Free 2-propen-1-amine Derivative And Inclusion Complexes With β-cyclodextrin: Scanning Electron Microscopy, Dissolution, Cytotoxicity And Antimycobacterial Activity

Inclusion complexes and physical mixtures of isomeric mixture of E/Z (50:50) of 3-(4′-bromo-[1,1′-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N- dimethyl-2-propen-1-amine (BBAP) and β-cyclodextrin (β-CD) in the molar proportion of 1:1 and 1:2 were analyzed by scanning electron microscopy. The dissolution behavior of BBAP and of the inclusion complexes were also evaluated for six hours. By scanning electron microscopy (SEM), it was possible to observe an inclusion complex formed between BBAP and β-CD by co-evaporation, either in the molar proportion of 1:1 or 1:2. In the physical mixtures, no complex was observed as previously detected by physicochemical analysis. The dissolution studies showed that the inclusion complexes BBAP/β-CD 1:1 and 1:2 released respectively 49.07 ± 1.48 and 40.26 ± 3.90% of BBAP during six hours. Free BBAP was less soluble than the inclusion complex and reached 9.00 ± 0.75% of dissolution. Biological assays, such as cytotoxicity to J774 macrophages and to a permanent lung fibroblast cell line (V79), indicated that the BBAP does not exhibit any additional toxic effect with the β-CD complexes. However, the complexes were less cytotoxic to V79 cells than the free form. The BBAP/β-CD inclusion complexes were more effective (MIC) than the free compound on several mycobacteria strains. Similar behavior was observed for BBAP/β-CD complexes and rifampicin, a front-line antitubercular drug, on M. tuberculosis H37Rv growing inside J774 macrophages.155682689Bibby, D.C., Davies, N.M., Tucker, I.G., (2000) Int. J. Pharm., 197, p. 1De Souza, A.O., Sato, D.N., Aily, D.C.G., Durán, N., (1998) J. Antimicrob. Chemother., 42, p. 407Pereira, D.G., De Castro, S.L., Durán, N., (1998) Acta Tropica, 69, p. 205De Souza, A.O., Santos Júnior, R.R., Ferreira-Júlio, J.F., Rodrigues, J.A., Melo, P.S., Haun, M., Sato, D.N., Durán, N., (2001) Eur. J. Med. Chem., 36, p. 843De Souza, A.O., Hemerly, F.P., Busollo, A.C., Melo, P.S., Machado, G.M.C., Miranda, C.C., Santa-Rita, R.M., Durán, N., (2002) J. Antimicrob. Chemother., 50, p. 629De Conti, R., Gimenez, S.M.N., Haun, M., Pilli, R.A., De Castro, S.L., Durán, N., (1996) Eur. J. Med. Chem., 31, p. 915De Souza, A.O., Santos Jr., R.R., Sato, D.N., Lima, H.O.S., Andrade-Santana, M.H., Alderete, J.B., Faljoni-Alario, A., Durán, N., (2000) Abstracts of the 29 a Reunião Anual Da Sociedade Brasileira de Bioquímica, , Caxambu, BrazilHiguchi, T., Connors, K.A., (1965) Adv. Anal. Chem. Instrum., 4, p. 117Collins, L.A., Franzblau, S.G., (1997) Antimicrob. Agents Chemother., 41, p. 1004Oh, Y.K., Nix, D.E., Straubinger, R.M., (1995) Antimicrob Agents Chemother., 39, p. 2104Cingi, M.R., De Angelis, I., Fortunati, E., Reggiani, D., Bianchi, V., Tiozzo, R., Zucco, F., (1991) Toxicol. In Vitro, 5, p. 119Denizot, F., Lang, R., (1986) J. Immun. Methods, 89, p. 271Borenfreund, E., Puerner, J.A., (1984) J. Tiss. Cult. Meth., 9, p. 7Melo, P.S., Maria, S.S., Vidal, B.C., Haun, M., Durán, N., (2000) In Vitro Cell Rev. Biol. Animal, 36, p. 539Melo, P.S., Durán, N., Haun, M., (2001) Toxicology, 159, p. 135Shrivastava, R., John, G.W., Rispat, G., Chevalier, A., Massingham, R., (1991) ATLA - Alt. Lab. Anim., 19, p. 39

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4 (62.3 (55.1�70.8) million) to 6.4 (58.3 (47.6�70.7) million), but is predicted to remain above the World Health Organization�s Global Nutrition Target of <5 in over half of LMICs by 2025. Prevalence of overweight increased from 5.2 (30 (22.8�38.5) million) in 2000 to 6.0 (55.5 (44.8�67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Nanocytotoxicity: Violacein And Violacein-loaded Poly (d, L-lactide-co-glycolide) Nanoparticles Acting On Human Leukemic Cells

Violacein is a compound obtained from Chromobacterium violaceum, a bacterium found in the Amazonian region. Violacein-loaded poly (D, L-lactide-co-glycolide) nanoparticles has a similar inhibitory effect evaluated by trypan blue assay on leukemic HL60 cells than the free form. However, the cytotoxic effects evaluated by phosphatase activity and MTT reduction assays were lower for the encapsulated form than for free violacein. Based on morphological changes, violacein and violacein entrapped in nanoparticles were found to induce terminal differentiation (assessed by nitro blue tetrazolium reduction) in HL60 cells. Thus, both formulations inhibit HL60 cell growth in vitro, partly by inducing cytotoxic effects and cell differentiation. Flow cytometric analysis of HL60 cells after treatment for 12 h showed that violacein-loaded PLGA induced apoptosis, with maximum cell death at a concentration of 2 μM. Violacein and violacein/PLGA induced opposite effects on the mitochondrial swelling which indicates altered mitochondrial function. The mitochondrial activity was also checked by flow cytometry studies. Labelled cells with the probe JC1 displayed a basal hypopolarized status of the mitochondria in treated cells. Based on morphological changes, alterations in phospholipid asymmetry and changes in mitochondrial polarization, violacein and nanoparticles containing violacein were found to trigger cell death by apoptosis. These methodologies are promising as diagnostic and mechanistic effects of nanoparticles in cell cultures. Copyright © 2009 American Scientific Publishers All rights reserved.52192201Durán, N., Menck, C.F.M., Chromobacterium violaceum: A review of pharmacological and industrial perspectives (2001) Crit. Rev. Microbiol., 27, p. 201Melo, P.S., Justo, G.Z., De Azevedo, M.B.M., Durán, N., Haun, M., Violacein and its complexes induce apoptosis and differentiation in HL60 cells (2003) Toxicology, 186, p. 217Dessaux, Y., Elmerich, C., Faure, D., Violacein: A molecule of biological interest originating from the soil-borne bacterium Chromobacterium violaceum (2004) La Revue de Médecine Interne, 25, p. 659Saraiva, V.S., Marshall, J.C., Cools-Lartigue, J., Burnier, M.N., Cytotoxic effects of violacein in human uveal melanoma cell lines (2004) Melanoma Res., 14, p. 421Durán, N., Justo, G.Z., Ferreira, C.V., Melo, P.S., Cordi, L., Martins, D., Violacein: Properties and biological activities (2007) Biotechnol. Appl. Biochem., 48, p. 127Shenoy, D.B., Amiji, M.M., Poly(ethylene oxide)-modified poly(ε-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer (2005) Int. J. Pharm., 293, p. 261Rao, G.C., Kumar, M.S., Mathivanan, N., Rao, M.E., Nanosuspensions at the most promising approach in nanoparticulate drug delivery systems (2004) Pharmazie, 59, p. 5Jin, S., Ye, K.M., Nanoparticle-mediated drug delivery and gene therapy (2007) Biotechnol. Progr., 23, p. 32Kabanov, A.V., Batrakova, E.V., Miller, D.W., Pluronic block copolymers as modulators of drug efflux transporter activity in the blood-brain barrier (2003) Advan. Drug Deliv. Rev., 55, p. 151Minko, T., Batrakova, E.V., Li, S., Li, Y.L., Pakunlu, T.I., Alakhov, V.Y., Kabanov, A.V., Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells (2005) J. Control. Release, 105, p. 269Rapoport, N., Marin, A.P., Timoshin, A.A., Effect of a polymeric surfactant on electron transport in HL60 cells (2000) Arch. Biochem. Biophys., 384, p. 100Kohli, E., Han, H.Y., Zeman, A.D., Vinogradov, S.V., Formulations of biodegradable Nanogel carriers with 5′- triphosphates of nucleoside analogs that display a reduced cytotoxicity and enhanced drug activity (2007) J. Control. Release, 121, p. 19Uzunoglu, S., Uslu, R., Tobu, M., Saydam, G., Terzioglu, E., Buyukkececi, F., Omay, S.B., Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine/threonine protein phosphatase inhibitors (1999) Leukaemia Res., 23, p. 507Anazetti, M.C., Melo, P.S., Durán, N., Haun, M., Comparative cytotoxicity of dimethylamide-crotonin in the promyelocytic leukemia cell line (HL60) and human peripheral blood mononuclear cells (2003) Toxicology, 188, p. 261Redmond, K.M., Wilson, T.R., Johnston, P.G., Longley, D.B., Resistance mechanisms to cancer chemotherapy (2008) Frontiers Biosci., 13, p. 5138Melet, A., Song, K., Bucur, O., Jagani, Z., Grassian, A.R., Khosravi-Far, R., Apoptotic pathways in tumor progression and therapy (2008) Advan. Exper. Med. Biol., 615, p. 47Debatin, K.M., Activation of apoptosis pathways by anticancer treatment (2000) Toxicol. Lett., 112, p. 41Inayat-Hussain, S.H., Osman, A.B., Din, L.B., Taniguchi, N., Altholactone, a novel styryl-lactone induces apoptosis via oxidative stress in human HL60 leukemia cells (2002) Toxicol. Lett., 131, p. 153Kim, R., Emi, M., Tanabe, K., The role of apoptosis in câncer cell survival and therapeutic outcome (2006) Cancer Biol. Ther., 30, p. 5Anuradha, C.D., Kanno, S., Hirano, S., Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL60 cells (2001) Free Radic. Biol. Med., 31, p. 367Stoetzer, O.J., Progrebniak, A., Pelka-Fleischer, R., Hasmann, M., Hiddemann, W., Nuessler, V., Modulation of apoptosis by mitochondrial uncouplers: Apoptosis-delying features despite intrinsic cytotoxicity (2002) Biochem. Pharmacol., 63, p. 471Ujihara, M., Nomura, K., Yamada, O., Deura, H., Establishment of a stable HL60 subline having the potential for monocytic differentiation using granulocyte-macrophage colony-stimulating factor: Possible use for the study of monocytic differentiation and oxidative stress (1998) Atherosclerosis, 139, p. 301Sokoloski, J.A., Sartorelli, A.C., Induction of the differentiation of HL60 promyelocytic leukemia cells by nonsteroidal anti-inflammatory agents in combination with low levels of vitamin D 3 (1997) Leukemia. Res., 22, p. 153Wyllie, A.H., Kerr, J.F.K., Currie, A.R., Cell Death: The significance of apoptosis (1980) Int. Rev. Cytol., 68, p. 251Israels, L.G., Israels, E.D., Apoptosis (1999) Steam Cells, 17, p. 306Kohroki, J., Norio, M.A., Tanaka, T., Itoh, N., Inada, A., Tanaka, K., Induction of differentiation and apoptosis by dithizone in human myeloid leukemia cell lines (1998) Leukemia Res., 22, p. 405Minko, T., Kopecková, P., Kopecek, J., Preliminary evaluation of caspases-dependent apoptosis signaling pathways of free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells (2001) J. Control. Release, 71, p. 227Minko, T., Pakunlu, R.I., Wang, Y., Khandar, J.J., Saad, M., New generation of liposomal drugs for cancer (2006) Anticancer Agents Med. Chem., 6, p. 537Kodach, L.L., Bos, C.L., Durán, N., Peppelenbosch, M.P., Ferreira, C.V., Hardwick, J.C., Violacein synegistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in humancolorectal cancer cells (2006) Carcinogenesis, 27, p. 508De Carvalho, D.D., Costa, F.T.M., Durán, N., Haun, M., Cytotoxic activity of violacein in human colon cancer cells (2006) Toxicol. in Vitro, 20, p. 1514Rettori, D., Durán, N., Production, extraction and purification of violacein: An antibiotic produced by Chromobacterium violaceum (1998) World J. Microbiol. Biotechnol., 14, p. 685Ferdous, A.J., Stembridge, N.Y., Singh, M., Role of monensin PLGA polymer nanoparticles and liposomes as potentiator of ricin a immunotoxins in vitro (1998) J. Control. Release, 50, p. 71Denizot, F., Lang, R., Rapid colorimetric assay for cell growth and survival, modifications to the tetrazolium dye procedure giving improved sensitivity and reliability (1986) J. Immunol. Methods, 89, p. 271Schneider, W.C., Hogeboom, G.H., Intracellular distribution of enzymes. V. Further studies of cytochrome c in rat liver homogenates (1950) J. Biol. Chem., 183, p. 123Anazetti, M.C., Melo, P.S., Durán, N., Haun, M., Dehydrocrotonin and its derivative, dimethylamide-crotonin induce apoptosis with lipid peroxidation and activation of caspases-2, -6 and -9 in human leukemic cells HL60 (2004) Toxicology, 203, p. 123Araragi, S., Kondoh, M., Kawase, M., Saito, S., Higashimoto, M., Sato, M., Mercuric chloride induces apoptosis via a mitochondrial-dependent pathway in human leukemia cells (2003) Toxicology, 184, p. 1Fillon, S., Lang, F., Jendrossek, V., Pseudomonas aeruginosa triggered apoptosis of human epithelial cells depends on the temperature during infection (2002) Cell Physiol. Biochem., 12, p. 207Melo, P.S., Maria, S.S., Vidal, B.C., Haun, M., Durán, N., Violacein cytotoxicity and induction of apoptosis in V79 cells (2000) In Vitro Cell. Develop. Biol.-Animal, 36, p. 539Pailard, F., Finot, F., Mouche, I., Prenez, A., Vericat, J.A., Use of primary cultures of rat hepatocytes to predict toxicity in the early development of new chemical entities (1999) Toxicol. in Vitro, 13, p. 693Mosmann, T., Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assay (1983) J. Immunol. Methods, 65, p. 55Freire, A.C.G., Aoyama, H., Haun, M., Ferreira, C.V., Relationship between phosphatase inhibitors, okadaic acid and pervanadate, on human myeloid leukaemia cell line (2003) J. Enzyme Inhib. Med. Chem., 18, p. 425Mehar, A., Macanas-Pirard, P., Mizokami, A., Takahashi, Y., Kass, G.E.N., Coley, H.M., The effects of cyclooxygenase-2 expression in prostate cancer cells: Modulation of response to cytotoxic agents (2008) J. Pharmacol. Exper. Ther., 324, p. 1181Rossi, D., Gaidano, G., Messengers of cell death: Apoptotic signalling in health and disease (2003) Haematologica, 88, p. 212Lee, J.Y., Hwang, W.I., Lim, S.T., Antioxidant and anticancer activities of organic extracts from Platycodon grandiflorum A. de Candolle roots (2004) J. Ethnopharmacol., 93, p. 409Facompré, M., Wattez, N., Kluza, J., Lansiaux, A., Bailly, C., Relationship between cell cycle changes and variations of the mitochondrial membrane potential induced by etoposide (2000) Mol. Cell Biol. Re. Comm., 4, p. 37Greenebaum, B., Blossfield, K., Hannig, J., Carrillo, C.S., Beckett, M.A., Weichselbaum, R.R., Lee, R.C., Poloxamer 188 prevents acute necrosis of adult skeletal muscle cells following high-dose irradiation (2004) Burns, 30, p. 539Luo, J., Borgens, R., Shi, R., Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury (2002) J. Neurochem., 83, p. 471Marks, J.D., Pan, C., Bushell, R., Cromie, W., Lee, R.C., Amphiphilic, tri-block copolymers provide potent, membrane-targeted neuroprotection (2001) FASEB J., 15, p. 1107Maskarinec, S.A., Lee, K.Y.C., Comparative study of poloxamer insertion into lipid monolayers (1809) Langmuir, 19, p. 2003Tharmalingam, T., Ghebeth, H., Wuerz, T., Butler, M., Pluronic enhances the robustness and reduces the cell attachment of mammalian cells (2008) Mol. Biotechnol., 39, p. 16

Co-circulation of genotypes IA and IB of hepatitis A virus in Northeast Brazil

The Northeast region is the location of most cases of acute hepatitis A virus (HAV) in Brazil. In the present study, the genotypes of HAV strains from Pernambuco State, one of most populous states in the Northeast region, were characterized. Blood samples positive for anti-HAV IgM from 145 individuals (mean age = 29.1 years), collected during 2002 and 2003, were submitted to nested RT-PCR for amplification of the 5'non-translated region (5'NTR) and VP1/2A regions of the HAV genome. The VP1/2A and 5'NTR regions were amplified in 39 and 21% of the samples, respectively. Nucleotide sequencing was carried out in 46% of VP1/2A and in 53% of 5'NTR isolates. The identity in nucleotide sequence of the VP1/2A region ranged from 93.6 to 100.0%. Phylogenetic analysis of the VP1/2A sequences showed that 65% belong to sub-genotype IA and 35% to sub-genotype IB. Co-circulation of both sub-genotypes was observed in the two years studied. Distinct clusters of highly related sequences were observed in both sub-genotypes, suggesting endemic circulation of HAV strains in this area. In the 5'NTR isolates, 92.7-99.2% identity was observed and two isolates presented one deletion at position 413. Phylogenetic analysis showed that genotype IA strains cluster in the tree in the same way as genotype IB strains, but one IIIA isolate from Spain clusters with genotype IB strains. These results do not allow us to state that 5'NTR could be used to genotype HAV sequences. This is the first report of co-circulation of sub-genotypes IA and IB in this region, providing additional information about the molecular epidemiology of HAV strains in Brazil