The HIV BioBank represents a novel approach to HIV research that might be of general interest not only for basic and clinical research teams working on HIV, but also for those groups trying to establish large networks focused on research on specific clinical problems. It also represents a model to stimulate cooperative research among large numbers of research groups working as a network on specific clinical problems. The main objective of this article is to show the structure and function of the HIV BioBank that allow it to very efficiently release samples to different research project not only in Spain but also in other countries.

A new family of amine- and ammonium-terminated carbosilane dendrimers of the type Gn-[Si(CH2)3N(Et)CH2CH2NMe2]x and Gn-{[Si(CH2)(3)N+R(Et)CH2CH2N+RMe2]x(X-)y} (where n = 1, 2 and 3; R = H, X = Cl; R = Me, X = I) respectively has been synthesized by hydrosilylation of N,N-dimethyl-N'-allyl-N'-ethyl-ethylenediamine, [(CH2=CH-CH2)(Et)N(CH2)2NMe2] with the corresponding hydride-terminated dendrimers and subsequent quaternization with HCl or MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods. The antibacterial properties of the quaternary ammonium functionalized dendrimers have been evaluated showing that they act as potent biocides in which the multivalency along with the biopermeability of the carbosilane dendritic skeleton play an important role in the antibactericidal activity of these compounds.

We have analyzed the intracellular signals that allow lymphoblasts from Alzheimer's disease (AD) patients to escape from serum deprivation-induced apoptosis. The following observations suggested that modulation of ERK1/2 activity by Ca(2+)/calmodulin (CaM) is involved in preventing apoptosis: (i) ERK1/2 activity seems to support lethality in control cells, as PD98059, the inhibitor of the activating MEK prevented cell death; (ii) control cells show a persistent and higher stimulation of ERK1/2 than that of AD cells in the absence of serum; (iii) CaM antagonists have no effects on control cells, but sensitize AD cells to death induced by serum withdrawal and increased ERK1/2 phosphorylation, and (iv) no apoptotic effects of CaM antagonists were observed in AD cells treated with PD98059. These results suggest the existence of an activation threshold of the ERK1/2 pathway setting by Ca(2+)/CaM-dependent mechanisms, which appears to be the critical factor controlling cell survival or death decision under trophic factor withdrawal.

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IntroductionThe asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO.ObjectivesWe aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO.MethodsThis is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity <0.70 recruited from outpatient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking >10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis.ResultsIn total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61–3.57] vs 1.11 [0.12–2.42] pg/mL, respectively; p=0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61–13.12] vs 7.03 [4.69–10.44] pg/mL, respectively; p<0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions.ConclusionAsthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions.

The vulnerability of children has long raised ethical concerns resulting in the lack of inclusion of children in research studies. This has impeded the development of relevant medical therapies specific for children. In response to these circumstances, international policies have begun to recognize the need to carry out research focused on children. Translational HIV infection research is highly dependent on many factors including the availability, quality, and traceability of samples and their associated data under a strict system of quality management. The primary objective of the Pediatric HIV BioBank is to contribute to the furthering of scientific knowledge about vertical HIV infection. To achieve this aim, the BioBank processes, stores, and provides distinct samples from HIV/AIDS children to research projects free of charge. Strict compliance to ethical norms is always guaranteed. At present the Pediatric HIV BioBank has 429 vials containing different sample types from 243 vertically HIV-infected children. The Pediatric HIV BioBank represents a novel approach to HIV research that might be of general interest not only for basic and clinical research teams working with HIV, but also for those groups trying to establish large networks focused on researching specific clinical problems. It also represents a model to stimulate cooperative research on specific clinical problems. The main objective of this article is to show the structure and function of the Pediatric HIV BioBank that allow it to efficiently provide samples to different research projects in Spain and in other countries.

Here we present a synthetic procedure for water-stable carbosilane dendrimers containing ammonium groups at the periphery of type Gn-{[Si(CH2)3N+(Me)(Et)CH2CH2N+Me3]x (CF3SO3 -)y} which have been used as non-viral vectors for transfecting different types of nucleic acids against two different medical problems, HIV and hepatocarcinoma. These systems have shown to be non-toxic in both PBMC and HepG2 cell lines under the experimental conditions and are able to form nanoconjugates with nucleic acids perfectly stable over time and in a wide range of pH values, which leads to the conclusion that the interaction between dendrimer and nucleic acid is very strong. In addition, a high degree of transfection using these nanoconjugates has been observed, ranging from 70-90% depending on the generation and in the particular case of PBMC transfection with anti-HIV oligonucleotides. However, besides of the good properties shown by the dendrimers here prepared as transfecting agents, only moderate effect was observed in functional experiments for hepatocarcinoma, as a result of the strong interaction between dendrimer and nucleic acid. Nevertheless, it is important to mention that an IRS-4 knock-down of 40% in HepG2 achieves an analogous degree of cell sensitization to cancer treatment, which may represent a major advance in the hepatocarcinoma treatment when appropriate dendrimers as transfection agents are used.