Serum from postmenopausal women treated with a by-product of olive-oil extraction process stimulates osteoblastogenesis and inhibits adipogenesis in human mesenchymal stem-cells (MSC).

Aging may enhance both oxidative stress and bone-marrow mesenchymal stem-cell (MSC) differentiation into adipocytes. That reduces osteoblastogenesis, thus favoring bone-mass loss and fracture, representing an important worldwide health-issue, mainly in countries with aging populations. Intake of antioxidant products may help to retain bone-mass density. Interestingly, a novel olive-pomace physical treatment to generate olive oil also yields by-products rich in functional antioxidants. Thus, diet of postmenopausal women was supplemented for two months with one of such by-products (distillate 6; D6), being rich in squalene. After treatment, serum from such women showed reduced both lipidic peroxidation and oxidized low-density lipoprotein (LDL). Besides, vitamin E and coenzyme Q10 levels increased. Furthermore, culture medium containing 10% of such serum both increased osteoblastogenesis and reduced adipogenesis in human MSC from bone marrow. Therefore, highly antioxidant by-products like D6 may represent a relevant source for development of functional products, for both prevention and treatment of degenerative pathologies associated with aging, like osteoporosis.

Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans.

Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/ß-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n = 151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/ß-TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year all-cause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way.

HIV-1 tropism evolution after short-term maraviroc monotherapy in HIV-1-infected patients.

We analyzed the evolution of viral tropism after 8 days of maraviroc monotherapy, i.e., we used the maraviroc clinical test (MCT), in 21 patients with and 14 without virological response to the drug (MCT(+) and MCT(-) patients, respectively). No increases in CXCR4 inferred viral loads (X4IVLs) were observed in MCT(+) patients, while X4IVLs increased only in MCT(-) patients, with X4IVLs of >2 log(10) HIV RNA copies/ml. These results shed light on the evolution of viral tropism under a CCR5 antagonist in vivo.

HIV infection-related premature immunosenescence: high rates of immune exhaustion after short time of infection.

Premature immunosenescence has been reported in different HIV scenarios. However, how premature is the HIV-related immunosenescent phenotype is still unknown. Thus, the aim of this study was to analyze the immunosenescent status of young viraemic naive HIV-infected individuals, with less than four years from infection. To this end, replicative senescence, activation and proliferation T-cell levels were analyzed in chronically HIV-infected young individuals and both, elderly and young healthy controls. We show that young HIV-infected viraemic patients, with less than four years from infection, have early immune exhaustion leading to a premature immunosenescence comparable to healthy people 40 years elder. In addition, memory T-cell subsets showed greater alterations than elder healthy controls and, in patients with high viral loads, CD57 expression at the memory T-cell subsets was correlated with lower viral increases but higher CD4 T-cell lost during follow up.

Long-term immunovirogical effect and tolerability of a maraviroc-containing regimen in routine clinical practice.

OBJECTIVES: to analyze the long-term immunovirological effect and tolerability of a maraviroc-containing antiretroviral therapy in viraemic and pretreated HIV-infected patients with a high prevalence of hepatitis C virus (HCV) coinfection. METHODS: forty-six R5 HIV-infected patients (48% HCV-coinfected) started a maraviroc-containing antiretroviral regimen, including patients with multidrug resistant virus and patients after first virologic failure. A retrospective study was performed, analysing percentage of patients with undetectable viral load, mean CD4+ gain, liver enzymes, clinical events and treatment modification up to week 48. RESULTS: Raltegravir plus a boosted protease inhibitor was combined with maraviroc in 65.2% of the patients (mainly patients with multidrug resistant virus), while the coformulation lamivudine/abacavir was combined with maraviroc in 26.1% (all of them patients after first virologic failure). After 48 weeks on maraviroc-containing regimen, 96.3% of the patients had achieved undetectability and a mean CD4+ count increase of 151 cells/mm3 was observed. Liver enzymes did not increase along the follow up. One patient died after 24 weeks follow up due to heroin overdose. One patient developed a non-Hodgkin lymphoma after 36 weeks follow up, despite undetectable viral load and significant CD4+ increase was achieved (the only AIDS-defining event observed). Treatment modification was performed in 19.6% of the patients: 77.7% of them experienced a treatment simplification and only 1/46 suspended maraviroc. CONCLUSIONS: maraviroc-containing regimen is long-term effective and well tolerated in HIV-infected patients in routine clinical practice and in different clinical scenarios.