bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cationic Solid Lipid Nanoparticles Loaded by Cystein Proteinase Genes as a Novel anti-Leishmaniasis DNA Vaccine Delivery System: Characterization and in vitro Evaluations
Authors: Doroud Delaram , Vatanara Alireza , Zahedifard Farnaz , Gholami Elham , Vahabpour Rouhollah , Rouholamini Najafabadi Abdolhossein , Rafati Sima 
Published: March 2016

Purpose: Leishmaniasis is a major health problem in many tropical and sub-tropical countries and development of a safe and easily-available vaccine has high priority. Although several antigens potentially capable of inducing protective immunity have been studied, in the absence of pharmaceutical industry interest they have remained as fine publications only. Amongst them, Cathepsin L-like cysteine proteinases (CPs) have received considerable attention and type I and II CPs have been used in a heterologous prime-boost vaccination regime for experimental visceral leishmaniasis in dogs. Due to the promising results of the mentioned vaccination regime, we aimed to evaluate cationic solid lipid nanoparticles (cSLNs) for in vitro delivery of cpa, cpb and cpbCTE intended to be used as a cocktail DNA vaccine in our forthcoming studies.
Methods: cSLNs were formulated of cetyl palmitate, cholesterol, DOTAP and Tween 80 via melt emulsification method followed by high shear homogenization. Different formulations were prepared by anchoring pDNAs on the surface of cSLNs via charge interaction. The formulations were characterized according to their size and zeta potential as well as pDNA integrity and stability against DNase I treatment. Lipoplexes' cytotoxicity was investigated on COS-7 cells by MTT test. The effect of the DOTAP:pDNA ratio on protection ability and cytotoxicity was also studied. In vitro transfection efficiency was qualified by florescent microscopy and quantified using flow cytometry technique.
Results: cSLN-pDNA complexes were formulated with suitable size and zeta potential. Efficiency/cytotoxicity ratio of cSLN-pDNAs formulations was comparable to linear PEI-25KD-pDNAs polyplexes while exhibiting significantly lower cytotoxicity.
Conclusion: Tested formulations were able to deliver immunogenic CP genes efficiently. This data proves the ability of this system as a promising DNA vaccine carrier for leishmaniasis to cover the main drawback of naked pDNA delivery that is rapid elimination from the circulation.
Random Allocation in Controlled Clinical Trials: A Review
Authors: Egbewale Bolaji Emmanuel 
Published: March 2016

PURPOSE: An allocation strategy that allows for chance placement of participants to study groups is crucial to the experimental nature of randomised controlled trials. Following decades of the discovery of randomisation considerable erroneous opinion and misrepresentations of its concept both in principle and practice still exists. In some circles, opinions are also divided on the strength and weaknesses of each of the random allocation strategies. This review provides an update on various random allocation techniques so as to correct existing misconceptions on this all important procedure. METHODS: This is a review of literatures published in the Pubmed database on concepts of common allocation techniques used in controlled clinical trials. RESULTS: Allocation methods that use; case record number, date of birth, date of presentation, haphazard or alternating assignment are non-random allocation techniques and should not be confused as random methods. Four main random allocation techniques were identified. Minimisation procedure though not fully a random technique, however, proffers solution to the limitations of stratification at balancing for multiple prognostic factors, as the procedure makes treatment groups similar in several important features even in small sample trials. CONCLUSIONS: Even though generation of allocation sequence by simple randomisation procedure is easily facilitated, a major drawback of the technique is that treatment groups can by chance end up being dissimilar both in size and composition of prognostic factors. More complex allocation techniques that yield more comparable treatment groups also have certain drawbacks. However, it is important that whichever allocation technique is employed, unpredictability of random assignment should not be compromised. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Statins Against Drug-Induced Nephrotoxicity
Authors: Dashti-Khavidaki Simin , Moghaddas Azadeh , Heydari Behrooz , Khalili Hossein , Lessan-Pezeshki Mahboob , Lessan-Pezeshki Mahbooh 
Published: March 2016

Drug-induced nephrotoxicity (DIN) accounts for up to 60% of hospital acquired acute kidney injury with considerable morbidity and mortality. Several efforts have been made to reduce drug-induced nephrotoxicity; however, DIN remains a matter of concern. Statins with their antioxidant, anti-inflammatory and anti-apoptotic effects may have the potential to protect kidney against DIN. The present review evaluated all of the available in vitro and in vivo studies that examined the use of statins as renoprotective agents against nephrotoxic drugs. Materials for this review were obtained by searching Medline, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. Key words used as search terms included “statin”, “3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, “HMG-CoA reductase inhibitors”, “nephroprotective”, “renoprotective”, “drug-induced renal diseases”, “drug-induced nephrotoxicity”, “drug-induced renal toxicity”, “drug-induced nephropathy”, “drug-induced renal side effects”, and “contrast-induced nephropathy”. This search was performed without time limitation. Only English language articles were included in this review. This review concluded that chronic statin user may be less prone to contrast-induced nephropathy (CIN) compared with statin non-users. Short-term high dose statin administration may also reduce the incidence of CIN in statin naïve patients. This renoprotective effect of statins against CIN is seen in low risk patients with normal kidney function or mild kidney dysfunction, but probably not in patients with moderate to severe renal dysfunction. Based on available animal data, statins may protect kidney against gentamicin-, cisplatin- and cyclosporine-induced nephrotoxicity, however, theses animal results have not yet been confirmed by human data. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Iron Complexation to Histone Deacetylase Inhibitors SAHA and LAQ824 in PEGylated Liposomes Can Considerably Improve Pharmacokinetics in Rats
Authors: Wang Yan , Tu Sheng , Steffen Dana , Xiong May 
Published: March 2016

PURPOSE. The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in vivo pharmacokinetic properties. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Selective Induction of Apoptosis by Azadarichta indica Leaf Extract by Targeting Oxidative Vulnerabilities in Human Cancer Cells
Authors: Roma Alessia , Ovadje Pamela , Steckle Matthew , Nicoletti Leah , Saleem Ammar , Pandey Siyaram 
Published: March 2016

Purpose: Natural products have been a great source of medications used in conventional medicines for the treatment of various diseases; more importantly, they have played a significant role in the development of anti-cancer drugs for a number of decades. The benefits to employing whole extracts of natural health products, rather than a single ingredient, for cancer treatment remains unexplored. Our research group has previously demonstrated the potential anti-cancer benefits of several natural health products (NHPs), prompting further studies into other NHPs, such as Neem (Azadarichta indica), a tree native to India and has been used in Ayurvedic medicine for over 4000 years. The objective of this study is to determine the possible anti-cancer potential of aqueous and ethanolic Neem leaf extracts (NLEs) and to identify the specific mode(s) of action. Methods: Cells were treated with NLE and cell viability was then assessed using a water-soluble tetrazolium salt. Cell death was confirmed using the fluorescent dye propidium iodide and apoptosis was identified using the Annexin-V binding assay. Mitochondrial membrane permeabilization was visualized using JC-1 staining and the production of whole cell and mitochondrial ROS was measured with 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) and Amplex Red, respectively. In vivo efficacy of aqueous NLE was assessed in human tumour xenografts in CD-1 nu/nu immunocompromised mice. Results: Results indicate that both ethanolic and aqueous extracts of Neem leaf were effective in inducing apoptosis in leukemia and colon cancer cells, following destabilization of the mitochondrial membrane. Furthermore, an increase in the production of reactive oxygen species (ROS) was observed in cancer cells treated with NLEs, indicating that oxidative stress may play a role in the mechanism of cell death. Additionally, in vivo results showed that aqueous NLE (delivered orally) was well tolerated and inhibited tumour growth of human xenografts in mice. Conclusions: These findings suggest the potential of NLEs as safer and effective alternatives to conventional chemotherapy. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Preparation and Preliminary Evaluation of Novel β-Cyclodextrin/IUDR Prodrug Formulations
Authors: Wiebe Leonard I. , Yang Xiao-Hong , Singh Shradha , Diakur Jim 
Published: March 2016

PURPOSE. Iododeoxyuridine (IUdR) has a very short in vivo half-life and consequently achieves low target-tissue concentrations with concomitant lower efficacy than would be predicted from in vitro studies. This work reports the preparation of IUdR:?-cyclodextrin (?-CyD) inclusion complexes designed to reduce in vivo inactivation of IUdR. METHODS. IUdR was derivatized with either 1-adamantanecarbonyl chloride or 4-(1-adamantyl-carbamoyl)butanoic acid, to prepare 5’-O-(1-adamantoyl)-5-iodo-2’-deoxyuridine 1 and 5’-O-(4-(1-adamantylcarbamoyl)butoyl)-5-iodo-2’-deoxy-uridine 4, respectively. ?-CyD complexes 5 and 6 were formed by vigorous stirring of 1:1 solutions of ?-CyD and 1 or 4, respectively, in D2O under argon. Complexation was inferred from DSC, powder x-ray diffractometry and NMR spectrometry. The dissociation of 5 in water and under cholesterol challenge, and the effect of complexation on the stability of 1 was determined by incubation in plasma. RESULTS. IUdR coupling with adamantanecarbonyl chloride proceeded smoothly to afford 1 (69 %) and the di-substituted derivative, 3’,5’-di-O-(1-adamantoyl)-5-iodo-2’-deoxyuridine 2 (8 %); 4 was obtained in 42 % yield. The formation of 1:1 complexes 5 and 6 was inferred from NMR chemical shift data. In serum, 1 was 90 % hydrolyzed to IUdR in 30 min, compared to 10 % hydrolysis of 1 to IUdR when from complex 5. CONCLUSIONS. Inclusion complexes were formed between ?-CyD and adamantamine-IUdR conjugates at 1:1 molar ratios.
The complex 5 was resistant to dissociation by cholesterol challenge, and 5 was more slowly converted to IUdR than non-complexed 1. In vivo studies are required to further exploit the ?-CyD inclusion complex approach for improved delivery of nucleoside derivatives.
Evaluation of Synthesized Cross Linked Polyvinyl Alcohol as Potential Disintegrant
Authors: Patel Ashok , Vavia Pradeep 
Published: March 2016

PURPOSE: The present study deals with evaluation of crosslinked poly vinyl alcohol (PVA) as a potential disintegrant.
METHODS: Crosslinking of PVA was carried out using glutaraldehyde as a crosslinker, in presence of acidic conditions. The crosslinking reaction was optimized for a) polymer: crosslinker ratio; b) temperature requirement and c) reaction duration. Certain physical parameters of the disintegrant (including sedimentation volume, hydration capacity, specific surface area and bulk and tap density) were determined and compared to the known disintegrants. Characterization was carried out using FT-IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also studied for acute toxicity in rats and found to be safe for oral use.
RESULTS: Disintegration property of formed product was compared to known disintegrant (Ac-Di-Sol) and it was found to give better results. The disintegration mechanism of developed disintegrant was postulated based on results obtained from various physical evaluations including: Study of effect of disintegrant concentration, fillers, and hardness, mode of incorporation and method of granulation on disintegration activity.
CONCLUSIONS: By changing the condition parameters of well known crosslinking reaction of PVA, we obtained a crosslinked product which had excellent disintegration activity, good flow and optimal tableting properties.
PERFORMANCE OF A CAD SCHEME APPLIED TO IMAGES OBTAINED FROM MAMMOGRAPHIC FILM DIGITIZATION AND FULL-FIELD DIGITAL MAMMOGRAPHY (FFDM)
Authors: Angelo Michele Fúlvia , Schiabel Homero , Patrocinio Ana Claudia 
Published: March 2016

This work has as purpose to compare the effects of a CAD scheme applied to digitized and direct digital mamograms sets. A routine designed to be applied to mammogram in DICOM standard was developed and a schema based on the Watershed Transform to masses detection was applied to 252 ROIs from 130 digitized mammograms, resulting in 92% of true positive and 10% of false positives. For clustered microcalcifications detection, another procedure was applied to 165 ROIs from 120 mammograms, resulting in 93% of true positive and 16% of false positive. By using the same procedures to 154 digital mammograms obtained from FFDM, the rates have shown a little decrease in the scheme performance: 89% of true positive and 16% of false positive for masses detection; 90% of true positive and 27% of false positive for clusters detection. Although the tests with digital mammograms have been carried with a smaller number of images and different cases compared to the digitized ones, including several dense breasts images, the results can be considered comparable, mainly for clustered microcalcifications detection with a difference of only 3% between the sensibility rates for the both images sets. Another important feature affecting these results is the contrast difference between the two images set. This implies the need of extensive investigations not only with a larger number of cases from FFDM but also on the parameters related to its image acquisition as well as to its corresponding processing
PROPOSTA DE UNIDADE TERAPÊUTICA DOMICILIAR DE BAIXO CUSTO BASEADA NO PROTOCOLO PEDIASUIT
Authors: Dallegrave Caroline Paola Mickosz , Neves Eduardo Borba , Gödke Francisco , Rosário Marcelo Oliveira , Costin Ana Cláudia Martins Szizypiorin , Chiarello Claudiana Renata 
Published: March 2016

A Paralisia Cerebral é uma doença neuromuscular que afeta o cérebro em desenvolvimento, causando alterações sensório-motoras que podem comprometer a coordenação motora fina, a manutenção da postura e a deambulação. O uso de tecnologias assistivas específicas é de grande importância para o desenvolvimento da criança portadora de Paralisia Cerebral, uma vez que pode permitir a correção de padrões corporais errôneos e auxiliar na realização de tarefas cotidianas. Este estudo teve como objetivo descrever o desenvolvimento de uma versão de baixo custo e baixa mecanização da Unidade de Tratamento Domiciliar (UTD), baseada no protocolo Pediasuit, bem como suas vantagens e desvantagens em relação ao projeto original. Foi utilizada uma abordagem qualitativa, baseada nos pareceres de terapeutas e responsáveis após um período de testes de seis meses, durante o qual o equipamento foi utilizado por 14 crianças entre 3 e 10 anos de idade, portadoras de desordens neuromotoras. Foi constatado que o produto exige menor uso de força pelo paciente sem comprometimento do padrão da marcha. Observou-se ainda que a confecção do equipamento foi facilitada pelo uso da matéria-prima (PVC) que não exige maquinário ou acabamentos específicos, fato que também contribuiu na redução do custo final do equipamento.
SOFTWARES PARA OS SERVIÇOS DE SAÚDE: UMA REVISÃO INTEGRATIVA A RESPEITO DE PESQUISAS BRASILEIRAS
Authors: Ribeiro Iramara Lima , Costa Iris do Céu Clara , Santa Rosa José Guilherme da Silva 
Published: March 2016

A população brasileira vem enfrentando modificações nos padrões de morbimortalidade, podendo as tecnologias auxiliar na organização dos serviços e prestação do cuidado. Esta revisão integrativa teve por objetivo analisar as contribuições do desenvolvimento de softwares no Brasil para a organização e a integração das ações e dos serviços de saúde. Foram analisados 17 materiais entre 2008 e 2013, sendo a maioria dos autores do Sudeste brasileiro, sinalizando uma quase hegemonia desta região. Quanto à finalidade principal, 47% destinava-se a organização dos serviços, 29,4% ao diagnóstico e 23,6% ao monitoramento, prevenção e tratamento de doenças. Todos eles possuíam relação com a vigilância em saúde e nenhum abordava a promoção da saúde. Os usuários finais eram em maior parte profissionais da saúde (70,6%). Apesar de positiva a presença de softwares para organização dos serviços e diagnóstico, a carência de estudos quanto ao monitoramento, tratamento e prevenção de doenças, com ausência daqueles para a promoção da saúde, evidencia uma valorização de estudos voltados para a doença quando se poderia trabalhar também no sentido de evitar causas preveníveis. As proposições dos softwares podem trazer benefícios, mas aponta-se a necessidade de ampliar as opções de uso quanto à finalidade e aos usuários. Palavras-chave: Saúde, Software, Serviços de Saúde, Organização dos Serviços.
SUPERFÍCIES DE TITÂNIO MODIFICADAS POR OXIDAÇÃO À PLASMA EM CÁTODO OCO
Authors: Silva Marco Aurélio Medeiros da , Guerra Paulo Victor de Azevedo , Valentim Ricardo Alexsandro de Medeiros , Hékis Hélio Roberto , Coutinho Karilany Dantas , Junior Clodomiro Alves , Guerra Neto Custódio Leopoldino de Brito 
Published: March 2016

Uma nova metodologia de oxidação de superfícies de implantes de titânio foi desenvolvida com o intuito de remover previamente os óxidos primários formados espontaneamente durante a usinagem de peças de titânio. Com o objetivo de solucionar esse problema, utilizou-se neste trabalho o plasma como fonte energética tanto na remoção desses óxidos, como na oxidação de superfície de titânio. Nesse sentido, discos de Titânio tiveram seus óxidos previamente removidos por plasma com atmosfera de 50% Ar + 50% H2 seguidos da oxidação pela técnica de descarga por cátodo oco. A oxidação foi realizada numa mistura de argônio (60%) e oxigênio (40%) até atingir a pressão de 220 Pa durante 60 min a 500°C. Em seguida caracterizou-se as superfícies oxidadas e controle por difração de Rx (X-Ray diffraction), microscopia de força atômica AFM (Atômic Force Microscopy) e microscopia eletrônica de varredura (SEM) (Scanning Electron Microscopy). Resultados obtidos por X-Ray rasante indicou que o processo de remoção dos óxidos foi eficaz, reduzindo TiO2 para Tia. Com relação ao processo de oxidação, verificou-se que houve um aumento de 61% para 76% na concentração de O2 e a amostra oxidada apresentou-se rica em óxidos como TiO2. Na caracterização por AFM as amostras oxidadas apresentaram defeitos nas superfícies com geometria variada para picos e vales. As diferenças topográficas entre a superfície oxidada e controle são discutidas em termos das dimensões médias dos poros e dos parâmetros de rugosidade Ra, Rp e Rz. Ensaios biológicos foram também realizados com o intuito de observar a adesão e proliferação celular. No SEM observou-se espraiamento celular, uma maior quantidade de projeções de filopódios e diferenças morfológicas nas células das amostras oxidadas em comparação com a amostra controle. Na proliferação celular as células mostraram uma preferência por superfícies oxidadas onde o número de células aderidas foi comparativamente superior, em relação à amostra controle. Concluímos que o processo foi eficiente na remoção dos óxidos primários bem como na oxidação da superfície do titânio.