Transport properties of ibuprofen encapsulated in cyclodextrin nanosponge hydrogels: A proton HR-MAS NMR spectroscopy study

The chemical cross-linking of β-cyclodextrin (β-CD) with ethylenediaminetetraacetic dianhydride (EDTA) led to branched polymers referred to as cyclodextrin nanosponges (CDNSEDTA). Two different preparations are described with 1:4 and 1:8 CD-EDTA molar ratios. The corresponding cross-linked polymers were contacted with 0.27 M aqueous solution of ibuprofen sodium salt (IP) leading to homogeneous, colorless, drug loaded hydrogels. The systems were characterized by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Pulsed field gradient spin echo (PGSE) NMR spectroscopy was used to determine the mean square displacement (MSD) of IP inside the polymeric gel at different observation times td. The data were further processed in order to study the time dependence of MSD: MSD = f(td). The proposed methodology is useful to characterize the different diffusion regimes that, in principle, the solute may experience inside the hydrogel, namely normal or anomalous diffusion. The full protocols including the polymer preparation and purification, the obtainment of drug-loaded hydrogels, the NMR sample preparation, the measurement of MSD by HR-MAS NMR spectroscopy and the final data processing to achieve the time dependence of MSD are here reported and discussed. The presented experiments represent a paradigmatic case and the data are discussed in terms of innovative approach to the characterization of the transport properties of an encapsulated guest within a polymeric host of potential application for drug delivery

Naringenin Ameliorates Drosophila ReepA Hereditary Spastic Paraplegia-Linked Phenotypes

Defects in the endoplasmic reticulum (ER) membrane shaping and interaction with other organelles seem to be a crucial mechanism underlying Hereditary Spastic Paraplegia (HSP) neurodegeneration. REEP1, a transmembrane protein belonging to TB2/HVA22 family, is implicated in SPG31, an autosomal dominant form of HSP, and its interaction with Atlastin/SPG3A and Spastin/SPG4, the other two major HSP linked proteins, has been demonstrated to play a crucial role in modifying ER architecture. In addition, the Drosophila ortholog of REEP1, named ReepA, has been found to regulate the response to ER neuronal stress. Herein we investigated the role of ReepA in ER morphology and stress response. ReepA is upregulated under stress conditions and aging. Our data show that ReepA triggers a selective activation of Ire1 and Atf6 branches of Unfolded Protein Response (UPR) and modifies ER morphology. Drosophila lacking ReepA showed Atf6 and Ire1 activation, expansion of ER sheet-like structures, locomotor dysfunction and shortened lifespan. Furthermore, we found that naringenin, a flavonoid that possesses strong antioxidant and neuroprotective activity, can rescue the cellular phenotypes, the lifespan and locomotor disability associated with ReepA loss of function. Our data highlight the importance of ER homeostasis in nervous system functionality and HSP neurodegenerative mechanisms, opening new opportunities for HSP treatment

Expression of CD4 on human peripheral blood neutrophils

AbstractCD4, the primary receptor for entry of HIV, is known to be expressed on T cells and monocytes/macrophages; healthy natural killer (NK) lymphocytes; in vitro human herpesvirus 6 (HHV6)–infected CD8+, NK, and γδ T lymphocytes; CD34+ progenitor cells; and a subset of eosinophils and basophils. We here report the unconventional expression of CD4 at the surface of peripheral blood neutrophils derived from 4 of 51 (7.8%) HIV-1–infected and 3 of 25 (12%) uninfected donors, with similar frequency within the 2 groups. The percentage of CD4+ neutrophils ranged from 39% to 97% of the total neutrophil population. Both surface and cytoplasmic forms of CD4 were present in neutrophils. Quantitative RNA polymerase chain reaction (PCR) revealed that neutrophils contain levels of CD4 mRNA comparable to those of peripheral blood mononuclear cells derived from the same donor. The conformation of CD4 expressed at the surface of neutrophils was similar to that of CD4 expressed on T lymphocytes as determined by the binding of monoclonal antibodies specific for conformational epitopes and the binding of recombinant HIV-1 gp120. Thus, our data provide evidence that neutrophils express endogenous CD4 and bind HIV. Owing to their abundance in peripheral blood, CD4+ neutrophils may influence significantly the biodistribution of HIV delivering it to sites of inflammation or to additional tissue reservoirs

Influence of single- and double-aging treatments on the mechanical and corrosion resistance of Alloy 625

Nickel–chromium–molybdenum Alloy 625 exhibits an excellent combination of mechanical properties and corrosion resistance. However, the high-temperature plastic deformation process and the heat treatment represent critical aspects for the loss in mechanical strength by grain coarsening. This detrimental behavior is worsened by the absence of phase transformation temperatures. However, the chemical composition permits slow precipitation-hardening response upon single aging. Therefore, when the soft- or solution-annealed condition is associated with insufficient mechanical properties, this potentiality can be exploited to improve the mechanical strength. Since the gamma double prime precipitation can be accelerated by double-aging treatment, different time–temperature combinations of double aging at 732 °C and 621 °C are investigated. The simultaneous precipitation of intergranular carbides can dramatically affect the corrosion resistance. Such an undesired phenomenon occurs very quickly at 732 °C, but it is obtained only after very long exposure times at 621 °C. For this reason, a performance chart is developed to compare all the tested conditions. In particular, single aging at 621 °C for 72 h and 130 h are associated with an acceptable combination of mechanical and corrosion properties. Double aging permits a conspicuous acceleration of the aging response. For instance, with double aging at 732 °C 3 h and 621 °C 72 h, it is possible to obtain the same mechanical properties of single aging at 621 °C for 260 h. Such acceleration is accompanied by a more critical corrosion behavior, especially because of the primary step. However, even after its optimization, none of the tested conditions were acceptable

Optimization of the mechanical and corrosion resistance of Alloy 625 through aging treatments

In the as-annealed condition, the nickel-based Alloy 625 has excellent mechanical and corrosion properties compared to those of common stainless steels. This peculiarity enables its exploitation in several industrial fields at cryogenic and high temperatures and in the presence of severely corrosive atmospheres. However, in this alloy, when high-temperature plastic deformation processes and heat treatments are not carefully optimized, the occurrence of excessive grain coarsening can irremediably deteriorate the mechanical strength, possibly leading to incompatibility with the standard requirements. Therefore, this research work investigated the possibility of adopting single- and double-aging treatments aimed at improving such strength loss. Their optimization involved identifying the best compromise between the hardening effect and the loss in corrosion resistance induced by the simultaneous formation of intergranular chromium-rich carbides during aging. The investigation of the aging treatments was performed using hardness, tensile and intergranular corrosion tests considering different time–temperature combinations in a range from 621 °C to 732 °C. Double aging resulted in a considerable acceleration in the hardening response compared to single aging. However, even after its optimization in terms of both temperature and time, the intergranular corrosion resistance remained a critical aspect. Among all the tested conditions, only single aging at 621 °C for 72 h was acceptable in terms of both mechanical and corrosion properties. The influence of longer exposures will be investigated in a future study

Retroviral Interference on STAT Activation in Individuals Coinfected with Human T Cell Leukemia Virus Type 2 and HIV-1

AbstractHuman T cell leukemia virus (HTLV) type-2 is a human retrovirus whose infection has not been tightly linked to human diseases. However, the fairly high prevalence of this infection among HIV-1-positive individuals indicates the importance of better understanding the potential interference of HTLV-2 infection on HIV-1 infection and AIDS. We previously demonstrated that one signature of PBMC freshly derived from HIV-1-infected individuals is the constitutive activation of a C-terminal truncated STAT5 (STAT5Δ). Therefore, we analyzed the potential activation of STATs in HTLV-2 monoinfected and HTLV-2/HIV-1 dually infected individuals. We observed that PBMC of HTLV-2-infected individuals do not show STAT activation unless they are cultivated ex vivo, in the absence of any mitogenic stimuli, for at least 8 h. The emergence of STAT activation, namely of STAT1, in culture was mostly related to the secretion of IFN-γ. Of note, this phenomenon is not only a characteristic feature of HTLV-2-infected individuals but also occurred with PBMC of HIV-1+ individuals. Surprisingly, HTLV-2/HIV-1 coinfection resulted in low/absent STAT activation in vivo that paralleled a diminished secretion of IFN-γ after ex vivo cultivation. Our findings indicate that both HTLV-2 and HIV-1 infection prime T lymphocytes for STAT1 activation, but they also highlight an interference exerted by HTLV-2 on HIV-1-induced STAT1 activation. Although the nature of such a phenomenon is unclear at the present, these findings support the hypothesis that HTLV-2 may interfere with HIV-1 infection at multiple levels

The spinodal decomposition of ferrite in 2507 biphasic stainless steels: embrittlement and possible toughness recovery

Biphasic stainless steels provide an excellent combination of mechanical and corrosion properties. The occurrence of ferrite spinodal decomposition during processing and heat treatment can induce a dramatic drop in impact energy. In this paper, a forged rod of 480 mm diameter made of 2507 biphasic stainless steel was studied. The spinodal decomposition phenomenon upon aging at 475 degrees C (748 K) was investigated by macro- and micro-hardness tests on the constituent phases and by Charpy impact tests. Then, the influence of the microstructural constituents and their morphology on the crack path was studied by optical microscopy, noting possible correlations with the impact energy. Successively, the fracture surfaces of selected specimens were analyzed by a scanning electron microscope (SEM). Finally, reversion heat treatments at 550 degrees C (823 K) and 600 degrees C (873 K) were investigated to evaluate the possibility of recovering the detrimental effects of the alpha' embrittlement. According to the literature, this procedure works well with some biphasic steels, but these steels are characterized by a chromium content lower than that of 2507 grade steel. Regarding the 2507 grade steel studied in this work, complete reversion was obtained by solution-annealing treatment, while reversion heat treatments at both 600 degrees C (873 K) and 550 degrees C (823 K) allowed only a partial recovery

HIV Shedding in Cervico-Vaginal Secretions in Pregnant Women.

Objective: The purpose of this study was to evaluate the presence of HIV-1 in cervicovaginal secretions of pregnant as compared to non-pregnant HIV-seropositive women Patients and Methods: We compared 43 known HIV seropositive pregnant patients versus 241 age-matched (± 2 years) control non-pregnant HIV-seropositive subjects. In pregnant patients blood and cervicovaginal samples were obtained during each trimester of pregnancy. In control subjects the same samples were obtained at enrolment. HIV-1 RNA was measured in plasma; proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA in cervicovaginal secretion by competitive polymerase chain reaction (cRT-PCR) and reverse transcriptase PCR. Results: The genital shedding of HIV-DNA (22/43 as compared to 79/241, p = 0.02), and cell-free HIV-RNA detection (26/43 as compared to 72/241, p <.001) was more common in first-trimester pregnant than in non pregnant women. Pregnancy correlated with a significant positive trend in the cervicovaginal load of HIV-DNA (Spearman Rho= 0.149, p=0.012), and cell-free HIV-RNA (Spearman Rho= 0.253, p<.001), but not of HIV-RNA transcripts (Spearman Rho = 0.06, p= 0.31). After correction for potential confounders, first trimester pregnant women had increased rates of genital HIVDNA (odds ratio = 1.94, 95\% confidence interval = 1.01 - 3.78) and cell-free HIV-RNA (odds ratio = 4.07, 95\% confidence interval = 1.97 - 8.41) detection compared to nonpregnant controls. Conclusion: The shedding of genital HIV was increased in pregnant compared to non pregnant subjects, even in patients with undetectable viremia. In this low-risk HIV-positive population the risks of vertical or horizontal transmissions should not be underestimated