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The prediction of plasma and brain levels of 2,3,5,6-tetramethylpyrazine following transdermal application

Qi, Xiaohong; Ackermann, Chrisita; Sun, Duxin; Liu, Rong (Ron); Sheng, Minli; Hou, Huimin
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em 13/12/2002 Português
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The purpose of this study was to construct a pharmacokinetic (PK) model and to determine PK parameters of 2,3,5,6-tetramethylpyrazine (TMP) after application of TMP transdermal delivery system. Data were obtained in Sprague-Dawley (SD) rats following a single dose of TMP transdermal delivery system. Blood samples were obtained at 0, 0.25, 0.5, 1, 2, 4, 6, 16, and 24 hours after the transdermal application. In the brain level study, 18 SD rats were divided into 6 groups. Three SD rats before and after transdermal application were culled and sacrificed at each of the following time intervals: 2, 4, 6, 16, and 24 hours after the TMP-TTS application. TMP concentrations in plasma and brain tissues were determined using high performance liquid chromatography and data were fitted using a zero-order absorption and a firstorder-elimination 3-compartment PK model. Fitted parameters included 2 volumes of distribution (V1, V2) and 2 elimination rate constants (k10, k20). The elimination half-life for TMP in plasma and brain was 26.5 and 31.2 minutes, respectively. The proposed PK model fit observed concentrations of TMP very well. This model is useful for predicting drug concentrations in plasma and brain and for assisting in the development of transdermal systems.

Evaluation of Subepithelial Abnormalities of the Appendix by Endoscopic Ultrasound

Uradomo, Lance T.; Darwin, Peter E.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
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Background. The use of through-the-scope (TTS) miniprobe catheter endoscopic ultrasound is a valuable technique for evaluating subepithelial lesions in the proximal colon. Few reports include the evaluation of the appendix by EUS. Objective. To describe endoscopic and endosonographic characteristics of subepithelial lesions of the appendix. Methods. Retrospective case series in a single academic medical center. Adult patients referred for evaluation of subepithelial lesions of the appendix identified by colonoscopy between April 1, 2003 to February 29, 2008. Data were abstracted from an electronic endoscopic database for all patients undergoing miniprobe endoscopic ultrasound examination of the appendix. Medical records were reviewed for patient followup and outcomes. Results. Nine cases were identified. Seven (78%) patients were female. Seven (78%) utilized the 12 MHz miniprobe device and two (22%) used the 20 MHz device. Three mucoceles were described and confirmed by surgical resection. Cases also included one inverted appendix, one gastrointestinal stromal tumor, and one lipoma. In three cases, no abnormality was found. Conclusions. EUS evaluation of the appendix is feasible with standard miniprobe devices and may assist in the selection of patients who may benefit from surgical management.

TTS Mapping: integrative WEB tool for analysis of triplex formation target DNA Sequences, G-quadruplets and non-protein coding regulatory DNA elements in the human genome

Jenjaroenpun, Piroon; Kuznetsov, Vladimir A
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 03/12/2009 Português
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Tetracycline transcriptional silencer (tTS) tightly controls transgene expression in the skeletal muscle: in vivo intramuscular IL-10 DNA electrotransfer application to arthritis

Perez, N; Plence, P; Millet, V; Minot, C; Noël, D; Danos, O; Jorgensen, C; Apparailly, F
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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Monte Carlo Simulation Study on the Time Resolution of a PMT-Quadrant-Sharing LSO Detector Block for Time-of-Flight PET

Liu, Shitao; Li, Hongdi; Zhang, Yuxuan; Ramirez, Rocio A.; Baghaei, Hossain; An, Shaohui; Wang, Chao; Liu, Jiguo; Wong, Wai-Hoi
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
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We developed a detailed Monte Carlo simulation method to study the time resolution of detectors for time-of-flight positron emission tomography (TOF PET). The process of gamma ray interaction in detectors, scintillation light emission and transport inside the detectors, the photoelectron generation and anode signal generation in the photomultiplier tube (PMT), and the electronics process of discriminator are simulated. We tested this simulation method using published experimental data, and found that it can generate reliable results. Using this method, we simulated the time resolution for a 13 × 13 detector block of 4 × 4 × 20 mm3 lutetium orthosilicate (LSO) crystals coupled to four 2-inch PMTs using PMT-quadrant-sharing (PQS) technology. We analyzed the effects of several factors, including the number of photoelectrons, light transport, transit time spread (TTS), and the depth of interaction (DOI). The simulation results indicated that system time resolution of 360 ps should be possible with currently available fast PMTs. This simulation method can also be used to simulate the time resolution of other detector design method.

FAST (Flexible Accelerated STOP TetO-knockin): a versatile and efficient new gene modulating system

Tanaka, Kenji F.; Ahmari, Susanne E.; Leonardo, E. David; Richardson-Jones, Jesse W.; Budreck, Elaine C.; Scheiffele, Peter; Sugio, Shouta; Inamura, Naoko; Ikenaka, Kazuhiro; Hen, René
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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We created the FAST (Flexible Accelerated STOP TetO-knockin) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. A single gene targeting event yields 2 distinct knockin mice –STOP-tetO and tetO knockin– which permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue; 3) tTA-mediated misexpression; 4) tTA-mediated overexpression; and 5) tTS-mediated conditional knockout/knockdown. Using the FAST system, multiple gain- and loss-of-function strains can therefore be generated on a timescale not previously achievable. These strains can then be screened for clinically-relevant abnormalities. We demonstrate the flexibility and broad applicability of the FAST system by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, Neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

Discovery of Novel Secreted Virulence Factors from Salmonella enterica Serovar Typhimurium by Proteomic Analysis of Culture Supernatants ▿ #

Niemann, George S.; Brown, Roslyn N.; Gustin, Jean K.; Stufkens, Afke; Shaikh-Kidwai, Afshan S.; Li, Jie; McDermott, Jason E.; Brewer, Heather M.; Schepmoes, Athena; Smith, Richard D.; Adkins, Joshua N.; Heffron, Fred
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
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Salmonella enterica serovar Typhimurium is a leading cause of acute gastroenteritis throughout the world. This pathogen has two type III secretion systems (TTSS) encoded in Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) that deliver virulence factors (effectors) to the host cell cytoplasm and are required for virulence. While many effectors have been identified and at least partially characterized, the full repertoire of effectors has not been catalogued. In this proteomic study, we identified effector proteins secreted into defined minimal medium designed to induce expression of the SPI-2 TTSS and its effectors. We compared the secretomes of the parent strain to those of strains missing essential (ssaK::cat) or regulatory (ΔssaL) components of the SPI-2 TTSS. We identified 20 known SPI-2 effectors. Excluding the translocon components SseBCD, all SPI-2 effectors were biased for identification in the ΔssaL mutant, substantiating the regulatory role of SsaL in TTS. To identify novel effector proteins, we coupled our secretome data with a machine learning algorithm (SIEVE, SVM-based identification and evaluation of virulence effectors) and selected 12 candidate proteins for further characterization. Using CyaA′ reporter fusions...

Genome-Wide Mapping of DNA Methylation in Chicken

Li, Qinghe; Li, Ning; Hu, Xiaoxiang; Li, Jinxiu; Du, Zhuo; Chen, Li; Yin, Guangliang; Duan, Jinjie; Zhang, Haichao; Zhao, Yaofeng; Wang, Jun; Li, Ning
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 05/05/2011 Português
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Cytosine DNA methylation is an important epigenetic modification termed as the fifth base that functions in diverse processes. Till now, the genome-wide DNA methylation maps of many organisms has been reported, such as human, Arabidopsis, rice and silkworm, but the methylation pattern of bird remains rarely studied. Here we show the genome-wide DNA methylation map of bird, using the chicken as a model organism and an immunocapturing approach followed by high-throughput sequencing. In both of the red jungle fowl and the avian broiler, DNA methylation was described separately for the liver and muscle tissue. Generally, chicken displays analogous methylation pattern with that of animals and plants. DNA methylation is enriched in the gene body regions and the repetitive sequences, and depleted in the transcription start site (TSS) and the transcription termination site (TTS). Most of the CpG islands in the chicken genome are kept in unmethylated state. Promoter methylation is negatively correlated with the gene expression level, indicating its suppressive role in regulating gene transcription. This work contributes to our understanding of epigenetics in birds.

Structural Instability Tuning as a Regulatory Mechanism in Protein-Protein Interactions

Chen, Li; Balabanidou, Vassilia; Remeta, David P.; Minetti, Conceição A.S.A.; Portaliou, Athina G.; Economou, Anastassios; Kalodimos, Charalampos G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 09/12/2011 Português
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Protein-protein interactions mediate a vast number of cellular processes. Here we present a regulatory mechanism in protein-protein interactions mediated by finely-tuned structural instability coupled with molecular mimicry. We show that a set of type III secretion (TTS) autoinhibited homodimeric chaperones adopt a molten-globule-like state that transiently exposes the substrate binding site as a means to become rapidly poised for binding to their cognate protein substrates. Packing defects at the homodimeric interface stimulate binding whereas correction of these defects results in less labile chaperones that give rise to non-functional biological systems. The protein substrates use structural mimicry to offset the “weak spots” in the chaperones and to counteract their autoinhibitory conformation. This regulatory mechanism of protein activity is evolutionary conserved among several TSS systems and presents a lucid example of functional advantage conferred upon a biological system by finely-tuned structural instability.

Heme Reactivity is Uncoupled from Quaternary Structure in Gel-encapsulated Hemoglobin: A Resonance Raman Spectroscopic Study

Jones, Eric M.; Balakrishnan, Gurusamy; Spiro, Thomas G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Encapsulation of hemoglobin (Hb) in silica gel preserves structure and function, but greatly slows protein motion, thereby providing access to intermediates along the allosteric pathway that are inaccessible in solution. Resonance Raman (RR) spectroscopy with visible and ultraviolet laser excitation provides probes of heme reactivity and of key tertiary and quaternary contacts. These probes were monitored in gels after deoxygenation of oxyHb and after CO binding to deoxyHb, which intiate conformational change in the R-T and T-R directions, respectively. The spectra establish that quaternary structure change in the gel takes a week or more, but that the evolution of heme reactivity, as monitored by the Fe-histidine stretching vibration, νFeHis, is completed within two days, and is therefore uncoupled from the quaternary structure. Within each quaternary structure, the evolving νFeHis frequencies span the full range of values between those previously associated with the high- and low-affinity end states, R and T. This result supports the tertiary two-state (TTS) model, in which the Hb subunits can adopt high- and low-affinity tertiary structures, r and t, within each quaternary state. The spectra also reveal different tertiary pathways...

Interventional balloon-enteroscopy

Albert, Jörg G
Fonte: Landes Bioscience Publicador: Landes Bioscience
Tipo: Artigo de Revista Científica
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Balloon assisted enteroscopy (BE) expands greatly the therapeutic options in interventional endoscopy; bleeding sites, strictures, polyps, and other small bowel lesions are increasingly been treated by use of BE in the last 10 years. Treatment options for small bowel bleeding include Argon plasma coagulation (APC), injection therapy, and application of TTS metal clips, and thereby bleeding is stopped in most cases. Dilating symptomatic strictures, resecting polyps as seen in Peutz-Jeghers syndrome (PJS), and removing foreign bodies, BE carries most endoscopic treatment techniques to the small bowel. Another new indication field for BE are interventions at the biliary system in patients with surgically modified anatomy such as Roux-Y anastomosis. This review offers a full overview on indications of BE and refers to the practical use of the method for all endoscopic interventions.

Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs

Dehmel, Susanne; Eisinger, Daniel; Shore, Susan E.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 31/05/2012 Português
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Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony...

Posttraumatic Parotid Fistula Treated with Transdermal Scopolamine: A Case Report

Pagliuca, Giulio; Martellucci, Salvatore; Rosato, Chiara; Gallipoli, Camilla; Gallo, Andrea
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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A parotid fistula is a rare and extremely unpleasant condition. In this paper, we present the case of a 53-year-old woman with a diagnosis of posttraumatic fistula of the parotid gland. After exclusion of other therapeutic alternatives, it was decided to use transdermal scopolamine patches at sustained release (Scopoderm TTS). This technique consists in the application every three days of a patch with 1.5 mg of scopolamine in the area of the mastoid apophysis; the patch releases a dose of 0.5 mg of the active substance over each 24-hour period. The patient underwent periodic clinical followup over a period of three years, achieving satisfactory results with no significant adverse effects.

A Fast MEANSHIFT Algorithm-Based Target Tracking System

Sun, Jian
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 13/06/2012 Português
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Tracking moving targets in complex scenes using an active video camera is a challenging task. Tracking accuracy and efficiency are two key yet generally incompatible aspects of a Target Tracking System (TTS). A compromise scheme will be studied in this paper. A fast mean-shift-based Target Tracking scheme is designed and realized, which is robust to partial occlusion and changes in object appearance. The physical simulation shows that the image signal processing speed is >50 frame/s.

Impulse noise trauma during army weapon firing

Munjal, K. R.; Singh, V. P.
Fonte: Springer India Publicador: Springer India
Tipo: Artigo de Revista Científica
Publicado em /04/1997 Português
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A 100 infanty personnel firing modern weapons such as the Anti Tank Guided Missile, 106mm Recoiless Gun (RCL), 84mm Rocket Launcher (RL) and 81mm Mortar were studied for the effect of impulse noise on the ear and the evolution of the Temporary Threshold Shift (TTS), Recovery Time (RT) and Permanent Threshold Shift (PTS) was traced.

Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/2012 Português
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Noise over-exposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus – possible basis for tinnitus-related hyperactivity?

Dehmel, Susanne; Pradhan, Shashwati; Koehler, Seth; Bledsoe, Sanford; Shore, Susan
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/02/2012 Português
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The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically-evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Zeng et al., 2009; Shore et al., 2008). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine if plastic changes in long lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically-evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift (TTS) in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions (RLFs). Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals...

Surgical resection of thalamic tumors: a report of four cases

Mohammadi, Hassan Reza; Azimi, Parisa
Fonte: Kermanshah University of Medical Sciences Publicador: Kermanshah University of Medical Sciences
Tipo: Artigo de Revista Científica
Publicado em /11/2012 Português
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Thalamic tumors (TTs) are rare which represent about 4% of all brain tumors.

The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor on Noise- Induced Hearing Loss

Pourbakht, Akram
Fonte: Mashhad University of Medical Sciences Publicador: Mashhad University of Medical Sciences
Tipo: Artigo de Revista Científica
Publicado em /05/2013 Português
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Objective(s): Noise-induced hearing loss (NIHL) is the major cause of acquired hearing loss. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, is a non- steroidal anti- inflammatory drug (NSAID) with known antioxidant and antineoplastic activity. Therefore, we monitored the extent of temporary noise- induced threshold shifts (TTS) and cochlear damage caused by high level 4- kHz noise exposure to verify the differences with those pretreated with celecoxib.

Performance of the Tourniquet Test for Diagnosing Dengue in Peru

Halsey, Eric S.; Vilcarromero, Stalin; Forshey, Brett M.; Rocha, Claudio; Bazan, Isabel; Stoddard, Steven T.; Kochel, Tadeusz J.; Casapia, Martin; Scott, Thomas W.; Morrison, Amy C.
Fonte: The American Society of Tropical Medicine and Hygiene Publicador: The American Society of Tropical Medicine and Hygiene
Tipo: Artigo de Revista Científica
Publicado em 10/07/2013 Português
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The tourniquet test (TT) is a physical examination maneuver often performed on patients suspected of having dengue. It has been incorporated into dengue diagnostic guidelines and is used in clinical studies. However, little is known about TT performance characteristics in different patient types or epidemiologic conditions. In the dengue-endemic city of Iquitos, Peru, we performed TTs and dengue laboratory assays on 13,548 persons with febrile disease, recruited through either active (n = 1,095) or passive (n = 12,453) surveillance. The sensitivity was 52% and 56%, the specificity was 58% and 68%, the positive predictive value was 45% and 55%, and the negative predictive value was 64% and 69% for persons enrolled in active and passive surveillance, respectively. We demonstrated that the TT was more sensitive identifying dengue disease in women and those of younger age and that sensitivity increased the later a person came to a medical clinic for care.