Katia Falasca

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome.

In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation. A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.

Metabolic syndrome and cardiovascular risk in HIV-infected patients with lipodystrophy.

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2 ± 8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95% IC: 1.04–1.19); and patients in the top tertile of IL-18 (those with IL-18 ≥ 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium fertiles of IL-18 (patients with IL-18 < 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.

Use of Epoetin Beta During Combination Therapy of Infection With Hepatitis C Virus With Ribavirin Improves a Sustained Viral Response

The aim of the study was to evaluate the effects of epoetin‐beta on anemia and sustained viral response in patients with chronic hepatitis C receiving treatment with pegylated interferon and ribavirin. Forty‐two Caucasian patients with chronic hepatitis C infection, treated with pegylated interferon α‐2a or α‐2b plus ribavirin, who experienced at least a 2 log decline in HCV‐RNA in the first month of therapy and a ≥2.5 g/dl hemoglobin drop from baseline, were recruited. They were divided into two groups: 22 patients received epoetin‐beta 30,000 U administered s.c. q.w. (group A) and 20 patients received a reduced ribavirin dose of 600 mg daily (group B). The end‐of‐treatment response was 95.4% (21/22) in group A and 80% (16/20) (P = 0.2) in group B. Sustained viral response in group A was 81.8% (18/22), statistically higher than in group B (45%, 9/20) (P = 0.03). Mean corpuscular volume of erythrocytes was statistically lower in group A than in group B 4 weeks after starting epoetin‐beta or reduced ribavirin dose (P < 0.001), end‐of‐treatment (P < 0.001) and after 6 months follow‐up (P < 0.001). A negative correlation between the levels of ferritin serum was found in group A at the baseline and mean corpuscular volume value after 1 month of combination antiviral therapy (r = −0.45; P = 0.35), 4 weeks after starting epoetin‐beta (r = −0.43; P = 0.04) and after 6 months follow‐up (r = −0.45; P = 0.03). Administration of epoetin‐beta increases sustained viral response rates among patients developing anemia, because the standard dose of ribavirin is maintained, thereby reducing the side‐effects of antiviral treatment. J. Med. Virol. 82:49–56, 2010.

Endothelial progenitor cell trafficking in human immunodeficiency virus-infected persons.

Objective:Human immunodeficiency virus (HIV)-infected people exhibit a high incidence of vascular diseases. Since in the general population the high cardiovascular risk has been associated with an impaired endothelial cell function, we investigated circulating endothelial progenitor cells in HIV-positive patients. Design:We evaluated circulating colony-forming unit–endothelial cell (CFU-EC) and endothelial colony-forming cell (ECFC) progenitors in 14 antiviral therapy-naive HIV-positive patients, in comparison with 15 normal controls. Methods:CFU-EC and ECFC derived from peripheral blood mononuclear cells from HIV-infected and HIV-uninfected individuals were recovered and evaluated for HIV genome presence by PCR. Vascular endothelial growth factor (VEGF) and apolipoprotein B mRNA-editing enzyme catalytic polypeptide like (APOBEC) subunits expression were evaluated in infected colonies by real-time PCR. Results:We found that circulating CFU-EC but not ECFC were significantly reduced in HIV-positive patients and that proviral HIV DNA was detectable only in CFU-EC but not in ECFC. Furthermore, the expression of APOBEC subunits was significantly lower in CFU-EC than in circulating monocytes. Accordingly, the CFU-EC displayed a high content of proviral DNA copies, suggesting that these cells have a high sensitivity to the HIV infection. Conclusions:Although HIV does not affect the ‘true endothelial progenitor’ compartment, it infects and strongly depletes circulating endothelial progenitors with hematopoietic signature. We unravel a novel pathogenetic mechanism by which HIV infection might cause vascular diseases.

Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy.

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro‐immunological parameters, triglycerides (TGs), total cholesterol (TCh), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterol, fasting glucose, HOMA‐IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles. J. Med. Virol. 85:755–759, 2013.

Antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients.

BACKGROUND Hypertension is more prevalent among HIV-infected individuals than in the general population and contributes to increased cardiovascular risk. The angiotensin II receptor blocker telmisartan is also a partial peroxisome proliferator activated receptor-γ agonist with documented effects on glucose and lipid homeostasis. The aim of this study was to evaluate the antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients. METHODS A total of 18 HIV-positive men treated with antiretroviral therapy and recently diagnosed with hypertension were administered 80 mg telmisartan daily. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), viroimmunological and metabolic parameters, insulin resistance, C-reactive protein, microalbuminuria, cystatin C and plasma levels of interleukin-18 and endothelin-1 were measured at baseline (T0), 1 month (T1), 3 months (T3) and 6 months (T6). RESULTS Treatment with telmisartan not only decreased SBP and DBP levels, but also improved insulin resistance and microalbuminuria by T1. Levels of triglycerides significantly decreased and high-density lipoprotein cholesterol increased at T1, whereas total and low-density lipoprotein cholesterol levels were statistically reduced at T3 and T6. Cystatin C and endothelin-1 showed a significant reduction at T1, whereas interleukin-18 decreased at both T3 and T6. CONCLUSIONS Telmisartan was effective in reducing blood pressure and improving lipid metabolism and renal function. Reduction of endothelin-1 might be related to an endothelial protective effect. On the basis of these findings, and because of properties unrelated to blood pressure lowering, telmisartan might be the first choice antihypertensive drug for the treatment of HIV-positive patients.

Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study

Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p < 0.001) and IL-1β expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.

The proinflammatory interleukin-21 elicits anti-tumor response and mediates autoimmunity.

Interleukins (IL) are inflammatory proteins (except IL-4 and IL-10) that modulate the immune system (1-4). IL-2l induced inflammation in vivo, based on recruitment of neutrophil and monocyte populations (5-8). This cytokine is similar in primary sequence and structure to IL-2 and IL-15 and is a member of the type I cytokine superfamily which includes IL-2, IL-4, IL-7, IL-9, IL-ll, IL-12, IL-13, IL-15 and Colony Stimulating Factors (CSFs). IL-2l is a multifunctional cytokine having roles in both innate and adaptive immune responses of the Th 1 type (9-11) with an effect on proliferation, apoptosis and differentiation of T cells, NK cells, dendritic cells and B cells (12-15) and lymphocytes function (16-18) (Fig. 1). IL-21, like other members of this family, is a gamma-chain dependent cytokine playing a prominent role in promoting and maintaining T cell populations (19-21). Human and murine IL-2l are 57% identical at the amino acid level, display a 4helix-bundle-type with homology to IL-2, IL-4 and IL-15 and have a unique receptor, IL-21R. The exon and intron structure of the IL-2 and IL-2l genes are very similar and are related to each other. IL21R is a type I cytokine receptor that acts through the interaction with the common gamma chain and is expressed in lymphoid tissues: thymus, spleen, peripheral blood leukocytes such as T cells (CD4+ and CD8+), B cells, NK cells, dendritic cells and several cell lines (22-24). IL-2l R possesses alpha, beta and gamma chain heterotrimer. The beta and gamma chain are essential for signal transduction while the alpha subunit seems to be more involved in high-affinity binding conversion. An anti-gamma chain antibody inhibits cell proliferation induced by IL-2l, suggesting that the gamma chain plays an essential role in IL-2l signal transduction (2527). The generation of IL-21R-deficient mice with normal lymphoid cells revealed dysfunction in immunoglobulin IgG1 production and an increase in IgE responses in immunized animals (28-30). IL-2l needs the common gamma chain to mediate the intracellular survival and/or mitogenic signalling, which occurs through the essential transducermolecule JAK3 (5, 31); however, three major pathways are involved in IL-2l signalling ( JAKISTAT, MAPK and PI3K) to promote and maintain T lymphocyte populations (32-34). Survival and differentiation of B cells is mediated by IL-2l through down-regulation of anti-apoptotic proteins and up-regulation of proapoptotic proteins (35-38).

Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis treated with linezolid

Linezolid is not yet recognized as a standard therapy for infective endocarditis but its use becomes a necessity when infection is due to multidrug-resistant microorganisms. This report describes 1 patient with endocarditis treated with linezolid and 45 similar cases from the medical literature.

Different strategies of 25OH vitamin D supplementation in HIV-positive subjects

Summary A high incidence of 25OH vitamin D deficiency has been observed in HIV-infected subjects. The objective of this study was to evaluate the effect of cholecalciferol administration on serum 25OH vitamin D levels in HIV-infected patients. This prospective cohort study included 153 HIV-positive subjects; 47 were treated with 300,000 IU intramuscular cholecalciferol, 67 with 25,000 IU oral cholecalciferol monthly, while the remaining 39 did not receive any treatment. The group treated orally had an increase of serum 25OH vitamin D concentration, changing from 15.7 ± 12.2 ng/mL to 27.4 ± 11.6 ng/mL after 10 months (T10). The group treated with intramuscular supplementation had an improvement, changing from 18.5 ± 10.5 ng/mL to 32.9.0 ± 12.2 ng/mL at T10. One-way repeated measures analysis of variance indicated a significant difference for 25OH vitamin D variation (p = 0.002) among the three groups. A significant effect of time (p < 0.001) and group × time interaction (p < 0.001) was found: at T10, 25OH vitamin D values were significantly higher in the oral and intramuscular groups with respect to the control group. Our findings showed that the supplementation with cholecalciferol in patients with HIV-infection improved 25OH vitamin D serum levels, and suggest that the two types of administration are equivalent, but are insufficient for severe forms of hypovitaminosis.