Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN). The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele) is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group) who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s), for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04) among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort

Timed rise from floor as a predictor of disease progression in Duchenne muscular dystrophy: An observational study

The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys.A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS).The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p<0.01).Both time to rise from the floor and baseline 6MWT were relevant for predicting 6MWT changes in the group above the age of 7 years, with no interaction between the two measures, as the impact of time to rise from the floor on 6MWT change was similar in the patients below and above 350 m. Our results suggest that, time to rise from the floor can be considered an additional important prognostic factor of 12 month changes on the 6MWT and, more generally, of disease progression

Bactericidal effects of Resveratrol-loaded glycosylated liposomes on Staphylococcus aureus and MRSA

Liposomes have unique characteristics of biocompatibility, versatility and simplicity of preparation, making them excellent candidates for drug delivery. These nanosystems can allow the release of drugs to target cells, reducing the dosage and avoiding healthy tissues and organs; moreover, due to their ability to fused with bacteria and to improve antibiotics activity, they hold the potential to overcome multi-drug resistance in bacterial infections [1]. Here we report the targeted delivery of trans-resveratrol (RSV), a Quorum Sensing Inhibitor, to two strains of resistant and biofilm forming bacteria, Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus (MRSA). RSV was encapsulated in cationic glycosylated liposomes formulated with 1,2-dioleoyl-sn-glycero-3-phosphocoline (DOPC), cholesterol (chol) and one glycoamphiphile featuring a galactosyl, mannosyl or glucosyl moiety, previously synthesized and used in our laboratory to target bacteria and biofilms (Figure 1) [2,3]. In fact, the synthetic glycolipids are able to increase liposomes specificity toward lectins, a class of non-enzymatic sugar-binding proteins involved in cellular recognition and adhesion, and sugar-protein transporters located on the outer membrane of bacterial cells

Glucocorticoids aggravate hyperoxia-induced lung injury through decreased nuclear factor-kappa B activity

We previously reported that exposure of mice to hyperoxia is characterized by extensive lung cell necrosis and apoptosis, mild inflammatory response, and elevated circulating levels of corticosterone. Administration of hydroxycortisone acetate during hyperoxia aggravated lung injury. Using adrenalectomized (ADX) and sham-operated (sham) mice, we studied the role of the glucocorticoids in hyperoxia-induced lung injury. Lung damage was attenuated in ADX mice as measured by lung weight and protein and cell content in bronchoalveolar lavage and as seen by light microscopy. Mortality was delayed by 10 h. Nuclear factor-kappaB (NF-kappaB) activity was significantly decreased in lungs of sham mice exposed to hyperoxia but was preserved in ADX mice. There was a correlation between NF-kappaB activity in ADX mice and decreased levels of IkappaBalpha. In contrast, activator protein-1 activity increased similarly in both groups of mice. Levels of interleukin-6 (IL-6), a transcriptional target of NF-kappaB, were higher in bronchoalveolar lavage and serum of ADX than sham mice. However, the protective effect of ADX was not mediated by IL-6, because administration of recombinant human IL-6 to sham mice did not prevent lung damage. These results demonstrate that the adrenal response aggravates alveolar injury and is likely to be mediated by the decrease of NF-kappaB function involved in cell survival

A New Testing Facility to Investigate the Removal Processes of Indoor Air Contaminants with Different Cleaning Technologies and to Better Assess and Exploit Their Performances

Residential air cleaners exploiting different technologies re commonly used today to remove air contaminants from indoor environments. Different methods have been developed in the USA and Europe to test their efficiency. The one used in the USA provides a more comprehensive view of indoor processes, because testing is performed in a large simulation chamber (28.5 m3), using anthropogenic emissions, such as cigarette smoke, to generate pollution. Testing rooms are also important to investigate new removal technologies, or to improve them. Since no such testing facilities exist in Italy, one of 12.4 m3 was built in which cigarette smoke, resuspended dust from agricultural soil and, for the first time, diesel exhaust emissions were used to generate indoor pollution. Performances were tested with two air cleaning systems, exploiting completely different removal technologies. Accurate values of decay rates of indoor pollutants were obtained using a suite of on-line and out-of-line monitors for the measurement of particulate matter, volatile organic compounds (VOCs) and some inorganic gases. Proton-transfer mass spectrometry (PTR-MS) provided an almost real-time detection of several VOCs and H2S, at trace levels (0.01 ppbv). A method using a common in vitro bioassay was developed to assess the ability of air cleaners to remove indoor toxic substances

A New Testing Facility to Investigate the Removal Processes of Indoor Air Contaminants with Different Cleaning Technologies and to Better Assess and Exploit Their Performances

Residential air cleaners exploiting different technologies re commonly used today to remove air contaminants from indoor environments. Different methods have been developed in the USA and Europe to test their efficiency. The one used in the USA provides a more comprehensive view of indoor processes, because testing is performed in a large simulation chamber (28.5 m3), using anthropogenic emissions, such as cigarette smoke, to generate pollution. Testing rooms are also important to investigate new removal technologies, or to improve them. Since no such testing facilities exist in Italy, one of 12.4 m3 was built in which cigarette smoke, resuspended dust from agricultural soil and, for the first time, diesel exhaust emissions were used to generate indoor pollution. Performances were tested with two air cleaning systems, exploiting completely different removal technologies. Accurate values of decay rates of indoor pollutants were obtained using a suite of on-line and out-of-line monitors for the measurement of particulate matter, volatile organic compounds (VOCs) and some inorganic gases. Proton-transfer mass spectrometry (PTR-MS) provided an almost real-time detection of several VOCs and H2S, at trace levels (0.01 ppbv). A method using a common in vitro bioassay was developed to assess the ability of air cleaners to remove indoor toxic substances