Grafting of cyclodextrins onto polypropylene nonwoven fabrics for the manufacture of reactive filters. II. Characterization

A novel method for the preparation of immobilized α, β, or γ‐cyclodextrins on polypropylene nonwoven supports has been previously presented. The obtained new materials were prepared by graft‐polymerization of glycidyl methacrylate onto polypropylene after activation of the support by the electron beam technique, followed by the coupling of cyclodextrins with the epoxide groups. The structure of the resulting materials is characterized in detail using Fourier transform infrared spectroscopy, solid state nuclear magnetic resonance analysis, differential scanning calorimetry, thermogravimetric analysis, and optical microscopy. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 2166–2173, 2000     

A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors—statins—via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene’s genetic variability.     

Dendritic Cells and Cancer Immunotherapy: The Adjuvant Effect

Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.     

Tau Cleavage Contributes to Cognitive Dysfunction in Strepto-Zotocin-Induced Sporadic Alzheimer’s Disease (sAD) Mouse Model

Tau cleavage plays a crucial role in the onset and progression of Alzheimer’s Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)—a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance—mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it’s in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity.     

Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug.Here,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were engineered.DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging agents.The resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"approach.Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof.Empty DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC₅₀=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than free-DTXL.With only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 days.All untreated mice succumbed before 90 days.Collectively,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.     

Solvent extraction of nickel from acidic solutions using synergistic mixtures containing pyridinecarboxylate esters. Part 3. Systems based on arylsulphonic acids

The solvent extraction of nickel and calcium from acidic solutions by mixtures of dinonylnaphthalene sulphonic acid (DNNSA) and different pyridinecarboxylate esters (2-, 3- and 4-C₅H₄.CO.OR, where R = n-octyl, 2-ethylhexyl and 2-octyl) in xylene was investigated. In contrast to extraction systems employing DNNSA alone, these mixtures permit the separation of nickel and calcium to be carried out, especially when an excess of the ester is used. The extractability of base metals from sulphate solutions by mixtures of DNNSA (0·25 M ) and isodecyl 3-pyridinecarboxylate (0·25 M ) in Shellsol K decreases through the series Cu > Ni > Al > Co > Ca > Zn > Fe(III) > Mg. Mixtures containing the 2- or 4-ester showed a slightly different selectivity series: Cu > Ni > Co > Zn > Al > Fe(III) ≥ Ca > Mg. In a batch countercurrent experiment, a simulated leach liquor containing Ni 2·15, Mg 5·05 and Ca 0·42 g dm⁻³ (initial pH 3·0) was extracted with the mixed reagent (0·25 M DNNSA plus 0·25 M 4-ester) in four stages at unit phase ratio, without any pH adjustment. The recovery of nickel was 91%, with co-extractions of calcium and magnesium of 14 and 8%, respectively. When the concentration of the 4-ester was increased to 0·50 M , the recovery of nickel increased to 95%, whilst the co-extractions of calcium and magnesium decreased to 4 and 3%, respectively. © 1998 SCI.     

Effect of food intake on protein quality measured in chicks by traditional or biochemical methods

Previous studies have shown that the activities of the hepatic enzymes xanthine dehydrogenase and nucleoside phosphorylase, as well as the uric acid excreted, can be used to determine the quality of the protein consumed in chickens, in a short time and using a small amount of the test protein. A common observation in protein quality evaluation is that the food intake of the control animals is considerably greater than that observed in those receiving proteins of low quality. Since this can affect the results, this study measured the quality of garbanzo bean and black bean proteins in chickens fed these beans ad libitum, feeding the bean diets at the level observed in the controls (soy protein+methionine) by enteral intubation or pair feeding the controls with the amount of food consumed by the chickens receiving the bean diets. In every case, protein quality was determined by protein efficiency ratio, net protein utilisation or the biochemical methods used in this study. The results showed that, when fed ad libitum, the animals assigned to the bean diets exhibited a lower food intake than the controls but, by tube feeding, food intake was made equal in both groups. Equal consumption, between these groups, was also obtained by reducing the amount of food offered to the controls to the levels measured in the groups assigned to the bean diets (pair feeding). These feeding strategies had a marked effect on growth, carcass protein content, protein catabolism and also in the results of protein quality. Thus, the control whose intake was reduced grew less, accumulated less protein in tissues and catabolised more of the protein consumed than the control fed ad libitum. In contrast, the chickens assigned to the bean diets, but whose food intake was increased by tube feeding, grew better, accumulated more protein in tissues and catabolised less protein. In general, the results of these experiments confirm the effectiveness of the biochemical methods for estimating protein quality and indicate that the protein quality of both garbanzo beans and black beans increased when it was measured at a food intake equivalent to that measured in the control animals. Since the overall purpose of this study was to evaluate techniques for protein quality determination meant to be applicable to humans nutrition rather than poultry nutrition, single proteins were used instead of combinations of proteins. © 1998 Society of Chemical Industry.     

Changes in phenolic composition of apple juices by HPLC with direct injection

An analytical procedure for the quantitative determination of the major polyphenols in apple juices which successfully employs a RP-HPLC system without prior treatment of the sample is described. Apple juices were clarified by microfiltration and ultrafiltration without previous treatment. Polyphenols monitored were influenced by clarification technology employed for stabilising the apple juices. The p-coumaric acid derivative was significantly affected by membrane type and filtration time, while (−)-epicatechin and phloridzin were influenced by filtration time. © 1998 Society of Chemical Industry.