[Multifocal tuberculosis despite immunocompetence]. / Tuberculose multifocale en dépit d'une immunocompétence.

Tuberculosis is one of the deadliest infectious disease. Its annual incidence was 10 million cases in 2019. We report the case of a 40 years old immunocompetent patient presenting with two large subcutaneous masses in his back. The diagnosis work-up will reveal multifocal tuberculosis with pulmmonary, vertebral, muscular and lymph node lesions. This case is unusual due to its presentation in an immunocompetent patient. Several laboratories have conducted experiments to isolate characteristics of the host that would allow the infection to spread despite the absence of an immunosuppressive medical condition. We also analyze the role of the PET scanner in the initial assessment and its interest in the monitoring of extra-pulmonary disease under anti-tuberculosis treatment. Multifocal tuberculosis cases are no longer the preserve of the immunocompromised and can be found in our industrialized countries. We must enonciate this diagnosis in front of unusual presentations. The delay in consultation, but also the delay of treatment, allows more widespread infections.

La tuberculose est une des maladies infectieuses les plus mortelles. Son incidence annuelle était de 10 millions de cas en 2019. Nous rapportons le cas d'un patient immunocompétent de 40 ans qui se présente avec deux volumineuses masses sous-cutanées au niveau du dos. La mise au point révélera une tuberculose multifocale avec une atteinte pulmonaire, vertébrale, ganglionnaire et des collections abcédées musculaires plurifocales. Ce cas est atypique de par sa présentation chez un patient immunocompétent. Plusieurs laboratoires ont essayé d'isoler des caractéristiques de l'hôte qui permettraient à l'infection une extension disséminée malgré l'absence de condition médicale immunodépressive. Nous analysons également le rôle du PET scanner dans le bilan initial et son intérêt dans le suivi des foyers extra-pulmonaires sous traitement anti-tuberculeux. Les cas de tuberculose multifocale ne sont plus l'apanage des patients immunodéprimés et peuvent se rencontrer dans les pays industrialisés. Le diagnostic doit pouvoir être évoqué devant des présentations atypiques. Le retard du diagnostic et de la prise en charge thérapeutique favorise des infections plus étendues.

[Screening and management of metabolic acidosis in patients with chronic kidney disease]. / Intérêt du dépistage et du traitement de l'acidose métabolique chez l'insuffisant rénal chronique.

Metabolic acidosis is a frequent and early biological abnormality of chronic kidney disease (CKD). Chronic metabolic acidosis affects the global homeostasis of the human body, including the metabolism of bone and muscles. Numerous studies have proved a causal relationship between metabolic acidosis and accelerated CKD progression. Hence, the measure of serum bicarbonate level should be part of the systematic follow-up of CKD patients of whom glomerular filtration rate decreases below 50 ml/min/1.73m². Both screening and treatment of metabolic acidosis are easy and cheap. Correcting metabolic acidosis, namely by the daily administration of sodium bicarbonate, helps slow down kidney decline.

L'acidose métabolique est une anomalie biologique fréquente et précoce de l'insuffisance rénale chronique (IRC). Les complications liées à cet état sont multiples et touchent notamment l'os, le muscle et le métabolisme protidique, sans parler du risque accru d'hyperkaliémie. Une causalité entre acidose métabolique et accélération du déclin rénal a été démontrée. La mesure du taux de bicarbonate sérique doit, dès lors, faire partie du suivi biologique systématique du patient en IRC dont le taux de filtration glomérulaire s'abaisse en dessous de 50 ml/min/1,73 m². Le dépistage et le traitement de l'acidose métabolique sont en effet simples et peu coûteux. La correction de l'acidose métabolique, notamment par le bicarbonate de sodium, permet de ralentir la progression de l'insuffisance rénale.

Azobenzene-based supramolecular polymers for processing MWCNTs.

Photothermally responsive supramolecular polymers containing azobenzene units have been synthesised and employed as dispersants for multi-walled carbon nanotubes (MWCNTs) in organic solvents. Upon triggering the trans-cis isomerisation of the supramolecular polymer intermolecular interactions between MWCNTs and the polymer are established, reversibly affecting the suspensions of the MWCNTs, either favouring it (by heating, i.e. cis→trans isomerisation) or inducing the CNTs' precipitation (upon irradiation, trans→cis isomerisation). Taking advantage of the chromophoric properties of the molecular subunits, the solubilisation/precipitation processes have been monitored by UV-Vis absorption spectroscopy. The structural properties of the resulting MWCNT-polymer hybrid materials have been thoroughly investigated via thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and atomic force microscopy (AFM) and modelled with molecular dynamics simulations.

Synthesis, biological evaluation and molecular modeling studies of quinolonyl diketo acid derivatives: new structural insight into the HIV-1 integrase inhibition.

New quinolonyl diketo acid compounds bearing various substituents at position 6 of the quinolone scaffold were designed and synthesized as potential HIV-1 integrase inhibitors. These new compounds were evaluated for their antiviral and anti-integrase activity and showed inhibitory potency similar to that of 6-bromide analog 2. Molecular modeling and docking studies were performed to rationalize these data and to provide a detailed understanding of the mechanism of inhibition for this class of compounds.

Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor.

Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30 degrees ). Docking studies suggest binding modes in agreement with structure-activity relationships.

New pyridinone derivatives as potent HIV-1 nonnucleoside reverse transcriptase inhibitors.

Several 5-ethyl-6-methyl-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized and evaluated for their anti HIV-1 activities against wild-type virus and clinically relevant mutant strains. A racemic mixture (10) with methyl substituents at positions 3 and 5 of the cyclohexyloxy moiety had potent antiviral activity against wild-type HIV-1. Subsequent stereoselective synthesis of a stereoisomer displaying both methyl groups in equatorial position was found to have the best EC(50). Further modulations focused on position 3 of the pyridinone ring improved the antiviral activity against mutant viral strains. Compounds bearing a 3-ethyl (22) or 3-isopropyl group (23) had the highest activity against wild-type HIV-1 and displayed low-nanomolar potency against several clinically relevant mutant strains.

Renal lesions associated with IgM-secreting monoclonal proliferations: revisiting the disease spectrum.

BACKGROUND AND OBJECTIVES: Since the first description of pathology of the kidney in Waldenström disease in 1970, there have been few reports on kidney complications of IgM-secreting monoclonal proliferations. Here, we aimed to revisit the spectrum of renal lesions occurring in patients with a serum monoclonal IgM. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fourteen patients with a circulating monoclonal IgM and a kidney disease related to B cell proliferation were identified retrospectively. Demographic, clinical, and laboratory data were assessed for each patient at the time of kidney biopsy. RESULTS: Seven patients had a nephrotic syndrome. Patients without nephrotic syndrome all had impaired renal function. Mean serum creatinine was 238 micromol/L. For five patients, the diagnosis of monoclonal IgM preceded the kidney disease by 28.8 mo (range 12 to 60). Seven patients had Waldenström disease, two had a small B cell non-Hodgkin lymphoma, one had an IgM-excreting multiple myeloma, one had a marginal zone B cell lymphoma, and three had an IgM-related disorder. Renal lesions included (1) intracapillary monoclonal deposits disease with granular, electron-dense IgM thrombi occluding capillary lumens (5); (2) atypical membranoproliferative glomerulonephritis (3); (3) lambda light chain amyloidosis (2) associated with mu deposits in one patient; (4) acute tubular necrosis (1); and (5) CD20(+) lymphomatous infiltration (3). Remission of the nephrotic syndrome was attained in three of seven patients, and renal function improved after chemotherapy. CONCLUSIONS: Although renal complications of IgM proliferations are rare, a wide spectrum of kidney lesions is observed, without correlation with the type of hematologic disorder.