References of "Moutschen, Michel"
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See detailIgG4-related disease causing rapid evolution of a severe aortic valvular stenosis
BRULS, Samuel ULg; Courtois, Audrey ULg; DELVENNE, Philippe ULg 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 ULg 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 ULg; Bodart, Gwennaëlle ULg; Desmet, Christophe ULg 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; Moutschen, Michel ULg

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 detailKnowledge, attitudes and clinical practice of blood products prescribers in Niamey.
Mayaki, Z.; Kabo, R.; Moutschen, Michel ULg et al

in Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine (2016), 23(2), 78-85

AIM OF THE STUDY: The lack of traceability and monitoring of blood donors and transfused patients constitute a barrier to the most basic rules of haemovigilance and overall good transfusion practices ... [more ▼]

AIM OF THE STUDY: The lack of traceability and monitoring of blood donors and transfused patients constitute a barrier to the most basic rules of haemovigilance and overall good transfusion practices. This study draws up an inventory of knowledge, attitudes and clinical practice of blood prescribers in Niamey. MATERIALS AND METHODS: A questionnaire was administered to 180 prescribers of blood products in Niamey in 2011. Questions were related to basic informations on blood transfusion and clinical use of blood. Analyses were performed using SAS 9.3 version. RESULTS: The sample consisted of 180 respondents from several professional categories: 51 physicians (28.33%), 10 medical students (5.56%), 84 nurses (46.67%), 15 anaesthesiologist assistant (8.33%) and 20 midwives (11.11%). Among these, 22.2% received training in blood transfusion safety. Half of the respondents (50.8%) got between 50 and 75% of correct answers, 45.8% got less than 50% correct while 3.35% scored more than 75% correct answers. The overall quality of responses was higher among physicians compared to other prescribers (P<0.0001); among respondents who received training in transfusion safety (P<0.0001); and among males (P=0.0306). For some items, subjects with more experience scored the best. CONCLUSION: The level of knowledge is still inadequate. More training in transfusion practices is necessary for prescribers of blood products. Accompanying measures to improve transfusion practice must be considered or strengthened through assessments, knowledge update/upgrade (regular, ongoing training) and establishment of active and motivated hospital transfusion committees. [less ▲]

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See detailEfficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature.
van der Hilst, Jeroen Ch; Moutschen, Michel ULg; Messiaen, Peter E. et al

in Biologics: Targets & Therapy (2016), 10

INTRODUCTION: In 5%-10% of patients with familial Mediterranean fever (FMF), colchicine is not effective in preventing inflammatory attacks. Another 5%-10% of patients are intolerant to effective doses of ... [more ▼]

INTRODUCTION: In 5%-10% of patients with familial Mediterranean fever (FMF), colchicine is not effective in preventing inflammatory attacks. Another 5%-10% of patients are intolerant to effective doses of colchicine and experience serious side effects. Treatment with anti-interleukin-1 (IL-1) drugs may be an alternative for these patients, although it is not reimbursed for this indication in many countries. METHODS: We systematically searched PubMed, Web of Science, and Scopus for reports of anti-IL-1 treatment in FMF patients. RESULTS: Out of 284 potentially relevant articles, 27 eligible reports were identified and included in the data analysis. CONCLUSION: A complete response to therapy without a single attack during treatment was reported in 76.5% of patients on anakinra treatment and in 67.5% of patients during canakinumab treatment. In patients with established type AA amyloidosis, anti-IL-1 treatment can reverse proteinuria. Anti-IL-1 therapy seems to be a safe and effective alternative for patients with FMF who do not respond to or cannot tolerate colchicine. [less ▲]

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See detailObservational Study of a French and Belgian Multicenter Cohort of 23 Patients Diagnosed in Adulthood With Mevalonate Kinase Deficiency.
Durel, Cecile-Audrey; Aouba, Achille; Bienvenu, Boris et al

in Medicine (2016), 95(11), 3027

The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational ... [more ▼]

The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission. [less ▲]

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See detailGenetic depletion of the dual specificity protein phosphatase DUSP3 promotes LLC Lung tumour metastasis
Vandereyken, Maud ULg; Amand, Mathieu; Van Overmeire, Eva et al

Poster (2015, June)

DUSP3, also called Vaccinia-H1 Related (VHR) is a small dual specificity phosphatase dephosphorylating both tyrosine and serine/threonine phosphorylated residues. DUSP3 plays an important role in cell ... [more ▼]

DUSP3, also called Vaccinia-H1 Related (VHR) is a small dual specificity phosphatase dephosphorylating both tyrosine and serine/threonine phosphorylated residues. DUSP3 plays an important role in cell cycle regulation and is up-regulated in several human cancers. The physiological role of this phosphatase is, however, poorly understood. We have recently generated a DUSP3 knockout mouse by homologous recombination. The obtained mice have no spontaneous phenotype or pathology. However, DUSP3 deficiency prevented neo-vascularization of subcutaneously transplanted Matrigel plugs and Lung Lewis Carcinoma (LLC) tumours, suggesting an involvement of DUSP3 in tumour angiogenesis. Considering the importance of angiogenesis in metastatic formation, our study aimed to investigate the role of DUSP3 in metastatic dissemination. To do so, we used the LLC experimental metastasis model that shortcuts the intravasation/extravasation processes by injecting intravenously the LLC and the B16 (metastatic melanoma cell line) cells. Surprisingly, LLC, but not B16, lung metastasis developed twice faster in DUSP3-KO than WT mice. The enhanced LLC metastatic growth in DUSP3-/- mice was transferable to WT mice via DUSP3-/- bone marrow adoptive transfer, suggesting an involvement of the hematopoietic compartment in the observed phenotype. This was confirmed by a higher infiltration of neutrophils and macrophages in the lungs of DUSP3-KO compared to WT mice after LLC injection. This infiltration was correlated with higher expression of the chemokine receptor CCR2 in LLC-bearing DUSP3-KO lungs macrophages. Interestingly, LLC, but not B16 cells, were found to secrete high level of CCL2/MCP1, the CCR ligand chemokine. In line with this observation, we found that DUSP3-/- bone marrow derived-macrophages have a higher migration potential in response to LLC, but not B16, -conditionned medium. Altogether, our results suggest that DUSP3 plays an important role in metastatic dissemination/growth by a mechanism involving the control of CCR2-CCL2 chemoattraction axis in macrophages. [less ▲]

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See detailDUSP3 genetic deletion confers M2-like−macrophage-dependent tolerance to septic shock
Singh, Pratibha; Dejager, Lien; Amand, Mathieu ULg et al

in Journal of Immunology (2015), 194(10), 4951-62

DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages and that its ... [more ▼]

DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages and that its deficiency in mice promotes tolerance to lipopolysaccharide (LPS)-induced endotoxin shock and to polymicrobial septic shock following cecal ligation and puncture. By using adoptive transfer experiments, we demonstrate that resistance to endotoxin is macrophage-dependent and transferable and that this protection is associated with a striking increase of M2-like macrophages in DUSP3-/- mice in both the LPS and cecal ligation and puncture models. We show that the altered response of DUSP3-/- mice to sepsis is reflected in decreased TNF production and impaired ERK1/2 activation. Our results demonstrate that DUSP3 plays a key and non-redundant role as a regulator of innate immune responses by mechanisms involving the control of ERK1/2 activation, TNF secretion and macrophage polarization. [less ▲]

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See detailL’infection par le VIH : une maladie chronique redéfinissant la collaboration entre généralistes et spécialistes. Obstacles et opportunités
Belche, Jean ULg; Kang, Thida; Ketterer, Frédéric ULg et al

in Santé Publique : Revue Multidisciplinaire pour la Recherche et l'Action (2015), 27(3/2015), 373-381

Purpose : With the development of antiretroviral therapy, Human Immunodeficiency Virus (HIV) infection has become a chronic disease. In order to develop an efficient response to this new challenge, there ... [more ▼]

Purpose : With the development of antiretroviral therapy, Human Immunodeficiency Virus (HIV) infection has become a chronic disease. In order to develop an efficient response to this new challenge, there is a need for closer collaboration between specialized units and general practitioners. This article identifies the opportunities for and the barriers to this collaboration. Methods : Semi-structured interviews were conducted with patients living with HIV, general practitioners working in multidisciplinary group practice using the capitation system and infectiologists from one Belgian urban area. Interviews focused on experiences and expectations in relation to diagnosis, follow-up and collaboration between general practitioners and infectiologists. Results : Overall, infectiologists and general practitioners aspire to improved communication and collaboration. There are overlaps between general practitioner’s and infectiologist’s field of action. The general practitioner’s intervention is sometimes restricted to common uncomplicated or psychosocial problems, in the context of unplanned and short contacts. Infectiologists prefer to focus on HIV problems, leaving general practitioners to take care of these patients’ other health problems. The patient may be an obstacle to greater involvement of general practitioners due to fear of stigmatization from his family and social circle or lack of confidence in the general practitioner’s skills. Conclusion : This research underlines the difficulties and gaps in the care of HIV patients and provides preliminary explanations for the lack of active cooperation between general practitioners and infectiologists. Overlaps between the areas of professional skills can result in uncovered aspects of care, which can have a negative impact on patients, but also on general practitioners and infectiologists. Collaboration between general practitioners and infectiologists should be based on a concerted decision, with clear allocation of tasks, taking into account the patient’s expectations. [less ▲]

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See detailDeficiency of Interleukin-1 Receptor-associated Kinase 4 Presenting as Fatal Pseudomonas aeruginosa Bacteremia in Two Siblings.
STERGIOPOULOU, Theodouli ULg; Walsh, Thomas J.; SEGHAYE, Marie-Christine ULg et al

in The Pediatric infectious disease journal (2015), 34(3), 299-300

Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immunodeficiency of innate immunity. This is the case of a previous healthy toddler and his sibling, who both died of fulminant ... [more ▼]

Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immunodeficiency of innate immunity. This is the case of a previous healthy toddler and his sibling, who both died of fulminant sepsis due to Pseudomonas aeruginosa. Subsequent genetic analysis demonstrated IRAK-4 deficiency with compound heterozygous splice mutations. Fulminant fatal Pseudomonas aeruginosa sepsis may be the first manifestation of IRAK-4 deficiency. [less ▲]

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See detailDUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis
Musumeci, Lucia ULg; Kuijpers, Marijke; Gilio, Karen et al

in Circulation (2015), 131(7), 656-68

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]

Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug. [less ▲]

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See detail18F-FDG PET/CT in the Management of Aortitis.
Bruls, Samuel; Courtois, Audrey ULg; Nusgens-Richelle, Betty ULg et al

in Clinical nuclear medicine (2015)

BACKGROUND: Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall ... [more ▼]

BACKGROUND: Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall, resulting in potentially life-threatening vascular complications. Therefore, it is important to establish a diagnosis as early as possible. PATIENTS AND METHODS: During a 4-year period, 428 consecutive patients referred to our department for aortic diseases underwent FDG PET/CT examinations. Among these, 18 patients (4.2%) were suspected to have aortitis. All of them had an initial positive FDG PET/CT uptake occurring in the aorta and major branches as evaluated by visual analysis of images and assessed with the final diagnosis of aortitis. During follow-up, after surgery and/or upon immunosuppressive treatment, each of these patients underwent a second PET/CT that was compared with the initial evaluation. In all cases, normalization of FDG uptake was correlated with clinical improvement. CONCLUSIONS: Our study aimed to illustrate the potential clinical value of functional monitoring with PET/CT in the management of aortitis. FDG PET/CT constitutes a valuable imaging modality to establish an early diagnosis, monitor disease progression and treatment, and evaluate vascular complication and relapse. We highlight the importance of an early detection of inflammatory large-vessel pathology, which may represent a major threat. [less ▲]

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See detailAn In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression.
Darcis, Gilles; Kula, Anna; Bouchat, Sophie et al

in PLoS pathogens (2015), 11(7), 1005063

The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and ... [more ▼]

The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies to purge these reservoirs are needed and activation of viral gene expression in latently infected cells is one promising strategy. Bromodomain and Extraterminal (BET) bromodomain inhibitors (BETi) are compounds able to reactivate latent proviruses in a positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential of protein kinase C (PKC) agonists (prostratin, bryostatin-1 and ingenol-B), which are known to activate NF-kappaB signaling pathway as well as P-TEFb, used alone or in combination with P-TEFb-releasing agents (HMBA and BETi (JQ1, I-BET, I-BET151)). Using in vitro HIV-1 post-integration latency model cell lines of T-lymphoid and myeloid lineages, we demonstrated that PKC agonists and P-TEFb-releasing agents alone acted as potent latency-reversing agents (LRAs) and that their combinations led to synergistic activation of HIV-1 expression at the viral mRNA and protein levels. Mechanistically, combined treatments led to higher activations of P-TEFb and NF-kappaB than the corresponding individual drug treatments. Importantly, we observed in ex vivo cultures of CD8+-depleted PBMCs from 35 cART-treated HIV-1+ aviremic patients that the percentage of reactivated cultures following combinatory bryostatin-1+JQ1 treatment was identical to the percentage observed with anti-CD3+anti-CD28 antibodies positive control stimulation. Remarkably, in ex vivo cultures of resting CD4+ T cells isolated from 15 HIV-1+ cART-treated aviremic patients, the combinations bryostatin-1+JQ1 and ingenol-B+JQ1 released infectious viruses to levels similar to that obtained with the positive control stimulation. The potent effects of these two combination treatments were already detected 24 hours post-stimulation. These results constitute the first demonstration of LRA combinations exhibiting such a potent effect and represent a proof-of-concept for the co-administration of two different types of LRAs as a potential strategy to reduce the size of the latent HIV-1 reservoirs. [less ▲]

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See detailModelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.
FRIPPIAT, Frédéric ULg; Musuamba, Flora Tshinanu; Seidel, Laurence ULg et al

in Journal of Antimicrobial Chemotherapy (2014), 70

OBJECTIVES: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. PATIENTS AND METHODS: Among 55 patients in ... [more ▼]

OBJECTIVES: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. PATIENTS AND METHODS: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method. RESULTS: Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean +/- SEM: 0.29 +/- 0.030 versus 0.20 +/- 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma. CONCLUSIONS: The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF. [less ▲]

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See detailThe RIAD peptidomimetic inhibits HIV-1 replication in humanized NSG mice
Singh, Maneesh; Singh, Pratibha; Vaira, Dolores et al

in European Journal of Clinical Investigation (2014), 44(2), 146-152

Background Increased intracellular concentration of cyclic AMP (cAMP) in T cells is associated with various immunodeficiency conditions including human immunodeficiency virus (HIV) infection. Several ... [more ▼]

Background Increased intracellular concentration of cyclic AMP (cAMP) in T cells is associated with various immunodeficiency conditions including human immunodeficiency virus (HIV) infection. Several reports indicate a critical role of activated protein kinase A (PKA) in the susceptibility of cells to HIV infection. We have used a cell permeable, stable peptidomimetic version (P3) of the RI-anchoring disruptor (RIAD), which prevents PKA interaction with A-kinase-anchoring proteins (AKAPs). It is known that RIAD peptide abrogates effects of localized cAMP signalling through anchored type I PKA in lymphocytes and prevents murine AIDS (MAIDS) infection when expressed as a transgene in mice. Methods and Results In vitro HIV-infected human peripheral blood mononuclear cells (PBMCs) show reduced levels of p24 and intracellular cAMP in T cells when treated with RIAD peptidomimetic (RIAD-P3). Humanized NOD/SCID/IL2cnull (NSG) mice infected with HIV-1 JRCSF and treated with RIAD-P3 (3􏰀5 mg) once every 2 weeks showed significantly reduced levels of viral load at +28, +42 and +56 days and increased CD4 numbers at +56 days after the start of treatment. RIAD-P3-treated humanized mice had lower levels of intracellular cAMP in T cells sorted from splenocytes. Conclusions Treatment with RIAD-P3 limits HIV-1 viral replication and stabilizes CD4 levels by mechanisms involving cAMP/PKA-I pathway in human PBMCs and humanized NSG mice. [less ▲]

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