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Tissue Penetration (tissue + penetration)

Distribution by Scientific Domains

Medical Sciences	71%
Life Sciences	14%

Selected Abstracts

70 vs 120 W thulium:yttrium-aluminium-garnet 2 µm continuous-wave laser for the treatment of benign prostatic hyperplasia: a systematic ex-vivo evaluation

BJU INTERNATIONAL, Issue 3 2010
Thorsten Bach
Study Type , Aetiology (case series) Level of Evidence 4 OBJECTIVE To evaluate the ablative and haemostatic properties of the recently introduced 120-W thulium:yttrium-aluminium-garnet (Tm-YAG) laser and to assess these results against those of the previously introduced 70-W Tm-YAG laser. MATERIALS AND METHODS The ex-vivo model of the isolated blood-perfused porcine kidney was used to determine the ablation capacity, haemostatic properties and coagulation depth of a 2 µm continuous-wave Tm-YAG laser. The energy was delivered using a 550-µm and an 800-µm bare-ended fibre. The results of the recently introduced 120-W Tm-YAG were compared to the established 70-W device. Kidney tissue was embedded for histological evaluation. After staining (haematoxylin and eosin, H&E; and NADH) of the specimen, the coagulation zone and depth of the necrotic tissue layer were measured. RESULTS With increased power output, the mean (sd) rate of vaporization of tissue increased, from 9.80 (3.03) g/10 min at 70 W to 16.41 (5.2) g/10 min at 120 W using the 550 µm fibre. The total amount of ablated tissue using the 800 µm fibre was lower than with the 550 µm fibre. With increasing power output the bleeding rate remained stable in either group. Tissue penetration remained shallow, even with increasing power output. In contrast to H&E staining, where the coagulation zone was measured, NADH staining showed an inner zone of necrotic tissue, again with no difference between the 70- and the 120-W Tm-YAG. CONCLUSION The 120-W Tm-YAG offers significantly higher ablation rates than the 70-W device, and despite the increased rate of ablation with the 120-W Tm-YAG, the bleeding rate and depth of tissue penetration were comparable to those using the 70-W device. [source]

Localized delivery of growth factors for periodontal tissue regeneration: Role, strategies, and perspectives,

MEDICINAL RESEARCH REVIEWS, Issue 3 2009
Fa-Ming Chen
Abstract Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 3, 472-513, 2009 [source]

Organic anion-transporting polypeptide (OATP) transporter family and drug disposition

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2003
R. B. Kim
Abstract Drug transporters are increasingly recognized as a key determinant of drug disposition. Recent studies have revealed that targeted expression of drug uptake and efflux transporters to specific cell membrane domains allows for the efficient directional movement of many drugs in clinical use. While the role of certain efflux transporters such as MDR1 (P-glycoprotein) in drug disposition has been extensively studied, emerging evidence suggests that uptake transporters may also be important to the intestinal absorption and renal or hepatic elimination of drugs. Members of the organic anion-transporting polypeptide (OATP) family of drug uptake transporters have been found capable of transporting a large array of structurally divergent drugs. Moreover, expression of OATP isoforms in the gastrointestinal tract, liver and kidney, as well as at the level of the blood,brain barrier, has important implications for our understanding of the factors governing drug absorption, elimination and tissue penetration. [source]

Importance of P-glycoprotein for drug disposition in humans

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2003
M. F. Fromm
The ATP-binding cassette transporter P-glycoprotein is now recognized as an important determinant for disposition of multiple drugs. The use of P-glycoprotein-expressing cell lines, the generation of P-glycoprotein knockout mice as well as studies in animals and humans contributed to a better understanding on the role of active transport processes for drug disposition. P-glycoprotein is located in tissues with excretory function such as intestine, liver and kidney. Moreover, due to its expression in important blood,tissue barriers (blood,brain and blood,testis barriers), in lymphocytes and in placenta it limits tissue penetration of its substrates. Induction and inhibition of P-glycoprotein have now been identified as important underlying mechanisms of drug interactions in humans. Using selected examples, this review summarizes currently available data on the impact of P-glycoprotein for bioavailability of drugs, drug interactions and drug effects. [source]

Controlled Growth Factor Delivery for Tissue Engineering

ADVANCED MATERIALS, Issue 32-33 2009
Prakriti Tayalia
Abstract Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular. [source]

Functional and molecular MR imaging of angiogenesis: Seeing the target, seeing it work

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002
Michal NeemanArticle first published online: 16 JAN 200
Abstract Intensive research over the last years led to the discovery of multiple molecular pathways and intricate regulatory network controlling the growth and regression of blood vessels in general and angiogenesis in particular. The difficulties in elucidation of the regulation of angiogenesis, stems from the inherent complexity due to participation of many cell types, under a dominant impact of physiological and environmental effects of flow, perfusion, and oxygenation. Major advances were achieved with the use of sophisticated transgenic mice models engineered so as to provide spatially and temporally controlled expression of specific factors alone or in combination. In vivo analysis of these models frequently requires the use of non-invasive imaging modalities for measurement of functional parameters of the vasculature along with dynamic molecular information. Optical methods are extensively applied for the study of angiogenesis [Brown et al., 2001] but provide very limited tissue penetration. MRI offers the advantage of being non-invasive with uniform and relatively high spatial resolution for deep tissues. Multiple MRI approaches for monitoring angiogenesis were developed over the last years, each looking at a particular step in the process. The aim of this paper is to analyze the clinical, pharmaceutical, and biological needs for imaging of angiogenesis, and to critically evaluate the strengths and weaknesses of functional and molecular imaging for monitoring angiogenesis. The inherent problem of validation of different measures of angiogenesis, and the advantages and limitations associated with application of MRI based methods, as surrogates for other measurements of angiogenesis will be discussed. The terms molecular imaging and functional imaging are frequently loosely defined with a significant overlap between the two. For the sake of this paper we will apply a narrower definition of both terms, where molecular imaging will apply to methods directed towards detection of specific biological molecules that participate directly in (regulation of) a physiological process; while functional imaging will be used to describe those methods that aim to detect the physiological response to a defined (molecular) stimulus. J. Cell. Biochem. Suppl. 39: 11,17, 2002. © 2002 Wiley-Liss, Inc. [source]

Host collagen signal induces antigen I/II adhesin and invasin gene expression in oral Streptococcus gordonii

MOLECULAR MICROBIOLOGY, Issue 2 2003
Catherine Heddle
Summary Microbial interactions with host molecules, and programmed responses to host environmental stimuli, are critical for colonization and initiation of pathogenesis. Bacteria of the genus Streptococcus are primary colonizers of the human mouth. They express multiple cell-surface adhesins that bind salivary components and other oral bacteria and enable the development of polymicrobial biofilms associated with tooth decay and periodontal disease. However, the mechanisms by which streptococci invade dentine to infect the tooth pulp and periapical tissues are poorly understood. Here we show that production of the antigen I/II (AgI/II) family polypeptide adhesin and invasin SspA in Streptococcus gordonii is specifically upregulated in response to a collagen type I signal, minimally the tri-peptide Gly-Pro-Xaa (where Xaa is hydroxyproline or alanine). Increased AgI/II polypeptide expression promotes bacterial adhesion and extended growth of streptococcal cell chains along collagen type I fibrils that are characteristically found within dentinal tubules. These observations define a new model of host matrix signal-induced tissue penetration by bacteria and open the way for novel therapy opportunities for oral invasive diseases. [source]

Periodontitis as an infectious disease: specific features and their implications

ORAL DISEASES, Issue 2003
A Mombelli
Periodontitis may be viewed as an infectious disease with a number of specific characteristics. Pathogens of the subgingival microbiota can interact with host tissues even without direct tissue penetration. Hence, antimicrobial agents must be available at a sufficiently high concentration not only within the periodontal tissues, but also outside, in the environment of the periodontal pocket. The subgingival microbiota accumulate on the root surface to form an adherent layer of plaque with the characteristics of a biofilm. Several mechanisms, such as diffusion barriers, and selective inactivation of agents lead to an increased resistance of bacteria in biofilms. Mechanical supragingival plaque control is indispensable to prevent the re-emergence of periodontal pathogens and the re-establishment of a biofilm in treated sites. Since specific features have important implications for the use of antimicrobial agents in periodontal therapy, extrapolations from experiences made in the therapy of other infections are only partially valid. The ultimate evidence for the efficacy of systemic or local chemotherapy must be obtained from treatment studies in humans with adequate follow-up. [source]

Phased-Array Intracardiac Echocardiography for Guiding Transseptal Catheter Placement: Utility and Learning Curve

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2002
SUSAN B. JOHNSON
JOHNSON, S.B., et al.: Phased-Array Intracardiac Echocardiography for Guiding Transseptal Catheter Placement: Utility and Learning Curve. The utility of a new intracardiac 64-element, phased-array, longitudinal ultrasound imaging system for guiding transseptal catheterization was assessed during 69 crossing attempts in 45 dogs because of the inherent limitations of fluoroscopy and mechanical ultrasound. Multifrequency (7.5,8.5 MHZ) imaging of the membranous fossa ovalis, posterior left atrium, and left atrial appendage was conducted from the right atrium. Contact of the Brockenbrough needle with the interatrial septum as reflected by membranous fossa ovalis "tenting" was uniformly identified. Transseptal crossing and advancement of the dilator and sheath were adequately imaged because of deeper ultrasound tissue penetration. Transseptal catheterization was successfully accomplished in 44 of 45 dogs: on the first attempt in 40 and with additional attempts in 4 and confirmed by direct far-field imaging of nonagitated saline injection via the sheath. Total transseptal catheterization time was 3.0 ± 1.8 minutes. Unsuccessful first attempts and/or subsequent sheath pullback into the right atrium with catheter manipulation were also readily recognized. Insertion of the transseptal needle beyond the ultrasound imaging plane resulted in perforation of the posterior left atrial wall in three attempts. Accompanying effusions in these animals and three others related to subsequent intracardiac ablation catheter manipulation were readily identified and monitored echocardiographically. In conclusion, phased-array intracardiac imaging provides a highly reliable means of guiding transseptal access to the left atrium. In addition, inadvertent complications such as perforation and pericardial effusion development can be readily recognized. [source]

Pharmacokinetics and tissue distribution of intravenous pefloxacin for antibiotic prophylaxis in biliary surgery

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2002
A.R. Gascón
Abstract The plasma levels and tissue penetration of pefloxacin were studied after prophylactic administration to patients undergoing elective biliary surgery. Pefloxacin was administered as a single dose of 800 mg given intravenously as an infusion 1 h before surgery. Over a period of two years, cultures of bile and stone were performed after cholecystectomy in order to find the main pathogens present in the geographical area of the hospital of Txagorritxu (Vitoria, Spain), as well as to test the antimicrobial susceptibility of these bacteria to pefloxacin. Thirty seven per cent of the bile and stone cultures were positive, and 75 different species were isolated. E. coli was the predominant microorganism (25%). Other frequent microorganisms were E. faecium (9.3%), S. epidermidis (6.6%) and Cl. perfringens (6.6%). Most species isolated were susceptible to pefloxacin, with MIC90 values of 0.125 ,g/ml for E. coli, 0.5 ,g/ml for S. epidermidis and 1 ,g/ml for Cl. perfringens. E. faecium was resistant, with a MIC90 value of 8 ,g/ml but a MIC50 of 4 ,g/ml (intermediate). After pefloxacin infusion, adequate drug plasma levels (>MIC90) for the most frequent pathogens were found throughout the procedure. Elimination half-life was estimated as 22.03±6.91 h; the area under the concentration,time curve from zero to infinite had a value of 275.07±130.02 mg h/l and the values for volume of distribution at steady-state and plasma clearance were 96.48±28.65 L and 3.60±1.83 l/h, respectively. Bile pefloxacin concentrations generally exceeded the minimum inhibitory concentrations for most relevant pathogens. Drug levels in gallbladder and subcutaneous tissues were also above the MIC90 for extended periods. Patients were observed daily throughout their hospital stay. This included examination of the surgical wound and recording of body temperature. No cases of anaerobic infection were noted in the study patients. Other constants such as hospitalization stay and time of recuperation were normal for this type of surgery. According to these results, pefloxacin presents many features that make it suitable for use as a therapeutic prophylactic agent, such as its broad spectrum of antimicrobial activity and favorable pharmacokinetic properties. Copyright © 2002 John Wiley & Sons, Ltd. [source]

70 vs 120 W thulium:yttrium-aluminium-garnet 2 µm continuous-wave laser for the treatment of benign prostatic hyperplasia: a systematic ex-vivo evaluation

2453: Optic disc in the picture: novel imaging techniques

ACTA OPHTHALMOLOGICA, Issue 2010
W DREXLER
Purpose Advances in light sources and detection technologies enabled a paradigm shift in retinal OCT imaging performance. ,Snap-shot OCT' enabling isotropic sampling over 512x512x1024 voxels with 600 frames/second in less than a second is now possible. Methods The resolution advantage in conjunction with full volumetric sampling has enabled the development of more informative indices of axonal damage in glaucoma compared with measurements of RNFL thickness and cup to disc ratio provided by other devices. A novel mapping method was developed, the three-dimensional minimal distance (3D-MDM) as the optical correlate of true retinal nerve fiber layer thickness around the optic nerve head region. In a preliminary study relation between the cross-sectional areas of the retinal nerve fiber layer and the optic nerve was found to be a sensitive measure of axon loss. Results In addition to all the major layers of the retina, the entire choroid down to the lamina cribrosa and sclera can now be visualized. This enables unprecedented information about choroidal vasculature without any contrast agents, choroidal thickness and will enable quantification of choroidal blood flow in the near future. Furthermore this technique allows tissue to be imaged in vitro with an image resolution better than 1-2 µm, allowing to image single cells and detect pre-apoptotic signatures using OCT. RGC-5 cells were imaged using a sampling rate 1024x512x1024 voxel at 800 nm central wavelength and a bandwidth of 230 nm, enabling the detection of optical signatures at different pre-stages of programmed cell death. Conclusion Significantly increased OCT imaging speed and tissue penetration might enable novel insights and diagnostic opportunities in the diagnosis and therapy monitoring of glaucoma. Commercial interest [source]

Diagnostic testing in suspected fluoroquinolone hypersensitivity

CLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2009
C. S. Seitz
Summary Background Because of their broad antibacterial activity in the gram-negative and gram-positive spectrum, high oral bioavailability, and good tissue penetration, fluoroquinolone antibiotics are widely used. Besides direct drug-related side-effects, fluoroquinolones may cause hypersensitivity reactions. Objective The aim of this retrospective analysis was to present the results of diagnostic testing in cases of clinically suspected fluoroquinolone-induced immediate or delayed hypersensitivity. Methods We studied 101 patients with a history of immediate or delayed hypersensitivity symptoms in temporal relation to treatment with a fluoroquinolone antibiotic using standardized skin testing, followed by oral challenges. Patients with anaphylaxis symptoms were further evaluated with in vitro tests. Results Fluoroquinolone hypersensitivity was excluded in 71 patients by tolerated oral challenge tests. During positive challenge tests, six patients (three out of these had positive and three had negative skin prick tests) developed anaphylaxis symptoms but the presumed IgE-mediated mechanism could not be confirmed by in vitro tests. Patch testing was constantly negative; however, in two patients a rash was induced by the challenge tests. Conclusion History alone leads clearly to a considerable over-estimation of fluoroquinolone hypersensitivity. Moreover, skin or in vitro tests do not seem to be very useful in identifying hypersensitive patients. Challenge tests appear to be necessary for definitely confirming or ruling out fluoroquinolone hypersensitivity. [source]

Key considerations in the treatment of complicated staphylococcal infections

CLINICAL MICROBIOLOGY AND INFECTION, Issue 2008
R. N. Jones
Abstract Substantial increases in antimicrobial resistance among Gram-positive pathogens, particularly Staphylococcus aureus, are compromising traditional therapies for serious bacterial infections. There has been an alarming increase in the rates of methicillin-resistant S. aureus (MRSA) over the past two decades, and the more recent emergence of heterogenous vancomycin-intermediate (hVISA), vancomycin-intermediate (VISA) and vancomycin-resistant S. aureus (VRSA) strains limits the use of vancomycin, the current standard of care for MRSA infections. Tolerance to vancomycin, which represents a lack of bactericidal activity of vancomycin, is another troublesome property of some S. aureus strains that can adversely affect the outcome of antimicrobial therapy. Increasing MICs of vancomycin for staphylococci, poor tissue penetration by the drug and a slow rate of bactericidal action of the drug have also raised concerns about its efficacy in the contemporary treatment of MRSA infections. There is an increasingly apparent need for new agents for the treatment of staphylococcal infections, ideally with potent bactericidal activity against MRSA, hVISA, VISA and VRSA and with superior susceptibility profiles as compared with glycopeptides. [source]