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PubMed1994

Haemopoietic cell renewal in radiation fields.

Space flight activities are inevitably associated with a chronic exposure of astronauts to a complex mixture of ionising radiation. Although no acute radiation consequences are to be expected as a rule, the possibility of Solar Particle Events (SPE) associated with relatively high doses of radiation (1 or more Gray) cannot be excluded. It is the responsibility of physicians in charge of the health of astronauts to evaluate before, during and after space flight activities the functional status of haemopoietic cell renewal. Chronic low level exposure of dogs indicate that daily gamma-exposure doses below about 2 cGy are tolerated for several years as far as blood cell concentrations are concerned. However, the stem cell pool may be severely affected. The maintenance of sufficient blood cell counts is possible only through increased cell production to compensate for the radiation inflicted excess cell loss. This behaviour of haemopoietic cell renewal during chronic low level exposure can be simulated by bioengineering models of granulocytopoiesis. It is possible to define a "turbulence region" for cell loss rates, below which an prolonged adaptation to increased radiation fields can be expected to be tolerated. On the basis of these experimental results, it is recommended to develop new biological indicators to monitor haemopoietic cell renewal at the level of the stem cell pool using blood stem cells in addition to the determination of cytokine concentrations in the serum (and other novel approaches). To prepare for unexpected haemopoietic effects during prolonged space missions, research should be increased to modify the radiation sensitivity of haemopoietic stem cells (for instance by the application of certain regulatory molecules). In addition, a "blood stem cell bank" might be established for the autologous storage of stem cells and for use in space activities keeping them in a radiation protected container.

Aerospace Medicine↗

PubMed1989

Short-term effects of topical 17 beta-oestradiol on human post-menopausal skin.

Early studies performed between 1946 and 1952 reported that cutaneously applied oestrogens had local effects in spite of probable systemic absorption. In order to test the validity of these observations the epidermal effects of topically applied 17 beta-oestradiol (E2) of 8 post-menopausal women were studied in a double-blind placebo-controlled cross-over study using non-invasive bioengineering techniques. E2 or placebo was applied twice daily for 45-50 days in a gel (at concentrations of 0.1 mg/g and 1.0 mg/g) and the results were compared. Changes in epidermal hydration (electrical capacitance and conductance) and mechanical properties were studied. We were unable to confirm the short-term local oestrogenic effects on post-menopausal human skin reported in the earlier studies. Thus, in spite of its high number of oestrogen receptors, the epidermis does not appear to be a target organ for oestrogens under clinical conditions.

Administration, Topical↗

PubMed1994

Applications of modified cyclodextrins.

One of the key areas of importance in biotechnology and bioengineering is molecular complexation (MC). MC is useful in selectivity, separation, and solubilization of biomolecules. While many complex, natural MC agents exist, such as proteins and antibodies, relatively few engineered MC materials are available. Inorganic, insoluble MC agents, such as zeolites, are widely used in petroleum catalysis. Carbon Buckminster fullerenes ("bucky balls") can complex small neutral molecules, but are relatively insoluble and difficult to manufacture. Crown ethers have been used for molecular complexation, but are costly to synthesize and have limited capacities. One class of highly useful MC agents are cyclodextrins (CDs). These naturally-occurring, water-soluble cyclic glucans are used in a variety of food, pharmaceutical, and analytical applications. Due to the availability of multiple reactive hydroxyl groups, the functionality of CDs can be greatly increased through chemical modification. A host of new applications are being explored, including enzyme mimicry, molecular recognition, chromatographic separation, and solubilization. This review describes recent applications of modified cyclodextrins in bioprocessing and medicine.

Journal Article↗

PubMedDate not supplied

Evaluation of biomechanical properties of human skin.

Measurement of the physical properties of skin may seem "esoteric" and of little relevance to clinical science; however, the noninvasive nature of available techniques provides unique opportunities for monitoring the effects of disease, drugs, or cosmetics over time on exactly the same area of skin. In vitro testing gives repeatable standardized methods that can supply basic elastic and viscoelastic moduli for skin, which for low strain are comparable to results obtained from in vivo tests. Interpretation of in vivo tests can be difficult, as no analytical model has been developed that can relate measurements from these tests directly to basic skin properties. Each method and each implementation of that method has subtle differences from every other method so that results between studies are difficult to compare; however, the alternative to the bioengineering tests is the hand and eye, which provide subjective (and often biased), nonlinear, and notoriously variable data between individuals. Judging the severity of involvement, the changes due to treatment or progress of disease, and the efficacy of competing treatments is very difficult, even for an experienced clinician. Objective, numerical information on the effects of different active compounds and their formulations is essential if new preparations are to be optimized. Measurement of mechanical properties is one aspect of this important field of endeavor.

Biomechanical Phenomena↗

PubMedDate not supplied

Evaluation of skin blood flow by laser Doppler flowmetry.

Laser Doppler flowmetry is an excellent noninvasive technique for the measurement of cutaneous microcirculation. The list of applications of laser Doppler flowmetry in dermatology is long. It can be applied to monitor inflammation caused by various drugs, chemicals, and allergens related to blood flow. To measure certain inflammatory reactions a combination of other bioengineering measurements is desirable. Flaps can be monitored, and burn depth measured by laser Doppler flowmetry. Through blood flow measurement, the pathophysiology of various skin diseases can be verified and certain treatments can be partially monitored. Although it is not as directly applicable to daily clinical practice, except in a few cases, laser Doppler flowmetry is a very useful technique in various kinds of dermatologic research.

Dermatitis↗

PubMed1995

20 MHz sonography, colorimetry and image analysis in the evaluation of psoriasis vulgaris.

For objective evaluation of the treatment of psoriasis vulgaris standard techniques are desirable. They should be reproducible, sensitive and non-invasive. In this study non-invasive bioengineering techniques, especially high frequency/high resolution ultrasound for measurement of the healing of psoriasis vulgaris were evaluated. Fifty patients with chronic stationary plaque type psoriasis participated in a prospective study; in each patient two psoriatic plaques were examined by means of sonography, colorimetry and image analysis during treatment until complete resolution had occurred. Skin thickness and density could be quantified by means of high frequency ultrasound. In active psoriatic lesions, an echopoor area underneath the entry echo in the ultrasound image caused by acanthosis and inflammatory infiltrate is typical. Under therapy the thickness of this echopoor area diminishes while its density increases. Intensity of the erythema especially the decrease of erythema through healing could not exactly be quantified with the colorimeter because the 'Lab'-CIE-colour representation system cannot distinguish well enough between the colours red and brown. Image analysis allowed to measure the sizes of the psoriatic plaques and to quantify their resolution under therapy. The measuring of plaque size by the aid of computer based image analysis is possible and useful.

Colorimetry↗

PubMed1995

[Perspective of use of rhDNase and new therapeutics for cystic fibrosis].

The prognosis of cystic fibrosis has dramatically improved during the last three decades. This improvement was due to optimization of symptomatic treatment: antibiotics to combat infection, nutritional support, emphasis on bronchial drainage by physiotherapy and aerosols. The discovery of the gene responsible for the disease and the encoded protein opens the way to a specific and curative approach based upon the knowledge of the intrinsic properties of the protein, and its role in ionic flux. Recently, owing to the development of bioengineering, a recombinant human DNase has become available for clinical use. When aerosolized in the patients, it leads to deep changes in rheological parameters of the secretions that facilitate bronchial drainage and clearing of the airways. Gene therapy, the ultimate expression of these advances, will soon enter the era of clinical applications. Unsolved methodological and ethical issues still preclude immediate use in the patients. The results of transplantation surgery have also dramatically improved since the beginning. Indications are more precisely defined and restricted to the more advanced forms of the disease, according to severe criteria of inclusion.

Administration, Inhalation↗

PubMed1991

Gastrointestinal bleeding: endoscopic treatment of peptic ulcer haemorrhage.

The development and study of haemostatic methods that can be used through flexible endoscopes has been one area of gastroenterology in which major advances have been made over the last 15 years. Bioengineering research with lasers and thermal probes as well as the study and application of simple injection techniques has given the endoscopist a range of tools with which to stop bleeding. Randomized controlled trials have provided fairly convincing evidence that these methods can be of value in the treatment of human peptic ulcer bleeding.

Animals↗

PubMed1994

Treatment of inflammatory bowel disease from now to the millennium.

After decades of therapeutic stasis, treatment advances are occurring in inflammatory bowel disease. Recognition that mesalazine was the active moiety of sulphasalazine has led to a number of new methods of delivering mesalazine without sulphapyridine, with improved toxicity ratios. Current attempts to deliver topical steroids directly to the large bowel have yet to be established as therapeutically effective. Immunosuppressive treatment has been used for many years but recent evidence has firmly established its value and cyclosporin has recently been added to the therapeutic armamentarium. Increasing understanding of the basic processes of inflammation has yielded targets for anti-inflammatory treatments aimed both at the processes of immune activation and of attraction by chemotaxis of neutrophils from the circulation to the lamina propria. Some of these novel treatments, which will be assessed in forthcoming years, involve large molecular weight bioengineered peptides and antibodies that are likely to be expensive and difficult to administer. Other treatment, e.g. 5-lipoxygenase or thromboxane synthesis inhibitors or platelet-activating factor antagonists, are conventional lower molecular weight compounds that are easier to produce and are orally active. It is predicted that 5-lipoxygenase inhibitors will be the next therapeutic advance in inflammatory bowel disease. Such a prediction may founder if blanket suppression of multiple inflammatory mechanisms, rather than targeted actions, is required in inflammation.

Adrenal Cortex Hormones↗

PubMed1994

A simple method for the determination of the fundamental frequency of vibration of bones.

Knowledge of the fundamental frequency of transverse vibrations of bones is of interest in bioengineering applications. The finite method is probably the best tool for the numerical determination of natural frequencies and mode shapes of any type of structural system. The present study proposes a simple approach based on the optimized Rayleigh-Ritz method which yields satisfactory answers for many practical applications.

Biophysics↗

PubMed2006

Computer-aided classification of interstitial lung diseases via MDCT: 3D adaptive multiple feature method (3D AMFM).

RATIONALE AND OBJECTIVES: Computer-aided detection algorithms applied to multidetector row CT (MDCT) lung image data sets have the potential to significantly alter clinical practice through the early, quantitative detection of pulmonary pathology. In this project, we have further developed a computer-aided detection tool, the adaptive multiple feature method (AMFM), for the detection of interstitial lung diseases based on MDCT-generated volumetric data. MATERIALS AND METHODS: We performed MDCT (Siemens Sensation 16 or 64 120 kV, B50f convolution kernel, and <or=0.75-mm slice thickness) on 20 human volunteers recruited from four cohorts studied under an National Institutes of Health-sponsored Bioengineering Research Partnership Grant: 1) normal never smokers; 2) normal smokers; 3) those with emphysema, and 4) those with interstitial lung disease (total: 11 males, 9 females; age range 20-75 years, mean age 40 years). A total of 1,184 volumes of interest (VOIs; 21 x 21 pixels in plane) were marked by a senior radiologist and a senior pulmonologist as emphysema (EMPH, n = 287); ground-glass (GG, n = 147), honeycombing (HC, n = 137), normal nonsmokers (NN, n = 287), and normal smokers (NS, n = 326). For each VOI, we calculated 24 volumetric features, including statistical features (first-order features, run-length, and co-occurrence features), histogram, and fractal features. We compared two methods of classification (a Support Vector Machine (SVM) and a Bayesian classifier) using a 10-fold cross validation method and McNemar's test. RESULTS: The sensitivity of five patterns in the form of Bayesian/SVM was: EMPH: 91/93%; GG: 89/86%; HC: 93/90%; NN: 90/73%; and NS: 75/82%. The specificity of five patterns in the form of Bayesian/support vector machine was: EMPH: 98/98%; GG: 98/98%; HC: 99/99%; NN: 90/94%; and NS: 96/91%. CONCLUSION: We conclude that volumetric features including statistical features, histogram and fractal features can be successfully used in differentiation of parenchymal pathology associated with both emphysema and interstitial lung diseases. Additionally, support vector machine and Bayesian methods are comparable classifiers for characterization of interstitial lung diseases on MDCT images.

Adult↗

PubMed2004

Growth and development: hereditary and mechanical modulations.

Growth and development is the net result of environmental modulation of genetic inheritance. Mesenchymal cells differentiate into chondrogenic, osteogenic, and fibrogenic cells: the first 2 are chiefly responsible for endochondral ossification, and the last 2 for sutural growth. Cells are influenced by genes and environmental cues to migrate, proliferate, differentiate, and synthesize extracellular matrix in specific directions and magnitudes, ultimately resulting in macroscopic shapes such as the nose and the chin. Mechanical forces, the most studied environmental cues, readily modulate bone and cartilage growth. Recent experimental evidence demonstrates that cyclic forces evoke greater anabolic responses of not only craniofacial sutures, but also cranial base cartilage. Mechanical forces are transmitted as tissue-borne and cell-borne mechanical strain that in turn regulates gene expression, cell proliferation, differentiation, maturation, and matrix synthesis, the totality of which is growth and development. Thus, hereditary and mechanical modulations of growth and development share a common pathway via genes. Combined approaches using genetics, bioengineering, and quantitative biology are expected to bring new insight into growth and development, and might lead to innovative therapies for craniofacial skeletal dysplasia including malocclusion, dentofacial deformities, and craniofacial anomalies such as cleft palate and craniosynostosis, as well as disorders associated with the temporomandibular joint.

Animals↗

PubMed2004

Clinical response to allergies in patients.

Allergenic reactions are becoming a more prevalent concern of practitioners in health-related fields. As patient susceptibility increases, the need for understanding and successfully treating such heterogeneous responses becomes paramount. This article presents a theoretical bioengineering model that considers the influences of specific concentrations on their chemical effects. This model then is applied to contemporary orthodontics in which nickel and, to a lesser extent, chromium are antagonists in as many as 1 in 500 patients-which, for North America, amounts to about 4000 patients per year. For the occasional patient who responds positively to a questionnaire, a skin patch test would be administered to establish whether alternative alloys could be used, whether they be gold, platinum, nickel-free stainless steel, or titatnium-molybdenum alloys.

Biomedical Engineering↗

PubMed2004

Comparison of rapidity of coronary recanalization in men with tenecteplase versus alteplase in acute myocardial infarction.

To determine whether tenecteplase (TNK-t-PA), a bioengineered variant of tissue-type plasminogen activator (t-PA) designed to accelerate thrombolysis, exhibits favorable properties compared with those of alteplase, 266 men were studied </=6 hours after the onset of symptoms and signs of acute myocardial infarction. The primary end point was the rapidity of recanalization as judged from analysis of serial changes in the concentrations in blood of isoforms of creatine kinase-MM in serially obtained blood samples. Additional end points included enzymatically estimated infarct size and mortality. Patients were treated quite promptly after the onset of symptoms. The interval from the onset of chest pain to recanalization seen with TNK-t-PA was 208 +/- 10 (SE) minutes compared with 237 +/- 9 minutes seen with alteplase (p = 0.04). Thirty-day mortality was low with the use of the 2 agents (2%). TNK-t-PA appears to induce recanalization more rapidly than alteplase, and thrombolysis initiated early after the onset of symptoms is associated with remarkably low mortality.

Adult↗

PubMed2005

Novel tissue-engineered biodegradable material for reconstruction of vascular wall.

BACKGROUND: To solve several problems with artificial grafts, we sought to develop a novel bioengineered material that can promote tissue regeneration without ex vivo cell seeding and that has sufficient durability to be used for artery reconstruction. Here, we tested whether this biodegradable material could accelerate the in situ regeneration of autologous cardiovascular tissue, especially of the arterial wall, in various models of cardiovascular surgeries. METHODS: The tissue-engineered patch was fabricated by compounding a collagen-microsponge with a biodegradable polymeric scaffold composed of polyglycolic acid knitted mesh, reinforced on the outside with woven polylactic acid. Tissue-engineered patches without precellularization were grafted into the porcine descending aorta (n = 5), the porcine pulmonary arterial trunk (n = 8), or the canine right ventricular outflow tract (as the large graft model; n = 4). Histologic and biochemical assessments were performed 1, 2, and 6 months after the implantation. RESULTS: There was no thrombus formation in any animal. Two months after grafting, all the grafts showed good in situ cellularization by hematoxylin/eosin and immunostaining. The quantification of the cell population by polymerase chain reaction showed a large number of endothelial and smooth muscle cells 2 months after implantation. In the large graft model, the architecture of the patch was similar to that of native tissue 6 months after implantation. CONCLUSIONS: A tissue-engineered patch made of our biodegradable polymer and collagen-microsponge provided good in situ regeneration at both the venous and arterial wall, suggesting that this patch can be used as a novel surgical material for the repair of the cardiovascular system.

Absorbable Implants↗

PubMed2006

Constructing a novel Nanodevice powered by delta-free FoF1-ATPase.

A Nanodevice was constructed by delta-free F(o)F(1)-ATPase within chromatophores and actin filaments through biotinlipid-streptavidin-biotin-(AC(5))(2)Sulfo-OSu system. One actin filament linking with many chromatophores functions as the Nanodevice body and many delta-free F(o)F(1)-ATPase as the Nanodevice motors. Movement of the Nanodevice was observed directly by fluorescence microscopy with CCD camera after illumination. The moving speed was about 2.17-24.43mum/s for various length Nanodevices and most of them were stopped by adding CCCP. This means that the Nanodevice was driven by PMF (proton-motive force) in the cooperating delta-free F(o)F(1)-ATPase. From bioengineering point of view, the cooperation of F(o)F(1)-ATPase is a very important research field in the future.

Actins↗

PubMed2004

Tissue repair in rheumatoid arthritis: challenges and opportunities in the face of a systemic inflammatory disease.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that can elicit a variable disease course, can influence a variable number of joints, and can exhibit a variable response to treatment. All of these factors contribute to the degree and extent of damage to joint components, as well as the potential for repair of other injured joint tissues/components. Furthermore, some of the RA treatments/drugs themselves can influence repair and injury responses, as well as the outcome of surgical interventions for advanced disease. However, as treatments and interventions become more sophisticated and successful in patient populations, the opportunity to initiate the repair/replacement of the damaged joint tissues also becomes more of a reality. This review will address the current clinical findings in the literature, and then discuss the issues and opportunities to initiate repair of damaged or injured joint tissues in order to restore joint function. These include growth factors, gene therapy, and bioengineered tissues, alone or in combination to augment endogenous repair or replace tissue damaged beyond such repair capabilities.

Animals↗

PubMed2004

Tenascins.

Tenascins are a family of large multimeric extracellular matrix (ECM) proteins. Vertebrates express four tenascins termed tenascin-C, -R, -X and -W present in their connective tissues. Each tenascin has a specific expression pattern. To the contrary of many other ECM proteins, tenascins promote only weak cell adhesion and do not activate cell spreading. They have been classified as anti-adhesive, adhesion-modulating or even repellent ECM proteins. Tenascin-C and tenascin-R deficient mice show abnormalities in the nervous system and tenascin-C deficient mice, in addition, have defects in several regenerative processes. Mice lacking tenascin-X display hyperelastic skin much like Ehlers Danlos patients with mutations in their tenascin-X gene. Since tenascin-C is highly overexpressed in tumor stroma antibodies against tenascin-C have been used in tumor diagnosis and therapy. Since tenascins are known to influence cell shape, migration and growth they represent good candidate molecules for inclusion in artificial bioengineered tissue implants.

Animals↗