Sustainable unfired bricks manufacturing from construction and demolition wastes

The management of construction and demolition wastes is a huge challenge for most Governments. Thegreatest component of such wastes is concrete and masonry fragments or remains. Among the most com-mon approaches to valorization of such w astes is to convert them to recycled aggregates, however thismay be hampered by low quality of some recycled aggregates compared to natural aggregates. This paperpresents the results of experimental investigation where concrete and ceramic remains were used to par-tially substitute clay soil in producing unfired bricks. The bricks were then tested for mechanical strength,water absorption freeze-thaw resistance. Additionally the environmental impact of the bricks wasassessed based on Life Cycle Analysis (LCA). It was established that concrete waste could be used to sub-stitute up to 50% of the clay whereas ceramic wastes could only substitute a maximum of 30% of the clay.Blended bricks made from clay and concrete waste mixes had a lower mechanical strength than thosemade from clay and ceramic waste. As regards water absorption, there was no marked differencebetween the two blends of brick however reduction in water resistance was slightly greater in bricks con-taining concrete waste that in those containing ceramic wastes. Also, tests showed that freeze-thawresistance was greater in bricks blended with concrete wastes than in those incorporating ceramicwastes. Life Cycle analyses demonstrated that it is the binder content in the mix that largely determinesthe environmental impact of the blended bricks. Lastly, it was demonstrated that the most desirable tech-nical and environmental credentials of brick material mixes resulted from using the binder combination:CL-90-S+GGBS 2/8

Nanoparticles from Gantrez® AN-poly(ethylene glycol) conjugates as carriers for oral delivery of docetaxel

The oral delivery of docetaxel (DTX) is challenging due to a low bioavailability, related to an important pre-systemic metabolism. With the aim of improving the bioavailability of this cytotoxic agent, nanoparticles from conjugates based on the copolymer of methyl vinyl ether and maleic anhydride (poly(anhydride)) and two different types of PEG, PEG2000 (PEG2) or methoxyPEG2000 (mPEG2), were evaluated. Nanoparticles, with a DTX loading close to 10%, were prepared by desolvation and stabilized with calcium, before purification and lyophilization. For the pharmacokinetic study, nanoparticles were orally administered to mice at a single dose of 30 mg/kg. The plasma levels of DTX were high, prolonged in time and, importantly, quantified within the therapeutic window. The relative oral bioavailability was calculated to be up to 56% when DTX was loaded in nanoparticles from poly(anhydride)-mPEG2000 conjugate (DTX-NP-mPEG2). Finally, a comparative toxicity study between equitoxic doses of free iv DTX and oral DTX-NP-mPEG2 was conducted in mice. Animals orally treated with DTX-loaded nanoparticles displayed less severe signs of hypersensitivity reactions, peripheral neurotoxicity, myelosuppression and hepatotoxicity than free iv docetaxel. In summary, poly(anhydride)-PEG conjugate nanoparticles appears to be adequate carries for the oral delivery of docetaxel

Selenium Derivatives as Promising Therapy for Chagas Disease: In Vitro and In Vivo Studies

This work was financially supported by the Ministerio de Economia, Industria y Competitividad (CONSOLIDER CSD2010-00065 and CTQ2017-90852-REDC). R.M.-E. is grateful for the fellowship from the Alfonso Martin Escudero Foundation.Chagas disease is a tropical infection caused by the protozoan parasite Trypanosoma cruzi and a global public health concern. It is a paradigmatic example of a chronic disease without an effective treatment. Current treatments targeting T. cruzi are limited to two obsolete nitroheterocyclic drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Hence, new, more effective, safer, and affordable drugs are urgently needed. Selenium and their derivatives have emerged as an interesting strategy for the treatment of different prozotoan diseases, such as African trypanosomiasis, leishmaniasis, and malaria. In the case of Chagas disease, diverse selenium scaffolds have been reported with antichagasic activity in vitro and in vivo. On the basis of these premises, we describe the in vitro and in vivo trypanocidal activity of 41 selenocompounds against the three morphological forms of different T. cruzi strains. For the most active selenocompounds, their effect on the metabolic and mitochondrial levels and superoxide dismutase enzyme inhibition capacity were measured in order to determine the possible mechanism of action. Derivative 26, with a selenocyanate motif, fulfills the most stringent in vitro requirements for potential antichagasic agents and exhibits a better profile than benznidazole in vivo. This finding provides a step forward for the development of a new antichagasic agent.Spanish Government CONSOLIDER CSD2010-00065 CTQ2017-90852-REDCAlfonso Martin Escudero Foundatio

Nanoparticles from Gantrez-based conjugates for the oral delivery of camptothecin

Camptothecin (CPT) exhibits a number of challenges for its oral administration, including a low aqueous solu-bility, a lactone ring susceptible to hydrolysis, and an affinity to the intestinal P-gp. The aim of this work was to evaluate nanoparticles from Gantrez-based conjugates as carriers for the oral delivery of CPT. For this purpose two different conjugates (G-mPEG and G-HPCD), obtained by the covalent binding of either HP-beta-CD or methoxy-PEG (m-PEG) to the polymer backbone of GantrezTM AN, were synthetized and characterized. Both excipients (m -PEG and HPCD) were selected due to their reported abilities to stabilize the lactone ring of CPT and disturb the effect of intestinal P-gp. The resulting nanoparticles (G-mPEG-NP and G-HPCD-NP) presented a similar size (about 200 nm) and zeta potential (close to-35 mV); although, G-mPEG-NP presented a higher CPT payload than G-HPCD-NP. On the contrary, in rats, nanoparticles based on Gantrez conjugates appeared to be capable of crossing the protective mucus layer and reach the intestinal epithelium, whereas conventional Gantrez nano-particles displayed a mucoadhesive profile. Finally, the pharmacokinetic study revealed that both formulations were able to enhance the relative oral bioavailability of CPT; although this value was found to be 2.6-times higher for G-mPEG-NP than for G-HPCD-NP

Practice guideline: Preparation for CAR T-cell therapy in children and young adults with B-acute lymphoblastic leukaemia

The objective of this guideline, prepared by the ALL subgroup of the Advanced Cell Therapy Sub-Committee of BSBMTCT (British Society of Blood and Marrow Transplantation), is to provide healthcare professionals with practical guidance on the preparation of children and young adults with B-acute lymphoblastic leukaemia from the point of referral to that of admission for CAR T-cell treatment. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate the levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org

Molecular buckets: cyclodextrins for oral cancer therapy

The oral route is preferred by patients for drug administration due to its convenience, resulting in improved compliance. Unfortunately, for a number of drugs (e.g., anticancer drugs), this route of administration remains a challenge. Oral chemotherapy may be an attractive option and especially appropriate for chronic treatment of cancer. However, this route of administration is particularly complicated for the administration of anticancer drugs ascribed to Class IV of the Biopharmaceutical Classification System. This group of compounds is characterized by low aqueous solubility and low intestinal permeability. This review focuses on the use of cyclodextrins alone or in combination with bioadhesive nanoparticles for oral delivery of drugs. The state-of-the-art technology and challenges in this area is also discussed

Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial

BACKGROUND AND AIMS: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies. METHODS: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm. RESULTS: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively. CONCLUSIONS: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion

Assesment of β-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB/c mice

Abstract Patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. Lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. In this study, we proposed the loading of β-lapachone (β- LP) in lecithin-chitosan nanoparticles (NP) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. The loading of β-LP in lecithin-chitosan NP was critical to achieve important drug accumulation in the dermis and permeation through the skin. In addition, it did not influence the drug antileishmanial activity. When topically applied in L. major infected BALB/c mice, 2 β-LP NP achieved no parasite reduction but they stopped the lesion progression. Immuno-histopatological assays in CL lesions and quantitative mRNA studies in draining lymph nodes confirmed that β-LP exhibited anti-inflammatory activity leading to the downregulation of IL-1β and COX-2 expression and a decrease of neutrophils infiltrate

Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions

The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 ¿M) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL