Variations in the lipid profile of patients with chronic renal failure treated with pyridoxine

BACKGROUND: Hyperhomocysteinemia and lipid abnormalities are commonly found in patients with chronic renal failure; both are recognized as risk factors for atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial. This study was performed to determine the effect of a high dose of pyridoxine (300 mg i.v. three times a week) on plasma and red blood cell lipid profile and plasma homocysteine concentration in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (basal 1), after 30 and 60 days of treatment and 4 months after withdrawal (basal 2). RESULTS: Pyridoxine supplementation induced a significant decrease in total plasma homocysteine level and also a lowering effect in plasma total cholesterol and triglycerides. These biochemical data increased when the samples were taken at basal 2, reaching the levels obtained at the beginning of the experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl-hexatriene. CONCLUSIONS: We conclude that high doses of pyridoxine represent an effective strategy to ameliorate both plasma homocysteine levels and lipid profiles in chronic renal failure patients, protecting them from atherosclerosis. Further research using a long-term treatment would be necessary in an attempt to restore the fatty acid pattern and the fluidity of red cell membranes

Carbon nanodots for on demand chemophotothermal therapy combination to elicit necroptosis: Overcoming apoptosis resistance in breast cancer cell lines

Background: Engineered luminescent carbon nanodots (CDs) are appealing nanomaterials for cancer image-guided photothermal therapy combining near infrared (NIR)–triggered hyperthermia, imaging, and drug delivery in a single platform for efficient killing of cancer cells. This approach would allow eliciting synergistic regulated cell death (RCD) routes such as necroptosis, targeting breast cancer cells refractory to apoptosis, thus overcoming drug resistance. Methods: We report the preparation of CDs bearing biotin as a targeting agent (CDs-PEG-BT), which are able to load high amounts of irinotecan (23.7%) to be released in a pulsed on-demand fashion. CDs-PEG-BT have narrow size distribution, stable red luminescence, and high photothermal conversion in the NIR region, allowing imaging of MDA-MB231 and MCF-7 cancer cells and killing them by photothermal and chemotherapeutic insults. Results: Cellular uptake, viability profiles, and RCD gene expression analyses provided insights about the observed biocompatibility of CDs-PEG-BT, indicating that necroptosis can be induced on-demand after the photothermal activation. Besides, photothermal activation of drug-loaded CDs-PEG-BT implies both necroptosis and apoptosis by the TNFα and RIPK1 pathway. Conclusions: The controlled activation of necroptosis and apoptosis by combining phototherapy and on-demand release of irinotecan is the hallmark of efficient anticancer response in refractory breast cancer cell lines in view of precision medicine applications

Rapamycin-loaded polymeric nanoparticles as an advanced formulation for macrophage targeting in atherosclerosis

Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques; however, its use requires site-specific accumulation in the vessels involved in the formation of the plaques to avoid the systemic effects resulting from its indiscriminate biodistribution. In this work, a stable pharmaceutical formulation for Rapa was realized as a dried powder to be dispersed extemporaneously before administration. The latter was constituted by man-nitol (Man) as an excipient and a Rapa-loaded polymeric nanoparticle carrier. These nanoparticles were obtained by nanoprecipitation and using as a starting polymeric material a polycaprolactone (PCL)/α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) graft copolymer. To obtain nanoparti-cles targeted to macrophages, an oxidized phospholipid with a high affinity for the CD36 receptor of macrophages, the 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdia-PC), was added to the starting organic phase. The chemical–physical and technological characterization of the obtained nanoparticles demonstrated that: both the drug loading (DL%) and the entrapment efficiency (EE%) entrapped drug are high; the entrapped drug is in the amorphous state, protected from degradation and slowly released from the polymeric matrix; and the KOdia-PC is on the nanoparticle surface (KP-Nano). The biological characterization demonstrated that both systems are quickly internalized by macrophages while maintaining the activity of the drug. In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug

Nanostructured Lipid Carriers-Containing Anticancer Compounds: Preparation, Characterization, and Cytotoxicity Studies

This article describes the development of nanostructured lipid carriers (NLC) as colloidal carriers for two antitumor compounds that possess a remarkable antineoplastic activity. But their limited stability and low solubility in water could give a very low parenteral bioavailability. Results revealed an enhancement of the cytotoxicity effect of drug-loaded NLC on human prostate cancer (PC-3) and human hepatocellular carcinoma (HuH-6, HuH-7) cell lines with respect to that of both free drugs. Results of characterization studies strongly support the potential application of these drugs-loaded NLC as prolonged delivery systems for lipophilic drugs by several administration routes, in particular for intravenous administration

Nursing workload and staff allocation in an Italian hospital: a quality improvement initiative based on nursing care score

Aim: To develop, implement, and evaluate a Nursing Care Score (NCS) system, built into the electronic health record, to optimize nursing workload and staff allocation. Design: A quality improvement (QI) initiative with a pre- and post-implementation design was conducted by an interprofessional team in the 33-bed cardio-thoracic unit of a 72-bed hospital in Palermo, Italy. Methods: A seven-phase process was used to develop, implement, and evaluate the NCS, which lists 53 nursing work tasks, each assigned a score from 1.5 to 5.0. The nurse-to-patient ratio on all shifts was determined by the NCS. Nurse satisfaction with both the existing system and the NCS workload system was assessed. Descriptive statistics and McNemar's test were used to analyze the data. Results: At pre-implementation, 92.5% of nurses reported that the existing system was not effective, 87.5% reported it did not enable them to provide adequate nursing care, and 20.0% believed that workload was fairly distributed. At post-implementation, 75.0% of nurses reported that the NCS system was effective (p = 0.0348), 85.0% reported that the NCS system enabled them to provide adequate care, and 85.0% believed that workload was fairly distributed. An NCS score of 65 ± 5 was found to distribute workload most fairly. Conclusion: An automatic electronic operating system to generate a daily workload report based on the NCS was successfully implemented and evaluated. The NCS provided relevant information to guide nurse managers in defining nurse-to-patient ratio and determining staff allocation. Nurses were satisfied with the NCS system. The steps used to develop, implement, and evaluate the NCS system may be transferable to other units and other hospitals

5PSQ-100 Comparative analysis of the safety and tolerability profile of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis

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Combined platelet-rich plasma and lipofilling treatment provides great improvement in facial skin-induced lesion regeneration for scleroderma patients

Background: The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). Methods: Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic-phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc patients. The adipose tissue-derived cell fraction, the so-called stromal vascular fraction (SVF), was coinjected with PRP in the perioral area of SSc patients. Results: Histopathological and phenotypical analysis of adipose tissue from SSc patients revealed a disorganization of its distinct architecture coupled with an altered cell composition. Although AD-MSCs derived from SSc patients showed high multipotency, they failed to sustain a terminally differentiated progeny. Furthermore, SVFs derived from SSc patients differed from healthy donors in their MSC-like traits coupled with an aberrant cytokine production profile. Finally, the administration of PRP in combination with autologous SVF improved buccal's rhyme, skin elasticity and vascularization for all of the SSc patients enrolled in this study. Conclusions: This innovative regenerative therapy could be exploited for the treatment of chronic connective tissue diseases, including SSc

By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy

Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which shows that low expression of miR-100 is a negative prognostic factor and is associated with gene signatures of high grade undifferentiated tumors. Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments

Ultrafast Interface Charge Separation in Carbon Nanodot-Nanotube Hybrids

Carbon dots are an emerging family of zero-dimensional nanocarbons behaving as tunable light harvesters and photoactivated charge donors. Coupling them to carbon nanotubes, which are well-known electron acceptors with excellent charge transport capabilities, is very promising for several applications. Here, we first devised a route to achieve the stable electrostatic binding of carbon dots to multi- or single-walled carbon nanotubes, as confirmed by several experimental observations. The photoluminescence of carbon dots is strongly quenched when they contact either semiconductive or conductive nanotubes, indicating a strong electronic coupling to both. Theoretical simulations predict a favorable energy level alignment within these complexes, suggesting a photoinduced electron transfer from dots to nanotubes, which is a process of high functional interest. Femtosecond transient absorption confirms indeed an ultrafast (<100 fs) electron transfer independent of nanotubes being conductive or semiconductive in nature, followed by a much slower back electron transfer (≈60 ps) from the nanotube to the carbon dots. The high degree of charge separation and delocalization achieved in these nanohybrids entails significant photocatalytic properties, as we demonstrate by the reduction of silver ions in solution. The results are very promising in view of using these “all-carbon” nanohybrids as efficient light harvesters for applications in artificial photocatalysis and photosynthesis

BIOCOMPATIBILITY AND BIODEGRADABILITY OF ELECTROSPUN PHEA-PLA SCAFFOLDS: OUR PRELIMINARY EXPERIENCE IN A MURINE ANIMAL MODEL

We obtained a nano-fibrillar scaffold starting from a polymeric solution which, through electrospinning, gave a biodegradable material with optimal mechanical features and the capacity to allow cell adhesion. In this paper we report the in-vivo application on a murine animal model of two electrospun biodegradable materials, specifically designed to create tubular structures. In one case PHEA-PLA was co-spun with silk fibroin (Fibro-PHEAPLA) by a parallel electrospinning process to obtain a scaffold with two different polymeric fibers. In the other case, PHEA-PLA was mixed with polycaprolactone (PCLPHEA-PLA) to obtain a hybrid fibers scaffold. The in-vitro assay showed fibroblast colonization in both materials. The scaffolds were implanted in the dorsal fascial pouch of rats to evaluate their in-vivo Biocompatibility and tissue integration. Histopathological findings showed that after implantation a neutrophilic reaction associated to colliquative necrosis was predominant, particularly for PCL-PHEA-PLA. Fibro-PCL-PHEA caused a non organized stromal reaction. Cell adhesion was confirmed at SEM scan. Both materials were totally absorbed after 40 days with an inflammatory reaction. This preliminary study showed that biocompatibility of the scaffolds needs further investigation. The capability of the materials to be functionalized could allow us to modulate the inflammatory host response