In Vitro Downregulation of Matrix Metalloproteinase-9 in Rat Glial Cells by CCR5 Antagonist Maraviroc: Therapeutic Implication for HIV Brain Infection

BACKGROUND: Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP activity might represent an attractive therapeutic challenge. Recent studies suggest that CCR5 antagonist maraviroc (MVC) exerts immunomodulant and anti-inflammatory activity beyond its anti-HIV properties. We investigated the in vitro effect of MVC on the activity of MMPs in astrocyte and microglia cultures. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of rat astrocytes and microglia were activated by exposure to phorbol myristate acetate (PMA) or lypopolysaccharide (LPS) and treated in vitro with MVC. Culture supernatants were subjected to gelatin zymography and quantitative determination of MMP-9 and MMP-2 was done by computerized scanning densitometry. MMP-9 levels were significantly elevated in culture supernatants from both LPS- and PMA-activated astrocytes and microglia in comparison to controls. The treatment with MVC significantly inhibited in a dose-dependent manner the levels and expression of MMP-9 in PMA-activated astrocytes (p<0,05) and, to a lesser extent, in PMA-activated microglia. By contrast, levels of MMP-2 did not significantly change, although a tendency to decrease was seen in PMA-activated astrocytes after treatment with MVC. The inhibition of levels and expression of MMP-9 in PMA-activated glial cells did not depend on cytotoxic effects of MVC. No inhibition of MMP-9 and MMP-2 were found in both LPS-activated astrocytes and microglia. CONCLUSIONS: The present in vitro study suggests that CCR5 antagonist compounds, through their ability to inhibit MMP-9 expression and levels, might have a great potential for the treatment of HIV-associated neurologic damage

Bacterial and Mycotic Infections in immunocompromised hosts: Clinical and Microbiological Aspects

Causative organisms (Fungi) 2. Pathological Basis and Morphological Features 3. Gynecological Infections in Immunocompromised Hosts 4. Sexually Transmitted Diseases 5. Central Nervous System Infections in Immunocompromised Hosts 6. Skin and Soft Tissues Infections - 7. Sepsis in an Immunocompromised Host 8. Microsporidia Infections in Immunocompromised Hosts 9. Yeasts: Candida and Cryptococcus 10. Dimorph and Filamentous Fungi 11. Brucellosis: A Global Re-emerging Zoonosis: History, Epidemiology, Microbiology, Immunology and Genetic 12. Brucellosis: A Global Re-emerging Zoonosis: Clinical Aspects, Associations and Brucellosis in Specific Conditions 13. Brucellosis: A Global Re-emerging Zoonosis: Diagnosis, Treatment and PreventionThis book deals with bacterial and mycotic infections considering the particular aspects involved in the immunocompromised host. It is addressed to all people (microbiologists or pathologists) who for their activity have to face every day the clinical and microbiological features of these diseases. The immunocompromised hosts are a real problem for the peculiar characteristic that these subjects show and for the problems arisen in their treatment. We tried to examine most of infectious diseases such as the gynecological infections, the sexually transmitted diseases , the sepsis , the CNS infections and so on, stressing the diagnosis , the management and the prevention of the diseases and considering the newest aspects i.e. the formation of the bacterial biofilm in the devices or prostheses and the consequent resistance to the antimicrobial agents

ANTIMICROBIAL ACTIVITY OF CALLUNA VULGARIS

Antimicrobial activity of several (aqueous, ethanolic, ethereal) extracts of Calluna vulgaris aerial parts were studied in vitro, in camparison with some of its pure compounds (arbutin, hydroquinone, ursolic acid), against clinically-isolated bacteria and yeasts. Only aqueous extract was active in that inhibited the growth of some microorganisms (S. aureus, S. epidermidis, C. albicans, C. neoformans). Among pure compounds ursolic acid markedly inhibited the growth of S. aureus

Therapeutic strategy for pandrug-resistant Klebsiella pneumoniae severe infections: short-course treatment with colistin increases the in vivo and in vitro activity of double carbapenem regimen

Infections due to carbapenemase-producing Klebsiella pneumoniae represent an emerging threat due to the high mortality rate and lack of valid antimicrobial combinations, especially when the strain is colistin-resistant. We report a case of bloodstream infection due to pandrug-resistant K. pneumoniae treated successfully with an innovative regimen comprising a combination of colistin plus double carbapenem, along with an in vitro analysis showing the synergistic and bactericidal effect

Pacemaker Lead Endocarditis Due to Multidrug-Resistant Corynebacterium striatum Detected with Sonication of the Device ▿

Corynebacterium striatum is a commensal of human skin and has been recently recognized as an emerging pathogen. A case of nosocomial pacemaker lead endocarditis due to a multidrug-resistant C. striatum strain is described, highlighting the role of sonication as a diagnostic tool in cardiac device infections