Clinical characteristics of very old patients hospitalized in internal medicine wards for heart failure: a sub-analysis of the FADOI-CONFINE Study Group

The incidence and prevalence of chronic heart failure are increasing worldwide, as is the number of very old patients (>85 years) affected by this disease. The aim of this sub-analysis of the multicenter, observational CONFINE study was to detect clinical and therapeutic peculiarities in patients with chronic heart failure aged >85 years. We recruited patients admitted with a diagnosis of chronic heart failure and present in the hospital in five index days, in 91 Units of Internal Medicine. The patients' clinical characteristics, functional and cognitive status, and the management of the heart failure were analyzed. A total of 1444 subjects were evaluated, of whom 329 (23.1%) were over 85 years old. Signs and symptoms of chronic heart failure were more common in very old patients, as were severe renal insufficiency, anemia, disability and cognitive impairment. The present survey found important age-related differences (concomitant diseases, cognitive status) among patients with chronic heart failure, as well as different therapeutic strategies and clinical outcome for patients over 85 years old. Since these patients are usually excluded from clinical trials and their management remains empirical, specific studies focused on the treatment of very old patients with chronic heart failure are needed

Effects of Antiretroviral Molecules on Survival and Gene Expression of An Osteoblast-like Cell Line

The advent of combined antiretroviral therapy effectively undermined the evolution of HIV disease. Nevertheless, clinical observations indicated a clear association between therapy and the impairment of bone mineral density

Effects of Antiretroviral Molecules on Survival and Gene Expression of an Osteoblast-like Cell Line

Background The advent of combined antiretroviral therapy effectively undermined the evolution of HIV disease. Nevertheless, clinical observations indicated a clear association between therapy and the impairment of bone mineral density. Objective We selected some antiretroviral compounds used in clinical practice, to study their impact on bone health and their possible implication in the onset of bone disease. Method Scalar concentrations of several antiretroviral drugs (used in single and in combination) were tested on an osteoblast-like cell line, HOBIT cells, to analyse cell survival and gene expression of selected bone markers. Results None of the tested concentrations of Tenofovir, Emtricitabine, Nevirapine, Maraviroc or Raltegravir induced any significant apoptosis activation at our experimental conditions. Only some protease inhibitors and Efavirenz, at high concentration, determined a significant activation of programmed cell death. In parallel experiments, protease inhibitors used in combination with Tenofovir and Emtricitabine, increased apoptosis . Furthermore, we performed a study of mRNA expression of specific genes involved in osteoblast biology and in bone synthesis and observed that some protease inhibitors induced a selective decrease of some osteogenic markers. Conclusion All the protease inhibitors included in this study trigger apoptosis at the highest concentration analysed, suggesting great caution in HIV-patients co-infected with HBV or HCV, where elevated plasma concentrations of drugs could be reached as a consequence of liver failure. Lastly, an increased apoptosis rate and an impairment of osteogenic markers were recorded only in presence of Nelfinavir, suggesting a role of protease inhibitors in the alteration of osteoblast biology

Optimizing the alignment of thermoresponsive poly(N-isopropyl acrylamide) electrospun nanofibers for tissue engineering applications: A factorial design of experiments approach.

Thermoresponsive polymers, such as poly(N-isopropyl acrylamide) (PNIPAM), have been identified and used as cell culture substrates, taking advantage of the polymer's lower critical solution temperature (LCST) to mechanically harvest cells. This technology bypasses the use of biochemical enzymes that cleave important cell-cell and cell-matrix interactions. In this study, the process of electrospinning is used to fabricate and characterize aligned PNIPAM nanofiber scaffolds that are biocompatible and thermoresponsive. Nanofiber scaffolds produced by electrospinning possess a 3D architecture that mimics native extracellular matrix, providing physical and chemical cues to drive cell function and phenotype. We present a factorial design of experiments (DOE) approach to systematically determine the effects of different electrospinning process parameters on PNIPAM nanofiber diameter and alignment. Results show that high molecular weight PNIPAM can be successfully electrospun into both random and uniaxially aligned nanofiber mats with similar fiber diameters by simply altering the speed of the rotating mandrel collector from 10,000 to 33,000 RPM. PNIPAM nanofibers were crosslinked with OpePOSS, which was verified using FTIR. The mechanical properties of the scaffolds were characterized using dynamic mechanical analysis, revealing an order of magnitude difference in storage modulus (MPa) between cured and uncured samples. In summary, cross-linked PNIPAM nanofiber scaffolds were determined to be stable in aqueous culture, biocompatible, and thermoresponsive, enabling their use in diverse cell culture applications

HIV-1 gp120 impairs the differentiation and survival of cord blood CD34+ HPCs induced to the erythroid lineage

Anemia is the most common hematological abnormality in human immunodeficiency virus (HIV)-infected patients. Besides chronic disease, opportunistic infections, nutritional deficiencies and antiretroviral drug toxicity, the direct role of HIV in the development of anemia has not yet been fully investigated. To explore the HIV-related mechanisms involved in the genesis of anemia, we used two experimental designs. In the first, HPCs purified from cord blood were challenged with HIV-1IIIb or recombinant gp120 (rgp120) and then committed to erythrocyte differentiation (EPO-post-treated HPCs). In the second, HPCs were first committed to differentiate towards the erythroid lineage and only afterwards challenged with HIV-1IIIb or rgp120 (EPO-pre-treated HPCs). Our results showed that HPCs and EPO-induced HPCs were not susceptible to HIV-1 infection. In addition, the two experimental designs (EPO post or pre-treated HPCs) independently showed that HIV-1IIIb or rgp120 were able to induce the impairment of survival, proliferation, and differentiation albeit differing in kinetics and extent. Interestingly, the gp120 interaction with CD4 and CXCR4 played a pivotal role in the impairment of erythrocyte differentiation by inducing TGF-b1 expression. These observations reveal an important additional mechanism involved in the genesis of anemia suggesting a complex competition between EPO-positive regulation and HIV-negative priming regarding erythrocyte survival, proliferation and maturation

Durable viral suppression in an HIV-infected patient in the absence of antiretroviral therapy

We describe the case of a young woman with an acute HIV infection characterized at onset by neurological features. The patient spontaneously controlled her HIV infection and recovered in a short period of time. The patient's clinical and virological history showed a peculiar evolution of HIV infection, with an MDR HIV-1 in CSF and a wild HIV strain in PBMCs. The patient's PBMC showed a rapid shift from a wild type to an MDR strain in few days

HIV and kidney: A dangerous liaison

Kidney disease represents an important health concern among HIV-infected individuals, with an estimated prevalence ranging between 2.4 and 17%. The widespread use of antiretroviral drugs has changed the epidemiology of kidney disease in the HIV positive population, drastically reducing the percentage of patients affected by HIV-associated nephropathy (HIVAN), a complication characterized by apoptosis and de-differentiation of renal epithelial cells and podocytes. However, impaired kidney function remains an important issue among HIV-infected patients because of their long-term exposure to antiretroviral drugs and the growing burden of traditional risk factors associated with chronic renal disease. Furthermore, since HIV infects renal epithelial cells, kidney is a potential reservoir site that needs to be considered in future eradication studies. This review summarizes the main risk factors associated with chronic kidney disease in HIV-infected patients and discusses the contribution of viral infection and antiretroviral therapy to the pathogenesis of renal damage, emphasizing the need to monitor kidney status during the follow-up of HIV-infected patients

Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.

Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs) that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1) strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs) and, importantly, the surface plasmon resonance (SPR) assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1

Durable viral suppression in an HIV-infected patient in the absence of antiretroviral therapy

We describe the case of a young woman with an acute HIV infection characterized at onset by neurological features. The patient spontaneously controlled her HIV infection and recovered in a short period of time. The patient's clinical and virological history showed a peculiar evolution of HIV infection, with an MDR HIV-1 in CSF and a wild HIV strain in PBMCs. The patient's PBMC showed a rapid shift from a wild type to an MDR strain in few days

Flow cytometry analysis of binding between SB105-A10 and heparan sulphates.

<p>Typical experiments were shown. (<b>A</b>), Different concentrations of FITC-conjugated SB105-A10 (from 0 to 250 µg/ml) were assayed for 1 hour at 4°C on activated PBMCs (5×10⁶/ml). The saturation was achieved at 25 µg/ml. (<b>B</b>), Activated PBMCs (5×10⁶/ml) were treated with 25 µg/ml of FITC-conjugated SB105-A10 for 1 hour at 4°C and then washed with PBS containing 2 M NaCl, a treatment known to remove cationic polypeptides from cell surface HSPGs. (<b>C</b>), Activated PBMCs (5×10⁶/ml) were incubated with heparinase III for 2 h at 37°C or left untreated before the binding assay with 25 µg/ml of FITC-conjugated SB105-A10. Both heparinase III and 2 M NaCl treatments reduce but not abolish the specific fluorescence signal suggesting an interaction between SB105-A10 and cell membrane that is not related to HSPGs.</p