ABSTRACT
AIM: Aim of the study was to investigate plasma levels of intercellular adhesion molecule-1 (s-ICAM-1) and vascular cellular adhesion molecule-1 (s-VCAM-1) in a cohort of type 2 diabetic patients, compared to healthy control subjects, to verify whether there are differences between these two molecules and to evaluate a possible correlation with the presence of microangiopathy. METHODS: Plasma ICAM-1 and VCAM-1 levels in 49 type 2 diabetic patients, 28 microalbuminuria patients and 21 normoalbuminuria patients were investigated and compared to same levels of 15 healthy control subjects. ICAM-1 and VCAM-1 were assayed by EIA commercial kit (R&D System Co, Abington, UK), according to procedures described by the manufacturer and concentrations expressed as ng/mL. Mean +/- standard deviation (SD) values for each group were compared by t test for unpaired data and Kruskall-Wallis test. Statistical significance was set at P<0.05. RESULTS: Mean +/- SD plasma ICAM-1 was 12.96 +/- 1.08 ng/mL in controls, 18.56 +/- 2.3 ng/mL in normoalbuminuria patients and 26.25 +/- 4.1 ng/mL in microalbuminuria patients, respectively. Mean +/- SD plasma VCAM-1 was 15.96 +/- 4.02 ng/mL in controls, 17.13 +/- 7.5 ng/mL in normoalbuminuria patients and 26.84 +/- 5.99 ng/mL in microalbuminuria patients, respectively. Statistical analysis showed a significant difference in ICAM-1 levels between controls and normoalbuminuria patients (P<0.05) and between these and microalbuminuria patients (P<0.05). VCAM-1 levels were significantly higher in microalbuminuria than in normoalbuminuria patients (P<0.05), but no significant difference was found between normoalbuminuria patients and control subjects (P>0.05). CONCLUSION: Reported results show that circulating ICAM-1 is higher in microalbuminuria than in normoalbuminuria patients and also in normoalbuminuria patients than in control subjects. Circulating VCAM-1 has increased only in microalbuminuria patients. Therefore, these two molecules have different ability to assess temporal relationship between inflammatory activity and microvascular complications.
Subject(s)
Albuminuria/blood , Diabetes Mellitus, Type 2/blood , Intercellular Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/blood , Case-Control Studies , Female , Humans , Male , Middle Aged , Statistics, NonparametricABSTRACT
T cell apoptosis represents a common mechanism of T cell depletion in HIV-1-infected individuals reflecting maturational and functional T cell abnormalities either directly or indirectly induced by the virus. In the present study, the effects of highly active antiretroviral therapy (HAART) on the spontaneous apoptosis of distinct T cell subsets were investigated during a 6-month follow-up in a cohort of HIV-1-infected individuals with CD4(+) cell counts between 100 and 500 cells/microliter and plasma HIV-1 RNA levels >/=10, 000 copies/ml. We determined that the rapid and sustained increase of both naive (CD45RA(+)CD62L(+)) and memory (CD45R0(+) and CD45RA(+)/CD62L(-)) CD4(+) and, to as lesser extent, CD8(+) T cells in peripheral blood was associated with a significant decrease of apoptotic CD4(+) and CD8(+) as well as CD3(+)CD4(-)CD8(-) T cells. Among CD4(+) lymphocytes, at enrollment, the highest frequency of apoptotic cells was observed within the memory compartment, as defined by CD45R0 expression. During HAART, however, the frequency of CD4(+)CD45R0(+) apoptotic T cells progressively decreased in association with a significant downregulation of surface activation markers that indicated decreased levels of systemic immune stimulation. These results indicate that effective viral suppression can contribute to progressive normalization of maturational and functional T cell abnormalities responsible for the high levels of T cell apoptosis in HIV-1-infected individuals. This, in turn, may contribute to a reduced rate of T cell loss and immune reconstitution during HAART.
Subject(s)
Antiretroviral Therapy, Highly Active , T-Lymphocytes/cytology , Adult , Apoptosis/drug effects , Apoptosis/genetics , Cohort Studies , Female , Flow Cytometry , Humans , In Situ Nick-End Labeling , Male , Middle Aged , Phenotype , Prospective Studies , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/drug effects , Viral LoadABSTRACT
This study reports an analysis of clinical, virological, and immunologic outcomes in a cohort of 77 multidrug-experienced AIDS patients during 24 months of highly active antiretroviral therapy (HAART). Our results have shown a reduced risk of AIDS complications, prolonged survival, and immunologic benefit even in the absence of sustained virus suppression. The degree of immunodepression, the risk factors for HIV-1 infection, the use of 2 drugs instead of 3, and a change in protease inhibitor were independently correlated with virological failure. In the majority of studied patients, an increase in CD4+ T cells was observed after HAART. However, the increase was more pronounced in patients who showed a decrease in virus load than in those who did not. Moreover, we observed an absence of relapses among patients who permanently discontinued prophylaxis for Cytomegalovirus retinitis and atypical mycobacterial infections. Peripheral lipodystrophy developed in the majority of patients, regardless of treatment used and virological outcome.