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Find video protocols related to scientific articles indexed in Pubmed.
High prevalence of multidrug-resistant Escherichia coli and Enterococcus spp. in river water, upstream and downstream of a wastewater treatment plant.
J Water Health
PUBLISHED: 09-25-2014
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In this study, microbial quality and antimicrobial resistance of faecal bacteria from a Portuguese river were assessed. River water samples collected upstream and downstream of a wastewater treatment plant, throughout a 3-month period, were used for the enumeration of Escherichia coli and Enterococcus spp. The highest numbers found for E. coli and enterococci were 1.1 × 10? and 1.2 × 10? colony forming units (CFU)/100 ml, respectively. In total, 144 isolates of E. coli and 144 of enterococci were recovered and tested for antimicrobial susceptibility; 104 E. coli and 78 Enterococcus spp. showed resistance to one or more antimicrobial drugs. Overall, 70 and 32 different resistance patterns were found for E. coli and enterococci, respectively. One E. coli showed resistance to imipenem and 29 isolates were extended spectrum ?-lactamase-producers. Multidrug-resistant E. coli belonged mostly to groups A, B1 and group D. Enterococcus spp. were mostly resistant to rifampicin, tetracycline, azithromycin and erythromycin; six isolates showed resistance to vancomycin, presenting the VanA phenotype. The high levels of E. coli and enterococci and the remarkable variety of antimicrobial resistance profiles, reinforces the theory that these river waters can be a pool of antimicrobial resistance determinants, which can be easily spread among different bacteria and reach other environments and hosts.
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The pterocarpanquinone LQB-118 induces apoptosis in acute myeloid leukemia cells of distinct molecular subtypes and targets FoxO3a and FoxM1 transcription factors.
Int. J. Oncol.
PUBLISHED: 08-21-2014
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Acute myeloid leukemia (AML) patients' outcome is usually poor, mainly because of drug resistance phenotype. The identification of new drugs able to overcome mechanisms of chemoresistance is essential. The pterocarpanquinone LQB-118 compound has been shown to have a potent cytotoxic activity in myeloid leukemia cell lines and patient cells. Our aim was to investigate if LQB-118 is able to target FoxO3a and FoxM1 signaling pathways while sensitizing AML cell lines. LQB-118 induced apoptosis in both AML cell lines HL60 (M3 FAB subtype) and U937 (M4/M5 FAB subtype). Cell death occurred independently of alterations in cell cycle distribution. In vivo administration revealed that LQB-118 was not cytotoxic to normal bone marrow-derived cells isolated from mice. LQB-118 induced FoxO3a nuclear translocation and upregulation of its direct transcriptional target Bim, in HL60 cells. However, LQB-118 induced FoxO3a nuclear exclusion, followed by Bim downregulation, in U937 cells. Concomitantly, LQB-118 exposure reduced FoxM1 and Survivin expression in U937 cells, but this effect was more subtle in HL60 cells. Taken together, our data suggest that LQB-118 has a selective and potent antitumor activity against AML cells with distinct molecular subtypes, and it involves differential modulation of the signaling pathways associated with FoxO3a and FoxM1 transcription factors.
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New isocoumarin derivatives and meroterpenoids from the marine sponge-associated fungus Aspergillus similanensis sp. nov. KUFA 0013.
Mar Drugs
PUBLISHED: 07-28-2014
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Two new isocoumarin derivatives, including a new 5-hydroxy-8-methyl-2H, 6H-pyrano[3,4-g]chromen-2,6-dione (1) and 6,8-dihydroxy-3,7-dimethylisocoumarin (2b), a new chevalone derivative, named chevalone E (3), and a new natural product pyripyropene S (6) were isolated together with 6, 8-dihydroxy-3-methylisocoumarin (2a), reticulol (2c), p-hydroxybenzaldehyde, chevalone B, chevalone C, S14-95 (4), and pyripyropene E (5) from the ethyl acetate extract of the undescribed marine sponge-associated fungus Aspergillus similanensis KUFA 0013. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and in the case of compound 3, X-ray analysis was used to confirm its structure and the absolute configuration of its stereogenic carbons. Compounds 1, 2a-c and 3-6 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, Candida albicans ATCC 10231, and multidrug-resistant isolates from the environment. Chevalone E (3) was found to show synergism with the antibiotic oxacillin against methicillin-resistant Staphylococcus aureus (MRSA).
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Influence of Fc?RIIIb polymorphism on its ability to cooperate with Fc?RIIa and CR3 in mediating the oxidative burst of human neutrophils.
Hum. Immunol.
PUBLISHED: 05-18-2014
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Considering that human neutrophil Fc?RIIa and Fc?RIIIb receptors interact synergistically with CR3 in triggering neutrophil functional responses, allelic polymorphisms in these receptors might influence such interactions. We assessed whether Fc?RIIIb polymorphisms affect Fc?R/CR cooperation in mediating the neutrophil oxidative burst (OB), in particular the Fc?RIIIb/CR3 cooperation that occurs via lectin-saccharide-like interactions. The OB of human neutrophil antigen (HNA)-1a-, HNA-1b-, and HNA-1a/-1b-neutrophils stimulated with immune complexes, opsonized or not with serum complement, was measured by the luminol-enhanced chemiluminescence assay. Compared with HNA-1a-neutrophils, HNA-1b-neutrophils exhibited reduced Fc?R-stimulated OB, but increased Fc?R/CR-stimulated OB. It suggests that (i) Fc?R and CR cooperate more effectively in HNA-1b-neutrophils, and (ii) the HNA-1b allotype influences the Fc?RIIIb cooperation with Fc?RIIa, but not with CR3. HNA-1a- and HNA-1b-neutrophils exhibited similar OB responses elicited via CR3 alone or via Fc?R/CR-independent pathways. In addition, the level of Fc?RIIIb, Fc?RIIa, and CR3 expression did not differ significantly among the neutrophil groups studied. Together, these results demonstrate that the HNA-1b allotype influences the functional cooperation between Fc?RIIIb and Fc?RIIa, and suggest that the difference in the glycosylation pattern between HNA-1a and HNA-1b does not affect the Fc?RIIIb cooperation with CR3.
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Identification of water-conditioned Pseudomonas aeruginosa by Raman microspectroscopy on a single cell level.
Syst. Appl. Microbiol.
PUBLISHED: 04-30-2014
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The identification of Pseudomonas aeruginosa from samples of bottled natural mineral water by the analysis of subcultures is time consuming and other species of the authentic Pseudomonas group can be a problem. Therefore, this study aimed to investigate the influence of different aquatic environmental conditions (pH, mineral content) and growth phases on the cultivation-free differentiation between water-conditioned Pseudomonas spp. by applying Raman microspectroscopy. The final dataset was comprised of over 7500 single-cell Raman spectra, including the species Pseudomonas aeruginosa, P. fluorescens and P. putida, in order to prove the feasibility of the introduced approach. The collection of spectra was standardized by automated measurements of viable stained bacterial cells. The discrimination was influenced by the growth phase at the beginning of the water adaptation period and by the type of mineral water. Different combinations of the parameters were tested and they resulted in accuracies of up to 85% for the identification of P. aeruginosa from independent samples by applying chemometric analysis.
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Convergent evolution of IL-6 in two leporids (Oryctolagus and Pentalagus) originated an extended protein.
Immunogenetics
PUBLISHED: 04-28-2014
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Interleukin 6 (IL-6) is a class-I helical cytokine with a broad spectrum of biological activities and a gene structure conserved throughout vertebrates, with five coding exons. IL-6 from European rabbits belonging to the subspecies Oryctolagus cuniculus cuniculus was previously shown to differ from other mammals by extending an additional 27 amino acids. However, in other leporids (Sylvilagus spp and Lepus spp) that diverged from the European rabbit ~12 million years ago this mutation was not present. In this study, we extended the study of IL-6 for the Oryctolagus cuniculus algirus subspecies and five additional lagomorphs' genera (Brachylagus, Bunolagus, Pentalagus, Romerolagus, and Ochotona). We confirmed the presence of the mutated stop codon in both O. c. cuniculus and O. c. algirus. We found that the typical stop codon is present in Sylvilagus bachmani and Lepus europaeus, in agreement with previous reports, but also in Bunolagus, Brachylagus, and Ochotona. Remarkably, in Pentalagus we detected a deletion of the stop codon causing an extension of IL-6 for 17 extra residues. Our results indicate that the IL-6 extension in those species occurred by two independent events: one occurred between 2 and 8 million years ago in the ancestral of the Oryctolagus subspecies, and the other occurred in a Pentalagus ancestral at a maximum of 9 million years ago. The absence of this IL-6 extension in Bunolagus, sister genus of Oryctolagus, shows that this evolutionary event happened by convergence suggesting some functional relevance.
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Switch from intravitreal ranibizumab to bevacizumab for the treatment of neovascular age-related macular degeneration: clinical comparison.
Ophthalmologica
PUBLISHED: 04-26-2014
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To compare outcomes after switching from intravitreal ranibizumab to bevacizumab in neovascular age-related macular degeneration (AMD).
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Exacerbation of asthma and airway infection: is the virus the villain?
J Pediatr (Rio J)
PUBLISHED: 04-24-2014
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to review the available literature on the association between acute viral respiratory tract infection and the onset of asthma exacerbations, identifying the most prevalent viruses, detection methods, as well as preventive and therapeutic aspects.
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Magnetic resonance imaging-guided occult breast lesion localization and simultaneous sentinel lymph node mapping.
World J Surg Oncol
PUBLISHED: 04-10-2014
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Radio-guided occult lesion localization is a valid technique for the diagnosis of suspicious non-palpable lesions. Here we determine the feasibility of pre-operative localization of occult suspect non-palpable breast lesions using radio-guided occult lesion localization, as well as for identifying the sentinel lymph node.
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Tris-thiourea tripodal-based molecules as chloride transmembrane transporters: insights from molecular dynamics simulations.
Soft Matter
PUBLISHED: 03-24-2014
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The interaction of six tripodal synthetic chloride transmembrane transporters with a POPC bilayer was investigated by means of molecular dynamics simulations using the general Amber force field (GAFF) for the transporters and the LIPID11 force field for phospholipids. These transporters are structurally simple molecules, based on the tris(2-aminoethyl)amine scaffold, containing three thiourea binding units coupled with three n-butyl (1), phenyl (2), fluorophenyl (3), pentafluorophenyl (4), trifluoromethylphenyl (5), or bis(trifluoromethyl)phenyl (6) substituents. The passive diffusion of 1-6? Cl(-) was evaluated with the complexes initially positioned either in the water phase or inside the bilayer. In the first scenario the chloride is released in the water solution before the synthetic molecules achieve the water-lipid interface and permeate the membrane. In the latter one, only when the chloride complex reaches the interface is the anion released to the water phase, with the transporter losing the initial ggg tripodal shape. Independently of the transporter used in the membrane system, the bilayer structure is preserved and the synthetic molecules interact with the POPC molecules at the phosphate headgroup level, via N-H···O hydrogen bonds. Overall, the molecular dynamics simulations' results indicate that the small tripodal molecules in this series have a low impact on the bilayer and are able to diffuse with chloride inside the lipid environment. Indeed, these are essential conditions for these molecules to promote the transmembrane transport as anion carriers, in agreement with experimental efflux data.
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Evolutionarily conserved mechanisms of male germline development in flowering plants and animals.
Biochem. Soc. Trans.
PUBLISHED: 03-21-2014
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Sexual reproduction is the main reproductive strategy of the overwhelming majority of eukaryotes. This suggests that the last eukaryotic common ancestor was able to reproduce sexually. Sexual reproduction reflects the ability to perform meiosis, and ultimately generating gametes, which are cells that carry recombined half sets of the parental genome and are able to fertilize. These functions have been allocated to a highly specialized cell lineage: the germline. Given its significant evolutionary conservation, it is to be expected that the germline programme shares common molecular bases across extremely divergent eukaryotic species. In the present review, we aim to identify the unifying principles of male germline establishment and development by comparing two very disparate kingdoms: plants and animals. We argue that male meiosis defines two temporally regulated gene expression programmes: the first is required for meiotic commitment, and the second is required for the acquisition of fertilizing ability. Small RNA pathways are a further key communality, ultimately ensuring the epigenetic stability of the information conveyed by the male germline.
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11a-N-Tosyl-5-deoxi-pterocarpan (LQB-223), a promising prototype for targeting MDR leukemia cell lines.
Eur J Med Chem
PUBLISHED: 03-13-2014
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Aza-deoxi-pterocarpans (1) were synthesized through palladium-catalyzed aza-arylation of dihydronaphtalen, and showed antineoplastic effect on MDR leukemic cell lines (K562, Lucena-1 and FEPS). Compounds 1c-d were prepared to identify the pharmacophoric group responsible for the activity as well as compounds 2a-c were prepared to evaluate the structural requirements in the D-ring. LQB-223 (1b) is the most promising antileukemic agent since it was the most active on MDR cells without detectable toxicity to normal immune system cells.
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Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 03-11-2014
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The hepatitis C virus (HCV) encodes approximately 10 different structural and non-structural proteins, including the envelope glycoprotein 2 (E2). HCV proteins, especially the envelope proteins, bind to cell receptors and can damage tissues. Endothelial inflammation is the most important determinant of fibrosis progression and, consequently, cirrhosis. The aim of this study was to evaluate and compare the inflammatory response of endothelial cells to two recombinant forms of the HCV E2 protein produced in different expression systems (Escherichia coli and Pichia pastoris). We observed the induction of cell death and the production of nitric oxide, hydrogen peroxide, interleukin-8 and vascular endothelial growth factor A in human umbilical vein endothelial cells (HUVECs) stimulated by the two recombinant E2 proteins. The E2-induced apoptosis of HUVECs was confirmed using the molecular marker PARP. The apoptosis rescue observed when the antioxidant N-acetylcysteine was used suggests that reactive oxygen species are involved in E2-induced apoptosis. We propose that these proteins are involved in the chronic inflammation caused by HCV.
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Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 03-11-2014
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The hepatitis C virus (HCV) encodes approximately 10 different structural and non-structural proteins, including the envelope glycoprotein 2 (E2). HCV proteins, especially the envelope proteins, bind to cell receptors and can damage tissues. Endothelial inflammation is the most important determinant of fibrosis progression and, consequently, cirrhosis. The aim of this study was to evaluate and compare the inflammatory response of endothelial cells to two recombinant forms of the HCV E2 protein produced in different expression systems (Escherichia coli and Pichia pastoris). We observed the induction of cell death and the production of nitric oxide, hydrogen peroxide, interleukin-8 and vascular endothelial growth factor A in human umbilical vein endothelial cells (HUVECs) stimulated by the two recombinant E2 proteins. The E2-induced apoptosis of HUVECs was confirmed using the molecular marker PARP. The apoptosis rescue observed when the antioxidant N-acetylcysteine was used suggests that reactive oxygen species are involved in E2-induced apoptosis. We propose that these proteins are involved in the chronic inflammation caused by HCV.
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Spread of multidrug-resistant Enterococcus faecalis within the household setting.
Microb. Drug Resist.
PUBLISHED: 03-11-2014
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Advances in veterinary medicine have resulted in the survival of many animals with severe illness or infectious diseases. In addition, increased usage of antimicrobial agents for veterinary purposes has contributed to the worldwide problem of increasing antimicrobial resistance. The objective of this study was to contribute to better understand the potential and implications for the spread of antimicrobial-resistant enterococci between pets receiving antimicrobial treatments and their owners. Three household aggregates (HA A, B, and C) were selected for this study. Information was collected on individual and clinical parameters of both humans and animals that cohabit. For this study, samples of feces, oral secretions, skin and fur of pets, as well as owners' feces and hands and exposed household surfaces and objects were also collected. All enterococci isolates were analyzed for antimicrobial susceptibility. Based on the antimicrobial resistance patterns and origin of isolates, ERIC-PCR analysis was performed on selected isolates to evaluate phylogenetic relationships. In all three HA, Enterococcus faecalis clonal spread was detected between pets and the respective owners, confirming the in-home interanimal species dissemination. Additionally, fecal enterococci colonization of other body parts of the same animal and dissemination of those same enterococci to household surfaces and objects were also observed. Our results demonstrate that enterococcal clones were found in pets in multiple body sites, their human cohabitants, and shared domestic objects.
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[Evaluation of antiangiogenic treatment results in choroidal neovascularization related to pathological myopia].
Acta Med Port
PUBLISHED: 02-28-2014
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Choroidal neovascularization secondary to pathological myopia is one of the leading causes of irreversible central vision loss in younger patients. The purposes of our study is to evaluate the long-term results of antiangiogenic treatment, with ranibizumab and/or bevacizumab, in myopic choroidal neovascularization and define the predictive factors for visual and anatomic outcomes.
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CNN Pincer Ruthenium Catalysts for Hydrogenation and Transfer Hydrogenation of Ketones: Experimental and Computational Studies.
Chemistry
PUBLISHED: 02-17-2014
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Reaction of [RuCl(CNN)(dppb)] (1-Cl) (HCNN=2-aminomethyl-6-(4-methylphenyl)pyridine; dppb=Ph2 P(CH2 )4 PPh2 ) with NaOCH2 CF3 leads to the amine-alkoxide [Ru(CNN)(OCH2 CF3 )(dppb)] (1-OCH2 CF3 ), whose neutron diffraction study reveals a short RuO???HN bond length. Treatment of 1-Cl with NaOEt and EtOH affords the alkoxide [Ru(CNN)(OEt)(dppb)]?(EtOH)n (1-OEt?n?EtOH), which equilibrates with the hydride [RuH(CNN)(dppb)] (1-H) and acetaldehyde. Compound 1-OEt?n?EtOH reacts reversibly with H2 leading to 1-H and EtOH through dihydrogen splitting. NMR spectroscopic studies on 1-OEt?n?EtOH and 1-H reveal hydrogen bond interactions and exchange processes. The chloride 1-Cl catalyzes the hydrogenation (5?atm of H2 ) of ketones to alcohols (turnover frequency (TOF) up to 6.5×10(4) ?h(-1) , 40?°C). DFT calculations were performed on the reaction of [RuH(CNN')(dmpb)] (2-H) (HCNN'=2-aminomethyl-6-(phenyl)pyridine; dmpb=Me2 P(CH2 )4 PMe2 ) with acetone and with one molecule of 2-propanol, in alcohol, with the alkoxide complex being the most stable species. In the first step, the Ru-hydride transfers one hydrogen atom to the carbon of the ketone, whereas the second hydrogen transfer from NH2 is mediated by the alcohol and leads to the key "amide" intermediate. Regeneration of the hydride complex may occur by reaction with 2-propanol or with H2 ; both pathways have low barriers and are alcohol assisted.
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Prevalence of antimicrobial resistance in enteric Escherichia coli from domestic pets and assessment of associated risk markers using a generalized linear mixed model.
Prev. Vet. Med.
PUBLISHED: 02-03-2014
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Antimicrobial resistance (AMR) is a growing global public health problem, which is caused by the use of antimicrobials in both human and animal medical practice. The objectives of the present cross-sectional study were as follows: (1) to determine the prevalence of resistance in Escherichia coli isolated from the feces of pets from the Porto region of Portugal against 19 antimicrobial agents and (2) to assess the individual, clinical and environmental characteristics associated with each pet as risk markers for the AMR of the E. coli isolates. From September 2009 to May 2012, rectal swabs were collected from pets selected using a systematic random procedure from the ordinary population of animals attending the Veterinary Hospital of Porto University. A total of 78 dogs and 22 cats were sampled with the objective of isolating E. coli. The animals' owners, who allowed the collection of fecal samples from their pets, answered a questionnaire to collect information about the markers that could influence the AMR of the enteric E. coli. Chromocult tryptone bile X-glucuronide agar was used for E. coli isolation, and the disk diffusion method was used to determine the antimicrobial susceptibility. The data were analyzed using a multilevel, univariable and multivariable generalized linear mixed model (GLMM). Several (49.7%) of the 396 isolates obtained in this study were multidrug-resistant. The E. coli isolates exhibited resistance to the antimicrobial agent's ampicillin (51.3%), cephalothin (46.7%), tetracycline (45.2%) and streptomycin (43.4%). Previous quinolone treatment was the main risk marker for the presence of AMR for 12 (ampicillin, cephalothin, ceftazidime, cefotaxime, nalidixic acid, ciprofloxacin, gentamicin, tetracycline, streptomycin, chloramphenicol, trimethoprim-sulfamethoxazole and aztreonam) of the 15 antimicrobials assessed. Coprophagic habits were also positively associated with an increased risk of AMR for six drugs, ampicillin, amoxicillin-clavulanic acid, cephamycin, ciprofloxacin, streptomycin, and trimethoprim-sulfamethoxazole. In summary, pets with a record of one or more previous quinolone treatments and exhibiting coprophagic habits were at an increased risk of harboring multidrug-resistant E. coli strains in their feces compared to pets without these characteristics. AMR is a serious global problem, and assessing the risk markers for the presence of drug-resistant bacteria in pets, a very close source of resistance determinants to humans, is essential for the implementation of safe handling procedures for companion animals and for the prudent selection of antimicrobial compounds in veterinary practice.
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Bacterial cellulose membranes as transdermal delivery systems for diclofenac: in vitro dissolution and permeation studies.
Carbohydr Polym
PUBLISHED: 02-03-2014
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Bacterial cellulose (BC) membranes were explored as novel nanostructured transdermal delivery systems for diclofenac sodium salt (a typical non-steroidal anti-inflammatory drug). Diclofenac sodium salt loaded BC membranes were prepared through a simple methodology, using glycerol as plasticizer, and characterized in terms of structure, morphology and swelling behavior. The membranes were very homogeneous, quite flexible and presented a considerably higher swelling behavior when compared with pure BC. In vitro diffusion studies with Franz cells, were conducted using human epidermal membranes, and showed that the incorporation of diclofenac in BC membranes provided similar permeation rates to those obtained with commercial patches and substantially lower than those observed with a commercial gel. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes clearly indicates the enormous potentialities of using BC membranes for transdermal administration of diclofenac.
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Anti-VEGF therapy in myopic choroidal neovascularization: long-term results.
Ophthalmologica
PUBLISHED: 02-01-2014
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To evaluate the medium- and long-term efficacy of anti-VEGF agents in the treatment of choroidal neovascularization secondary to pathologic myopia (mCNV).
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Developing a rapid and sensitive method for determination of trans-fatty acids in edible oils using middle-infrared spectroscopy.
Food Chem
PUBLISHED: 01-31-2014
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Several countries have adopted labelling policy concerning the declaration of trans fatty acids (TFAs) content in the nutritional facts panel of processed food. Consequently, the food industry requires rapid methods to measure low levels of TFAs. This paper reports the development of a rapid method to determine TFAs <1% in edible oils (palm, peanut, soybean and sunflower) and oils/fat samples extracted from finished products using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). Traditional linear regression and Partial Least Squares (PLS) statistical tools were applied to model the spectroscopic data. The calibration models of edible oils/fat samples showed a coefficient-of-correlation ?0.982 and standard error of prediction (SEP) between 0.03% and 0.06%. The ATR-FTIR results of extracted oils/fat are in good agreement with the capillary gas chromatography with flame ionisation detector (GC/FID). This study has demonstrated that ATR-FTIR technique can be used to rapidly determine trans fatty acids <1% in oils/fat.
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Evaluation of clinical and laboratory variables associated with anemia in pediatric patients on hemodialysis.
J Pediatr (Rio J)
PUBLISHED: 01-22-2014
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to identify the occurrence of anemia in pediatric patients on hemodialysis and the association between hemoglobin levels and anemia in CKD-related variables.
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Use of local intelligence to reduce energy consumption of wireless sensor nodes in elderly health monitoring systems.
Sensors (Basel)
PUBLISHED: 01-17-2014
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The percentage of elderly people in European countries is increasing. Such conjuncture affects socio-economic structures and creates demands for resourceful solutions, such as Ambient Assisted Living (AAL), which is a possible methodology to foster health care for elderly people. In this context, sensor-based devices play a leading role in surveying, e.g., health conditions of elderly people, to alert care personnel in case of an incident. However, the adoption of such devices strongly depends on the comfort of wearing the devices. In most cases, the bottleneck is the battery lifetime, which impacts the effectiveness of the system. In this paper we propose an approach to reduce the energy consumption of sensors' by use of local sensors' intelligence. By increasing the intelligence of the sensor node, a substantial decrease in the necessary communication payload can be achieved. The results show a significant potential to preserve energy and decrease the actual size of the sensor device units.
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Antibacterial and antibiofilm activities of tryptoquivalines and meroditerpenes isolated from the marine-derived fungi Neosartorya paulistensis, N. laciniosa, N. tsunodae, and the soil fungi N. fischeri and N. siamensis.
Mar Drugs
PUBLISHED: 01-17-2014
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A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines L (1a), H (1b), F (1c), 3'-(4-oxoquinazolin-3-yl) spiro [1H-indole-3,5']-2,2'-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a-d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.
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The role of KIR2DS1 in multiple sclerosis--KIR in Portuguese MS patients.
J. Neuroimmunol.
PUBLISHED: 01-16-2014
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Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. We observed a negative association between the activating KIR2DS1 gene and MS (adjusted OR=0.450, p=0.030) independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells.
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CC chemokine receptor polymorphism CCR5?32 in Portuguese Behçet's disease patients.
Clin. Exp. Rheumatol.
PUBLISHED: 01-13-2014
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To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (BD) in a Portuguese population.
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A quantitative risk assessment model for Vibrio parahaemolyticus in raw oysters in Sao Paulo State, Brazil.
Int. J. Food Microbiol.
PUBLISHED: 01-13-2014
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A risk assessment of Vibrio parahaemolyticus associated with raw oysters produced and consumed in São Paulo State was developed. The model was built according to the United States Food and Drug Administration framework for risk assessment. The outcome of the exposure assessment estimated the prevalence and density of pathogenic V. parahaemolyticus in raw oysters from harvest to consumption. The result of the exposure step was combined with a Beta-Poisson dose-response model to estimate the probability of illness. The model predicted that the average risks per serving of raw oysters were 4.7×10(-4), 6.0×10(-4), 4.7×10(-4) and 3.1×10(-4) for spring, summer, fall and winter, respectively. Sensitivity analyses indicated that the most influential variables on the risk of illness were the total density of V. parahaemolyticus at harvest, transport temperature, relative prevalence of pathogenic strains and storage time at retail. Only storage time under refrigeration at retail showed negative correlation with the risk of illness.
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[Esophageal Cancer: Surgical Strategies.]
Acta Med Port
PUBLISHED: 01-10-2014
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Introduction: Oesophagectomy for cancer is associated to a significant morbidity and mortality. The superiority of transthoracic vs transhiatal is still a matter of controversy. The aim of this paper is to discuss the results of a series of patients submitted to either a transthoracic or a transhiatal according to the anatomic location regarding the carina.Material and Methods: Retrospective analysis of 52 consecutive patients, with oesophageal carcinoma, 7 female and 45 males, median age 64 [46-85] years. Location: cervical - 1; above carina - 22; below or at carina level - 19; cardia type I -10. 19 adenocarcinoma, 32 squamous cells, 1 lymphoma. Twenty patients (40%) - neo-adjuvant therapy. Thoracoabdominal approach - 3, cervico-thoracoabdominal - 20, transhiatal - 27, exploratory thoracotomy - 2. Gastric pull-up 49 (cervical anastomosis - 46; thoracic - 3); cervical oesofagocoloplasty -1.Results: Pathologic staging: complete remission - 8; Ib - 3; IIa - 9; IIb - 4; IIa - 11; IIIb -2; IIIc - 10; IV - 1; non-stageable - 3. Major complications: 37%. Resectability: 96% (50/52). Mortality: 4th week - 6%; in-hospital - 14%. Median survival 18 months [3-80]. Survival Curves (Kaplan-Meier): 2 years - 47%; 5 years - 19% (transthoracic vs transhiatal p > 0.05).Discussion: Selection of surgical approach based on the anatomic location of the tumour regarding the carina was safe, the resectability was high and similar when a transthoracic or a transhiatal was planed and carry-on.Conclusions: In this series of oesophageal cancer patients, in advanced pathologic condition (52% p Stages III/IV) the overall survival was similar for transthoracic and transhiatal. Neo-adjuvant treatments definitively contributed to enhance resectability.
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Usefulness of genetic characterization of narcolepsy and hypersomnia on phenotype definition: a study in Portuguese patients.
Rev Neurol
PUBLISHED: 01-09-2014
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The determination of human leukocyte antigen (HLA) class II genotype is widely used to confirm the diagnosis of narcolepsy with or without cataplexy. The HLA genotyping is reliable, easy to perform and reassures the clinician. It is also less invasive than other methodologies and is in accordance with the autoimmune hypothesis for the origin of narcolepsy. AIM. To assess the usefulness of genetic markers (HLA) in the differential diagnosis between different sleep disorders and their relevance in the context of our population.
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The pterocarpanquinone LQB-118 inhibits tumor cell proliferation by downregulation of c-Myc and cyclins D1 and B1 mRNA and upregulation of p21 cell cycle inhibitor expression.
Bioorg. Med. Chem.
PUBLISHED: 01-06-2014
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The incidence of cancer grows annually worldwide and in Brazil it is the second cause of death. The search for anti-cancer drugs has then become urgent. It depends on the studies of natural and chemical synthesis products. The antitumor action of LQB-118, a pterocarpanquinone structurally related to lapachol, has been demonstrated to induce mechanisms linked to leukemia cell apoptosis. This work investigated some mechanisms of the in vitro antitumor action of LQB-118 on prostate cancer cells. LQB-118 reduced the expression of the c-Myc transcription factor, downregulated the cyclin D1 and cyclin B1 mRNA levels and upregulated the p21 cell cycle inhibitor. These effects resulted in cell cycle arrest in the S and G2/M phases and inhibition of tumor cell proliferation. LQB-118 also induced programmed cell death of the prostate cancer cells, as evidenced by internucleosomal DNA fragmentation and annexin-V positive cells. Except the cell cycle arrest in the S phase and enhanced c-Myc expression, all the mechanisms observed here for the in vitro antitumor action of LQB-118 were also found for Paclitaxel, a traditional antineoplastic drug. These findings suggest new molecular mechanisms for the LQB-118 in vitro antitumor action.
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Chemical constituents and toxicological studies of leaves from Mimosa caesalpiniifolia Benth., a Brazilian honey plant.
Pharmacogn Mag
PUBLISHED: 01-05-2014
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Mimosa caesalpiniifolia Benth. (Leguminosae) is widely found in the Brazilian Northeast region and markedly contributes to production of pollen and honey, being considered an important honey plant in this region.
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Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth factor receptor-mediated signaling pathway in bradykinin-stimulated angiogenesis.
Arch. Biochem. Biophys.
PUBLISHED: 01-02-2014
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Nitric oxide (NO) is involved in angiogenesis and stimulates the EGF-R signaling pathway. Stimulation of different endothelial cell lines with bradykinin (BK) activates the endothelial NO synthase (eNOS) and promotes EGF-R tyrosine phosphorylation. Increase in NO production correlated with enhanced phosphorylation of tyrosine residues and S-nitrosylation of the EGF-R. NO-mediated stimulatory effects on tyrosine phosphorylation of the EGF-R, where cGMP independent. Inhibition of soluble guanylyl cyclase followed by BK stimulation of human umbilical vein endothelial cells (HUVECs) did not change tyrosine phosphorylation levels of EGF-R. BK-stimulation of HUVEC promoted S-nitrosylation of the phosphatase SHP-1 and of p21Ras. Phosphorylation and activation of the ERK1/2 MAP kinases mediated by BK was dependent on the activation of the B2 receptor, of the EGF-R, and of p21 Ras. Inhibition of BK-stimulated S-nitrosylation prevented the activation of the ERK1/2 MAP kinases. Furthermore, activated ERK1/2 MAP kinases inhibited internalization of EGF-R by phosphorylating specific Thr residues of its cytoplasmic domain. BK-induced proliferation of endothelial cells was partially inhibited by the NOS inhibitor (L-NAME) and by the MEK inhibitor (PD98059). BK stimulated the expression of vascular endothelial growth factor (VEGF). VEGF expression was dependent on the activation of the EGF-R, the B2 receptor, p21Ras, and on NO generation. A Matrigel®-based in vitro assay for angiogenesis showed that BK induced the formation of capillary-like structures in HUVEC, but not in those cells expressing a mutant of the EGF-R lacking tyrosine kinase activity. Additionally, pre-treatment of BK-stimulated HUVEC with L-NAME, PD98059, and with SU5416, a specific inhibitor of VEGFR resulted in inhibition of in vitro angiogenesis. Our findings indicate that BK-mediated angiogenesis in endothelial cells involves the induction of the expression of VEGF associated with the activation of the NO/EGF-R/p21Ras/ERK1/2 MAP kinases signaling pathway.
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Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters.
PLoS ONE
PUBLISHED: 01-01-2014
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Previous results demonstrate that the hybrid synthetic pterocarpanquinone LQB-118 presents antileishmanial activity against Leishmania amazonensis in a mouse model. The aim of the present study was to use a hamster model to investigate whether LQB-118 presents antileishmanial activity against Leishmania (Viannia) braziliensis, which is the major Leishmania species related to American tegumentary leishmaniasis. The in vitro antileishmanial activity of LQB-118 on L. braziliensis was tested on the promastigote and intracellular amastigote forms. The cell death induced by LQB-118 in the L. braziliensis promastigotes was analyzed using an annexin V-FITC/PI kit, the oxidative stress was evaluated by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and the ATP content by luminescence. In situ labeling of DNA fragments by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis in the intracellular amastigotes. L. braziliensis-infected hamsters were treated from the seventh day of infection with LQB-118 administered intralesionally (26 µg/kg/day, three times a week) or orally (4,3 mg/kg/day, five times a week) for eight weeks. LQB-118 was active against the L. braziliensis promastigotes and intracellular amastigotes, producing IC50 (50% inhibitory concentration) values of 3,4±0,1 and 7,5±0,8 µM, respectively. LQB-118 induced promastigote phosphatidylserine externalization accompanied by increased reactive oxygen species production and ATP depletion. Intracellular amastigote DNA fragmentation was also observed, without affecting the viability of macrophages. The treatment of L. braziliensis-infected hamsters with LQB-118, either orally or intralesionally, was effective in the control of lesion size, parasite load and increase intradermal reaction to parasite antigen. Taken together, these results show that the antileishmanial effect of LQB-118 extends to L. braziliensis in the hamster model, involves the induction of parasite apoptosis and shows promising therapeutic option by oral or local routes in leishmaniasis.
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Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathy.
Mol. Vis.
PUBLISHED: 01-01-2014
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Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma.
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Regulation of Hfq mRNA and protein levels in Escherichia coli and Pseudomonas aeruginosa by the Burkholderia cenocepacia MtvR sRNA.
PLoS ONE
PUBLISHED: 01-01-2014
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Small non-coding RNAs (sRNAs) are important players of gene expression regulation in bacterial pathogens. MtvR is a 136-nucleotide long sRNA previously identified in the human pathogen Burkholderia cenocepacia J2315 and with homologues restricted to bacteria of the Burkholderia cepacia complex. In this work we have investigated the effects of expressing MtvR in Escherichia coli and Pseudomonas aeruginosa. Results are presented showing that MtvR negatively regulates the hfq mRNA levels in both bacterial species. In the case of E. coli, this negative regulation is shown to involve binding of MtvR to the 5'-UTR region of the hfqEc mRNA. Results presented also show that expression of MtvR in E. coli and P. aeruginosa originates multiple phenotypes, including reduced resistance to selected stresses, biofilm formation ability, and increased susceptibility to various antibiotics.
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Major complications following total en bloc spondylectomy for giant-cell tumor.
J Surg Case Rep
PUBLISHED: 01-01-2014
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The authors present the case of a 32-year-old Caucasian female with a giant-cell tumor of the eighth thoracic vertebra, causing unremitting pain, segmental kyphosis and imminent local instability. A total en bloc spondylectomy by a posterior-only approach was performed, complemented with anterior-column reconstruction with a titanium mesh and structural allograft, as well as pedicle screw fixation. Despite the surgery being uneventful, several complications developed over the ensuing weeks: bilateral hemothorax, empyema and sepsis, requiring numerous revision surgeries for postoperative infection. The same pathogen was identified in different samples collected, including a sample from the allograft used. Only the aggressive therapeutic measures adopted allowed improvement in clinical and analytic parameters. The present report alerts to the possible complications following major spine surgery, and raises concerns on the safety of the bone allografts provided, renewing the interest in the development of alternative bone substitutes.
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Theoretical and experimental studies of new modified isoflavonoids as potential inhibitors of topoisomerase I from Plasmodium falciparum.
PLoS ONE
PUBLISHED: 01-01-2014
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DNA topoisomerase I from Plasmodium falciparum (PfTopoI), a potential selective target for chemotherapy and drug development against malaria, is used here, together with human Topo I (HssTopoI), for docking, molecular dynamics (MD) studies and experimental assays. Six synthetic isoflavonoid derivatives and the known PfTopoI inhibitors camptothecin and topotecan were evaluated in parallel. Theoretical results suggest that these compounds dock in the binding site of camptothecin and topotecan inside both enzymes and that LQB223 binds selectively in PfTopoI. In vitro tests against P. falciparum blood parasites corroborated the theoretical findings. The selectivity index (SI) of LQB223 ? 98 suggests that this molecule is the most promising in the group of compounds tested. In vivo experiments in mice infected with P. berghei showed that LQB223 has an antimalarial activity similar to that of chloroquine.
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Exposure assessment of extended-spectrum beta-lactamases/AmpC beta-lactamases-producing Escherichia coli in meat in Denmark.
Infect Ecol Epidemiol
PUBLISHED: 01-01-2014
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Extended-spectrum beta-lactamases (ESBL) and AmpC beta-lactamases (AmpC) are of concern for veterinary and public health because of their ability to cause treatment failure due to antimicrobial resistance in Enterobacteriaceae. The main objective was to assess the relative contribution (RC) of different types of meat to the exposure of consumers to ESBL/AmpC and their potential importance for human infections in Denmark.
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Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin.
An Bras Dermatol
PUBLISHED: 12-19-2013
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Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.
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Choroidal and macular thickness changes induced by cataract surgery.
Clin Ophthalmol
PUBLISHED: 12-16-2013
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The aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid.
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Characterization of an antioxidant surfactant-free topical formulation containing Castanea sativa leaf extract.
Drug Dev Ind Pharm
PUBLISHED: 11-06-2013
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Abstract Context: Inclusion of antioxidants in topical formulations can contribute to minimize oxidative stress in the skin, which has been associated with photoaging, several dermatosis and cancer. Objective: A Castanea sativa leaf extract with established antioxidant activity was incorporated into a semisolid surfactant-free formulation. The objective of this study was to perform a comprehensive characterization of this formulation. Materials and methods: Physical, microbiological and functional stability were evaluated during 6?months storage at 20?°C and 40?°C. Microstructure elucidation (cryo-SEM), in vitro release and in vivo moisturizing effect (Corneometer® CM 825) were also assessed. Results and discussion: Minor changes were observed in the textural and rheological properties of the formulation when stored at 20?°C for 6?months and the antioxidant activity of the plant extract remained constant throughout the storage period. Microbiological quality was confirmed at the end of the study. Under accelerated conditions, higher modifications of the evaluated parameters were observed. Cryo-SEM analysis revealed the presence of oil droplets dispersed into a gelified external phase. The release rate of the antioxidant compounds (610?±?70?µgh(-0.5)) followed Higuchi model. A significant in vivo moisturizing effect was demonstrated, that lasted at least 4?h after products application. Conclusion: The physical, functional and microbiological stability of the antioxidant formulation was established. Specific storage conditions should be recommended considering the influence of temperature on the stability. A skin hydration effect and good skin tolerance were also found which suggests that this preparation can be useful in the prevention or treatment of oxidative stress-mediated dysfunctions.
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Structural Studies on Dinuclear Ruthenium(II) Complexes That Bind Diastereoselectively to an Antiparallel Folded Human Telomere Sequence.
J. Med. Chem.
PUBLISHED: 10-23-2013
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We report DNA binding studies of the dinuclear ruthenium ligand [{Ru(phen)2}2tpphz](4+) in enantiomerically pure forms. As expected from previous studies of related complexes, both isomers bind with similar affinity to B-DNA and have enhanced luminescence. However, when tested against the G-quadruplex from human telomeres (which we show to form an antiparallel basket structure with a diagonal loop across one end), the ?? isomer binds approximately 40 times more tightly than the ??, with a stronger luminescence. NMR studies show that the complex binds at both ends of the quadruplex. Modeling studies, based on experimentally derived restraints obtained for the closely related [{Ru(bipy)2}2tpphz](4+), show that the ?? isomer fits neatly under the diagonal loop, whereas the ?? isomer is unable to bind here and binds at the lateral loop end. Molecular dynamics simulations show that the ?? isomer is prevented from binding under the diagonal loop by the rigidity of the loop. We thus present a novel enantioselective binding substrate for antiparallel basket G-quadruplexes, with features that make it a useful tool for quadruplex studies.
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Five-year follow-up of modified implant-supported overdenture in an iliac crest autograft failure: clinical report.
J Craniofac Surg
PUBLISHED: 09-17-2013
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The treatment of extensive pathologic lesions in the jaw, most of the time, can generate rehabilitation problems to the patient. The solid ameloblastoma is a locally invasive odontogenic tumor with a high recurrence rate. Its treatment is aggressive and accomplished through resection with safety margin. The criterion standard for reconstruction is autogenous bone, but it can provide a high degree of resorption, causing inconvenience to the patient because of lack of rehabilitative option. This study aimed to describe a patient with ameloblastoma treated through resection and reconstruction with autogenous bone graft, in which, after an extensive resorption of the graft was made, a modified bar was applied to support a prosthetic implant overdenture.
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Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.
Brain
PUBLISHED: 09-06-2013
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Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.
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Increased halide recognition strength by enhanced intercomponent preorganisation in triazolium containing [2]rotaxanes.
Chemistry
PUBLISHED: 08-07-2013
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Three triazolium-based [2]rotaxanes containing different sized axle and macrocycle components were synthesised in good yields (40-57?%) through chloride anion templation. The anion recognition properties of the interlocked receptor systems were investigated using (1) H?NMR titration experiments: all three rotaxanes display impressive selectivities for halide anions over the more basic oxoanion acetate. The rotaxanes incorporating shorter, more rigid axle components with aryl-substituted triazolium groups display substantially higher anion binding affinities than those with longer, bis-alkyl-substituted heterocycles, which is attributed to the increased intercomponent preorganisation afforded by the smaller axle component. Computational DFT and molecular dynamics simulations composed of unconstrained and umbrella sampling simulations corroborate the experimental observations.
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The therapeutical potential of a novel pterocarpanquinone LQB-118 to target inhibitor of apoptosis proteins in acute myeloid leukemia cells.
Anticancer Agents Med Chem
PUBLISHED: 08-06-2013
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Acute myeloid leukemia (AML) is a challenging neoplasm that despite therapeutic advances requires efforts to overcome the multidrug resistance (MDR) phenotype, the major cause of relapse. The pterocarpanquinone LQB-118 is a new compound that induces apoptosis in leukemia cells. The objective of this work was to analyze the role of LQB-118 in inhibiting the inhibitor of apoptosis proteins (IAPs), XIAP and survivin, as well as in modulating the subcellular localization of NF?B, in comparison with idarubicin. LQB- 118 was more effective in inducing apoptosis than idarubicin in both AML Kasumi-1 cell line and cells from patients despite their MDR phenotype. LQB-118-induced apoptosis was accompanied by a marked inhibition of IAPs, and cytoplasmatic NF?B subcellular localization. On the other hand, idarubicin increased the IAPs expression and translocated NF?B to the nucleus. The inhibition profile of survivin induced by LQB-118 was comparable to the survivin inhibition profile when we investigated the efficiency of survivin-small interfering RNA (siRNA) treatment. LQB-118 as well as survivin-siRNA contributed similarly to the increase in apoptosis rate of Kasumi-1 cells. The data indicated that there is a functional interaction between the survivin, XIAP and NF?B, which appears to be involved in idarubicin resistance of Kasumi-1 cells. The efficacy of LQB-118 to induce cell death through inhibiting survivin suggests that this IAP may be involved in the chemoresistance phenotype in AML cells. Our findings suggest that LQB-118 might be a promising therapeutic approach for AML patients through survivin downregulation.
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Coronary computed tomography angiography with 320-row detector and using the AIDR-3D: initial experience.
Einstein (Sao Paulo)
PUBLISHED: 07-05-2013
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Coronary computed tomography angiography (coronary CTA) is a powerful non-invasive imaging method to evaluate coronary artery disease. Nowadays, coronary CTA estimated effective radiation dose can be dramatically reduced using state-of-the-art scanners, such as 320-row detector CT (320-CT), without changing coronary CTA diagnostic accuracy. To optimize and further reduce the radiation dose, new iterative reconstruction algorithms were released recently by several CT manufacturers, and now they are used routinely in coronary CTA. This paper presents our first experience using coronary CTA with 320-CT and the Adaptive Iterative Dose Reduction 3D (AIDR-3D). In addition, we describe the current indications for coronary CTA in our practice as well as the acquisition standard protocols and protocols related to CT application for radiation dose reduction. In conclusion, coronary CTA radiation dose can be dramatically reduced following the "as low as reasonable achievable" principle by combination of exam indication and well-documented technics for radiation dose reduction, such as beta blockers, low-kV, and also the newest iterative dose reduction software as AIDR-3D.
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The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas.
Diagn Pathol
PUBLISHED: 07-02-2013
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Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors.
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Quinolone-resistant Escherichia coli isolated from birds of prey in Portugal are genetically distinct from those isolated from water environments and gulls in Portugal, Spain and Sweden.
Environ. Microbiol.
PUBLISHED: 06-05-2013
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The influence of geographic distribution and type of habitat on the molecular epidemiology of ciprofloxacin resistant Escherichia coli was investigated. Ciprofloxacin resistant E. coli from wastewater, urban water with faecal contamination and faeces of gulls, pigeons and birds of prey, from Portugal, Spain and Sweden were compared based on multi-locus sequence typing (MLST) and quinolone resistance genetic determinants. Multi-locus sequence typing allowed the differentiation of E. coli lineages associated with birds of prey from those inhabiting gulls and waters. E. coli lineages of clinical relevance, such as the complex ST131, were detected in wastewater, streams and gulls in Portugal, Spain and Sweden. Quinolone resistance was due to gyrA and parC mutations, although distinct mutations were detected in birds of prey and in wastewater, streams and gulls isolates. These differences were correlated with specific MLST lineages, suggesting resistance inheritance. Among the plasmid-mediated quinolone resistance genes, only aac(6)-ib-cr and qnrS were detected in wastewater, streams and gulls isolates, but not in birds of prey. The horizontal transfer of the gene aac(6)-ib-cr could be inferred from its occurrence in different MLST lineages.
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Expression of the mevalonate pathway enzymes in the Lutzomyia longipalpis (Diptera: Psychodidae) sex pheromone gland demonstrated by an integrated proteomic approach.
J Proteomics
PUBLISHED: 06-02-2013
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In Latin America, Lutzomyia longipalpis is the main vector of the protozoan parasite Leishmania infantum, which is the causal agent of American Visceral Leishmaniasis. This insect uses male-produced pheromones for mate recognition. Elucidation of pheromone biogenesis or its regulation may enable molecular strategies for mating disruption and, consequently, the vectors population management. Motivated by our recent results of the transcriptomic characterization of the L. longipalpis pheromone gland, we performed a proteomic analysis of this tissue combining SDS-PAGE, and mass spectrometry followed by an integrative data analysis. Considering that annotated genome sequences of this sand fly are not available, we designed an alternative workflow searching MS/MS data against two customized databases using three search engines: Mascot, OMSSA and ProLuCID. A total of 542 proteins were confidently characterized, 445 of them using a Uniref100-insect protein database, and 97 using a transcript translated database. In addition, use of PEAKS for de novo peptide sequencing of MS/MS data confirmed ~90% identifications made with the combination of the three search engines. Our results include the identification of six of the seven enzymes of the mevalonate-pathway, plus the enzymes involved in sesquiterpenoid biosynthesis, all of which are proposed to be involved in pheromone production in L. longipalpis.
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MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia.
J. Bacteriol.
PUBLISHED: 05-31-2013
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Burkholderia cenocepacia J2315 is a highly epidemic and transmissible clinical isolate of the Burkholderia cepacia complex (Bcc), a group of bacteria causing life-threatening respiratory infections among cystic fibrosis patients. This work describes the functional analysis of the 136-nucleotide (nt)-long MtvR small noncoding RNA (sRNA) from the Bcc member B. cenocepacia J2315, with homologues restricted to the genus Burkholderia. Bioinformatic target predictions revealed a total of 309 mRNAs to be putative MtvR targets. The mRNA levels corresponding to 17 of 19 selected genes were found to be affected when MtvR was either overexpressed or silenced. Analysis of the interaction between MtvR and the hfq mRNA, one of its targets, showed that the sRNA binds exclusively to the 5 untranslated region (UTR) of the hfq mRNA. This interaction resulted in decreased protein synthesis, suggesting a negative regulatory effect of MtvR on the RNA chaperone Hfq. Bacterial strains with MtvR silenced or overexpressed exhibited pleiotropic phenotypes related to growth and survival after several stresses, swimming and swarming motilities, biofilm formation, resistance to antibiotics, and ability to colonize and kill the nematode Caenorhabditis elegans. Together, the results indicate that the MtvR sRNA is a major posttranscriptional regulator in B. cenocepacia.
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The pterocarpanquinone LQB 118 induces apoptosis in tumor cells through the intrinsic pathway and the endoplasmic reticulum stress pathway.
Anticancer Drugs
PUBLISHED: 05-10-2013
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LQB 118 is a pterocarpanquinone compound synthesized by our group. It has already been shown that it acts against different leukemia cell lines. However, little is known about the pathway through which this compound induces the death of these cells. In this work, we analyzed the cell death process induced by LQB 118 in K562, a chronic myeloid leukemia cell line, and in Jurkat, a lymphoblastic acute leukemia cell line. For this, we carried out a cell viability assay by MTT, an apoptosis/necrosis assay through the annexin/propidium iodide label, cell cycle by flow cytometry, assessed changes in the mitochondrial membrane potential using DiOC6(3), cytoplasmic calcium analysis by Fluo-3-AM, and a caspase-9 and caspase-12 activity assay. We found that LQB 118 induced apoptosis in both cell lines, measuring caspase-12 and caspase-9 activation, phosphatidylserine externalization, and DNA fragmentation. The compound induced an increase in cytoplasmic calcium on both cell lines. However, the compound could only induce mitochondrial membrane depolarization on K562 cells. Our data show that LQB 118 may have potential therapeutic value for leukemia, being able to overcome multiple resistance mechanisms.
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Morphologic evaluation of the fetal recurrent laryngeal nerve and motor units in the thyroarytenoid muscle.
J Voice
PUBLISHED: 04-27-2013
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This study is a morphologic description of the recurrent laryngeal nerve (RLN) and of the number and size of motor units (MUs) in the thyroarytenoid (TA) muscle bilaterally of a human fetus aged 25 weeks. A quantitative analysis of RLN and MUs is presented to investigate similarities with equivalent structures in adults. In the fetus used in our study, the morphologic organization of the RLN was similar to that commonly described in the adult RLN. Moreover, as is observed in adult TA, the TA of the analyzed fetus, particularly the right TA, showed MUs typical of muscles with great motor accuracy. These results may be used to increase our knowledge of the features of the voice in adults and newborns.
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Critical evaluation of justifications for the transfusion of red blood cells: the reality of a government emergency hospital.
Rev Bras Hematol Hemoter
PUBLISHED: 04-17-2013
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Blood products and derivatives are indispensable resources in medical therapies. However, it is important to note that the number of donations is far from ideal. Despite constant campaign efforts, a deficit of 1 million units is expected by 2030.
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Reproducibility in nerve morphometry: comparison between methods and among observers.
Biomed Res Int
PUBLISHED: 04-13-2013
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We investigated the reproducibility of a semiautomated method (computerized with manual intervention) for nerve morphometry (counting and measuring myelinated fibers) between three observers with different levels of expertise and experience with the method. Comparisons between automatic (fully computerized) and semiautomated morphometric methods performed by the same computer software using the same nerve images were also performed. Sural nerves of normal adult rats were used. Automatic and semiautomated morphometry of the myelinated fibers were made through the computer software KS-400. Semiautomated morphometry was conducted by three independent observers on the same images, using the semiautomated method. Automatic morphometry overestimated the myelin sheath area, thus overestimating the myelinated fiber size and underestimating the axon size. Fiber distributions overestimation was of 0.5? ? m. For the semiautomated morphometry, no differences were found between observers for myelinated fiber and axon size distributions. Overestimation of the myelin sheath size of normal fibers by the fully automatic method might have an impact when morphometry is used for diagnostic purposes. We suggest that not only semiautomated morphometry results can be compared between different centers in clinical trials but it can also be performed by more than one investigator in one single experiment, being a reliable and reproducible method.
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Effects of processing and storage on Pediococcus pentosaceus SB83 in vaginal formulations: lyophilized powder and tablets.
Biomed Res Int
PUBLISHED: 04-05-2013
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Vaginal probiotics have an important role in preventing the colonization of the vagina by pathogens. This study aimed to investigate different formulations with Pediococcus pentosaceus SB83 (lyophilized powder and tablets with and without retarding polymer) in order to verify its stability and antilisterial activity after manufacture and during storage. The bacteriocinogenic activity of P. pentosaceus SB83 against Listeria monocytogenes was evaluated in simulated vaginal fluid. Suspension of Pediococcus pentosaceus SB83 reduced the pathogen only after 2 h and the lyophilized bacteria after 24 h of contact, and, in the tablets, P. pentosaceus SB83 lost the antimicrobial activity. The pH of simulated vaginal fluid decreased for all the tested conditions. As lyophilized powder demonstrated better results concerning antimicrobial activity, this formulation was selected to evaluate the antilisterial activity during the 12 months of storage. During storage at room temperature, lyophilized bacteria totally inhibited the pathogen only until one month of storage. At 4°C, P. pentosaceus SB83 showed antimicrobial activity during all the time of storage investigated. Therefore, the better formulation of P. pentosaceus SB83 is the lyophilized powder stored at 4°C, which may be administered intravaginally as a washing solution.
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Evaluation of coumarin and neoflavone derivatives as HCV NS5B polymerase inhibitors.
Chem Biol Drug Des
PUBLISHED: 04-04-2013
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Coumarins and coumestans represent an important family of compounds with diverse pharmacological properties. We recently identified coumestans as novel inhibitors of hepatitis C virus NS5B polymerase and predicted their binding in thumb pocket-1 (TP-1) of NS5B. As the coumarins are structurally related to coumestans by virtue of their common A- and B-rings, we postulated them to also exhibit similar binding interaction with NS5B and inhibit its polymerase function. We therefore investigated 24 coumarin and neoflavone derivatives as candidate NS5B inhibitors and identified 14 compounds inhibiting NS5B polymerase activity with IC50 values between 17 and 63 ?m. Of these, the newly synthesized 6,8-diallyl-5,7-dihydroxycoumarin (8a) was produced in three steps in high chemical yield from floroglucinol and found to be the most potent of this series, exhibiting activity similar to the reference coumestan LQB-34. The binding site of 8a was mapped to TP-1 of NS5B by counter screening against P495L NS5B mutant, employed as a screen for TP-1 site binders. NS5B-TP-1-8a interaction map provided insight into 8a binding and offered clues for future SAR optimization.
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HI-bone: a scoring system for identifying phenylisothiocyanate-derivatized peptides based on precursor mass and high intensity fragment ions.
Anal. Chem.
PUBLISHED: 03-20-2013
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Peptide sequence matching algorithms used for peptide identification by tandem mass spectrometry (MS/MS) enumerate theoretical peptides from the database, predict their fragment ions, and match them to the experimental MS/MS spectra. Here, we present an approach for scoring MS/MS identifications based on the high mass accuracy matching of precursor ions, the identification of a high intensity b1 fragment ion, and partial sequence tags from phenylthiocarbamoyl-derivatized peptides. This derivatization process boosts the b1 fragment ion signal, which turns it into a powerful feature for peptide identification. We demonstrate the effectiveness of our scoring system by implementing it on a computational tool called "HI-bone" and by identifying mass spectra of an Escherichia coli sample acquired on an Orbitrap Velos instrument using Higher-energy C-trap dissociation. Following this strategy, we identified 1614 peptide spectrum matches with a peptide false discovery rate (FDR) below 1%. These results were significantly higher than those from Mascot and SEQUEST using a similar FDR.
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Interaction of a calix[4]arene derivative with a DOPC bilayer: Biomolecular simulations towards chloride transport.
Biochim. Biophys. Acta
PUBLISHED: 03-01-2013
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The ability of a calix[4]arene derivative (CX-1), bearing four protonated NH3(+) groups located in the upper rim and aliphatic tails in the lower rim, to interact with a 1,2-dioleoyl-sn-glycero-3-phosphorylcholine (DOPC) model bilayer and promote transmembrane chloride transport was investigated by molecular dynamics (MD) simulations. Unconstrained MD simulations show that the interaction of CX-1 with DOPC occurs via the NH3(+) groups, which are able to establish electrostatic interactions and multiple hydrogen bonds with the DOPC phosphate groups, while the aliphatic tails point towards the water phase (when CX-1 starts from the water phase) or to the membrane (when CX-1 is initially positioned within the bilayer). The interaction does not induce any relevant perturbation on the biophysical properties of the bilayer system (area per lipid, thickness, and hydration) apart from a systematic increase in the order parameter of the C2 carbon atom of the sn-1 lipid tail, meaning that the bilayer conserves its integrity. Since total internalization of CX-1 was not observed in the unconstrained MD time-scale, constant velocity steered molecular dynamics (SMD) simulations were performed in order to simulate the CX-1 permeation across the bilayer and at pulling velocities lower than 0.0075nmps(-1), chloride transport was observed. The Potential of Mean Force (PMF), calculated with the weighted histogram analysis method, indicates a barrier of ca. 58kJmol(-1) for this mobile carrier to cross the membrane.
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Anthracyclines induce DNA damage response-mediated protection against severe sepsis.
Immunity
PUBLISHED: 02-22-2013
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Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fancony Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis.
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Common phenotypic and genotypic antimicrobial resistance patterns found in a case study of multiresistant E. coli from cohabitant pets, humans, and household surfaces.
J Environ Health
PUBLISHED: 02-13-2013
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The objective of the study described in this article was to characterize the antimicrobial resistance profiles among E. coli strains isolated from cohabitant pets and humans, evaluating the concurrent colonization of pets, owners, and home surfaces by bacteria carrying the same antimicrobial-resistant genes. The authors also intended to assess whether household surfaces and objects could contribute to the within-household antimicrobial-resistant gene diffusion between human and animal cohabitants. A total of 124 E. coli strains were isolated displaying 24 different phenotypic patterns with a remarkable percentage of multiresistant ones. The same resistance patterns were isolated from the dogs urine, mouth, the laundry floor, the refrigerator door, and the dogs food bowl. Some other multiresistant phenotypes, as long as resistant genes, were found repeatedly in different inhabitants and surfaces of the house. Direct, close contact between all the cohabitants and the touch of contaminated household surfaces and objects could be an explanation for these observations.
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Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox.
Life Sci.
PUBLISHED: 02-12-2013
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Diabetes mellitus (DM) is a chronic metabolic disease characterized by the presence of hyperglycemia, which can lead to many complications over time. These complications, such as nephropathy, retinopathy, neuropathy, impaired wound healing and accelerated atherosclerosis, are implicated with a large number of cellular and subcellular changes on vessels. In agreement, evidence indicates that in retinopathy, nephropathy and atherosclerotic plaque, there is excessive angiogenesis, whereas in wound healing and myocardial perfusion, blood vessel growth is impaired. Despite the awareness of this angiogenic paradox, many questions remain unanswered. This review aims at highlighting the different microvascular and macrovascular complications that are often concurrent in diabetic patients. A revision of the recent findings published in the literature regarding the angiogenic paradox will be performed. Apparently, endothelial dysfunction, as well as molecules such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) play a major role in diabetic vascular complications. Specific tissues with impaired angiogenesis exhibit microenvironment features, such as increased PAI-1/uPA ratio and decreased blood flow, whereas TGFbeta increases extracellular matrix deposition, preventing the vascularization process. In addition, the monocytes/macrophages are important in endothelium activation for arteriogenesis and its arteriogenic response is reduced, leading to impaired collateral artery growth. Moreover, molecular mechanisms involved will be addressed, including abnormalities in growth factor, cytokines and metabolic derangements.
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Topical cyclosporine for severe dry eye disease in liver-transplanted Portuguese patients with familial amyloidotic polyneuropathy (ATTRV30M).
Eur J Ophthalmol
PUBLISHED: 02-11-2013
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PURPOSE. Evaluation of the use of topical cyclosporine eyedrops in the treatment of severe dry eye disease in liver transplanted patients with familial amyloidotic polyneuropathy (FAP) unresponsive to therapy with artificial tears and lacrimal plugs.
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Development of diagnostic methods and study of the immunoreactivity of a mixture of recombinant core and E2 proteins fused to GST with control serum positive for hepatitis C.
Talanta
PUBLISHED: 02-04-2013
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The hepatitis C virus (HCV) is an enveloped virus that is about 50-70 nm in diameter, has positive-strand RNA, and belongs to the genus Hepacivirus and the family Flaviridae. The detection and quantification of the core antigen, HCV nucleocapsid protein, has been successful in many trials and is considered a marker of viral replication since it presents a sequence of highly conserved amino acids, giving it high sensitivity and specificity. The E2 protein is an envelope glycoprotein of HCV with 11 glycosylation sites; most of these are well-conserved, making it a target antigen. The aim of this study is to develop high-sensitivity, low-cost diagnostic methods for HCV, which could be used for serological screening. The genomic regions encoding the core (part 136 aa) and E2 proteins of HCV were expressed in Escherichia coli Rosetta strain, cloned in expression vector pET-42a, and induced with 0.4 m mol L(-1) IPTG, producing recombinant proteins that were fused to glutathione S-transferase (GST) protein, which was then purified by affinity chromatography. The immunoreactivity was assessed by Western blot, Slot Blot, and developed and improved diagnostic methods (capture, indirect, and immunoblotting enzyme-linked immunosorbent assay (ELISA)). After applying the results to the formulas for determining the quality parameters, obtained for immunoblotting method 100% sensitivity and specificity and for ELISA 100% sensitivity and 87.5% specificity. The methods developed were more sensitive and specific using the mixture of the recombinant proteins fused to GST (core+E2).
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CD44/CD24 immunophenotypes on clinicopathologic features of salivary glands malignant neoplasms.
Diagn Pathol
PUBLISHED: 02-04-2013
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Salivary glands malignant neoplasms (SGMNs) account for 3-6% of head and neck cancers and 0.3% of all cancers. Tumor cells that express CD44 and CD24 exhibit a stem-cell-like behavior. CD44 is the binding site for hyaluronic acid, and CD24 is a receptor that interacts with P-selectin to induce metastasis and tumor progression. The present study aims to evaluate the expression of CD44 and CD24 on SGMNs and correlated these data with several clinicopathologic features.
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Optimization of a surfactant-free antioxidant formulation using response surface methodology.
Drug Dev Ind Pharm
PUBLISHED: 01-22-2013
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Abstract Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet radiation-mediated oxidative damage. In previous studies, a Castanea sativa leaf ethanol:water (7:3) extract exhibited scavenging activity against different reactive oxygen species that are thought to contribute to oxidative damage in the skin. Its stability was shown to be enhanced in the presence of glycerine, and therefore a glycerine-based formulation with Carbopol 940 and liquid paraffin (LP) was developed as base. In this work, the influence of the glycerine and LP contents on the textural properties of the topical base and on the antioxidant activity of the formulation with C. sativa extract was evaluated using response surface methodology after 30?d storage at 20?°C and 40?°C. The textural analysis was performed in a texturometer, by carrying out a spreadability test. Paretto charts showed that both glycerine and LP contents significantly influenced the textural properties of the formulations (p?
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Clinical and economic impact of remote monitoring on the follow-up of patients with implantable electronic cardiovascular devices: an observational study.
Telemed J E Health
PUBLISHED: 01-21-2013
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Traditional follow-up of patients with cardiovascular devices is still an activity that, in addition to serving an increasing population, requires a considerable amount of time and specialized human and technical resources. Our aim was to evaluate the applicability of the CareLink(®) (Medtronic, Minneapolis, MN) remote monitoring system as a complementary option to the follow-up of patients with implanted devices, between in-office visits. Evaluated outcomes included both clinical (event detection and time to diagnosis) and nonclinical (patients satisfaction and economic costs) aspects. An observational, longitudinal, prospective study was conducted with patients from a Portuguese central hospital sampled by convenience during 1 week (43 patients). Data were collected in four moments: two in-office visits and two remote evaluations, reproducing 1 year of clinical follow-up. Data sources included health records, implant reports, initial demographic data collection, follow-up printouts, and a questionnaire. After selection criteria were verified, 15 patients (11 men [73%]) were included, 63.4±10.8 years old, representing 14.0±6.3 implant months. Clinically, 15 events were detected (9 by remote monitoring and 6 by patient-initiated activation), of which only 9 were symptomatic. We verified that remote monitoring could detect both symptomatic and asymptomatic events, whereas patient-initiated activation only detected symptomatic ones (p=0.028). Moreover, the mean diagnosis anticipation in patients with events was approximately 58 days (p<0.001). In nonclinical terms, we observed high or very high satisfaction (67% and 33%, respectively) with using remote monitoring technology, but still 8 patients (53%) stated they preferred in-office visits. Finally, the introduction of remote monitoring technology has the ability to reduce total follow-up costs for patients by 25%. We conclude that the use of this system constitutes a viable complementary option to the follow-up of patients with implantable devices, between in-office visits.
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Transfer of multidrug-resistant bacteria between intermingled ecological niches: the interface between humans, animals and the environment.
Int J Environ Res Public Health
PUBLISHED: 01-09-2013
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The use of antimicrobial agents has been claimed to be the driving force for the emergence and spread of microbial resistance. However, several studies have reported the presence of multidrug-resistant bacteria in populations exposed to low levels of antimicrobial drugs or even never exposed. For many pathogens, especially those organisms for which asymptomatic colonization typically precedes infection (e.g., Enterococcus spp. and Escherichia coli), the selective effects of antimicrobial use can only be understood if we considerer all biological and environmental pathways which enable these bacteria, and the genes they carry, to spread between different biomes. This ecological framework provides an essential perspective for formulating antimicrobial use policies, precisely because it encompasses the root causes of these problems rather than merely their consequences.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.