Purpose
Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic ...inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal.
Methods
We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis.
Results
Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels.
Conclusions
Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.
Microglial cells are the main HIV-1 targets in the central nervous system (CNS) and constitute an important reservoir of latently infected cells. Establishment and persistence of these reservoirs ...rely on the chromatin structure of the integrated proviruses. We have previously demonstrated that the cellular cofactor CTIP2 forces heterochromatin formation and HIV-1 gene silencing by recruiting HDAC and HMT activities at the integrated viral promoter. In the present work, we report that the histone demethylase LSD1 represses HIV-1 transcription and viral expression in a synergistic manner with CTIP2. We show that recruitment of LSD1 at the HIV-1 proximal promoter is associated with both H3K4me3 and H3K9me3 epigenetic marks. Finally, our data suggest that LSD1-induced H3K4 trimethylation is linked to hSET1 recruitment at the integrated provirus.
The introduction of highly active antiretroviral therapy (HAART) has been an important breakthrough in the treatment of HIV-1 infection and has also a powerful tool to upset the equilibrium of viral ...production and HIV-1 pathogenesis. Despite the advent of potent combinations of this therapy, the long-lived HIV-1 reservoirs like cells from monocyte-macrophage lineage and resting memory CD4+ T cells which are established early during primary infection constitute a major obstacle to virus eradication. Further HAART interruption leads to immediate rebound viremia from latent reservoirs. This paper focuses on the essentials of the molecular mechanisms for the establishment of HIV-1 latency with special concern to present and future possible treatment strategies to completely purge and target viral persistence in the reservoirs.
On the basis of sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into 4 gB genotypes. The goal of the present study was to determine ...the distribution of CMV gB genotypes and the effect of gB type on clinical outcomes in a cohort of immunocompromised patients, including both transplant recipients and nonrecipients. The distribution of gB genotypes was as follows: gB1, 28.9% of patients; gB2, 19.6%; gB3, 23.7%; gB4, 2.0%; and mixed infection, 25.8%. In contrast to patients infected with a single gB genotype, patients infected with multiple gB genotypes developed progression to CMV disease, had an increased rate of graft rejection, had higher CMV loads, and were significantly more often infected with other herpesviruses. The presence of multiple gB genotypes, rather than the presence of a single gB genotype, could be a critical factor associated with severe clinical manifestations in immunocompromised patients.
Episodes of CMV-viruria have been reported in hematopoietic stem cell transplant (HSCT) recipients, but their context of occurrence, pathophysiology, and clinical significance remain misunderstood.
...Uurine samples from 517 recipients were collected. Clinical features of recipients with or without episodes of CMV-viruria were retrospectively compared.
CMV-viruria was detected in 15.5 % of cases. Age, sex, type of transplantation, HLA-matching, conditioning regimen, and immunosuppressive therapies did not differ between patients with and without CMV-viruria. CMV-seropositive status (R + ) was more frequent among CMV-viruric recipients. Cumulated mortality did not differ between the two groups but graft-versus-host diseases occurred more frequently among CMV-viruric patients (p = 0.04). No reduction of the estimated glomerular filtration rates was observed in CMV-viruric recipients.
CMV-viruria primarily occurs in CMV-seropositive recipients and is not related to the degree of immunosuppression. We suggest that CMV-viruria is primarily related to the inability of the graft immune system to contain CMV-replication in R + patients. CMV-viruria is not associated with increased mortality or renal dysfunction.
Cytokine receptor signalling and aging Fulop, T.; Larbi, A.; Douziech, N. ...
Mechanisms of ageing and development,
06/2006, Letnik:
127, Številka:
6
Journal Article
Recenzirano
With ageing the immune system is deregulated and this leads to the development of immunosenescence mainly affecting the adaptive immune response. There is much knowledge accumulated concerning ...various receptor functions and signalling with ageing such as TCR, FcRs, TLRs. Cytokines are playing a major role in haematopoietic cell functions and in the harmonious and integrated coordination of the innate and adaptive immune response. There exists a large amount of data on cytokine production changes with ageing, as IL-2 production is decreasing, while IL-6 production is increasing. In contrast, there is only scarce knowledge concerning the cytokine receptors and their signalling in ageing. However, there is some evidence that the signalling of IL-2 receptors is altered in T cells and macrophages, mainly in relation to the JAK/STAT pathway. We present here evidence that the IL-6 induced signalling is also altered in T cells with ageing. An alteration in the JAKs and STATs activations in T cells and macrophages was demonstrated. The exact cause of these altered activations is not known and future studies are needed to elucidate them. In this review we summarise our present knowledge on cytokine signalling with ageing, mainly focusing on IL-2 and IL-6 receptors signalling.
A large body of experimental research indicates that oxidative stress contributes to the processes related to aging and age-related diseases. Trace elements, particularly zinc (Zn), are essential ...components of the endogenous enzymatic antioxidant defenses. The aim of this study was to determine the activity of three main antioxidant enzymes in plasma i.e. superoxide dismutase (pSOD), catalase (CAT), glutathione peroxidase (GPx) and of SOD in erythrocyte (eSOD) in a group of 1108 healthy elderly subjects from different European countries. The same enzymatic activities were evaluated in a subgroup of 108 subjects before and after Zn supplementation. We observed that eSOD activity increased with age, whereas plasma Zn decreased. Moreover, we found that women showed higher eSOD activity and lower plasma Zn compared to men. There were no age and gender-related differences in the activities of pSOD, CAT and GPx. After Zn supplementation, the activities of Zn-dependent enzymes (pSOD and eSOD), as well as plasma Zn concentration, were significantly higher than before supplementation. These results were not influenced by age, gender, plasma Zn variations (Δ Zn) and geographic area. These data suggest the potential beneficial effects of Zn supplementation on Zn-dependent antioxidant enzymes in healthy elderly subjects.
...our patient was an asymptomatic HBV carrier, without any increase in serum ALT recorded over a long follow up period. ...although she received methotrexate, which may favour HBV reactivation ...through its immunosuppressive properties 1 and induce subfulminant HBV reactivation after its withdrawal, 2, 3 no change in HBV DNA load was seen during the 9 months of methotrexate monotherapy.
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