Specific fluorogenic substrates for neprilysin (neutral endopeptidase, EC 3.4.24.11) which are highly resistant to serine- and metalloproteases

Two intramolecularly quenched fluorogenic peptides containing o-aminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (EDDnp) groups at amino- and carboxyl-terminal amino acid residues, Abz-DArg-Arg-Leu-EDDnp (Abz-DRRL-EDDnp) and Abz-DArg-Arg-Phe-EDDnp (Abz-DRRF-EDDnp), were selectively hydrolyzed by neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) at the Arg-Leu and Arg-Phe bonds, respectively. The kinetic parameters for the NEP-catalyzed hydrolysis of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp were Km = 2.8 µM, kcat = 5.3 min-1, kcat/Km = 2 min-1 µM-1 and Km = 5.0 µM, kcat = 7.0 min-1, kcat/Km = 1.4 min-1 µM-1, respectively. The high specificity of these substrates was demonstrated by their resistance to hydrolysis by metalloproteases [thermolysin (EC 3.4.24.2), angiotensin-converting enzyme (ACE; EC 3.4.24.15)], serineproteases [trypsin (EC 3.4.21.4), a-chymotrypsin (EC 3.4.21.1)] and proteases present in tissue homogenates from kidney, lung, brain and testis. The blocked amino- and carboxyl-terminal amino acids protected these substrates against the action of aminopeptidases, carboxypeptidases and ACE. Furthermore, DR amino acids ensured total protection of Abz-DRRL-EDDnp and Abz-DRRF-EDDnp against the action of thermolysin and trypsin. Leu-EDDnp and Phe-EDDnp were resistant to hydrolysis by a-chymotrypsin. The high specifity of these substrates suggests their use for specific NEP assays in crude enzyme preparationsUniversidade Federal do CearáUniversité de MontréalUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Cytotoxicity and antitumoral activity of dichloromethane extract and its fractions from Pothomorphe umbellata

The cytotoxicity of the dichloromethane crude extract (DCE), obtained from the aerial parts of Pothomorphe umbellata (L.) Miq (Piperaceae), was evaluated against nine human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460, 786-O, UACC-62, K-562). The DCE presented antiproliferative activity with good potency against all cell lines at low concentrations (between 4.0 and 9.5 µg/mL) and with selectivity (1.55 µg/mL) for the leukemia cell line (K-652). DCE (100, 200, 300 and 400 mg/kg, ip) was also evaluated in the Ehrlich ascites tumor model. Both the survival number and the life span of the animals that died increased by at least 45 and 50%, respectively (8 animals per group), demonstrating P. umbellata extract potential anticancer activity. The results of the in vivo antitumor activity prompted the fractionation of the crude extract. The crude extract was submitted to dry column chromatography with dichloromethane-methanol (99:1). The column effluent fractions were extracted with methanol, dried under vacuum yielding fractions FR1 (less polar), FR2 (medium polarity), and FR3 (polar), which were analyzed for their growth inhibition or cytotoxic properties by a 48-h sulforhodamine B cell viability assay by measuring the total protein content. FR1 demonstrated high potency and cytotoxicity, a result compatible with the high toxicity of oxalic acid; FR2, containing 4-nerolidylcathecol, presented the lowest cytotoxic activity compared to the other two fractions but with selectivity for prostate cancer cell line; FR3, containing a mixture of steroids described in the literature as possessing various biological activities, also presented potent anticancer in vitro activity. These results suggest that P. umbellata DCE in vivo antitumor activity may be a consequence of the activity of different active principles.41141

Distrofia Miotônica Tipo 1: Frequência Dos Achados Oftalmológicos

The purpose of the study was to evaluate the frequency of ophthalmologic abnormalities in a cohort of myotonic dystrophy type 1 (DM1) patients and to correlate them with motor function. We reviewed the pathophysiology of cataract and low intraocular pressure (IOP). Method: Patients were included after clinical and laboratory diagnosis and after signed informed consent. They were evaluated by Motor Function Measure scale, Portuguese version (MFM-P) and ophthalmic protocol. Results: We evaluated 42 patients aged 17 to 64 years (mean 40.7 ± 12.5), 22 of which were men. IOP (n = 41) was reduced in all but one. We found cataract or positivity for surgery in 38 (90.48%) and ptosis in 23 (54.76%). These signs but not IOP were significantly correlated with severity of motor dysfunction. Abnormalities in ocular motility and stereopsis were observed. Conclusion: Cataract and ptosis are frequent in DM1 and associated to motor dysfunction. Reduced IOP is also common, but appears not to be related with motor impairment. © 2016, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.74318318

Antiulcerogenic activity of peptide concentrates obtained from hydrolysis of whey proteins by proteases from Cynara cardunculus

Peptide concentrates generated by hydrolysis of whey with aqueous extracts of flowers of Cynara cardunculus were studied for possible protection of the stomach mucosa against ulcerative lesions caused by oral administration of absolute ethanol. Both the whole peptide fraction obtained via hydrolysis of whey protein concentrate (peptide concentrate, PepC) and its fraction below 3 kDa (PepCF) were able to reduce gastric injuries to significant levels (p < 0.05). Single-dose experiments, using 100 mg kg(-1) body weight (bw) of either PepCF or PepC, led to 68.5% and 37.4% protection, respectively - which compare well with 93.4% protection by 200 mg kg (1) bw carbenoxolone (a positive control). No dose-response correlation could be demonstrated. Gastric cytoprotection by PepCF appears to depend on sulphydryl-containing moieties, whereas PepC likely protects the gastric mucosa via the prostaglandin cycle and production of nitric oxide.info:eu-repo/semantics/acceptedVersio

Visual Impairment, Rehabilitation And International Classification Of Functioning, Disability And Health

Objective: To describe the characteristics of people with visual impairment who participated in the Visual Rehabilitation Groups, according to the ICD-10 and the International Classification of Functioning, Disability and Health (ICF). Methods: Quantitative, cross-sectional survey, developed in a university rehabilitation research center between october and december 2012. The users from the Visual Rehabilitation Groups were invited; 13 of them agreed to participate. We performed an occupational therapy evaluation - with anamnesis, performance evaluation and functional vision assessment - an analysis of medical charts and patient description with the use of the ICF. Results: The major causes of visual impairment were diabetic retinopathy, glaucoma, optical neuritis and keratoconus. Some functions and structures of the body, performance and capabilities in activities and participation, environmental factors facilitators or limiters were highlighted in this study, allowing the description of the characteristics of each participant through the functionality and the improvement of the therapeutic planning. Assistive technologies, optical and nonoptical aids used and their everyday benefits were presented. Conclusion: Visual loss, at any level, led to functional impairments, limiting and restricting the participation and performance in everyday activities, interfering with the individuals' independence, autonomy and quality of life. However, the use of optical aids, non-optical aids and environmental adaptations proved to be beneficial for increasing the functionality, showing the influence of external factors on the performance. Knowing and recognizing the existence of diversities within the visual impairment universe allows us to understand who the treated individual is, avoiding the generalization by the visual condition. The ICF showed to have a fundamental role in this context.735291301Vision 2020 - The Right to Sight: Global initiative for the elimination of avoidable blindness - Action plan 2006-2011 [Internet] (2007), http://www.who.int/blindness/Vision2020_report.pdf, [cited 2012 Oct 13]Action Plan for the Prevention of Avoidable Blindness and Visual Impairment - 2009-2013 [Internet] (2010), http://www.who.int/blindness/ACTION_PLAN_WHA62-1-English.pdf, [cited 2012 Oct 10]Resnikoff, S., Pascolini, D., Mariotti, S.P., Pokharel, G.P., Global magnitude of visual impairment caused by uncorrected refractive errors in 2004 (2008) Bull World Health Org., 86 (1), pp. 63-70Salomão, S.R., Mitsuhiro, M.R., Belfort Jr, R., Visual impairment and blindness: an overview of prevalence and causes in Brazil (2009) An Acad Bras Ciênc., 81 (3), pp. 539-549Visual impairment and blindness [Internet] http://www.who.int/mediacentre/factsheets/fs282/en/, Updated October 2013. [cited 2012 July 20]Global data on visual impairment 2010 (2012), http://www.who.int/blindness/Globaldatafinalforweb.pdf, [Internet]. WHO, [cited 2012 Oct 10]Sanchez, P.A., Deficiencias visuales y psicomotricidad: teoría y práctica (1994), Madrid: Organización Nacional de Ciegos Españoles, Sección de EducaciónCunha, A.C., Enumo, S.R., Desenvolvimento da criança com deficiência visual (DV) e interacção mãe-criança: algumas considerações (2003) Psicol Saúde Doenças., 4 (1), pp. 33-46Mancini, M.C., Braga, M.A., Albuquerque, K.A., Ramos, T.M., Chagas, P.S., Comparação do desempenho funcional de crianças com visão subnormal e crianças com desenvolvimento normal aos 2 e 6 anos de idade (2010) Rev Ter Ocup Univ São Paulo., 21 (3), pp. 215-222West, S.K., Rubin, G.S., Broman, A.T., Muñoz, B., Bandeen-Roche, K., Turano, K., How does visual impairment affect performance on tasks of everyday life? (2002) Arch Ophthalmol, 120 (6), pp. 774-780Marback, R., Temporini, E., Kara-Júnior, N., Emotional factors prior to cataract surgery (2007) Clinics., 62 (4), pp. 433-438Lamoureux, E.L., Pallant, J.F., Pesudovs, K., Rees, G., Hassell, J.B., Keeffe, J.E., The effectiveness of low-vision rehabilitation on participation in daily living and quality of life (2007) Invest Ophthalmol Vis Sci., 48 (4), pp. 1476-1482Aciem, T.M., Mazzotta, M.J., Autonomia pessoal e social de pessoas com deficiência visual após reabilitação (2013) Rev Bras Oftalmol., 72 (4), pp. 261-267Steiner, W.A., Ryser, L., Huber, E., Uebelhart, D., Aeschlimann, A., Stucki, G., Use of the ICF model as a clinical problem-solving tool in physical therapy and rehabilitation medicine (2002) Phys Ther., 82 (11), pp. 1098-1107Sampaio, M.W., Haddad, M.A., Avaliação oftalmológica da pessoa com baixa visão (2010) Baixa visão e cegueira: os caminhos para a reabilitação, a educação e a inclusão, pp. 45-50. , In: Sampaio MW, Haddad MA, Costa Filho HA, Siaulys MO, Rio de Janeiro: Cultura MédicaGuanabara KooganBittencourt, Z.Z., Montilha, R.C., Gasparetto, M.E., Temporini, E.R., Carvalho, K.M., Diabetic retinopathy and visual disabilities among patients in a rehabilitation program (2011) Rev Bras Oftalmol., 70 (6), pp. 342-348CIF: Classificação Internacional de Funcionalidade, Incapacidade e Saúde (2003), Tradução: Centro Colaborador da Organização Mundial da Saúde para a Família de Classificações Internacionais. São Paulo: EDUSPClassificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde: CID-10 Tenth review (1996) Translation: Centro Colaborador da Organização Mundial da Saúde para a Classificação de Doenças em Português, , 3a ed. São Paulo: EDUSPResnikoff, S., Pascolini, D., Etya'Ale, D., Kocur, I., Pararajasegaram, R., Pokharel, G.P., Mariotti, S.P., Global data on visual impairment in the year 2002 (2004) Bull World Health Organ., 82 (11), pp. 844-851Schellini, S.A., Durkin, S.R., Hoyama, E., Hirai, F., Cordeiro, R., Casson, R.J., Prevalence and causes of visual impairment in a Brazilian population: The Botucatu Eye Study (2009) BMC Ophthalmology., 9, p. 8Resnikoff, S., Keys, T.U., Future trends in global blindness (2012) Indian J Ophthalmol., 60 (5), pp. 387-395Dandona, L., Dandona, R., What is the global burden of visual impairment? (2006) BMC Medicine, 4, p. 6Carvalho, K.M., Monteiro, G.B.M., Isaac, C.R., Shiroma, L.O., Amaral, M.S., Causes of low vision and use of optical aids in the elderly (2002) Rev Hosp Clín Fac Med São Paulo., 59 (4), pp. 157-160Rosenberg, E.A., Sperazza, L.C., The visually impaired patient (2008) Am Fam Physician., 77 (10), pp. 1431-1436Weih, L.M., VanNewkirk, M.R., McCarty, C.A., Taylor, H.R., Age-specific causes of bilateral visual impairment (2000) Arch Ophthalmol., 118 (2), pp. 264-269Yau, J.W., Rogers, S.L., Kawasaki, R., Lamoureux, E.L., Kowalski, J.W., Chen, S.J., Dekker, J.M., Wong, T.Y., Global prevalence and major risk factors of diabetic retinopathy (2012) Diabetes Care., 35 (3), pp. 556-564Sawyer, D.O., Leite, I.C., Alexandrino, R., Perfis de utilização de serviços de saúde no Brasil (2002) Ciênc Saúde Coletiva., 7 (4), pp. 757-776Temporini, E.R., Kara-Júnior, N., Kara-José, N., Holzchuh, N., Popular beliefs regarding the treatment of senile cataract (2002) Revista de Saúde Pública., 36 (3), pp. 343-349Douglas, G., Pavey, S., Corcoran, C., Clements, B., Evaluating the use of the ICF as a framework for the interviewing people with a visual impairment about their mobility and travel (2012) Br J Visual Impairment., 30 (1), pp. 6-21Lucas, M.B., Leal, D.B., Tavares, S.S., Barros, E.A., Aranha, S.T., Condutas reabilitacionais em pacientes com baixa visão (2003) Arq Bras Oftalmol., 66 (1), pp. 77-82Montilha, R.C., Temporini, E.R., Nobre, M.I., Gasparetto, M.E., Kara-Jose, N., Utilização de recursos ópticos e equipamentos por escolares com deficiência visual (2006) Arq Bras Oftalmol., 69 (2), pp. 207-211Haddad, M.A., Sampaio, M.W., Haddad, M., Auxílios para baixa visão (2010) Baixa visão e cegueira: os caminhos para a reabilitação, a educação e a inclusão, pp. 113-139. , In: Sampaio MW, Haddad MA, Costa Filho HA, Siaulys MO, Rio de Janeiro: Cultura MédicaGuanabara KooganOwsley, C., McGwin Jr, G., Lee, P.P., Wasserman, N., Searcey, K., Characteristics of low-vision rehabilitation services in the United States (2009) Arch Ophthalmol., 127 (5), pp. 681-68

Behavioral and electroencephalographic analysis of seizures induced by intrahippocampal injection of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera

In this study, the behavioral and electroencephalographic (EEG) analysis of seizures induced by the intrahippocampal injection in rats of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera, was determined. The first alterations occurred during microinjection of granulitoxin (8 µg) into the dorsal hippocampus and consisted of seizure activity that began in the hippocampus and spread rapidly to the occipital cortex. This activity lasted 20-30 s, and during this period the rats presented immobility. During the first 40-50 min after its administration, three to four other similar short EEG seizure periods occurred and the rats presented the following behavioral alterations: akinesia, facial automatisms, head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements. Within 40-50 min, the status epilepticus was established and lasted 8-12 h. These results are similar to those observed in the acute phase of the pilocarpine model of temporal lobe epilepsy and suggest that granulitoxin may be a useful tool not only to study the sodium channels, but also to develop a new experimental model of status epilepticus.Universidade Estadual do Ceará Departamento de Ciências Fisiológicas Laboratório de NeurofarmacologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Neurologia e Neurocirurgia Laboratório de Neurologia ExperimentalUniversidade de Brasília Departamento de Biologia Celular Centro Brasileiro de Serviços e Pesquisas em ProteínasUNIFESP, Depto. de Neurologia e Neurocirurgia Laboratório de Neurologia ExperimentalSciEL

The Influence Of Assistive Technology Devices On The Performance Of Activities By Visually Impaired

Objective: To establish the influence of assistive technology devices (ATDs) on the performance of activities by visually impaired schoolchildren in the resource room. Methods: A qualitative study that comprised observation and an educational intervention in the resource room. The study population comprised six visually impaired schoolchildren aged 12 to 14 years old. The participants were subjected to an eye examination, prescribed ATDs comprising optical and non-optical devices, and provided an orientation on the use of computers. The participants were assessed based on eye/object distance, font size, and time to read a computer screen and printed text. Results: The ophthalmological conditions included corneal opacity, retinochoroiditis, retinopathy of prematurity, aniridia, and congenital cataracts. Far visual acuity varied from 20/200 to 20/800 and near visual acuity from 0.8 to 6 M. Telescopes, spherical lenses, and support magnifying glasses were prescribed. Three out of five participants with low vision after intervention could decrease the font size on the screen computer, and most participants (83.3%) reduced their reading time at the second observation session. Relative to the printed text, all the participants with low vision were able to read text written in smaller font sizes and reduced their reading time at the second observation session. Conclusion: Reading skills improved after the use of ATDs, which allowed the participants to perform their school tasks equally to their classmates.732103107Resnikoff, S., Pascolini, D., Etya'ale, D., Kocur, I., Pararajasegaram, R., Pokharel, G.P., Global data on visual impairment in the year 2002 (2004) Bull World HealthOrgan., 82 (11), pp. 844-851Visual standards: aspects and ranges of vision loss with emphasis on population surveys. (2002) 29th International Congress of Ophthalmology., , www.icoph.org/pdf/visualstandardsreport.pdf, International Council of Ophthalmology [Internet]. Sydney, Australia, April. Available fromAmorim, A., Paraguay, A.I., Barbosa, E.M., Spelta, L.L., Martinelli, M.A., Bersch, R.C., Comissão temática 1:conceituação e estudo de normas. (2009), pp. 13-39. , http://www.pessoacomdeficiencia.gov.br/app/sites/default/files/publicacoes/livro-tecnologia-assistiva.pdf, In: Brasil. Subsecretaria Nacional de Promoção dos Direitos da Pessoa com DeficiênciaTecnologia Assistiva. Brasília: Corde;Burton, M., Nieuwenhuijsen, E.R., Epstein, M.J., Computer-related assistivetechnology: satisfaction and experiences among users with disabilities (2008) AssistTechnol., 20 (2), pp. 99-106. , quiz 84-85Fok, D., Polgar, J.M., Shaw, L., Jutai, J.W., Low vision assistive technology deviceusage and importance in daily occupations (2011) Work., 39 (1), pp. 37-48Alves, C.C., Monteiro, G.B., Rabello, S., Gasparetto, M.E., de Carvalho, K.M., Assistivetechnology applied to education of students with visual impairment (2009) Rev Panam Salud Publica., 26 (2), pp. 148-152Carvalho, K.M., Freitas, C.C., Kimolto, E.M., Gasparetto, M.E., [Assessment and management of low vision students attended in a room with resources for visual deficiency] (2002) Arq Bras Oftalmol., 65 (4), pp. 445-449. , Portuguesehttp://www.prg.unicamp.br/auxiliosopticos/, Auxílios ópticos Faculdade de Ciências Médicas Universidade Estadual de Campinas. [Optical aids]. Available fromArrigucci Jr., D., Os melhores contos de Rubem Braga. (1997), São Paulo: Global;Pacheco, J., Quando eu for grande quero ir à primavera e outras histórias. (2003), São Paulo: Didática Suplegraf;Montilha, R.C., Temporini, E.R., Nobre, M.I., Gasparetto, M.E., Kara-José, N., [Utilization of optical devices and equipments by students with visual impairment] (2006) Arq Bras Oftalmol., 69 (2), pp. 207-211. , PortugueseHerrero, M.J., Mateus, G.G., García, M., Ramón, M.P., Moasquete, M.J., Characteristics of reading in people with low vision. (1997), Madrid: Once;Freire, F.M., Escrita/leitura e computadores: o uso do editor de texto na escolar. (2003), In: Valente JA, Prado ME, Almeida ME, editors. Educação a distância via internet. São Paulo: AvercampChiang, M.F., Cole, R.G., Gupta, S., Kaiser, G.E., Starren, J.B., Computer and World WideWeb accessibility by visually disabled patients: problems and solutions (2005) SurvOphthalmol., 50 (4), pp. 394-405. , ReviewWatson, A.H., Ito, M., Smith, R.O., Andersen, L.T., Effect of assistive technology in apublic school setting (2010) Am J Occup Ther., 64 (1), pp. 18-2

Partial sequence and toxic effects of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera

A neurotoxic peptide, granulitoxin (GRX), was isolated from the sea anemone Bunodosoma granulifera. The N-terminal amino acid sequence of GRX is AKTGILDSDGPTVAGNSLSGT and its molecular mass is 4958 Da by electrospray mass spectrometry. This sequence presents a partial degree of homology with other toxins from sea anemones such as Bunodosoma caissarum, Anthopleura fuscoviridis and Anemonia sulcata. However, important differences were found: the first six amino acids of the sequence are different, Arg-14 was replaced by Ala and no cysteine residues were present in the partial sequence, while two cysteine residues were present in the first 21 amino acids of other toxins described above. Purified GRX injected ip (800 µg/kg) into mice produced severe neurotoxic effects such as circular movements, aggressive behavior, dyspnea, tonic-clonic convulsion and death. The 2-h LD50 of GRX was 400 ± 83 µg/kg

A New Relativistic High Temperature Bose-Einstein Condensation

We discuss the properties of an ideal relativistic gas of events possessing Bose-Einstein statistics. We find that the mass spectrum of such a system is bounded by $\mu \leq m\leq 2M/\mu _K,$ where $\mu$ is the usual chemical potential, $M$ is an intrinsic dimensional scale parameter for the motion of an event in space-time, and $\mu _K$ is an additional mass potential of the ensemble. For the system including both particles and antiparticles, with nonzero chemical potential $\mu ,$ the mass spectrum is shown to be bounded by $|\mu |\leq m\leq 2M/\mu _K,$ and a special type of high-temperature Bose-Einstein condensation can occur. We study this Bose-Einstein condensation, and show that it corresponds to a phase transition from the sector of continuous relativistic mass distributions to a sector in which the boson mass distribution becomes sharp at a definite mass $M/\mu _K.$ This phenomenon provides a mechanism for the mass distribution of the particles to be sharp at some definite value.Comment: Latex, 22 page