with relapsing cutaneous lesions followed by rapidly progressing lymphadenopathies. Biopsy confirmed the diagnosis of leishmaniasis. Treatments by miltefosine, amphotericin B, N-methyl-glucamine antimoniate were subsequently initiated. She later presented a recurrent bone marrow involvement treated with intramuscular paromomycin and miltefosine. She died two years later from leukemia. At the time of death, she presented with a mucosal destruction of the nose. A Leishmania-specific PCR (Polymerase Chain Reaction) identified L. infantum as etiological agent. Conclusions: Clinicians should be aware of the potential concomitant or sequential involvement of multiple anatomic localizations of Leishmania in immunosuppressed patients. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaëlle ULiege; RENARD, Jeanne de Chantal ULiege et al

Poster (2017, May 23)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Renard, chantal et al

Poster (2017, May)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailIgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report
HUART, Justine ULiege; GROSCH, Stéphanie ULiege; BOVY, Christophe ULiege et al

in BMC Nephrology (2017), 18

Abstract Background: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney ... [more ▼]

Abstract Background: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. Case presentation: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. Discussion and conclusion: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease. [less ▲]

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See detailGuérir l'infection par le VIH: Un objectif réaliste?
DARCIS, Gilles ULiege; Moutschen, Michel ULiege

in Revue Médicale de Liège (2017), 72(9), 388-392

More than 30 years after its discovery, human immunodeficiency virus (HIV) continues to be a major global public health issue. Antiretroviral therapy increases survival and quality of life of HIV-infected ... [more ▼]

More than 30 years after its discovery, human immunodeficiency virus (HIV) continues to be a major global public health issue. Antiretroviral therapy increases survival and quality of life of HIV-infected patients but is not curative. Indeed, interruption of therapy invariably leads to the re-emergence of detectable viral replication, since HIV persists in extremely long-lived viral latent reservoirs. Those viral latent reservoirs constitute the major source of viral recovery following antiretroviral treatment interruption and are considered as the most important hurdle to HIV eradication. Multiple strategies aimed at targeting the HIV latent reservoirs are intensively being explored. We discuss here the most recent innovative works that will hopefully contribute to find a cure for HIV. [less ▲]

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See detailPrevalence of non-infectious comorbidities in the HIV-positive population in Belgium: a multicenter, retrospective study
Gunter, J.; Callens, S.; De Wit, S. et al

in Acta Clinica Belgica: International Journal of Clinical and Laboratory Medicine (2017)

Objectives: In Belgium, eleven AIDS Reference Centers (ARCs) and seven AIDS Reference Laboratories diagnose and treat HIV-positive individuals and track patients under care. As AIDS-related deaths are ... [more ▼]

Objectives: In Belgium, eleven AIDS Reference Centers (ARCs) and seven AIDS Reference Laboratories diagnose and treat HIV-positive individuals and track patients under care. As AIDS-related deaths are avoided and the HIV-positive population ages, non-infectious comorbidities (NICMs), such as cardiovascular disease, renal disease and certain cancers, play a larger role in the quality and length of patients’ lives. This study aims to characterize the HIV-positive population in Belgium in terms of the prevalence of key NICMs. Methods: We performed a retrospective study of 5787 HIV-positive patients under follow-up at four ARCs across Belgium between 1st of June 2014 and 1st of July 2016. Results: The mean age of patients under follow-up was 46.7 (SD = 11.6) years, and the mean nadir CD4 count was 268.8 cells/mm3 (SD = 189.5). The prevalence of diabetes mellitus, arterial hypertension and chronic kidney disease (CKD) were 5.9, 31 and 7.8%, respectively. Cardiovascular events, defined as the occurrence of myocardial infarction, stroke or an invasive coronary procedure, occurred in 2.9% of patients. The highest age-adjusted mortality rates were observed among patients 51–55 years of age. Mortality rates were also higher among patients with CKD and patients with viremic hepatitis C virus (p < 0.05). Conclusions: Helping the aging HIV-positive population avoids premature morbidity and mortality from NICMs represents a key challenge to further improve patient outcomes. Belgium has an advanced system of HIV care and patient management; however, standardized data collection across ARCs is needed to improve knowledge sharing and to support future countrywide analyses. Acta Clinica Belgica © 2017 [less ▲]

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See detailThe effect of treatment simplification on HIV reservoirs
DARCIS, Gilles ULiege; Moutschen, Michel ULiege

in The Lancet HIV (2017), 4(8), 328-329

[No abstract available]

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See detailDual-Specificity Phosphatase Deletion Protects Female, but Not Male, Mice from Endotoxemia- and Polymicrobial-Induced Septic Shock
Vandereyken, Maud; Singh, Pratibha; Wathieu, Caroline ULiege et al

in Journal of Immunology (2017)

Dual-specificity phosphatase 3 (DUSP3) is a small phosphatase with poorly known physiological functions and for which only a few substrates are known. Using DUSP3-deficient mice, we recently reported that ... [more ▼]

Dual-specificity phosphatase 3 (DUSP3) is a small phosphatase with poorly known physiological functions and for which only a few substrates are known. Using DUSP3-deficient mice, we recently reported that DUSP3 deficiency confers resistance to endotoxin- and polymicrobial-induced septic shock. We showed that this protection was macrophage dependent. In this study, we further investigated the role of DUSP3 in sepsis tolerance and showed that the resistance is sex dependent. Using adoptive-transfer experiments and ovariectomized mice, we highlighted the role of female sex hormones in the phenotype. Indeed, in ovariectomized female and male mice, the dominance of M2-like macrophages observed in DUSP32/2 female mice was reduced, suggesting a role for this cell subset in sepsis tolerance. At the molecular level, DUSP3 deletion was associated with estrogen dependent decreased phosphorylation of ERK1/2 and Akt in peritoneal macrophages stimulated ex vivo by LPS. Our results demonstrate that estrogens may modulate M2-like responses during endotoxemia in a DUSP3-dependent manner. [less ▲]

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See detailIgG4-related disease causing rapid evolution of a severe aortic valvular stenosis
BRULS, Samuel ULiege; Courtois, Audrey ULiege; DELVENNE, Philippe ULiege et al

in The Annals of Thoracic Surgery (2017)

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaelle; Martens, Henri ULiege et al

in Neuroimmunomodulation (2017)

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See detailSevere deficiency of the somatotrope GHRH/GH/IGF-1 axis induces a dramatic susceptibility to Streptococcus pneumoniae infection.
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Desmet, Christophe ULiege et al

Poster (2016, November 07)

Deletion of the growth hormone-releasing hormone gene (Ghrh) results in a severe deficiency of the somatotrope GHRH-GH-IGF-1 axis causing dwarf phenotype that can be reversed by GH or GHRH supplementation ... [more ▼]

Deletion of the growth hormone-releasing hormone gene (Ghrh) results in a severe deficiency of the somatotrope GHRH-GH-IGF-1 axis causing dwarf phenotype that can be reversed by GH or GHRH supplementation (Alba & Salvatori, Endocrinology 2004;145:4134). In basal conditions, the immunological phenotype of Ghrh-/- mice is not markedly disturbed except for a decrease in B cells and an increase in generation of thymic (t) Treg cells (submitted for publication). These data prompted us to investigate immune responses of Ghrh-/- mice using vaccination and infection by S. pneumoniae as models since the response to both stimuli rely on the innate immune system and B cells. Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH differently impacts on B-1, marginal zone B-2 or innate B-1 B cells. Furthermore, after intranasal instillation of a non-lethal dose of serotype 1 S. pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility reflected by bacteremia 24h after infection and a survival limit of 72 h, compared to WT C57BL/6 mice that need only 24h to clear infection. The possible impact of GH deficiency on components of the innate immune system that play an important role in defense of the respiratory tract against pneumococcal infection is under current investigation. (*Equal first and last authors. KF is supported by a research grant from the Lebanese Government; GB is Research Assistant, CD is Research Associate, and VG is Research Director at the NFSR of Belgium). [less ▲]

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See detailsCD14 is not a bona-fide biomarker of microbial translocation in HIV-1 infected Africans living in Belgium.
De Voeght, Adrien; Maes, Nathalie ULiege; Moutschen, Michel ULiege

in AIDS (London, England) (2016), 30 (6)

OBJECTIVE: To compare microbial translocation and its biomarkers in HIV-1 infected African and Caucasian patients of the Liege AIDS Reference Center. DESIGN: The study is based on a cross-sectional ... [more ▼]

OBJECTIVE: To compare microbial translocation and its biomarkers in HIV-1 infected African and Caucasian patients of the Liege AIDS Reference Center. DESIGN: The study is based on a cross-sectional dataset of HIV-infected patients treated at the Liege AIDS Reference Center. Groups of Caucasian and African patients have been randomly selected in order to be identical for sex, age and duration of treatment. METHODS: sCD14, Lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and routine HIV-follow-up parameters were measured on plasma samples. RESULTS: High values of LPS and LBP were observed in both groups of patients without significant difference between them. High values of sCD14 were observed in 53.1% of Caucasians and only in 18.8% of African patients (p = 0.0042). A correlation between LPS and sCD14 was observed in Caucasians but not African patients. CONCLUSION: Our observation suggests that factors not related to microbial translocation are responsible for lower sCD14 value in Africans. [less ▲]

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See detailActualité thérapeutique dans le VIH: Le ténofovir alafénamide
SAUVAGE, Anne-Sophie ULiege; DARCIS, Gilles ULiege; Moutschen, Michel ULiege

in Revue Médicale Suisse (2016), 12(527), 1367-1369

Since the first treatments against human immunodeficiency virus (HIV) have appeared in 1987, important progress has been accomplished. Twenty-four molecules are currently available but only some of them ... [more ▼]

Since the first treatments against human immunodeficiency virus (HIV) have appeared in 1987, important progress has been accomplished. Twenty-four molecules are currently available but only some of them are in common use on account of their easy administration or their weak adverse effects. Tenofovir disoproxil fumarate (TDF) is a commonly used nucleoside reverse-transcriptase inhibitor (NRTI) of HIV. However, taking TDF is sometimes associated with renal toxicity and increased bone demineralization. Tenofovir alafenamide (TAF) is a new prodrug of tenofovir (TFV) whose security profile is more interesting as far as renal and bone complications are concerned, due to a much lower serum concentration and a high intracellular concentration. [less ▲]

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