Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

PubMed

Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

2006-03-01

Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage.

PubMed

Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo; Grauslund, Morten; Juhl, Birgitte Ravn; Jensen, Peter Buhl; Sehested, Maxwell

2010-02-28

The bisdioxopiperazine topoisomerase II catalytic inhibitor dexrazoxane has successfully been introduced into the clinic as an antidote to accidental anthracycline extravasation based on our preclinical mouse studies. The histology of this mouse extravasation model was investigated and found to be similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing with dense dermal connective tissue. The extension of this fibrosis was quantified, and dexrazoxane intervention resulted in a statistically significant decrease in fibrosis extension, as also observed in the clinic. Several mechanisms have been proposed in anthracycline extravasation cytotoxicity, and we tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity of topoisomerase II alpha and thereby prevents access of anthracycline to the enzyme and thus cytotoxicity, and also acts as a strong iron chelator following opening of its two bisdioxopiperazine rings. Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation in the topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Thus, interaction with topoisomerase II alpha is not central in the pathogenesis of anthracycline-induced skin damage. In contrast to dexrazoxane, the iron-chelating bisdioxopiperazine ICRF-161 do not inhibit the catalytic cycle of topoisomerase II alpha. This compound was used to isolate and test the importance of iron in the wound pathogenesis. ICRF-161 was found ineffective in the treatment of anthracycline-induced skin damage, suggesting that iron does not play a dominant role in the genesis of wounds. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Endoscopic diode-laser applications in airway surgery

NASA Astrophysics Data System (ADS)

Pankratov, Michail M.; Wang, Zhi; Rebeiz, Elie E.; Perrault, Donald F., Jr.; Shapshay, Stanley M.; Gleich, Lyon L.

1994-09-01

A technique was developed to secure small mucosal grafts onto the airway wound with fibrin/albumin tissue adhesive mixed with ICG dye and irradiated with a 810 nm diode laser. An in vitro study of the tensile strength produced strong mucosal soldering which was adequate to fix grafts in place. In vivo studies showed that wounds with mucosal grafts were completely covered by regenerated squamous cells in 1 week and by ciliated epithelium in 2 weeks. Excellent healing was observed at 6 and 14 days postoperatively and the histology at 28 days found normal epithelium over the vocal cord lesion. This soldering technique is a less traumatic treatment for patients with extensive lesions of the larynx of various origin. Diode laser soldering with ICG-doped fibrin tissue adhesive was evaluated in tracheal anastomosis as a substitute for absorbable sutures. In vitro studies demonstrated strong anastomoses with minimal tissue damage. In vivo animal study showed that these anastomoses had less fibrosis and tissue damage than control animals repaired with sutures only.

Wound ballistics of firearm-related injuries--part 2: mechanisms of skeletal injury and characteristics of maxillofacial ballistic trauma.

PubMed

Stefanopoulos, P K; Soupiou, O T; Pazarakiotis, V C; Filippakis, K

2015-01-01

Maxillofacial firearm-related injuries vary in extent and severity because of the characteristics and behaviour of the projectile(s), and the complexity of the anatomical structures involved, whereas the degree of tissue disruption is also affected by the distance of the shot. In low-energy injuries there is limited damage to the underlying skeleton, which usually dominates the clinical picture, dictating a more straightforward therapeutic approach. High-energy injuries are associated with extensive hard and soft tissue disruption, and are characterized by a surrounding zone of damaged tissue that is prone to progressive necrosis as a result of compromised blood supply and wound sepsis. Current treatment protocols for these injuries emphasize the importance of serial debridement for effective wound control while favouring early definitive reconstruction. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The morphology and histopathology of Nephridiacanthus major (Acanthocephala: Oligacanthorhynchidae) from hedgehogs in Iran.

PubMed

Heckmann, Richard A; Amin, Omar M; Halajian, Ali; El-Naggar, Atif M

2013-02-01

The morphology of Nephridiacanthus major (Bremser 1811 in Westrumb 1821) Golvan, 1962 collected from the long-eared hedgehog Hemiechinus auritus (Gmelin 1770) and the Eastern European hedgehog Erinaceus concolor Martin, 1838 (Erinaceidae) is described using SEM for the first time. This acanthocephalan was previously described from hedgehogs in Europe, Asia, and Africa. Measurements of specimens from Iran, Bulgaria, Germany, Central Asia, Morocco, and Egypt show considerable variations in the size of the trunk, proboscis, proboscis hooks and receptacle, and eggs. The SEM studies add new perspectives to its morphology. Features observed for the first time include the near terminal position and shape of the female gonopore and orifice, among others. Histopathological studies for this species are reported for the first time. Tissue sections show extensive damage near the proboscis with hemorrhaging and formation of collagenous connective tissue, compression of the intestinal mucosa, obstruction of intestinal lumen, and extensive necrosis of host epithelial tissue.

Whole-Body Imaging of High-Dose Ionizing Irradiation-Induced Tissue Injuries Using 99mTc-Duramycin

PubMed Central

Johnson, Steven E.; Li, Zhixin; Liu, Yu; Moulder, John E.; Zhao, Ming

2013-01-01

High-dose ionizing irradiation can cause extensive injuries in susceptible tissues. A noninvasive imaging technique that detects a surrogate marker of apoptosis may help characterize the dynamics of radiation-induced tissue damage. The goal of this study was to prove the concept of imaging the temporal and spatial distribution of damage in susceptible tissues after high-dose radiation exposure, using 99mTc-duramycin as a phosphatidylethanolamine-binding radiopharmaceutical. Methods Rats were subjected to 15 Gy of total-body irradiation with x-rays. Planar whole-body 99mTc-duramycin scanning (n = 4 per time point) was conducted at 24, 48, and 72 h using a clinical γ-camera. On the basis of findings from planar imaging, preclinical SPECT data were acquired on control rats and on irradiated rats at 6 and 24 h after irradiation (n = 4 per time point). Imaging data were validated by γ-counting and histology, using harvested tissues in parallel groups of animals (n = 4). Results Prominent focal uptake was detected in the thymus as early as 6 h after irradiation, followed by a gradual decline in 99mTc-duramycin binding accompanied by extensive thymic atrophy. Early (6–24 h) radioactivity uptake in the gastrointestinal region was detected. Significant signal was seen in major bones in a slightly delayed fashion, at 24 h, which persisted for at least 2 d. This finding was paralleled by an elevation in signal intensity in the kidneys, spleen, and liver. The imaging results were consistent with ex vivo γ-counting results and histology. Relatively high levels of apoptosis were detected from histology in the thymus, guts, and bones, with the thymus undergoing substantial atrophy. Conclusion As a proof of principle, this study demonstrated a noninvasive imaging technique that allows characterization of the temporal and spatial dynamics of injuries in susceptible tissues during the acute phase after high-dose ionizing irradiation. Such an imaging capability will potentially be useful for global, whole-body, assessment of tissue damage after radiation exposure. These data, in turn, will contribute to our general knowledge of tissue susceptibility to ionizing irradiation, as well as the onset and progression of tissue injuries. PMID:23804327

Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

NASA Astrophysics Data System (ADS)

Marks, Edward D.

The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell culture media injections. Significant improvements in cardiac metrics, including ejection fraction and left ventricular end systolic volume, were seen compared to untreated animals, and were comparable to healthy controls. To our knowledge this is the first side-by-side comparison of cell culture media and stem cells to heal a predefined range of MI damage. We believe this simple, inexpensive treatment option is a new beneficial step towards healing damaged patient tissue after MI.

Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

2010-01-01

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

Changes in plasma chemistry after drug-induced liver disease or muscle necrosis in racing pigeons (Columba livia domestica).

PubMed

Lumeij, J T; Meidam, M; Wolfswinkel, J; Van der Hage, M H; Dorrestein, G M

1988-01-01

Changes in plasma variables as a result of liver damage induced by ethylene glycol (group A) or D-galactosamine (group B) and of muscle damage induced by doxycycline were compared. Plasma bile acid concentration was both a specific and a sensitive indicator of liver disease. Another specific, but less sensitive indicator of liver disease was 7-GT. Plasma AS AT activity was the most sensitive indicator of disease of the liver, but was not specific, since increased ASAT activities were also seen during muscle disease. ALAT activity was slightly more sensitive to liver damage than 7-GT, but was also not specific, being increased also after muscle damage. Plasma GLDH activity was increased only as a result of extensive liver necrosis. AP activity was of no value for detecting liver disease in the pigeon. CK activity was specific for muscle injury, though the activities of ALAT, ASAT and LD were also increased. Because of its long elimination half-life, increased ALAT activity persisted for 9 days after muscle damage, whereas CK activity returned to reference values within 3 days. LDH was a poor indicator of damage to liver and muscle, despite its relatively high tissue concentrations in both tissues. The rapid disappearance rate of LDH from plasma probably explains this observation.

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

PubMed

Lee, Seung S; Roche, Philip Jr; Giannopoulos, Paresa N; Mitmaker, Elliot J; Tamilia, Michael; Paliouras, Miltiadis; Trifiro, Mark A

2017-03-01

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage

PubMed Central

Rinchai, Darawan; Kewcharoenwong, Chidchamai; Kessler, Bianca; Lertmemongkolchai, Ganjana; Chaussabel, Damien

2016-01-01

Background: Members of the ADAM (a disintegrin and metalloprotease domain) family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1) The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2) changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs). 3) Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes. PMID:27990250

Extensive Necrosis After Radiation for Cancer: Experiences in Surgical Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

BENNETT, JAMES E.

1963-06-01

Radionecrosis in skin and deeper tissues and its surgical repair are described in 16 cases. The observed epithelial changes included both atrophy and hypertrophy, but atrophy was the dominant feature. Epidermal hypertrophy, which preceded malignant change, developed more slowly and was less likely to occur in areas subjected to deep irradiation than in skin treated with multiple small doses of x-ray over a long period. The indolent ulceration that developed in skin augmented the changes in underlying tissues so that successful management of these ulcerations required adequate excision of the damaged area and replacement with fat-bearing pedicle flap tissue. Whenmore » adjacent flaps were used, permanent blood supply to the region was assured. In cases of radiotherapy for basal cell carcinoma of the scalp, skin necrosis resulted in skull exposure with subsequent osteomyelitis and/or bone necrosis. Excision included the full thickness of the skull, and pedicle flap tissue from the scalp was used for coverage. Cranioplasty was performed after good skin and soft tissue cover had been obtained. Therapeutic radiation of the neck invariably produces marked skin changes, and when ulceration occurs, the vulnerability of underlying structures demands surgical treatment. Lesions of the upper extremity can be excised and covered with direct pedicle flaps from the trunk. Therapeutic radiation of the retroperitoneal area may produce extensive visceral damage as well as injury to the anterior abdominal wall, and anterior suprapubic ulcerations are particularly difficult to deal with since mobile adjacent tissue is scarce. The avascular midline is a limiting factor in flap design. Abdominal flaps extending onto the thigh can be used, but these require multiple delaying procedures to insure adequate blood supply. Patients being managed by these procedures are described. Most patients underwent their operative procedures with few serious complications. While postoperative bleeding and infection are inherent hazards, most complications were traceable to errors in planning or in operative technique. When the primary procedure fails, it is often many weeks before the wound is again ready for coverage and the availability of adjacent tissue has been compromised by the operation. Therefore, it is necessary to mobilize generous amounts of normal tissue to replace the area of injury, for this may be considerably more extensive than external inspection suggests. In addition, retraction of the wound edges following excision can be considerable since surrounding normal tissue may be drawn toward the area of involvement by scar contracture. When transposition or distant pedicle flaps are used, the flaps must be designed initially to allow for coverage of the eventual wound. However, when adjacent flaps are used, they may be outlined at the beginning of the procedure and appropriate alterations are then made, as necessary, after excision of the area of involvement. It is concluded that operation is not advisable until there is pain or ulceration in the region of radiation injury. Preferred treatment consists of excision of all damaged tlssue with pedicle flap replacement.« less

Bilateral limbic system destruction in man

PubMed Central

Feinstein, Justin S.; Rudrauf, David; Khalsa, Sahib S.; Cassell, Martin D.; Bruss, Joel; Grabowski, Thomas J.; Tranel, Daniel

2010-01-01

We report here a case study of a rare neurological patient with bilateral brain damage encompassing a substantial portion of the so-called “limbic system.” The patient, Roger, has been studied in our laboratory for over 14 years and the current article presents his complete neuroanatomical and neuropsychological profiles. The brain damage occurred in 1980 following an episode of herpes simplex encephalitis. The amount of destroyed neural tissue is extensive and includes bilateral damage to core limbic and paralimbic regions, including the hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right hemisphere is more extensively affected than the left, although the lesions are largely bilateral. Despite the magnitude of his brain damage, Roger has a normal IQ, average to above average attention, working memory, and executive functioning skills, and very good speech and language abilities. In fact, his only obvious presenting deficits are a dense global amnesia and a severe anosmia and ageusia. Roger's case presents a rare opportunity to advance our understanding of the critical functions underlying the human limbic system, and the neuropsychological and neuroanatomical data presented here provide a critical foundation for such investigations. PMID:19763994

Proliferation zones in the axolotl brain and regeneration of the telencephalon

PubMed Central

2013-01-01

Background Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. Results There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. Conclusion There is a continual generation of neuronal cells from neural progenitor cells located within the ventricular zone of the axolotl brain. Variable rates of proliferation were detected across brain regions. These neural progenitor cells appear to mediate telencephalic tissue regeneration through an injury-induced olfactory cue. Identification of this cue is our future goal. PMID:23327114

Proliferation zones in the axolotl brain and regeneration of the telencephalon.

PubMed

Maden, Malcolm; Manwell, Laurie A; Ormerod, Brandi K

2013-01-17

Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. There is a continual generation of neuronal cells from neural progenitor cells located within the ventricular zone of the axolotl brain. Variable rates of proliferation were detected across brain regions. These neural progenitor cells appear to mediate telencephalic tissue regeneration through an injury-induced olfactory cue. Identification of this cue is our future goal.

Distinct effects of acute and chronic sleep loss on DNA damage in rats.

PubMed

Andersen, M L; Ribeiro, D A; Bergamaschi, C T; Alvarenga, T A; Silva, A; Zager, A; Campos, R R; Tufik, S

2009-04-30

The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

Possibility of Aggravation of Tissue Sclerosis after Injection of Multipotent Mesenchymal Stromal Cells Near the Forming Cicatrix in the Experiment.

PubMed

Maiborodin, I V; Morozov, V V; Anikeev, A A; Figurenko, N F; Maslov, R V; Matveeva, V A; Chastikina, G A; Maiborodina, V I

2017-08-01

The peculiarities of tissue sclerosis after injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and stained with Vybrant CM-Dil cell membrane dye were studied by light microscopy with luminescence. The surgical intervention consisting in ligation of the great vein was followed by tissue sclerotic transformation caused by direct damage and chronic inflammation caused by the presence of slowly resorbed ligature. Injection of stromal cells after this intervention led to formation of more extensive scar. This can attest to the possibility of stromal cells differentiation into connective tissue cells, fibroblasts, and stimulation of proliferation and collagen synthesis by host fibroblasts. A decrease in the volume of dense fibrous connective tissue due to scar reorganization at latter terms cannot not excluded.

Vitrification

NASA Astrophysics Data System (ADS)

A. Takahashi, Tsuneo

Vitrification is an alternative to customary approaches to cryopreserve cell, tissue and organ. In this method, ice formation can be prevented by a combination of high solute concentration and rapid cooling, a solution become glassy without ice crystalline formation at temperatures below-115°C. The cell and tissue damage associated with ice formation is avoided, but thawing should be rapid enough to prevent ice growth during warming and they should be equilibrated with the vitrification medium without injury. This approach has been extensively studied in the past few years, and has the potential to be an alternative approach to the cryopreservation of a wide range of biological systems.

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eisfeld, Amie J.; Halfmann, Peter J.; Wendler, Jason P.

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ’omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integratedmore » biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.« less

Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis.

PubMed

Eisfeld, Amie J; Halfmann, Peter J; Wendler, Jason P; Kyle, Jennifer E; Burnum-Johnson, Kristin E; Peralta, Zuleyma; Maemura, Tadashi; Walters, Kevin B; Watanabe, Tokiko; Fukuyama, Satoshi; Yamashita, Makoto; Jacobs, Jon M; Kim, Young-Mo; Casey, Cameron P; Stratton, Kelly G; Webb-Robertson, Bobbie-Jo M; Gritsenko, Marina A; Monroe, Matthew E; Weitz, Karl K; Shukla, Anil K; Tian, Mingyuan; Neumann, Gabriele; Reed, Jennifer L; van Bakel, Harm; Metz, Thomas O; Smith, Richard D; Waters, Katrina M; N'jai, Alhaji; Sahr, Foday; Kawaoka, Yoshihiro

2017-12-13

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform 'omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity. Copyright © 2017 Elsevier Inc. All rights reserved.

Rat injury model of docetaxel extravasation.

PubMed

Zhu, Jing-Jing; Fu, Jian-Fei; Yang, Jiao; Hu, Bing; Zhang, Hui; Yu, Jian-Hua

2014-09-01

Docetaxel is a novel type of chemotherapy drug that actively treats a number of malignant tumors. The aim of the present study was to explore the severity and natural course of tissue damage induced by docetaxel extravasation and to confirm the vesicant potential of docetaxel. Rats were selected for the establishment of the ulcer model. Different volumes and concentrations were explored to induce the skin ulcer and to confirm the optimum rational injection model. The natural course of tissue injury and pathological changes produced by docetaxel extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml volume and a 6 mg/ml concentration were the optimum rational injection model for the induction of the skin ulcer. The docetaxel extravasation induced local tissue necrosis, followed by granuloma formation and hyperpigmentation or scar formation. The severity of the injury depended on the concentration of the extravasation used in the rat model. The injury occurred on the first day following extravasation and lasted 4-6 weeks. The damage from docetaxel was weaker than vinorelbine in association with the depth and extension of necrosis. In conclusion, docetaxel extravasation can induce tissue necrosis. However, the severity of necrosis was weaker than that of vinorelbine. Docetaxel has superficial vesicant properties.

Rat injury model of docetaxel extravasation

PubMed Central

ZHU, JING-JING; FU, JIAN-FEI; YANG, JIAO; HU, BING; ZHANG, HUI; YU, JIAN-HUA

2014-01-01

Docetaxel is a novel type of chemotherapy drug that actively treats a number of malignant tumors. The aim of the present study was to explore the severity and natural course of tissue damage induced by docetaxel extravasation and to confirm the vesicant potential of docetaxel. Rats were selected for the establishment of the ulcer model. Different volumes and concentrations were explored to induce the skin ulcer and to confirm the optimum rational injection model. The natural course of tissue injury and pathological changes produced by docetaxel extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml volume and a 6 mg/ml concentration were the optimum rational injection model for the induction of the skin ulcer. The docetaxel extravasation induced local tissue necrosis, followed by granuloma formation and hyperpigmentation or scar formation. The severity of the injury depended on the concentration of the extravasation used in the rat model. The injury occurred on the first day following extravasation and lasted 4–6 weeks. The damage from docetaxel was weaker than vinorelbine in association with the depth and extension of necrosis. In conclusion, docetaxel extravasation can induce tissue necrosis. However, the severity of necrosis was weaker than that of vinorelbine. Docetaxel has superficial vesicant properties. PMID:25054005

Vehicle and positive control values from the in vivo rodent comet assay and biomonitoring studies using human lymphocytes: historical database and influence of technical aspects.

PubMed

Pant, Kamala; Springer, S; Bruce, S; Lawlor, T; Hewitt, N; Aardema, M J

2014-10-01

There is increased interest in the in vivo comet assay in rodents as a follow-up approach for determining the biological relevance of chemicals that are genotoxic in in vitro assays. This is partly because, unlike other assays, DNA damage can be assessed in this assay in virtually any tissue. Since background levels of DNA damage can vary with the species, tissue, and cell processing method, a robust historical control database covering multiple tissues is essential. We describe extensive vehicle and positive control data for multiple tissues from rats and mice. In addition, we report historical data from control and genotoxin-treated human blood. Technical issues impacting comet results are described, including the method of cell preparation and freezing. Cell preparation by scraping (stomach and other GI tract organs) resulted in higher % tail DNA than mincing (liver, spleen, kidney etc) or direct collection (blood or bone marrow). Treatment with the positive control genotoxicant, ethyl methanesulfonate (EMS) in rats and methyl methanesulfonate in mice, resulted in statistically significant increases in % tail DNA. Background DNA damage was not markedly increased when cell suspensions were stored frozen prior to preparing slides, and the outcome of the assay was unchanged (EMS was always positive). In conclusion, historical data from our laboratory for the in vivo comet assay for multiple tissues from rats and mice, as well as human blood show very good reproducibility. These data and recommendations provided are aimed at contributing to the design and proper interpretation of results from comet assays. © 2014 Wiley Periodicals, Inc.

Aging by epigenetics-A consequence of chromatin damage?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sedivy, John M.; Banumathy, Gowrishankar; Adams, Peter D.

Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases.

Pseudomonas aeruginosa rugose small-colony variants evade host clearance, are hyper-inflammatory, and persist in multiple host environments.

PubMed

Pestrak, Matthew J; Chaney, Sarah B; Eggleston, Heather C; Dellos-Nolan, Sheri; Dixit, Sriteja; Mathew-Steiner, Shomita S; Roy, Sashwati; Parsek, Matthew R; Sen, Chandan K; Wozniak, Daniel J

2018-02-01

Pseudomonas aeruginosa causes devastating infections in immunocompromised individuals. Once established, P. aeruginosa infections become incredibly difficult to treat due to the development of antibiotic tolerant, aggregated communities known as biofilms. A hyper-biofilm forming clinical variant of P. aeruginosa, known as a rugose small-colony variant (RSCV), is frequently isolated from chronic infections and is correlated with poor clinical outcome. The development of these mutants during infection suggests a selective advantage for this phenotype, but it remains unclear how this phenotype promotes persistence. While prior studies suggest RSCVs could survive by evading the host immune response, our study reveals infection with the RSCV, PAO1ΔwspF, stimulated an extensive inflammatory response that caused significant damage to the surrounding host tissue. In both a chronic wound model and acute pulmonary model of infection, we observed increased bacterial burden, host tissue damage, and a robust neutrophil response during RSCV infection. Given the essential role of neutrophils in P. aeruginosa-mediated disease, we investigated the impact of the RSCV phenotype on neutrophil function. The RSCV phenotype promoted phagocytic evasion and stimulated neutrophil reactive oxygen species (ROS) production. We also demonstrate that bacterial aggregation and TLR-mediated pro-inflammatory cytokine production contribute to the immune response to RSCVs. Additionally, RSCVs exhibited enhanced tolerance to neutrophil-produced antimicrobials including H2O2 and the antimicrobial peptide LL-37. Collectively, these data indicate RSCVs elicit a robust but ineffective neutrophil response that causes significant host tissue damage. This study provides new insight on RSCV persistence, and indicates this variant may have a critical role in the recurring tissue damage often associated with chronic infections.

Mechanostimulation protocols for cardiac tissue engineering.

PubMed

Govoni, Marco; Muscari, Claudio; Guarnieri, Carlo; Giordano, Emanuele

2013-01-01

Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

Mechanostimulation Protocols for Cardiac Tissue Engineering

PubMed Central

Govoni, Marco; Muscari, Claudio; Guarnieri, Carlo; Giordano, Emanuele

2013-01-01

Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field. PMID:23936858

Perspectives on biomechanical growth and remodeling mechanisms in glaucoma⋆

PubMed Central

Grytz, Rafael; Girkin, Christopher A.; Libertiaux, Vincent; Downs, J. Crawford

2012-01-01

Glaucoma is a blinding diseases in which damage to the axons results in loss of retinal ganglion cells. Experimental evidence indicates that chronic intraocular pressure elevation initiates axonal insult at the level of the lamina cribrosa. The lamina cribrosa is a porous collagen structure through which the axons pass on their path from the retina to the brain. Recent experimental studies revealed the extensive structural changes of the lamina cribrosa and its surrounding tissues during the development and progression of glaucoma. In this perspective paper we review the experimental evidence for growth and remodeling mechanisms in glaucoma including adaptation of tissue anisotropy, tissue thickening/thinning, tissue elongation/shortening and tissue migration. We discuss the existing predictive computational approaches that try to elucidate the potential biomechanical basis of theses growth and remodeling mechanisms and highlight open questions, challenges, and avenues for further development. PMID:23109748

Predicting cell viability within tissue scaffolds under equiaxial strain: multi-scale finite element model of collagen-cardiomyocytes constructs.

PubMed

Elsaadany, Mostafa; Yan, Karen Chang; Yildirim-Ayan, Eda

2017-06-01

Successful tissue engineering and regenerative therapy necessitate having extensive knowledge about mechanical milieu in engineered tissues and the resident cells. In this study, we have merged two powerful analysis tools, namely finite element analysis and stochastic analysis, to understand the mechanical strain within the tissue scaffold and residing cells and to predict the cell viability upon applying mechanical strains. A continuum-based multi-length scale finite element model (FEM) was created to simulate the physiologically relevant equiaxial strain exposure on cell-embedded tissue scaffold and to calculate strain transferred to the tissue scaffold (macro-scale) and residing cells (micro-scale) upon various equiaxial strains. The data from FEM were used to predict cell viability under various equiaxial strain magnitudes using stochastic damage criterion analysis. The model validation was conducted through mechanically straining the cardiomyocyte-encapsulated collagen constructs using a custom-built mechanical loading platform (EQUicycler). FEM quantified the strain gradients over the radial and longitudinal direction of the scaffolds and the cells residing in different areas of interest. With the use of the experimental viability data, stochastic damage criterion, and the average cellular strains obtained from multi-length scale models, cellular viability was predicted and successfully validated. This methodology can provide a great tool to characterize the mechanical stimulation of bioreactors used in tissue engineering applications in providing quantification of mechanical strain and predicting cellular viability variations due to applied mechanical strain.

Nanotopography-guided tissue engineering and regenerative medicine☆

PubMed Central

Kim, Hong Nam; Jiao, Alex; Hwang, Nathaniel S.; Kim, Min Sung; Kang, Do Hyun; Kim, Deok-Ho; Suh, Kahp-Yang

2017-01-01

Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end. PMID:22921841

Diffuse FDG uptake due to fat necrosis following transverse rectus abdominus myocutaneous (TRAM) flap reconstruction.

PubMed

Dobbs, Nathan B; Latifi, Hamid R

2013-08-01

We report a case of a 57-year-old female patient with right breast invasive ductal carcinoma. Bilateral mastectomy and TRAM flap reconstructions were performed. Postoperatively, a palpable focus was identified within the left breast. PET/CT showed hypermetabolism throughout the reconstructed left breast, correlating with mixed fat attenuation and inflammatory soft tissue. MRI showed extensive fat necrosis/oil cyst formation in the left breast. As a TRAM flap reconstruction with fat-rich tissue can be damaged intraoperatively due to surgical manipulation, abnormal FDG uptake in this setting is more likely related to fat necrosis than recurrent tumor.

Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering.

PubMed

Jayaraman, Praveena; Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Becker, David Laurence; Ramakrishna, Seeram; Srinivasan, Dinesh Kumar

2015-11-01

Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel approach for mechanical tissue characterization indicates decreased elastic strength in brain areas affected by experimental thromboembolic stroke.

PubMed

Michalski, Dominik; Härtig, Wolfgang; Krueger, Martin; Hobohm, Carsten; Käs, Josef A; Fuhs, Thomas

2015-07-08

As treatment of ischemic stroke remains a challenge with respect to the failure of numerous neuroprotective attempts, there is an ongoing need for better understanding of pathophysiological mechanisms causing tissue damage. Although ischemic outcomes have been studied extensively at the cellular and molecular level using histological and biochemical methods, properties of ischemia-affected brain tissue with respect to mechanical integrity have not been addressed so far. As a novel approach, this study used fluorescence-based detection of regions affected by experimental thromboembolic stroke in combination with scanning force microscopy to examine mechanical alterations in selected rat brain areas. Twenty-five hours after onset of ischemia, a decreased elastic strength in the striatum as the region primarily affected by ischemia was found compared with the contralateral nonaffected hemisphere. Additional intrahemispheric analyses showed decreased elastic strength in the ischemic border zone compared with the more severely affected striatum. In conclusion, these data strongly indicate a critical alteration in mechanical tissue integrity caused by focal cerebral ischemia. Further, on the basis of data that have been obtained in relation to the ischemic border zone, a shell-like pattern of mechanical tissue damage was found in good accordance with the penumbra concept. These findings might enable the development of specific therapeutic interventions to protect affected areas from critical loss of mechanical integrity.

Image-guided surgery in resection of benign cervicothoracic spinal tumors: a report of two cases.

PubMed

Moore, Timothy; McLain, Robert F

2005-01-01

Osseous spinal tumors are an uncommon cause of persistent axial pain and muscle spasm, but even benign lesions may grow to cause deformity or neurological signs. Traditional treatment approaches to resection can be debilitating even when the tumor is benign. Emerging technologies allow surgeons to diagnose and treat osseous neoplasms while minimizing the collateral damage caused by surgical exposure and tumor excision. Technical considerations are presented through two cases of benign osseous neoplasm occurring in the cervicothoracic spine of competitive athletes, demonstrating the meth-ods used to provide effective treatment while maintaining maximal functional capacity. Stereotactic imaging and intraoperative guidance was used as an adjunct to tumor care in these patients. Used in combination with minimally invasive, microsurgical techniques,stereotactic guidance localized and verified excision margins of benign vertebral lesions, minimizing soft tissue trauma and collateral damage. Computer-assisted stereotactic localization allowed us to successfully ablate these lesions from their anatomically challenging locations, without disrupting the shoulder girdle or neck musculature, and without extensive bony resection. Image guidance can accurately localize and guide excision of benign vertebral lesions while minimizing soft tissue trauma and collateral damage, allowing patients a rapid and complete return to high-demand function.

Liposomal Antioxidants for Protection against Oxidant-Induced Damage

PubMed Central

Suntres, Zacharias E.

2011-01-01

Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress. PMID:21876690

New fronts emerge in the influenza cytokine storm.

PubMed

Guo, Xi-Zhi J; Thomas, Paul G

2017-07-01

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33-amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

The cutting mechanism of the electrosurgical scalpel

NASA Astrophysics Data System (ADS)

Gjika, Eda; Pekker, Mikhail; Shashurin, Alexey; Shneider, Mikhail; Zhuang, Taisen; Canady, Jerome; Keidar, Michael

2017-01-01

Electrosurgical cutting is a well-known technique for creating incisions often used for the removal of benign and malignant tumors. The proposed mathematical model suggests that incisions are created due to the localized heating of the tissue. The model estimates a volume of tissue heating in the order of 2 · 10-4 mm3. This relatively small predicted volume explains why the heat generated from the very tip of the scalpel is unable to cause extensive damage to the tissue adjacent to the incision site. The scalpel exposes the target region to an RF field in 60 ms pulses until a temperature of around 100 °C is reached. This process leads to desiccation where the tissue is characterized by a significantly low electrical conductivity, which prevents further heating and charring. Subsequently, the incision is created from the mechanical scraping process that follows.

Photonic surgery with noncoherent light

NASA Astrophysics Data System (ADS)

Feuermann, Daniel; Gordon, Jeffrey M.; Ng, Tuck Wah

2006-03-01

Extensive photothermal surgical effects have been generated with artificial noncoherent light. Our ex vivo experiments produced the same type and extent of tissue damage ordinarily achieved with laser fiber-optic surgery, at comparable surgical efficacy, the motivation being the possibility of supplanting surgical lasers with a potentially far less expensive device. Maximum-flux optics reconstitute the immense power density at the core of an ultrabright discharge lamp inside an optical fiber the distal tip of which couples light into the organ.

Good news–bad news: the Yin and Yang of immune privilege in the eye

PubMed Central

Forrester, John V.; Xu, Heping

2012-01-01

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood–ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host. PMID:23230433

Deformation and reperfusion damages and their accumulation in subcutaneous tissues during loading and unloading: a theoretical modeling of deep tissue injuries.

PubMed

Mak, Arthur F T; Yu, Yanyan; Kwan, Linda P C; Sun, Lei; Tam, Eric W C

2011-11-21

Deep tissue injuries (DTI) involve damages in the subcutaneous tissues under intact skin incurred by prolonged excessive epidermal loadings. This paper presents a new theoretical model for the development of DTI, broadly based on the experimental evidence in the literatures. The model covers the loading damages implicitly inclusive of both the direct mechanical and ischemic injuries, and the additional reperfusion damages and the competing healing processes during the unloading phase. Given the damage accumulated at the end of the loading period, the relative strength of the reperfusion and the healing capacity of the involved tissues system, the model provides a description of the subsequent damage evolution during unloading. The model is used to study parametrically the scenario when reperfusion damage dominates over healing upon unloading and the opposite scenario when the loading and subsequent reperfusion damages remain small relative to the healing capacity of the tissues system. The theoretical model provides an integrated understanding of how tissue damage may further build-up paradoxically even with unloading, how long it would take for the loading and reperfusion damages in the tissues to become fully recovered, and how such loading and reperfusion damages, if not given sufficient time for recovery, may accumulate over multiple loading and unloading cycles, leading to clinical deep tissues ulceration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Retinotomy using an erbium:YAG laser on human autopsy eyes

NASA Astrophysics Data System (ADS)

Ellsworth, Lansing G.; Kramer, Theresa R.; Noecker, Robert J.; Snyder, Robert W.; Yarborough, J. Michael

1994-06-01

Mid-IR lasers that operate near the absorption peak of water have a short penetration depth in ocular tissues. Ablation of tissue can be accomplished with minimal coagulative damage to underlying structures. We used an erbium:YAG laser equipped with a contact probe to create retinotomy sites in the human retina of eye bank eyes. An erbium:YAG laser (2.94 micrometers ) equipped with an infrared transmitting glass fiber and a sapphire tip (400 micrometers ) was used to directly ablate the surface of the retina. We administered both single and multiple pulses to the macula and peripheral retina using energy levels from 4 to 16 mJ per pulse. The retinas were then examined histopathologically to evaluate the extent of ablation and coagulative damage. Single pulses at low energy levels were noted to cause ablative damage to the nerve fiber layer and ganglion cell layer without a notable coagulative effect. The mean ablation depth at lower energy levels was less than the mean ablation depth at higher energy levels. Extensive laser application produced disruption of the retinal pigment epithelium, choroid and sclera. the erbium:YAG laser equipped with a contact probe is an effective means of creating retinotomies in human autopsy eyes. When used in the single pulse mode at lower energy levels, the erbium:YAG laser appears capable of removing superficial retinal layers without damaging deeper structures.

Microwave thermal ablation: Effects of tissue properties variations on predictive models for treatment planning.

PubMed

Lopresto, Vanni; Pinto, Rosanna; Farina, Laura; Cavagnaro, Marta

2017-08-01

Microwave thermal ablation (MTA) therapy for cancer treatments relies on the absorption of electromagnetic energy at microwave frequencies to induce a very high and localized temperature increase, which causes an irreversible thermal damage in the target zone. Treatment planning in MTA is based on experimental observations of ablation zones in ex vivo tissue, while predicting the treatment outcomes could be greatly improved by reliable numerical models. In this work, a fully dynamical simulation model is exploited to look at effects of temperature-dependent variations in the dielectric and thermal properties of the targeted tissue on the prediction of the temperature increase and the extension of the thermally coagulated zone. In particular, the influence of measurement uncertainty of tissue parameters on the numerical results is investigated. Numerical data were compared with data from MTA experiments performed on ex vivo bovine liver tissue at 2.45GHz, with a power of 60W applied for 10min. By including in the simulation model an uncertainty budget (CI=95%) of ±25% in the properties of the tissue due to inaccuracy of measurements, numerical results were achieved in the range of experimental data. Obtained results also showed that the specific heat especially influences the extension of the thermally coagulated zone, with an increase of 27% in length and 7% in diameter when a variation of -25% is considered with respect to the value of the reference simulation model. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a potentially harmful or a useful event in radiotherapy. The elevation of damage to tumor cells not directly hit by radiation or the initiation of tumor cell differentiation may increase the therapeutic ratio. If, however, molecular species secreted by irradiated tumor cells in vivo damage neighboring normal cells (epithelial and endothelial cells, fibroblasts, or lymphocytes), the bystander effect would be harmful and could lead to increased side effects in normal tissue. This is especially important in modern radiotherapy, as 3D conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) are aimed at diminishing the radiation dose in normal tissues. Recent in vivo studies on animals indicate that bystander effects may appear in organs and tissues remote from the irradiated field and the extension of tissue damage seems to be tissue-type dependent. However, recent experimental results indicate that non-irradiated cells that are neighbors of irradiated cells may diminish radiation damage in the radiation-focused cells. Less is known about the bystander effect during fractionated irradiation. Thus the clinical implications of the bystander effect and its possible modification for radiotherapeutic usefulness is still under debate.

Nanotopography-guided tissue engineering and regenerative medicine.

PubMed

Kim, Hong Nam; Jiao, Alex; Hwang, Nathaniel S; Kim, Min Sung; Kang, Do Hyun; Kim, Deok-Ho; Suh, Kahp-Yang

2013-04-01

Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Tissue Damage Signaling Is a Prerequisite for Protective Neutrophil Recruitment to Microbial Infection in Zebrafish.

PubMed

Huang, Cong; Niethammer, Philipp

2018-05-15

Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A 2 (cPla 2 ), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.

Thermal injury secondary to laparoscopic fiber-optic cables.

PubMed

Hindle, A Katharine; Brody, Fred; Hopkins, Vernon; Rosales, Greg; Gonzalez, Florencia; Schwartz, Arnold

2009-08-01

Laparoscopy requires a reliable light source to provide adequate visualization. However, thermal energy is produced as a by-product from the optical cable. This study attempts to quantify the degree of possible thermal damage secondary to the fiber-optic light source. Using a digital thermometer, temperature measurements were recorded at the tip of optical cables from five different light sources (Karl Storz, Inc., Tuttlingen, Germany). Temperature measurements were recorded with new and old bulbs. The tip of the cable was applied to surgical drapes and the time to charring was recorded. Subsequently, the tip of the optical cable was applied to a porcine model and tissue samples were obtained after varying amounts of time (5, 15, 30, 60, and 90 s). Sections of the damaged tissue were prepared for microscopic evaluation. Parameters for thermal injury included extent of epidermal, dermal, and subcutaneous fat damage and necrosis. The lateral extent and depth of injury were measured. The maximum temperature at the tip of the optical cable varied between 119.5 degrees C and 268.6 degrees C. When surgical drapes were exposed to the tip of the light source, the time to char was 3-6 s. The degree and volume of injury increased with longer exposure times, and significant injury was recorded with the optical cable 3 mm from the skin. This study demonstrates that the temperature at the tip of the optical light cord can induce extensive damage. The by-product of light, heat, can produce immediate superficial tissue necrosis that can extend into the subcutaneous fat even when the optical tip is not in direct contact with the skin. In addition, our study shows the variation in temperature that exists between light sources and bulb status. Overall, surgeons must realize and respect the potential complications associated with optical technology.

Malignant external otitis: The diagnostic value of bone scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ostfeld, E.; Aviel, A.; Pelet, D.

1981-06-01

Technetium99m Methylene Diphosphate bone scintigraphy (BS) of the skull was performed in three patients with malignant external otitis (MEO). Pathological uptake of the radioisotope in the mastoid region was found during the early stages of MEO updating radiologic findings. The extent of the radioisotope accumulation during the early stages of MEO indicates that the actual tissue damage exceeds the clinical estimation. The follow-up BS findings correlate well with the clinical course of MEO indicating either healing or extension to the base of skull.

Chance-type flexion-distraction injuries in the thoracolumbar spine: MR imaging characteristics.

PubMed

Groves, Clare J; Cassar-Pullicino, Victor N; Tins, Bernhard J; Tyrrell, Prudencia N M; McCall, Iain W

2005-08-01

To evaluate retrospectively the magnetic resonance (MR) imaging features of Chance-type flexion-distraction injuries. The authors' institutional review board does not require its approval or patient informed consent for retrospective studies. Imaging data were reviewed retrospectively for 24 patients (15 male, nine female; mean age, 28 years; range, 9-71 years) who had sustained radiographically typical Chance-type flexion-distraction injuries. The posterior vertebral body height remained unchanged or was increased in these patients. Two radiologists recorded a variety of bone and soft-tissue abnormalities seen with MR imaging. Based on consensus, the documented findings were sequentially analyzed to determine their frequencies. Combined bone and soft-tissue injuries occurred in 23 (96%) of 24 patients, were more common than soft-tissue damage alone (one [4%] of 24 patients), and occurred primarily at the thoracolumbar junction. Contiguous vertebral injury was seen in 20 (83%) of 24 patients, usually in the form of anterosuperior vertebral endplate edema, while noncontiguous injury occurred in eight (33%) of 24 patients. Extensive subcutaneous and paraspinal muscle edema was seen in all patients and extended over several segments. Posterior osteoligamentous complex disruption also occurred in all patients. Horizontally oriented fractures of the posterior neural arches produced an MR imaging pattern that the authors call the sandwich sign, which consists of linear hemorrhage framed by marrow edema. This sign was seen in 12 (50%) of 24 patients. In seven (29%) of 24 patients, a fracture line extending from a damaged pedicle was seen to exit through the contralateral posterosuperior aspect of the vertebral body, with extension of the fracture fragments into the spinal canal. A spectrum of features is discernible with MR imaging in Chance-type injuries.

Origins of bone repair in the armour of fossil fish: response to a deep wound by cells depositing dentine instead of dermal bone.

PubMed

Johanson, Zerina; Smith, Moya; Kearsley, Anton; Pilecki, Peter; Mark-Kurik, Elga; Howard, Charles

2013-10-23

The outer armour of fossil jawless fishes (Heterostraci) is, predominantly, a bone with a superficial ornament of dentine tubercles surrounded by pores leading to flask-shaped crypts (ampullae). However, despite the extensive bone present in these early dermal skeletons, damage was repaired almost exclusively with dentine. Consolidation of bone, by dentine invading and filling the vascular spaces, was previously recognized in Psammolepis and other heterostracans but was associated with ageing and dermal shield wear (reparative). Here, we describe wound repair by deposition of dentine directly onto a bony scaffold of fragmented bone. An extensive wound response occurred from massive deposition of dentine (reactionary), traced from tubercle pulp cavities and surrounding ampullae. These structures may provide the cells to make reparative and reactionary dentine, as in mammalian teeth today in response to stimuli (functional wear or damage). We suggest in Psammolepis, repair involved mobilization of these cells in response to a local stimulatory mechanism, for example, predator damage. By comparison, almost no new bone is detected in repair of the Psammolepis shield. Dentine infilling bone vascular tissue spaces of both abraded dentine and wounded bone suggests that recruitment of this process has been evolutionarily conserved over 380 Myr and precedes osteogenic skeletal repair.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

PubMed

Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

2016-02-06

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering

PubMed Central

Nims, Robert J.; Durney, Krista M.; Cigan, Alexander D.; Hung, Clark T.; Ateshian, Gerard A.

2016-01-01

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

Fatigue Damage of Collagenous Tissues: Experiment, Modeling and Simulation Studies

PubMed Central

Martin, Caitlin; Sun, Wei

2017-01-01

Mechanical fatigue damage is a critical issue for soft tissues and tissue-derived materials, particularly for musculoskeletal and cardiovascular applications; yet, our understanding of the fatigue damage process is incomplete. Soft tissue fatigue experiments are often difficult and time-consuming to perform, which has hindered progress in this area. However, the recent development of soft-tissue fatigue-damage constitutive models has enabled simulation-based fatigue analyses of tissues under various conditions. Computational simulations facilitate highly controlled and quantitative analyses to study the distinct effects of various loading conditions and design features on tissue durability; thus, they are advantageous over complex fatigue experiments. Although significant work to calibrate the constitutive models from fatigue experiments and to validate predictability remains, further development in these areas will add to our knowledge of soft-tissue fatigue damage and will facilitate the design of durable treatments and devices. In this review, the experimental, modeling, and simulation efforts to study collagenous tissue fatigue damage are summarized and critically assessed. PMID:25955007

Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model

PubMed Central

Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

2014-01-01

The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. PMID:24689513

Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy

PubMed Central

Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Santos, Janine Hertzog

2016-01-01

Abstract Aims: Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. Results: We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. Innovation: This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. Conclusion: MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072–1083. PMID:26935406

Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy.

PubMed

Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Santos, Janine Hertzog; Jurkunas, Ula V

2016-06-20

Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072-1083.

Pathomorphism of spiral tibial fractures in computed tomography imaging.

PubMed

Guzik, Grzegorz

2011-01-01

Spiral fractures of the tibia are virtually homogeneous with regard to their pathomorphism. The differences that are seen concern the level of fracture of the fibula, and, to a lesser extent, the level of fracture of the tibia, the length of fracture cleft, and limb shortening following the trauma. While conventional radiographs provide sufficient information about the pathomorphism of fractures, computed tomography can be useful in demonstrating the spatial arrangement of bone fragments and topography of soft tissues surrounding the fracture site. Multiple cross-sectional computed tomography views of spiral fractures of the tibia show the details of the alignment of bone chips at the fracture site, axis of the tibial fracture cleft, and topography of soft tissues that are not visible on standard radiographs. A model of a spiral tibial fracture reveals periosteal stretching with increasing spiral and longitudinal displacement. The cleft in tibial fractures has a spiral shape and its line is invariable. Every spiral fracture of both crural bones results in extensive damage to the periosteum and may damage bellies of the long flexor muscle of toes, flexor hallucis longus as well as the posterior tibial muscle. Computed tomography images of spiral fractures of the tibia show details of damage that are otherwise invisible on standard radiographs. Moreover, CT images provide useful information about the spatial location of the bone chips as well as possible threats to soft tissues that surround the fracture site. Every spiral fracture of the tibia is associated with disruption of the periosteum. 1. Computed tomography images of spiral fractures of the tibia show details of damage otherwise invisible on standard radiographs, 2. The sharp end of the distal tibial chip can damage the tibialis posterior muscle, long flexor muscles of the toes and the flexor hallucis longus, 3. Every spiral fracture of the tibia is associated with disruption of the periosteum.

SpxA1 and SpxA2 Act Coordinately To Fine-Tune Stress Responses and Virulence in Streptococcus pyogenes.

PubMed

Port, Gary C; Cusumano, Zachary T; Tumminello, Paul R; Caparon, Michael G

2017-03-28

SpxA is a unique transcriptional regulator highly conserved among members of the phylum Firmicutes that binds RNA polymerase and can act as an antiactivator. Why some Firmicutes members have two highly similar SpxA paralogs is not understood. Here, we show that the SpxA paralogs of the pathogen Streptococcus pyogenes , SpxA1 and SpxA2, act coordinately to regulate virulence by fine-tuning toxin expression and stress resistance. Construction and analysis of mutants revealed that SpxA1 - mutants were defective for growth under aerobic conditions, while SpxA2 - mutants had severely attenuated responses to multiple stresses, including thermal and oxidative stresses. SpxA1 - mutants had enhanced resistance to the cationic antimicrobial molecule polymyxin B, while SpxA2 - mutants were more sensitive. In a murine model of soft tissue infection, a SpxA1 - mutant was highly attenuated. In contrast, the highly stress-sensitive SpxA2 - mutant was hypervirulent, exhibiting more extensive tissue damage and a greater bacterial burden than the wild-type strain. SpxA1 - attenuation was associated with reduced expression of several toxins, including the SpeB cysteine protease. In contrast, SpxA2 - hypervirulence correlated with toxin overexpression and could be suppressed to wild-type levels by deletion of speB These data show that SpxA1 and SpxA2 have opposing roles in virulence and stress resistance, suggesting that they act coordinately to fine-tune toxin expression in response to stress. SpxA2 - hypervirulence also shows that stress resistance is not always essential for S. pyogenes pathogenesis in soft tissue. IMPORTANCE For many pathogens, it is generally assumed that stress resistance is essential for pathogenesis. For Streptococcus pyogenes , environmental stress is also used as a signal to alter toxin expression. The amount of stress likely informs the bacterium of the strength of the host's defense response, allowing it to adjust its toxin expression to produce the ideal amount of tissue damage, balancing between too little damage, which will result in its elimination, and too much damage, which will debilitate the host. Here we identify components of a genetic circuit involved in stress resistance and toxin expression that has a fine-tuning function in tissue damage. The circuit consists of two versions of the protein SpxA that regulate transcription and are highly similar but have opposing effects on the severity of soft tissue damage. These results will help us understand how virulence is fine-tuned in other pathogens that have two SpxA proteins. Copyright © 2017 Port et al.

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

PubMed Central

Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cells function for soft tissue regeneration

PubMed Central

Li, Hong-Mian; Peng, Qi-Liu; Huang, Min-Hong; Li, De-Quan; Liang, Yi-Dan; Chi, Gang-Yi; Li, De-Hui; Yu, Bing-Chao; Huang, Ji-Rong

2016-01-01

Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering. PMID:27191987

Prodrug strategy for cancer cell-specific targeting: A recent overview.

PubMed

Zhang, Xian; Li, Xiang; You, Qidong; Zhang, Xiaojin

2017-10-20

The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tissues, cancer cells are characterized by unique aberrant markers, thus inactive prodrugs targeting these markers are excellent therapeutics to release active drugs, killing cancer cells without damaging normal tissues. In this review, we explore an integrated view of potential prodrugs applied in targeted cancer therapy based on aberrant cancer specific markers and some examples are provided for inspiring new ideas of prodrug strategy for cancer cell-specific targeting. Copyright © 2017. Published by Elsevier Masson SAS.

In vivo biocompatibility of boron nitride nanotubes: effects on stem cell biology and tissue regeneration in planarians.

PubMed

Salvetti, Alessandra; Rossi, Leonardo; Iacopetti, Paola; Li, Xia; Nitti, Simone; Pellegrino, Teresa; Mattoli, Virgilio; Golberg, Dmitri; Ciofani, Gianni

2015-07-01

Boron nitride nanotubes (BNNTs) represent an extremely interesting class of nanomaterials, and recent findings have suggested a number of applications in the biomedical field. Anyhow, extensive biocompatibility investigations are mandatory before any further advancement toward preclinical testing. Here, we report on the effects of multiwalled BNNTs in freshwater planarians, one of the best-characterized in vivo models for developmental biology and regeneration research. Obtained results indicate that BNNTs are biocompatible in the investigated model, since they do not induce oxidative DNA damage and apoptosis, and do not show adverse effects on planarian stem cell biology and on de novo tissue regeneration. In summary, collected findings represent another important step toward BNNT realistic applications in nanomedicine.

Pitavastatin is a potent anti-inflammatory agent in the rat paw model of acute inflammation.

PubMed

Qadir, Farida; Alam, Syed Mahboob; Siddiqi, Abeer Qamar; Kamran, Afshan

2014-11-01

Statins are used extensively as anti-hyperlipidemic agents. In addition to curtailing cholesterol synthesis they have been found to have multiple actions unrelated to cholesterol lowering "the pleiotropic effects," which includes inhibition of inflammation. We aimed at investigating the effect of pitavastatin a 3rd generation statin, in suppressing acute inflammation in rat paw edema model. Male Sprague-Dawley rats were randomly assigned to one of five groups (n=8): Control, indomethacin and pitavastatin (0.2mg/kg, 0.4mg/kg, 0.8mg/kg) treated. 1hour following treatment, inflammation was induced by sub-planter injection of egg albumin into the hind paw. Anti-inflammatory effect was evaluated by measurement of edema formation every half hour for three hours, assessment of polymorphonuclear leukocyte (PMNL) infiltration and measurement of tissue damage in skin biopsies. Ascending doses of pitavastatin were found to attenuate these parameters. The lowest dose of pitavastatin (0.2mg/kg) was found to significantly reduce edema volume, PMNL infiltration and tissue damage. The efficacy of the smallest dose was found comparable to indomethacin.

Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology, and Survival in the Mouse Model of Bubonic Plague.

PubMed

Levy, Yinon; Vagima, Yaron; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Gur, David; Fogel, Itay; Chitlaru, Theodor; Flashner, Yehuda; Mamroud, Emanuelle

2016-09-15

Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague. Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-Y. pestis antibodies alone or in combination with the corticosteroid methylprednisolone. The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase 9 in the tissues, and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs. Corticosteroids induce an unexpectedly effective antibacterial response apart from their antiinflammatory properties, thereby improving treatment efficacy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Identification of the IGF-1 processing product human Ec/rodent Eb peptide in various tissues: Evidence for its differential regulation after exercise-induced muscle damage in humans.

PubMed

Vassilakos, George; Philippou, Anastassios; Koutsilieris, Michael

2017-02-01

Insulin-like growth factor-1 (IGF-1) is a pleiotropic factor expressed in various tissues and plays a critical role in skeletal muscle physiology. Alternative splicing of the IGF-1 gene gives rise to different precursor polypeptides (isoforms) which could undergo post-translational cleavage, generating the common mature IGF-1 peptide and different carboxyl terminal extension (E-) peptides, with the fate of the latter being, so far, unknown. The objective if this study was to identify the IGF-1Ec forms or processing product(s), other than mature IGF-1, generated in different human and rodent tissues and particularly in human skeletal muscle after exercise-induced damage. Protein lysates from a wide range of human and rodent tissues were immunoblotted with a rabbit anti-human Ec polyclonal antibody raised against the last 24 amino acids of the C-terminal of the Ec peptide. This antibody can recognize the Ec peptide, both as part of IGF-1Ec and alone, and also the corresponding rodent forms, due to the high homology that the human Ec shares with the rodent Eb. We were able to confirm, for the first time, that the human Ec peptide and its rodent homologous Eb peptide are produced simultaneously with their precursor protein (pro-IGF-1Ec/Eb) in vivo, in a wide range of tissues (e.g. muscle, liver, heart). Proprotein convertase furin digestion of human muscle and liver protein lysates confirmed that the higher molecular form, pro-IGF-1Ec, can be cleaved to produce the free Ec peptide. Furthermore, initial evidence is provided that Ec peptide is differentially regulated during the process of muscle regeneration after exercise-induced damage in humans. The findings of this study possibly imply that the post-translational modification of the IGF-1Ec pro-peptide may regulate the bioavailability and activity of the processing product(s). Copyright © 2016. Published by Elsevier Ltd.

Open tibial fractures grade IIIC treated successfully with external fixation, negative-pressure wound therapy and recombinant human bone morphogenetic protein 7.

PubMed

Babiak, Ireneusz

2014-10-01

The aim of the therapy in open tibial fractures grade III was to cover the bone with soft tissue and achieve healed fracture without persistent infection. Open tibial fractures grade IIIC with massive soft tissue damage require combined orthopaedic, vascular and plastic-reconstructive procedures. Negative-pressure wound therapy (NPWT), used in two consecutive cases with open fracture grade IIIC of the tibia diaphysis, healed extensive soft tissue defect with exposure of the bone. NPWT eventually allowed for wound closure by split skin graft within 21-25 days. Ilizarov external fixator combined with application of recombinant human bone morphogenetic protein-7 at the site of delayed union enhanced definitive bone healing within 16-18 months. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Changes in optical properties during heating of ex vivo liver tissues

NASA Astrophysics Data System (ADS)

Nagarajan, Vivek Krishna; Gogineni, Venkateshwara R.; White, Sarah B.; Yu, Bing

2017-02-01

Thermal ablation is the use of heat to induce cell death through coagulative necrosis. Ideally, complete ablation of tumor cells with no damage to surrounding critical structures such as blood vessels, nerves or even organs is desired. Ablation monitoring techniques are often employed to ensure optimal tumor ablation. In thermal tissue ablation, tissue damage is known to be dependent on the temperature and time of exposure. Aptly, current methods for monitoring ablation rely profoundly on local tissue temperature and duration of heating to predict the degree of tissue damage. However, such methods do not take into account the microstructural and physiological changes in tissues as a result of thermocoagulation. Light propagation within biological tissues is known to be dependent on the tissue microstructure and physiology. During tissue denaturation, changes in tissue structure alter light propagations in tissue which could be used to directly assess the extent of thermal tissue damage. We report the use of a spectroscopic system for monitoring the tissue optical properties during heating of ex vivo liver tissues. We observed that during tissue denaturation, continuous changes in wavelength-averaged μa(λ) and μ's(λ) followed a sigmoidal trend and are correlated with damage predicted by Arrhenius model.

Tubular organ epithelialisation

PubMed Central

Saksena, Rhea; Gao, Chuanyu; Wicox, Mathew; de Mel, Achala

2016-01-01

Hollow, tubular organs including oesophagus, trachea, stomach, intestine, bladder and urethra may require repair or replacement due to disease. Current treatment is considered an unmet clinical need, and tissue engineering strategies aim to overcome these by fabricating synthetic constructs as tissue replacements. Smart, functionalised synthetic materials can act as a scaffold base of an organ and multiple cell types, including stem cells can be used to repopulate these scaffolds to replace or repair the damaged or diseased organs. Epithelial cells have not yet completely shown to have efficacious cell–scaffold interactions or good functionality in artificial organs, thus limiting the success of tissue-engineered grafts. Epithelial cells play an essential part of respective organs to maintain their function. Without successful epithelialisation, hollow organs are liable to stenosis, collapse, extensive fibrosis and infection that limit patency. It is clear that the source of cells and physicochemical properties of scaffolds determine the successful epithelialisation. This article presents a review of tissue engineering studies on oesophagus, trachea, stomach, small intestine, bladder and urethral constructs conducted to actualise epithelialised grafts. PMID:28228931

Development and characterisation of polymeric microparticle of poly(d,l-lactic acid) loaded with holmium acetylacetonate.

PubMed

de Azevedo, Mariangela de Burgos M; de Melo, Vitor H S; Soares, Carlos Roberto J; Miyamoto, Douglas M; Katayama, Ricardo A; Squair, Peterson L; Barros, Caio H N; Tasic, Ljubica

2018-06-14

Biodegradable polymers containing radioactive isotopes such as Holmium 166 ( 166 Ho) have potential applications as beta particle emitters in tumour tissues. It is also a gamma ray emitter, allowing nuclear imaging of any tissue to be acquired. It is frequently used in the form of complexes such as holmium acetylacetonate (HoAcAc), which may cause damages in tissues next to the targets cancer cells, as it is difficult to control its linkage or healthy tissues radiotherapy effects. Poly(d,l-lactic acid), PDLLA, was used to encapsulate holmium acetylacetonate (HoAcAc) using an emulsion solvent extraction/evaporation technique. Microspheres with sizes between 20-53 µm were extensively characterised. HoAcAc release from the microspheres was assessed through studies using Inductively Coupled Plasma - Optical Emission Spectroscopy, and the microspheres showed no holmium leakage after a period of 10 half-lives and following gamma irradiation. Thus, HoAcAc loaded microspheres are here presented as a potential system for brachytherapy and imaging purposes.

Cyanobacteria and cyanotoxins in fishponds and their effects on fish tissue.

PubMed

Drobac, Damjana; Tokodi, Nada; Lujić, Jelena; Marinović, Zoran; Subakov-Simić, Gordana; Dulić, Tamara; Važić, Tamara; Nybom, Sonja; Meriluoto, Jussi; Codd, Geoffrey A; Svirčev, Zorica

2016-05-01

Cyanobacteria can produce toxic metabolites known as cyanotoxins. Common and frequently investigated cyanotoxins include microcystins (MCs), nodularin (NOD) and saxitoxins (STXs). During the summer of 2011 extensive cyanobacterial growth was found in several fishponds in Serbia. Sampling of the water and fish (common carp, Cyprinus carpio) was performed. Water samples from 13 fishponds were found to contain saxitoxin, microcystin, and/or nodularin. LC-MS/MS showed that MC-RR was present in samples of fish muscle tissue. Histopathological analyses of fish grown in fishponds with cyanotoxin production showed histopathological damage to liver, kidney, gills, intestines and muscle tissues. This study is among the first so far to report severe hyperplasia of intestinal epithelium and severe degeneration of muscle tissue of fish after cyanobacterial exposure. These findings emphasize the importance of cyanobacterial and cyanotoxin monitoring in fishponds in order to recognize cyanotoxins and their potential effects on fish used for human consumption and, further, on human health. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

PubMed

Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric

2017-10-01

To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

Recent advances on biomedical applications of scaffolds in wound healing and dermal tissue engineering.

PubMed

Rahmani Del Bakhshayesh, Azizeh; Annabi, Nasim; Khalilov, Rovshan; Akbarzadeh, Abolfazl; Samiei, Mohammad; Alizadeh, Effat; Alizadeh-Ghodsi, Mohammadreza; Davaran, Soodabeh; Montaseri, Azadeh

2018-06-01

The tissue engineering field has developed in response to the shortcomings related to the replacement of the tissues lost to disease or trauma: donor tissue rejection, chronic inflammation and donor tissue shortages. The driving force behind the tissue engineering is to avoid the mentioned issues by creating the biological substitutes capable of replacing the damaged tissue. This is done by combining the scaffolds, cells and signals in order to create the living, physiological, three-dimensional tissues. A wide variety of skin substitutes are used in the treatment of full-thickness injuries. Substitutes made from skin can harbour the latent viruses, and artificial skin grafts can heal with the extensive scarring, failing to regenerate structures such as glands, nerves and hair follicles. New and practical skin scaffold materials remain to be developed. The current article describes the important information about wound healing scaffolds. The scaffold types which were used in these fields were classified according to the accepted guideline of the biological medicine. Moreover, the present article gave the brief overview on the fundamentals of the tissue engineering, biodegradable polymer properties and their application in skin wound healing. Also, the present review discusses the type of the tissue engineered skin substitutes and modern wound dressings which promote the wound healing.

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates.

PubMed

Grieves, J L; Dick, E J; Schlabritz-Loutsevich, N E; Butler, S D; Leland, M M; Price, S E; Schmidt, C R; Nathanielsz, P W; Hubbard, G B

2008-06-01

Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Effects Of Continuous Argon Laser Irradiation On Canine And Autopsied Human Cardiac Tissue

NASA Astrophysics Data System (ADS)

Ben-Shachar, Giora; Sivakoff, Mark; Bernard, Steven L.; Dahms, Beverly B.; Riemenschneider, Thomas A.

1984-10-01

In eight human formalin preserved cardiac specimens, various cardiac and vascular obstructions were relieved by argon laser irradiation. Interatrial communication was also produced by a transar'rial approach in a live dog. In-vivo fresh canine cardiac tissues required power density of at feast 80, 90, and 110 watts/cm2 for vaporization of myocardial, vascular and valvular tissues respectively. The fiber tip to tissue distance (effective irradiation distance) for effective vaporization was less than I mm for vascular and valvular tissues and less than 4 mm for myocardium. Light microscopy showed four zones of histological damage common to all tissues - central crater surrounded by layers of charring, vacuolization and coagulation necorsis. Myocardium showed additionally a layer of normal appearing muscle cells (skip area) surrounded by a peripheral coagulation halo. Laser irradiation effects on valvular tissue showed the most lateral extension of coagulation necrosis. It is concluded that palliation and treatment of certain congenital heart defects by laser irradiation is anatomi-cally feasible and may be safe for in vivo application when low power output and short exposure time are used from a very short irradiation distance.

Cavisoma magnum (Cavisomidae), a unique Pacific acanthocephalan redescribed from an unusual host, Mugil cephalus (Mugilidae), in the Arabian Gulf, with notes on histopathology and metal analysis

PubMed Central

Amin, Omar M.; Heckmann, Richard A.; Bannai, Majid A.

2018-01-01

Cavisoma magnum (Southwell, 1927) Van Cleave, 1931 was originally described from a sea bass, Serranus sp. and spotted surgeonfish, Ctenochaetus strigosus (Perciformes) off Sri Lanka before its more recent redescription from milkfish in the Philippines in 1995. These reports were based on only light infections of their host fishes. Of the few flathead grey mullets, Mugil cephalus (Mugilidae), that we examined in the Arabian Gulf, one fish was infected with 1,450 worms. One milkfish, Chanos chanos (Chanidae), from the same location in the Arabian Gulf, was also heavily infected with specimens of C. magnum. The descriptions of this unique large worm are revised and for the first time, we provide SEM images, new systematic observations, metal analysis of hooks showing extremely high levels of sulfur, and histopathology in the mullet intestinal tissue. Adjustments and corrections of previous descriptive accounts are made. The histopathology studies show extensive damage to the host intestinal tissue including epithelial necrosis, hemorrhaging and worm encapsulation. There is an extensive amount of host connective tissue surrounding the worm. Results of x-ray analysis displayed high levels of sulfur in proboscis hooks, especially at the tips and edges of these attachment structures. PMID:29424340

Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

PubMed

Andersen, Monica L; Ribeiro, Daniel A; Alvarenga, Tathiana A; Silva, Andressa; Araujo, Paula; Zager, Adriano; Tenorio, Neuli M; Tufik, Sergio

2010-02-01

The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones. Copyright 2009 Elsevier Inc. All rights reserved.

Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue.

PubMed

Schomacker, K T; Walsh, J T; Flotte, T J; Deutsch, T F

1990-01-01

Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

Comparison of a combination diode laser and radiofrequency device (Polaris) and a long-pulsed 1064-nm Nd:YAG laser (Lyra) on leg telangiectases. Histologic and immunohistochemical analysis.

PubMed

Prieto, Victor; Zhang, Peter; Sadick, Neil S

2006-12-01

Several devices have been proposed for the treatment of leg telangiectases. For most of these devices the histologic changes induced in the dermis are not well characterized. Three volunteers with class I-II red and blue 0.1-2.0 mm leg telangiectases were treated with the Lyra (Laserscope, San Jose, CA, USA) and the Polaris (Syneron Medical Ltd, Yokneam, Israel) devices to the left and right legs, respectively. Two 3-mm punches were taken from either site 7 days after treatment. The specimens were routinely processed and also stained for elastic tissue and collagen tissue. After treatment, specimens treated with both the Polaris and the Lyra showed intermediate-sized vessels with complete thrombosis and extensive hemorrhage in both the dermis and subcutis. The overlying epidermis also evidenced damage characterized as focal full-thickness necrosis. Special stains confirmed the damage to the vessels. All other skin structures were morphologically unremarkable. An average of 50-75% clinical clearing occurred using both modalities of a single treatment session. Our study confirms that both devices result in severe damage to small, intermediate-sized vessels, thus explaining the reported clinical improvement of leg telangiectases. The expression of hsp70 in the dermal vessels and overlying epidermis is consistent with a direct thermal effect delivered by either device.

Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

PubMed

Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

2014-10-01

The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia.

PubMed

Soetaert, Frederik; Dupré, Luc; Ivkov, Robert; Crevecoeur, Guillaume

2015-10-01

Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH).

Acute tissue reactions, inner segment pathology, and effects of the antioxidant α1-microglobulin in an in vitro model of retinal detachment.

PubMed

Ghosh, Fredrik; Åkerström, Bo; Bergwik, Jesper; Abdshill, Hodan; Gefors, Lina; Taylor, Linnéa

2018-04-18

The purpose of this study was to explore acute tissue reactions, ultrastructural photoreceptor morphology with emphasis on inner segments, and the effect of antioxidant treatment in an in vitro model of rhegmatogenous retinal detachment (RRD). A previously described method of RRD simulation was used with adult retinal porcine explants kept free-floating in culture medium with or without treatment with the radical scavenger α 1 -microglobulin (A1M). Explants were examined at 5 time points from 1 to 24 h using transmission electron microscopy as well as quantitative real-time PCR (RT-PCR) to quantify gene expression of the cell stress marker heat shock protein 70 (Hsp70) and oxidative stress marker heme oxygenase (HO-1). The culture medium level of the cell damage marker lactate dehydrogenase (LDH) and oxidative stress DNA damage marker 8-Oxo-2'-deoxyguanosine (8-OHdG) was also assessed at each time point. We found that the levels of Hsp70 and LDH rapidly increased in both groups, and at 3 and 6 h, Hsp70 was significantly higher in A1M treated retinas. At 24 h, Hsp70 and LDH, as well as 8-OHdG were significantly lower compared with controls, whereas the tissue level of HO-1 was significantly higher. Progressive ultrastructural photoreceptor changes were seen in untreated control explants from 1 h and onwards including outer segment shortening and loss, disruption of organelles within the inner segments and loss of perikarya in the outer nuclear layer. Inner segment pathology was more rapid and extensive in rods compared with in cones. In A1M treated counterparts, damage to rod inner segment mitochondria was significantly higher after 1 h of culture, but after this time, no statistical difference was found. At 24 h, cone inner segment mitochondrial disruption was significantly higher in control retinas and the number of surviving perikarya lower. From our results, we conclude that retinal explants elicit acute cell stress reactions when placed in culture without physical support simulating a detached retina floating in the vitreous space. Photoreceptors rapidly display degenerative changes including extensive damage to inner segment mitochondria indicating loss of energy transduction as an early key event. A1M increases initial mitochondrial stress in the rods, however, subsequent pathology is attenuated by the treatment, highlighting the dynamics of protective as well as disruptive oxidative stress reactions in the detached retina. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predictive analysis of photodynamic therapy applied to esophagus cancer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

2008-04-01

The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

Vulnerability of the Superficial Zone of Immature Articular Cartilage to Compressive Injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rolauffs, R.; Muehleman, C; Li, J

The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive moduli as well as collagen and sulfated glycosaminoglycan (sGAG) content also vary with depth. However, there is little understanding of the depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, this study was undertaken to characterize the zonal dependence of biomechanical, biochemical, and matrix-associated changes caused by compressive injury. Disks from the superficial and deeper zones of bovine calves were biomechanically characterized. Injury to the disks was achieved by applying amore » final strain of 50% compression at 100%/second, followed by biomechanical recharacterization. Tissue compaction upon injury as well as sGAG density, sGAG loss, and biosynthesis were measured. Collagen fiber orientation and matrix damage were assessed using histology, diffraction-enhanced x-ray imaging, and texture analysis. Injured superficial zone disks showed surface disruption, tissue compaction by 20.3 {+-} 4.3% (mean {+-} SEM), and immediate biomechanical impairment that was revealed by a mean {+-} SEM decrease in dynamic stiffness to 7.1 {+-} 3.3% of the value before injury and equilibrium moduli that were below the level of detection. Tissue areas that appeared intact on histology showed clear textural alterations. Injured deeper zone disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose sGAG immediately after injury, but lost 17.8 {+-} 1.4% of sGAG after 48 hours; deeper zone disks lost only 2.8 {+-} 0.3% of sGAG content. Biomechanical impairment was associated primarily with structural damage. The soft superficial zone of immature cartilage is vulnerable to compressive injury, causing superficial matrix disruption, extensive compaction, and textural alteration, which results in immediate loss of biomechanical function. In conjunction with delayed superficial sGAG loss, these changes may predispose the articular surface to further softening and tissue damage, thus increasing the risk of development of secondary osteoarthritis.« less

In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides

PubMed Central

2017-01-01

Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. Here, we show that a designed peptide (collagen hybridizing peptide: CHP), which specifically hybridizes to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues: labeled with 5-carboxyfluorescein and biotin, CHPs enabled direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. The results indicate the general correlation between the level of collagen remodeling and the amount of denatured collagen in tissue and show that the CHP probes can be used across species and collagen types, providing a versatile tool for not only pathology and developmental biology research but also histology-based disease diagnosis, staging, and therapeutic screening. This study lays the foundation for further testing CHP as a targeting moiety for theranostic delivery in various animal models. PMID:28877431

Subarachnoid-to-Subarachnoid Shunt for Correction of Nonfunctioning Baclofen Pump in a Severe Case of Chronic Debilitating Post-Spinal Cord Injury Spasticity.

PubMed

Bakare, Adewale A; Weyhenmeyer, Jonathan; Lee, Albert

2018-02-01

Perhaps the most disabling condition seen in patients with spinal cord injury (SCI) is spasticity. Spasticity is characterized as hyperreflexia and hypertonicity as a result of damage to the supraspinal tracts in the aftermath of SCI. Intrathecal baclofen (ITB) is the mainstay therapy for spasticity unresponsive to oral baclofen. One of the problems associated with post-SCI spasticity unresponsive to ITB is the development of scar tissue that prevents the diffusion of baclofen in the desired spinal cord area. This case offers a unique strategy to deal with multilevel scar tissue. This 46-year-old paraplegic male with a T8 SCI whose spasticity had been well managed with ITB therapy for many years recently suffered intractable spasticity necessitating multiple reoperations for a nonfunctioning ITB catheter secondary to extensive scar tissue and intrathecal adhesions. Placement of a subarachnoid-to-subarachnoid shunt eliminated the problem of extensive scar tissue preventing adequate baclofen therapy. After undergoing multilevel thoracic and lumbar laminectomies with subarachnoid-to-subarachnoid spinal shunt, the patient's spasticity was finally brought under control with adequate daily baclofen infusion. This case demonstrates a creative way to address ITB catheter failure before considering other measures, such as neuroablative procedures (e.g., rhizotomy, myelotomy). This case reinforces the recommendation that ablative procedures, which have far greater complications, should be reserved for patients who have failed medical or other nonablative therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling electrical power absorption and thermally-induced biological tissue damage.

PubMed

Zohdi, T I

2014-01-01

This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

PubMed

Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-01-02

Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation

PubMed Central

Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-01-01

ABSTRACT Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model. PMID:27690290

Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

NASA Astrophysics Data System (ADS)

Ross, Ryan D.; Cole, Lisa E.; Roeder, Ryan K.

2012-10-01

Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate ( l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

Assessment of penetrating thermal tissue damage/spread associated with PhotonBlade™, Valleylab™ Pencil, Valleylab™ EDGE™ Coated Pencil, PlasmaBlade® 3.0S and PlasmaBlade® 4.0 for intraoperative tissue dissection using the fresh extirpated porcine muscle model

NASA Astrophysics Data System (ADS)

Bennett, Haydon E.; Taylor, Scott D.; Fugett, James H.; Shrout, Joshua L.; Davison, Paul O.; Ryan, S. Eric; Coad, James E.

2017-02-01

Penetrating thermal tissue damage/spread is an important aspect of many electrosurgical devices and correlates with effective tissue cutting, hemostasis, preservation of adjacent critical structures and tissue healing. This study compared the thermal damage/spread associated with the PhotonBlade, Valleylab Pencil, Valleylab EDGE Coated Pencil, PlasmaBlade 3.0S and PlasmaBlade 4.0, when performing a single pass dynamic tissue cut in fresh extirpated porcine longissimus muscle. These devices were used in a fashion that emulated their use in the clinical setting. Each device's thermal damage/spread, at Minimum, Median and Maximum power input settings, was assessed with nitroblue tetrazolium viability staining in the WVU Pathology Laboratory for Translational Medicine. The thermal damage/spread associated with the PhotonBlade was compared with the other devices tested based on the individual treatment results (n=179 cuts combined). In summary, the PhotonBlade overall demonstrated the least penetrating thermal tissue damage/spread, followed by the PlasmaBlade 4.0, then Valleylab Pencil and PlasmaBlade 3.0S and then Valleylab EDGE Coated Pencil in order of increasing thermal damage/spread depths.

Conversion of external fixation to open reduction and internal fixation for complex distal radius fractures.

PubMed

Natoli, R M; Baer, M R; Bednar, M S

2016-05-01

Distal radius fractures are common injuries treated in a multitude of ways. One treatment paradigm not extensively studied is initial treatment by external fixation (EF) followed by conversion to open reduction internal fixation (ORIF). Such a paradigm may be beneficial in damage control situations, when there is extensive soft tissue injury, or when appropriate personnel/hospital resources are not available for immediate internal fixation. There is no increased risk of infection when converting EF to ORIF in the treatment of complex distal radius fractures when conversion occurs early or if EF pin sites are overlapped by the definitive fixation. Using an IRB approved protocol, medical records over nine years were queried to identify patients with distal radius fractures that had undergone initial EF and were later converted to ORIF. Charts were reviewed for demographic data, injury characteristics, operative details, time to conversion from EF to ORIF, assessment of whether the EF pin sites overlapped the definitive fixation, presence of infection after ORIF, complications, and occupational therapy measurements of range of motion and strength. In total, 16 patients were identified, only one of which developed an infection following conversion to ORIF. Fisher's exact testing showed that infection did not depend on open fracture, time to conversion of one week or less, presence of EF pin sites overlapping definitive fixation, fracture classification, high energy mechanism of injury, or concomitant injury to the DRUJ. Planned staged conversion from EF to ORIF for complex distal radius fractures does not appear to result in an increased rate of infection if conversion occurs early or if the EF pin sites are overlapped by definitive fixation. This treatment paradigm may be reasonable for treating complex distal radius fractures in damage control situations, when there is extensive soft tissue injury, or when appropriate personnel/hospital resources are not available for immediate internal fixation. IV, retrospective case series. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells

NASA Astrophysics Data System (ADS)

Jenkins, Phillip M.; Laughter, Melissa R.; Lee, David J.; Lee, Young M.; Freed, Curt R.; Park, Daewon

2015-06-01

Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.

Thermal modeling of lesion growth with radiofrequency ablation devices

PubMed Central

Chang, Isaac A; Nguyen, Uyen D

2004-01-01

Background Temperature is a frequently used parameter to describe the predicted size of lesions computed by computational models. In many cases, however, temperature correlates poorly with lesion size. Although many studies have been conducted to characterize the relationship between time-temperature exposure of tissue heating to cell damage, to date these relationships have not been employed in a finite element model. Methods We present an axisymmetric two-dimensional finite element model that calculates cell damage in tissues and compare lesion sizes using common tissue damage and iso-temperature contour definitions. The model accounts for both temperature-dependent changes in the electrical conductivity of tissue as well as tissue damage-dependent changes in local tissue perfusion. The data is validated using excised porcine liver tissues. Results The data demonstrate the size of thermal lesions is grossly overestimated when calculated using traditional temperature isocontours of 42°C and 47°C. The computational model results predicted lesion dimensions that were within 5% of the experimental measurements. Conclusion When modeling radiofrequency ablation problems, temperature isotherms may not be representative of actual tissue damage patterns. PMID:15298708

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

PubMed Central

Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

2013-01-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.

PubMed

Patsalos, Andreas; Pap, Attila; Varga, Tamas; Trencsenyi, Gyorgy; Contreras, Gerardo Alvarado; Garai, Ildiko; Papp, Zoltan; Dezso, Balazs; Pintye, Eva; Nagy, Laszlo

2017-09-01

The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6C high ) to a repair (Ly6C low ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves normal macrophage transition dynamics and subsequently muscle tissue regeneration. Taken together, our data suggest the existence of a more extensive and reciprocal cross-talk between muscle tissue compartments, including satellite cells, and infiltrating myeloid cells upon tissue damage. These interactions shape the macrophage in situ phenotypic shift, which is indispensable for normal muscle tissue repair dynamics. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Complex engagement of DNA damage response pathways in human cancer and in lung tumor progression.

PubMed

Nuciforo, Paolo Giovanni; Luise, Chiara; Capra, Maria; Pelosi, Giuseppe; d'Adda di Fagagna, Fabrizio

2007-10-01

Tumor initiation and progression provide a multitude of occasions for the generation of DNA damage and the consequent activation of the DNA damage response (DDR) pathway. DDR signaling involves the engagement of key factors such as ATM, CHK2, 53BP1 and the phosphorylation of histone H2AX (gamma-H2AX). The systematic study of DDR in human tumors and normal tissues by high-throughput tissue microarrays revealed that ATM and gamma-H2AX were engaged in cancer but the extent of their activation was strongly affected by the organ and cell type involved, whereas 53BP1 loss was the most consistent feature among the tumor studied. Unexpectedly, we also observed activated DDR markers in morphologically normal tissues, also in association with inflammation. Analysis of the dynamic engagement of DDR along the different stages of lung tumorigenesis showed that 53BP1 loss occurs early at the transition from normal to dysplastic change whereas the activated forms of ATM and CHK2, but not gamma-H2AX, initially accumulate in pre-invasive lesions and are then lost during tumor progression. In individual lung tumors, the activation of ATM, CHK2 and the presence of 53BP1 were consistently correlated, whereas gamma-H2AX did not correlate with activated ATM. Finally, the study of associations between critical clinicopathological parameters and activated DDR factors highlighted a statistically meaningful correlation between reduced local tumor extension and the phosphorylation of ATM, CHK2 and the presence of 53BP1, whereas no significant correlations with parameters such as survival or relapse of early-stage lung carcinomas were found.

Impact of acellular hemoglobin-based oxygen carriers on brain apoptosis in rats.

PubMed

Vandegriff, Kim D; Malavalli, Ashok; Lohman, Jeff; Young, Mark A; Terraneo, Laura; Virgili, Eleonora; Bianciardi, Paola; Caretti, Anna; Samaja, Michele

2014-08-01

Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under extensive consideration as oxygen therapeutics. Their effects on cellular mechanisms related to apoptosis are of particular interest, because the onset of proapoptotic pathways may give rise to tissue damage. The objective was to assess whether the properties of the Hb that replaces blood during an isovolemic hemodilution would modulate apoptotic-response mechanisms in rat brain and whether such signaling favors cytoprotection or damage. We exposed rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen affinity], and ααHb [αα-cross-linked HBOC with low oxygen affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at 2, 6, and 12 hours after ET; brain tissue was harvested and processed for analysis. In MP4OX animals, the number of neurons that overexpressed the hypoxia-inducible factor (HIF)-1α was higher than in ααHb, particularly at the early time points. In addition, MP4OX was associated with greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX < Hextend < ααHb. Even though both HBOCs showed increased levels of HIF-1α compared to shams or Hextend-treated animals, differences in signaling events resulted in very different outcomes for the two HBOCs. ααHb-treated brain tissue showed significant neuronal damage, measured as apoptosis. This was in stark contrast to the protection seen with MP4OX, apparently due to recruitment of Akt and neuronal specific HIF-1α pathways. © 2014 Sangart, Inc. Transfusion © 2014 AABB.

Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

DTIC Science & Technology

2011-07-01

Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage.

PubMed

Stephenson, Makeda K; Farris, Ashley L; Grayson, Warren L

2017-08-01

While the clinical potential of tissue engineering for treating joint damage has yet to be realized, research and commercialization efforts in the field are geared towards overcoming major obstacles to clinical translation, as well as towards achieving engineered grafts that recapitulate the unique structures, function, and physiology of the joint. In this review, we describe recent advances in technologies aimed at obtaining biomaterials, stem cells, and bioreactors that will enable the development of effective tissue-engineered treatments for repairing joint damage. 3D printing of scaffolds is aimed at improving the mechanical structure and microenvironment necessary for bone regeneration within a damaged joint. Advances in our understanding of stem cell biology and cell manufacturing processes are informing translational strategies for the therapeutic use of allogeneic and autologous cells. Finally, bioreactors used in combination with cells and biomaterials are promising strategies for generating large tissue grafts for repairing damaged tissues in pre-clinical models. Together, these advances along with ongoing research directions are making tissue engineering increasingly viable for the treatment of joint damage.

Phototoxicity to the retina: mechanisms of damage.

PubMed

Glickman, Randolph D

2002-01-01

Light damage to the retina occurs through three general mechanisms involving thermal, mechanical, or photochemical effects. The particular mechanism activated depends on the wavelength and exposure duration of the injuring light. The transitions between the various light damage mechanism may overlap to some extent. Energy confinement is a key concept in understanding or predicting the type of damage mechanism produced by a given light exposure. As light energy (either from a laser or an incoherent source) is deposited in the retina, its penetration through, and its absorption in, various tissue compartments is determined by its wavelength. Strongly absorbing tissue components will tend to "concentrate" the light energy. The effect of absorbed light energy largely depends on the rate of energy deposition, which is correlated with the exposure duration. If the rate of energy deposition is too low to produce an appreciable temperature increase in the tissue, then any resulting tissue damage necessarily occurs because of chemical (oxidative) reactions induced by absorption of energetic photons (photochemical damage). If the rate of energy deposition is faster than the rate of thermal diffusion (thermal confinement), then the temperature of the exposed tissue rises. If a critical temperature is reached (typically about 10 degrees C above basal), then thermal damage occurs. If the light energy is deposited faster than mechanical relaxation can occur (stress confinement), then a thermoelastic pressure wave is produced, and tissue is disrupted by shear forces or by cavitation-nonlinear effects. Very recent evidence suggests that ultrashort laser pulses can produce tissue damage through nonlinear and photochemical mechanisms; the latter because of two-photon excitation of cellular chromophores. In addition to tissue damage caused directly by light absorption, light toxicity can be produced by the presence of photosensitizing agents. Drugs excited to reactive states by ultraviolet (UV) or visible light produce damage by type I (free radical) and type II (oxygen dependent) mechanisms. Some commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and psychotherapeutic agents, as well as some popular herbal medicines, can produce ocular phototoxicity. Specific cellular effects and damage end points characteristic of light damage mechanisms are described.

Zygoma Implant-Supported Prosthetic Rehabilitation of a Patient After Bilateral Maxillectomy.

PubMed

Celakil, Tamer; Ayvalioglu, Demet Cagil; Sancakli, Erkan; Atalay, Belir; Doganay, Ozge; Kayhan, Kivanc Bektas

2015-10-01

Maxillectomy defects may vary from localized to extensive soft and hard tissue loss. In addition to physical and psychologic damages, functional and aesthetic aspects must be restored. This clinical report describes the rehabilitation of a patient with a zygoma implant-supported obturator prosthesis caused by a subtotal bilateral maxillectomy due to a squamous oral cell carcinoma. Prosthetic rehabilitation of this patient was performed after zygoma implant surgery. A maxillary obturator prosthesis supported by 2 osseointegrated zygoma implants was fabricated. Despite limited mouth opening and anatomic deficiencies, the patient's aesthetic and functional demands were fulfilled.

Apoptosis Modulation in the Immune System Reveals a Role of Neutrophils in Tissue Damage in a Murine Model of Chlamydial Genital Infection.

PubMed

Zortel, Tom; Schmitt-Graeff, Annette; Kirschnek, Susanne; Häcker, Georg

2018-05-05

Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown, but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of B-cell lymphoma 2 (Bcl-2) in hematopoietic cells (Bcl-2 mice), and mice where mature neutrophils are lacking due to the deletion of Myeloid cell leukemia 1 (Mcl-1) in myeloid cells (LysM-cre-mcl-1-flox mice; Mcl-1 mice). We monitored bacterial clearance, cellular infiltrate, and long-term tissue damage. Both mutant strains showed slightly delayed clearance of the acute infection. Bcl-2 mice had a strongly increased inflammatory infiltrate concerning almost all cell lineages. The infection of Bcl-2 mice caused increased tissue damage. The loss of neutrophils in Mcl-1 mice was associated with substantial quantitative and qualitative alterations of the inflammatory infiltrate. Mcl-1 mice had higher chlamydial burden and reduced tissue damage, including lower incidence of hydrosalpinx and less uterine dilation. Inhibition of apoptosis in the hematopoietic system increases inflammation and tissue damage. Neutrophils have broad functions, including a role in chlamydial clearance and in tissue destruction.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue

NASA Astrophysics Data System (ADS)

Jezernik, Sašo; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

PubMed

Jezernik, Saso; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Infrared laser-mediated local gene induction in medaka, zebrafish and Arabidopsis thaliana.

PubMed

Deguchi, Tomonori; Itoh, Mariko; Urawa, Hiroko; Matsumoto, Tomohiro; Nakayama, Sohei; Kawasaki, Takashi; Kitano, Takeshi; Oda, Shoji; Mitani, Hiroshi; Takahashi, Taku; Todo, Takeshi; Sato, Junichi; Okada, Kiyotaka; Hatta, Kohei; Yuba, Shunsuke; Kamei, Yasuhiro

2009-12-01

Heat shock promoters are powerful tools for the precise control of exogenous gene induction in living organisms. In addition to the temporal control of gene expression, the analysis of gene function can also require spatial restriction. Recently, we reported a new method for in vivo, single-cell gene induction using an infrared laser-evoked gene operator (IR-LEGO) system in living nematodes (Caenorhabditis elegans). It was demonstrated that infrared (IR) irradiation could induce gene expression in single cells without incurring cellular damage. Here, we report the application of IR-LEGO to the small fish, medaka (Japanese killifish; Oryzias latipes) and zebrafish (Danio rerio), and a higher plant (Arabidopsis thaliana). Using easily observable reporter genes, we successfully induced gene expression in various tissues in these living organisms. IR-LEGO has the potential to be a useful tool in extensive research fields for cell/tissue marking or targeted gene expression in local tissues of small fish and plants.

[Skin and soft tissue complications after orthopedic interventions on tumors : interdisciplinary management].

PubMed

Radtke, C; Calliess, T; Windhagen, H; Vogt, P

2015-03-01

Interdisciplinary collaboration between orthopedic and plastic surgeons is indicated in reconstructive surgery of the extremities for both traumatic orthopedic fractures with extensive soft tissue damage and musculoskeletal tumor resection. We want to emphasize the need for close cooperation starting in the preoperative planning for reconstruction after tumor resection in order to discuss and establish a unified approach. This is particularly important to establish a joint approach with special consideration of possibly necessary adjuvant therapies. One collaborative approach is for the orthopedic surgeon to resect the tumor and the plastic surgeon to carry out the defect reconstruction for exclusive soft tissue coverage including flap surgery as well as for functional reconstruction depending on the location and extent of tumor resection. Thus, careful preoperative and postoperative communication on the precise location, extent of tumor resection and the therapy timing between the orthopedic surgeon and the plastic surgeon will allow the most effective subsequent repair of the resection site.

Injury and immune response: applying the danger theory to mosquitoes

PubMed Central

Moreno-García, Miguel; Recio-Tótoro, Benito; Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

2014-01-01

The insect immune response can be activated by the recognition of both non-self and molecular by-products of tissue damage. Since pathogens and tissue damage usually arise at the same time during infection, the specific mechanisms of the immune response to microorganisms, and to tissue damage have not been unraveled. Consequently, some aspects of damage caused by microorganisms in vector-borne arthropods have been neglected. We herein reassess the Anopheles–Plasmodium interaction, incorporating Matzinger’s danger/damage hypothesis and George Salt’s injury assumptions. The invasive forms of the parasite cross the peritrophic matrix and midgut epithelia to reach the basal lamina and differentiate into an oocyst. The sporozoites produced in the oocyst are released into the hemolymph, and from there enter the salivary gland. During parasite development, wounds to midgut tissue and the basement membrane are produced. We describe the response of the different compartments where the parasite interacts with the mosquito. In the midgut, the response includes the expression of antimicrobial peptides, production of reactive oxygen species, and possible activation of midgut regenerative cells. In the basal membrane, wound repair mainly involves the production of molecules and the recruitment of hemocytes. We discuss the susceptibility to damage in tissues, and how the place and degree of damage may influence the differential response and the expression of damage associated molecular patterns (DAMPs). Knowledge about damage caused by parasites may lead to a deeper understanding of the relevance of tissue damage and the immune response it generates, as well as the origins and progression of infection in this insect–parasite interaction. PMID:25250040

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

Cavisoma magnum (Cavisomidae), a unique Pacific acanthocephalan redescribed from an unusual host, Mugil cephalus (Mugilidae), in the Arabian Gulf, with notes on histopathology and metal analysis.

PubMed

Amin, Omar M; Heckmann, Richard A; Bannai, Majid A

2018-01-01

Cavisoma magnum (Southwell, 1927) Van Cleave, 1931 was originally described from a sea bass, Serranus sp. and spotted surgeonfish, Ctenochaetus strigosus (Perciformes) off Sri Lanka before its more recent redescription from milkfish in the Philippines in 1995. These reports were based on only light infections of their host fishes. Of the few flathead grey mullets, Mugil cephalus (Mugilidae), that we examined in the Arabian Gulf, one fish was infected with 1,450 worms. One milkfish, Chanos chanos (Chanidae), from the same location in the Arabian Gulf, was also heavily infected with specimens of C. magnum. The descriptions of this unique large worm are revised and for the first time, we provide SEM images, new systematic observations, metal analysis of hooks showing extremely high levels of sulfur, and histopathology in the mullet intestinal tissue. Adjustments and corrections of previous descriptive accounts are made. The histopathology studies show extensive damage to the host intestinal tissue including epithelial necrosis, hemorrhaging and worm encapsulation. There is an extensive amount of host connective tissue surrounding the worm. Results of x-ray analysis displayed high levels of sulfur in proboscis hooks, especially at the tips and edges of these attachment structures. © O.M. Amin et al., published by EDP Sciences, 2018.

Human and bovine spinal disc mechanics subsequent to trypsin injection.

PubMed

Alsup, Jeremy; Bishop, Timothy; Eggett, Dennis; Bowden, Anton E

2017-10-01

To investigate the biomechanical effects of injections of a protease on the characteristics of bovine coccygeal and human lumbar disc motion segments. Mechanics of treated tissues were measured immediately after injection and 3 h after injection. Motion segments underwent axial rotation and flexion-extension loading. Stiffness and neutral zone parameters experienced significant changes over time, with bovine tissues more strongly affected than human cadaver tissues. This was true in both axial rotation and flexion-extension. The treatment type significantly affected the neutral zone measurements in axial rotation. Hysteresis parameters were impacted by control injections. The extrapolation of bovine coccygeal motion testing results to human lumbar disc mechanics is not yet practical. The injected treatment may have a smaller impact on disc mechanics than time in testing. Viscoelasticity of human lumbar discs may be impacted by any damage to the annulus fibrosis induced by needlestick. Preclinical testing of novel spinal devices is essential to the design validation and regulatory processes, but current testing techniques rely on cadaveric testing of primarily older spines with essentially random amounts of disc degeneration. The present work investigates the viability of using trypsin injections to create a more uniform preclinical model of disc degeneration from a mechanics perspective, for the purpose of testing spinal devices. Such a model would facilitate translation of new spinal technologies to clinical practice.

Dynamic control of type I IFN signalling by an integrated network of negative regulators.

PubMed

Porritt, Rebecca A; Hertzog, Paul J

2015-03-01

Whereas type I interferons (IFNs) have critical roles in protection from pathogens, excessive IFN responses contribute to pathology in both acute and chronic settings, pointing to the importance of balancing activating signals with regulatory mechanisms that appropriately tune the response. Here we review evidence for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways. We propose that the aim of this extensive network is to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude. Understanding the architecture and dynamics of this network, and how it differs in distinct tissues, will provide new insights into IFN biology and aid the design of more effective therapeutics. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

PubMed

Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

2016-11-01

The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano- and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.

PubMed

Borton, Anna Henry; Benson, Bryan L; Neilson, Lee E; Saunders, Ashley; Alaiti, M Amer; Huang, Alex Y; Jain, Mukesh K; Proweller, Aaron; Ramirez-Bergeron, Diana L

2018-06-01

Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia-inducible factors (HIFs) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells' (VSMCs') importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease. This study investigated the role of VSMC HIF in mediating peripheral ischemic responses. We used Arnt SMKO mice with smooth muscle-specific deletion of aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), required for HIF transcriptional activity, in a femoral artery ligation model of peripheral vascular disease. Arnt SMKO mice exhibit impaired perfusion recovery despite normal collateral vessel dilation and angiogenic capillary responses. Decreased blood flow manifests in extensive tissue damage and hypoxia in ligated limbs of Arnt SMKO mice. Furthermore, loss of aryl hydrocarbon receptor nuclear translocator changes the proliferation, migration, and transcriptional profile of cultured VSMCs. Arnt SMKO mice display disrupted VSMC morphologic features and wrapping around arterioles and increased vascular permeability linked to decreased local blood flow. Our data demonstrate that traditional vascular remodeling responses are insufficient to provide robust peripheral tissue reperfusion in Arnt SMKO mice. In all, this study highlights HIF responses to hypoxia in arteriole VSMCs critical for the phenotypic and functional stability of vessels that aid in the recovery of blood flow in ischemic peripheral tissues. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Muscle Damage following Maximal Eccentric Knee Extensions in Males and Females

PubMed Central

2016-01-01

Aim To investigate whether there is a sex difference in exercise induced muscle damage. Materials and Method Vastus Lateralis and patella tendon properties were measured in males and females using ultrasonography. During maximal voluntary eccentric knee extensions (12 reps x 6 sets), Vastus Lateralis fascicle lengthening and maximal voluntary eccentric knee extensions torque were recorded every 10° of knee joint angle (20–90°). Isometric torque, Creatine Kinase and muscle soreness were measured pre, post, 48, 96 and 168 hours post damage as markers of exercise induced muscle damage. Results Patella tendon stiffness and Vastus Lateralis fascicle lengthening were significantly higher in males compared to females (p<0.05). There was no sex difference in isometric torque loss and muscle soreness post exercise induced muscle damage (p>0.05). Creatine Kinase levels post exercise induced muscle damage were higher in males compared to females (p<0.05), and remained higher when maximal voluntary eccentric knee extension torque, relative to estimated quadriceps anatomical cross sectional area, was taken as a covariate (p<0.05). Conclusion Based on isometric torque loss, there is no sex difference in exercise induced muscle damage. The higher Creatine Kinase in males could not be explained by differences in maximal voluntary eccentric knee extension torque, Vastus Lateralis fascicle lengthening and patella tendon stiffness. Further research is required to understand the significant sex differences in Creatine Kinase levels following exercise induced muscle damage. PMID:26986066

The characterization of neural tissue ablation rate and corresponding heat affected zone of a 2 micron Tm3+ doped fiber laser(Conference Presentation)

NASA Astrophysics Data System (ADS)

Marques, Andrew J.; Jivraj, Jamil; Reyes, Robnier; Ramjist, Joel; Gu, Xijia J.; Yang, Victor X. D.

2017-02-01

Tissue removal using electrocautery is standard practice in neurosurgery since tissue can be cut and cauterized simultaneously. Thermally mediated tissue ablation using lasers can potentially possess the same benefits but with increased precision. However, given the critical nature of the spine, brain, and nerves, the effects of direct photo-thermal interaction on neural tissue needs to be known, yielding not only high precision of tissue removal but also increased control of peripheral heat damage. The proposed use of lasers as a neurosurgical tool requires that a common ground is found between ablation rates and resulting peripheral heat damage. Most surgical laser systems rely on the conversion of light energy into heat resulting in both desirable and undesirable thermal damage to the targeted tissue. Classifying the distribution of thermal energy in neural tissue, and thus characterizing the extent of undesirable thermal damage, can prove to be exceptionally challenging considering its highly inhomogenous composition when compared to other tissues such as muscle and bone. Here we present the characterization of neural tissue ablation rate and heat affected zone of a 1.94 micron thulium doped fiber laser for neural tissue ablation. In-Vivo ablation of porcine cerebral cortex is performed. Ablation volumes are studied in association with laser parameters. Histological samples are taken and examined to characterize the extent of peripheral heat damage.

Cochlear pathology following reimplantation of a multichannel scala tympani electrode array in the macaque.

PubMed

Shepherd, R K; Clark, G M; Xu, S A; Pyman, B C

1995-03-01

The histopathologic consequence of removing and reimplanting intracochlear electrode arrays on residual auditory nerve fibers is an important issue when evaluating the safety of cochlear prostheses. The authors have examined this issue by implanting multichannel intracochlear electrodes in macaque monkeys. Macaques were selected because of the similarity of the surgical technique used to insert electrodes into the cochlea compared to that in humans, in particular the ability to insert the arrays into the upper basal turn. Five macaques were bilaterally implanted with the Melbourne/Cochlear banded electrode array. Following a minimum implant period of 5 months, the electrode array on one side of each animal was removed and another immediately implanted. The animals were sacrificed a minimum of 5 months following the reinsertion procedure, and the cochleas prepared for histopathologic analysis. Long-term implantation of the electrode resulted in a relatively mild tissue response within the cochlea. Results also showed that inner and outer hair cell survival, although significantly reduced adjacent to the array, was normal in 8 of the 10 cochleas apicalward. Moreover, the electrode reinsertion procedure did not appear to adversely affect this apical hair cell population. Significant new bone formation was frequently observed in both control and reimplanted cochleas close to the electrode fenestration site and was associated with trauma to the endosteum and/or the introduction of bone chips into the cochlea at the time of surgery. Electrode insertion trauma, involving the osseous spiral lamina or basilar membrane, was more commonly observed in reimplanted cochleas. This damage was usually restricted to the lower basal turn and resulted in a more extensive ganglion cell loss. Finally, in a number of cochleas part of the electrode array was located within the scala media or scala vestibuli. These electrodes did not appear to evoke a more extensive tissue response or result in more extensive neural degeneration compared with electrodes located within the scala tympani. In conclusion, the present study has shown that the reimplantation of a multichannel scala, tympani electrode array can be achieved with minimal damage to the majority of cochlear structures. Increased insertion trauma, resulting in new bone formation and spiral ganglion cell loss, can occur in the lower basal turn in cases where the electrode entry point is difficult to identify due to proliferation of granulation and fibrous tissue.

[Danger from exploding fireworks and blank firearms].

PubMed

Just, T; Pau, H W; Kaduk, W; Hingst, V

2000-12-01

Explosive amusement and deterrent articles such as New Year's Eve cannons and rockets, toy pistols, and blank guns are not at all harmless items. Their potential dangerousness is often extremely underestimated. Two damaging mechanisms are important: during explosions, high pressures and temperatures develop and a considerable sound pressure level can be measured. If the explosion happens near the human body (intentionally or inadvertently), not only superficial lesions can occur, but also (mainly due to contact shots) serious, deep-seated tissue damage, especially in the head and neck region with its endangered sense organs such as eye and ear, the vessels and nerves supplying the brain, the speech- and voice-forming apparatus, and in particular the face, can be the consequence. Their mutilation can lead to serious and extensive interpersonalchanges. Accidents are published in the relevant otological and forensic medical papers, but nevertheless it seems important to us to point out the dangerousness of these readily available items.

Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

PubMed

M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

2017-10-01

The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells.

PubMed

França, L R; Leal, M C; Sasso-Cerri, E; Vasconcelos, A; Debeljuk, L; Russell, L D

2000-11-01

Cimetidine (Tagamet) is a potent histaminic H2-receptor antagonist, extensively prescribed for ulcers and now available without prescription. Cimetidine is a known testicular toxicant, but its mechanism of action remains uncertain. Rats were treated i.p. with cimetidine either at 50 mg/kg or 250 mg/kg body weight for 59 days. Accessory sex organ weights, but not testis weight, were significantly reduced in the high dose treated groups. FSH levels were significantly elevated in both treated groups, but testosterone levels were unchanged. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (15-17%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. TUNEL labeling confirmed extensive apoptotic cell death in peritubular cells, but revealed apoptosis of vascular smooth muscle. Given that 1) peritubular myoid cell apoptosis occurs in apparently normal tubules, that 2) basal lamina disorders are found, and that 3) peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.

A low molecular weight serine protease: Purification and characterization from Hippasa agelenoides (funnel web) spider venom gland extract.

PubMed

Devaraja, S; Nagaraju, S; Mahadeswaraswamy, Y H; Girish, K S; Kemparaju, K

2008-07-01

Despite the long history [Kaiser, E., 1956. Enzymatic activity of spider venoms. In: Buckley, E.E., Porges, N. (Eds.), Venoms. American Association for the Advancement of Science, Washington, DC, pp. 91-93] on proteolytic activity, no study so far claims the isolation of a serine protease from the spider venom/venom gland extract. Therefore, the present study describes the isolation and characterization of a low molecular weight serine protease from Hippasa agelenoides venom gland extract. The protease (Hag-protease) was purified to homogeneity using the combination of gel-permeation and ion-exchange chromatography. The molecular mass was found to be 16.350 kDa by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Hag-protease was optimally active at pH 7.5 and temperature of 37 degrees C. PMSF abolished the enzyme activity while EDTA, EGTA, IAA, 1, 10-phenanthrolene did not. It hydrolyzed proteins such as casein, fibronectin and collagen type-I dose dependently but did not degrade gelatin and collagen type-IV. The isolated protease was non-lethal and devoid of hemorrhagic, myotoxic and edema forming activities. The light microscopy of Hag-protease treated skin tissue sections at the site of injection showed extensive damage of extracellular matrix (ECM) of hypodermis without causing any damage to blood vessels and capillaries. Similar damage of ECM of muscle tissue sections without affecting myocytes was noticed. Hag-protease was found to be procoagulant in property when studied plasma recalcification time.

Theranostics and metabolotheranostics for precision medicine in oncology

NASA Astrophysics Data System (ADS)

Bhujwalla, Zaver M.; Kakkad, Samata; Chen, Zhihang; Jin, Jiefu; Hapuarachchige, Sudath; Artemov, Dmitri; Penet, Marie-France

2018-06-01

Most diseases, especially cancer, would significantly benefit from precision medicine where treatment is shaped for the individual. The concept of theragnostics or theranostics emerged around 2002 to describe the incorporation of diagnostic assays into the selection of therapy for this purpose. Increasingly, theranostics has been used for strategies that combine noninvasive imaging-based diagnostics with therapy. Within the past decade theranostic imaging has transformed into a rapidly expanding field that is located at the interface of diagnosis and therapy. A critical need in cancer treatment is to minimize damage to normal tissue. Molecular imaging can be applied to identify targets specific to cancer with imaging, design agents against these targets to visualize their delivery, and monitor response to treatment, with the overall purpose of minimizing collateral damage. Genomic and proteomic profiling can provide an extensive 'fingerprint' of each tumor. With this cancer fingerprint, theranostic agents can be designed to personalize treatment for precision medicine of cancer, and minimize damage to normal tissue. Here, for the first time, we have introduced the term 'metabolotheranostics' to describe strategies where disease-based alterations in metabolic pathways detected by MRS are specifically targeted with image-guided delivery platforms to achieve disease-specific therapy. The versatility of MRI and MRS in molecular and functional imaging makes these technologies especially important in theranostic MRI and 'metabolotheranostics'. Our purpose here is to provide insights into the capabilities and applications of this exciting new field in cancer treatment with a focus on MRI and MRS.

Perspectives for computational modeling of cell replacement for neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aimone, James B.; Weick, Jason P.

In mathematical modeling of anatomically-constrained neural networks we provide significant insights regarding the response of networks to neurological disorders or injury. Furthermore, a logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impactmore » circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

Perspectives for computational modeling of cell replacement for neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aimone, James B.; Weick, Jason P.

Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behaviormore » in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

Gender differences in muscle inflammation after eccentric exercise.

PubMed

Stupka, N; Lowther, S; Chorneyko, K; Bourgeois, J M; Hogben, C; Tarnopolsky, M A

2000-12-01

Unaccustomed exercise is followed by delayed-onset muscle soreness and morphological changes in skeletal muscle. Animal studies have demonstrated that women have an attenuated response to muscle damage. We studied the effect of eccentric exercise in untrained male (n = 8) and female (n = 8) subjects using a unilateral exercise design [exercise (Ex) and control (Con) legs]. Plasma granulocyte counts [before (Pre) and 48 h after exercise (+48h)] and creatine kinase activity [Pre, 24 h after exercise (+24h), +48h, and 6 days after exercise (+6d)] were determined before (Pre) and after (+24h, +48h, +6d) exercise, with biopsies taken from the vastus lateralis of each leg at +48h for determination of muscle damage and/or inflammation. Plasma granulocyte counts increased for men and decreased for women at +48h (P < 0.05), and creatine kinase activity increased for both genders at +48h and +6d (P < 0.01). There were significantly greater areas of both focal (P < 0.001) and extensive (P < 0.01) damage in the Ex vs. Con leg for both genders, which was assessed by using toluidine blue staining. The number of leukocyte common antigen-positive cells/mm(2) tissue increased with exercise (P < 0.05), and men tended to show more in their Ex vs. Con leg compared with women (P = 0.052). Men had a greater total (Ex and Con legs) number of bcl-2-positive cells/mm(2) tissue vs. women (P < 0.05). Atrophic fibers with homogeneous bcl-2-positive staining were seen only in men (n = 3). We conclude that muscle damage is similar between genders, yet the inflammatory response is attenuated in women vs. men. Finally, exercise may stimulate the expression of proteins involved in apoptosis in skeletal muscle.

Overexpression of IGF-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

PubMed Central

Ye, Fan; Mathur, Sunita; Liu, Min; Borst, Stephen E.; Walter, Glenn A.; Sweeney, H. Lee; Vandenborne, Krista

2014-01-01

Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Since insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of viral mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for two weeks to induce muscle atrophy in the soleus and ankle plantar flexor muscle group. Subsequently, the mice were allowed to reambulate and muscle damage and recovery was monitored over a period of 2 to 21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by MRI, a nonspecific marker of muscle damage, was significantly lower in IGF-1 injected, compared to contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1 injected soleus muscles was confirmed on histology, with a lower fraction area of abnormal muscle tissue in IGF-I injected muscles at 2 days reambulation (33.2±3.3%vs 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days), and elevated MyoD mRNA (7-fold at 2 days) in IGF-1 injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded skeletal muscles from damage and accelerating muscle repair and regeneration. PMID:23291913

Overexpression of insulin-like growth factor-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse.

PubMed

Ye, Fan; Mathur, Sunita; Liu, Min; Borst, Stephen E; Walter, Glenn A; Sweeney, H Lee; Vandenborne, Krista

2013-05-01

Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Given that insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of virally mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for 2 weeks to induce muscle atrophy in the soleus and ankle plantarflexor muscle group. Subsequently, the mice were allowed to reambulate, and muscle damage and recovery were monitored over a period of 2-21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by magnetic resonance imaging, a non-specific marker of muscle damage, was significantly lower in IGF-1-injected compared with contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1-injected soleus muscles was confirmed on histology, with a lower fractional area of abnormal muscle tissue in IGF-1-injected muscles at 2 days reambulation (33.2±3.3 versus 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days) and elevated MyoD mRNA (7-fold at 2 days) in IGF-1-injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded skeletal muscles from damage and accelerating muscle repair and regeneration.

Vitamin E Supplementation Ameliorates Newcastle Disease Virus-Induced Oxidative Stress and Alleviates Tissue Damage in the Brains of Chickens

PubMed Central

Rehman, Zaib Ur; Qiu, Xusheng; Sun, Yingjie; Liao, Ying; Tan, Lei; Song, Cuiping; Yu, Shengqing; Ding, Zhuang; Nair, Venugopal; Meng, Chunchun; Ding, Chan

2018-01-01

Newcastle disease (ND), characterized by visceral, respiratory, and neurological pathologies, causes heavy economic loss in the poultry industry around the globe. While significant advances have been made in effective diagnosis and vaccine development, molecular mechanisms of ND virus (NDV)-induced neuropathologies remain elusive. In this study, we report the magnitude of oxidative stress and histopathological changes induced by the virulent NDV (ZJ1 strain) and assess the impact of vitamin E in alleviating these pathologies. Comparative profiling of plasma and brains from mock and NDV-infected chicken demonstrated alterations in several oxidative stress makers such as nitric oxide, glutathione, malondialdehyde, total antioxidant capacity, glutathione S-transferase, superoxide dismutase, and catalases. While decreased levels of glutathione and total antioxidant capacity and increased concentrations of malondialdehyde and nitric oxide were observed in NDV-challenged birds at all time points, these alterations were eminent at latter time points (5 days post infection). Additionally, significant decreases in the activities of glutathione S-transferase, superoxide dismutase, and catalase were observed in the plasma and brains collected from NDV-infected chickens. Intriguingly, we observed that supplementation of vitamin E can significantly reduce the alteration of oxidative stress parameters. Under NDV infection, extensive histopathological alterations were observed in chicken brain including neural inflammation, capillary hyperemia, necrosis, and loss of prominent axons, which were reduced with the treatment of vitamin E. Taken together, our findings highlight that neurotropic NDV induces extensive tissue damage in the brain and alters plasma oxidative stress profiles. These findings also demonstrate that supplementing vitamin E ameliorates these pathologies in chickens and proposes its supplementation for NDV-induced stresses. PMID:29614025

Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

NASA Astrophysics Data System (ADS)

Ramesh, Govindarajan; Wu, Honglu

Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo.

PubMed

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-09-19

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25-100 μm wide) and minibeams (200-800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a(+) thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.

Parametric study of irreversible electroporation with different needle electrodes: electrical and thermal analysis.

PubMed

Nickfarjam, Abolfazl; Firoozabadi, S Mohammad P

2014-08-01

Irreversible electroporation (IRE) is a new tumour ablation method used in cancer treatment procedures. In a successful IRE treatment it is crucial to impose minimum thermal damage to the tumour and its surrounding healthy tissue, while subjecting the entire tumour to a strong electric field. Here we present a 3D model of a subcutaneous tumour in a four-layer skin using a geometry-based finite element approach. Four common needle electrode configurations were studied in this paper. The study evaluated six essential factors which are important in the electrical and thermal distributions in tumour and normal tissue. The results revealed that a hexagonal 3 × 3 geometry provides the maximum electrical coverage of the tumour, compared to other electrode configurations. However, in some cases the hexagonal 2 × 2 geometry can ablate the entire tumour with less damage to normal tissue. We found that the deeper insertion of 2- and 4-electrode geometries can lead to more damage to healthy tissue. The results also indicate that the insertion of the electrodes into tumour tissue can increase thermal damage dramatically due to existing large electrical conductivity. These findings suggest that needle electrodes should not be placed within the tumour tissue if the goal is to prevent thermal damage. This method can be used as a trade-off between electric field coverage in tumour tissue and thermal damage to both tumour and normal tissue.

Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase.

PubMed Central

Baker, G L; Corry, R J; Autor, A P

1985-01-01

Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIG. 3. FIG. 4. FIG. 5. FIG. 6. FIG. 7. PMID:3840348

Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

PubMed Central

Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

2012-01-01

Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

Ultrashort pulse laser processing of hard tissue, dental restoration materials, and biocompatibles

NASA Astrophysics Data System (ADS)

Yousif, A.; Strassl, M.; Beer, F.; Verhagen, L.; Wittschier, M.; Wintner, E.

2007-07-01

During the last few years, ultra-short laser pulses have proven their potential for application in medical tissue treatment in many ways. In hard tissue ablation, their aptitude for material ablation with negligible collateral damage provides many advantages. Especially teeth representing an anatomically and physiologically very special region with less blood circulation and lower healing rates than other tissues require most careful treatment. Hence, overheating of the pulp and induction of microcracks are some of the most problematic issues in dental preparation. Up till now it was shown by many authors that the application of picosecond or femtosecond pulses allows to perform ablation with very low damaging potential also fitting to the physiological requirements indicated. Beside the short interaction time with the irradiated matter, scanning of the ultra-short pulse trains turned out to be crucial for ablating cavities of the required quality. One main reason for this can be seen in the fact that during scanning the time period between two subsequent pulses incident on the same spot is so much extended that no heat accumulation effects occur and each pulse can be treated as a first one with respect to its local impact. Extension of this advantageous technique to biocompatible materials, i.e. in this case dental restoration materials and titanium plasma-sprayed implants, is just a matter of consequence. Recently published results on composites fit well with earlier data on dental hard tissue. In case of plaque which has to be removed from implants, it turns out that removal of at least the calcified version is harder than tissue removal. Therefore, besides ultra-short lasers, also Diode and Neodymium lasers, in cw and pulsed modes, have been studied with respect to plaque removal and sterilization. The temperature increase during laser exposure has been experimentally evaluated in parallel.

Comparison of ferromagnetic induction and bipolar electrosurgery and suction in corticotomies in pig cerebrum.

PubMed

Bowers, Christian A; Burns, Greg; Salzman, Karen; McGill, Lawrence; MacDonald, Joel D

2015-04-01

The effects of newer energy-based surgical dissection and coagulation modalities on cerebral tissue have not been investigated. Several instruments have been developed to address the limitations of traditional electrosurgical instruments in the nervous system. We compared the effects of standard bipolar electrocautery and suction (BPS) with those of a new ferromagnetic induction (FMI) device in corticotomies of pig cerebral tissue as assessed by magnetic resonance imaging (MRI) and histological analysis. Three adult pigs underwent bilateral corticotomies (3 cm long×1 cm deep) using both FMI and BPS. The acute cerebral tissue edema created by each method was measured on coronal volumetric T2-weighted MRI sequences immediately after surgery. A lateral thermal "damage index" was calculated by dividing the width of the visible T2 tissue edema by the measured depth. The radiographic damage indices with each method were compared statistically. Histological analysis of each incision was conducted to compare the extent of tissue damage. MRI showed that the mean radiographic damage index of each corticotomy was significantly lower with the FMI (0.30 ± 0.02 (0.28-0.32)) than with the BPS method (0.54 ± 0.11 (0.42-0.64)) (p = 0.02). Histological analysis suggested a correlation with the radiographic findings as the FMI tissue samples demonstrated less adjacent tissue damage than BPS. FMI appeared to cause less adjacent tissue damage than the BPS method in pig cerebral tissue based on quantitative radiographic and qualitative histological analysis. Future studies are needed to investigate the clinical implications of energy-based surgical dissection on cerebral tissue. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation.

PubMed

Robinson, Alan M; Stock, Stuart R; Soriano, Carmen; Xiao, Xianghui; Richter, Claus-Peter

2016-11-01

The aim of this study was to determine if X-ray micro-computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. A surgical CO 2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro-computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X-ray images with those visible by classic light microscopy histology were made. We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Evaluation of transurethral and transperineal tin ethyl etiopurpurin-photodynamic therapy on the canine prostate one week after drug injection

NASA Astrophysics Data System (ADS)

Selman, Steven H.; Keck, Rick W.; Kondo, Sandy; Albrecht, Detlef

1999-06-01

We have been investigating the potential applicability of photodynamic therapy for the treatment of benign and malignant disease of the prostate. Both transurethral and transperineal approaches to the delivery of light to the tin ethyl etiopurpurin sensitized canine prostate have been studied. Pharmacologic studies were performed and suggested that delaying light treatment for 7 days after drug administration would maximize the desired effect on the targeted prostatic tissue while minimizing the damage to surrounding bladder and rectum. A total of 12 dogs were treated with transurethral light alone (n=6) or the combination of transurethral light and transperineal light one week after tin ethyl etiopurpurin administration. (Previous studies have shown that light alone has no effect on prostate size or histology.) Animals were euthanized 48 hours and 3 weeks after completion of treatment (drug, 1mg/kg day 0, light [400mw/750sec]day 7). Tissue response was determined by gross and microscopic examination. Additionally, pre- and post- treatment transrectal ultrasounds were compared to assess changes in prostate volume and tissue echogenicity. The combination of transurethral and transperineal light results in extensive destruction of glandular epithelium with minimal damage to surrounding structures. Prostate volumes decreased by an average of 52%. Untreated areas were found to lie greater than 0.5 cm from the light diffuser. These studies have encouraged us to continue to investigate this modality as a technique for total ablation of prostatic glandular epithelium.

Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation: an experimental study using resected porcine esophagus, stomach, and colon.

PubMed

Fujishiro, Mitsuhiro; Yahagi, Naohisa; Nakamura, Masanori; Kakushima, Naomi; Kodashima, Shinya; Ono, Satoshi; Kobayashi, Katsuya; Hashimoto, Takuhei; Yamamichi, Nobutake; Tateishi, Ayako; Shimizu, Yasuhito; Oka, Masashi; Ichinose, Masao; Omata, Masao

2006-10-01

Argon plasma coagulation (APC) is considered to be a safe thermocoagulation technique, but some reports show perforation and deformity during and after APC. In this study, we investigated the usefulness of prior submucosal injection for APC. APC over the mucosa was performed on fresh resected porcine esophagus, stomach, and colon with prior submucosal injection of normal saline (injection group) and without it (control group). The depth of tissue damage increased linearly with pulse duration up to the shallower submucosal layer in both groups. After that, tissue damage in the injection group remained confined to the shallower submucosal layer under any condition, whereas that in the control group continued to extend. The tissue damages of the injection groups were significantly (P<0.05) shallower than those of the control groups that reached the deeper submucosal layer in all the organs. Submucosal injection of normal saline before the application of APC may limit tissue damage and prevent perforation and deformity.

Postoperative morbidity and histopathologic characteristics of tonsillar tissue following coblation tonsillectomy in children: a prospective randomized single-blind study.

PubMed

Roje, Zeljka; Racić, Goran; Dogas, Zoran; Pisac, Valdi Pesutić; Timms, Michael

2009-03-01

The aim of this prospective randomized single blind study was to determine the depth of thermal damage to tonsillar tissue due to coblation, and to compare it with thermal damage to tonsillar tissue following conventional tonsillectomy; to correlate the depth of thermal damage to tonsillar tissue with the parameters of postoperative morbidity, to compare intraoperative blood loss, postoperative pain severity, time to resuming normal physical activity, and incidence of postoperative bleeding between two groups of tonsillectomized children aged up to 16 years. 72 children aged 3-16 years scheduled for tonsillectomy randomly assigned into two groups submitted either to conventional tonsillectomy with bipolar diathermy coagulation or to coblation tonsillectomy, with a 14-day follow up. Statistically significant differences were observed in the depth of thermal damage to tonsillar tissue (p < 0.001), intraoperative blood loss (p < 0.004), in postoperative pain severity (p < 0.05) and in time to resuming normal physical activity between the two groups (p < 0.001). There was no case of reactionary or secondary bleeding in either group. In this paper for the first time we have correlated postoperative morbidity and thermal tissue damage: less thermal damage is associated with less postoperative morbidity.

A self-harm series and its relationship with childhood adversity among adolescents in mainland China: a cross-sectional study.

PubMed

Han, Azhu; Wang, Gengfu; Xu, Geng; Su, Puyu

2018-02-01

Self-harm (SH) is an emerging problem among Chinese adolescents. The present study aimed to measure the prevalence of SH behaviours and to explore the relationship between childhood adversity and different SH subtypes among Chinese adolescents. A total of 5726 middle school students were randomly selected in three cities of Anhui province, China, using a stratified cluster sampling method. SH was categorized into five subtypes (highly lethal self-harm, less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harmful behaviours with latency damage and psychological self-harm). Multivariate logistic regression was used to explore the relationships between childhood adversity and different subtypes of adolescent SH. The prevalence rates of highly lethal self-harm, less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harmful behaviours with latency damage and psychological self-harm were 6.1, 20.4, 32.0, 20.0 and 23.0%, respectively. Childhood sexual abuse and physical peer victimization were associated with each SH subtype with adjusted odds ratios (AORs) ranging from 1.23 to 1.76. Highly lethal self-harm was associated with childhood physical peer victimization, sexual abuse, emotional abuse, and emotional neglect. The less lethal SH subtypes (i.e., less lethal self-harm with visible tissue damage, self-harm without visible tissue damage, self-harmful behaviours with latency damage and psychological self-harm) were associated with childhood peer victimization, family life stress event scores and childhood sexual abuse. A high prevalence of SH exists among Chinese adolescents. The association of childhood adversity with SH merits serious attention in both future research and preventive interventions.

Unusual intraosseous fossilized soft tissues from the Middle Triassic Nothosaurus bone

NASA Astrophysics Data System (ADS)

Surmik, Dawid; Rothschild, Bruce M.; Pawlicki, Roman

2017-04-01

Fossilized soft tissues, occasionally found together with skeletal remains, provide insights to the physiology and functional morphology of extinct organisms. Herein, we present unusual fossilized structures from the cortical region of bone identified in isolated skeletal remains of Middle Triassic nothosaurs from Upper Silesia, Poland. The ribbed or annuli-shaped structures have been found in a sample of partially demineralized coracoid and are interpreted as either giant red blood cells or as blood vessel walls. The most probable function is reinforcing the blood vessels from changes of nitrogen pressure in air-breathing diving reptiles. These structures seem to have been built of extensible muscle layers which prevent the vessel damage during rapid ascent. Such suspected function presented here is parsimonious with results of previous studies, which indicate rarity of the pathological modification of bones associated with decompression syndrome in Middle Triassic nothosaurs.

Testicular cancer: a review.

PubMed

Hawkins, C; Miaskowski, C

1996-09-01

To describe the pathophysiologic mechanisms, histologic and clinical staging, diagnosis, and medical and nursing management of testicular cancer. Published studies, review articles, and Physician Data Query database. Testicular cancer is a complex disease resulting from transformation of gonadal tissues. The pathophysiologic mechanisms involve damage to tissue in utero and after birth. Orchiectomy is the treatment of choice for early-stage disease. Orchiectomy can have profound physiologic and psychological consequences for young males. Subsequent chemotherapy and radiation therapy also may have severe side effects including azoospermia, bone marrow suppression, nephrotoxicity, and pulmonary toxicity. Early detection of this disease results in improved patient outcomes. Patients treated with radical inguinal orchiectomy and radiation therapy have fewer long-term side effects and toxicities than patients who require more extensive surgery and chemotherapy. Nursing care must focus not only on relieving the patient's physical symptoms but on helping him deal with the psychosexual issues associated with the disease and its treatment.

Diagnostic issues in self-mutilation.

PubMed

Favazza, A R; Rosenthal, R J

1993-02-01

Pathological self-mutilation--the deliberate alteration or destruction of body tissue without conscious suicidal intent--was examined both as a symptom of mental disorders and as a distinct syndrome. Data from more than 250 articles and books were reviewed, as well as data obtained by the authors from their extensive clinical experience in treating self-mutilating patients. The diverse behaviors that constitute pathological self-mutilation can be categorized into three basic types: major--infrequent acts that result in significant tissue damage, usually associated with psychoses and acute intoxications; stereotypic--fixed, rhythmic behavior seemingly devoid of symbolism, commonly associated with mental retardation; and superficial or moderate--behavior such as skin cutting, burning, and scratching associated with a variety of mental disorders. The authors propose that a syndrome of repetitive superficial or moderate self-mutilation should be regarded as an axis I impulse disorder. In most cases, the syndrome coexists with character pathology.

Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair

PubMed Central

Freisinger, Chrissy; Rindy, Julie; Golenberg, Netta; Frecentese, Grace; Gibson, Angela; Eliceiri, Kevin W

2018-01-01

Tissue injury leads to early wound-associated reactive oxygen species (ROS) production that mediate tissue regeneration. To identify mechanisms that function downstream of redox signals that modulate regeneration, a vimentin reporter of mesenchymal cells was generated by driving GFP from the vimentin promoter in zebrafish. Early redox signaling mediated vimentin reporter activity at the wound margin. Moreover, both ROS and vimentin were necessary for collagen production and reorganization into projections at the leading edge of the wound. Second harmonic generation time-lapse imaging revealed that the collagen projections were associated with dynamic epithelial extensions at the wound edge during wound repair. Perturbing collagen organization by burn wound disrupted epithelial projections and subsequent wound healing. Taken together our findings suggest that ROS and vimentin integrate early wound signals to orchestrate the formation of collagen-based projections that guide regenerative growth during efficient wound repair. PMID:29336778

Effects of tempol and redox-cycling nitroxides in models of oxidative stress

PubMed Central

Wilcox, Christopher S.

2010-01-01

Tempol is a redox cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia. PMID:20153367

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

Nanocrystal ghosting: Extensive radiation damage in MgO induced by low-energy electrons

NASA Astrophysics Data System (ADS)

Frankenfield, Zackery; Kane, Kenneth; Sawyer, William H.

2017-03-01

We report direct evidence of extensive radiation damage in MgO nanocrystals due to intense bombardment (2 × 10 electrons/nm sec) by electrons with beam energies between 60 keV and 120 keV. Based upon a minimum intensity necessary to produce the observed damage, we present an explanation based on the Knotek-Feibelman process.

Biomechanics Analysis of Pressure Ulcer Using Damaged Interface Model between Bone and Muscle in the Human Buttock

NASA Astrophysics Data System (ADS)

Slamet, Samuel Susanto; Takano, Naoki; Tanabe, Yoshiyuki; Hatano, Asako; Nagasao, Tomohisa

This paper aims at building up a computational procedure to study the bio-mechanism of pressure ulcer using the finite element method. Pressure ulcer is a disease that occurs in the human body after 2 hours of continuous external force. In the very early stage of pressure ulcer, it is found that the tissues inside the body are damaged, even though skin surface looks normal. This study assumes that tension and/or shear strain will cause damage to loose fibril tissue between the bone and muscle and that propagation of damaged area will lead to fatal stage. Analysis was performed using the finite element method by modeling the damaged fibril tissue as a cutout. By varying the loading directions and watching both tensile and shear strains, the risk of fibril tissue damage and propagation of the damaged area is discussed, which may give new insight for the careful nursing for patients, particularly after surgical treatment. It was found that the pressure ulcer could reoccur for a surgical flap treatment. The bone cut and surgical flap surgery is not perfect to prevent the bone-muscle interfacial damage.

Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

PubMed Central

Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

2015-01-01

Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

The trigeminal trophic syndrome: an unusual cause of nasal ulceration.

PubMed

Monrad, Seetha U; Terrell, Jeffrey E; Aronoff, David M

2004-06-01

Trigeminal trophic syndrome (TTS) is an unusual complication after peripheral or central damage to the trigeminal nerve, characterized by anesthesia, paresthesias, and ala nasi ulceration. We describe a patient with classic TTS after trigeminal rhizotomy who underwent several extensive evaluations for nasal ulceration and received prolonged immunosuppressive therapy for a presumed autoimmune disorder before the correct diagnosis was made. An understanding of the predisposing factors and clinical presentation of TTS is important to ensure a timely diagnosis of this difficult-to-treat illness. Differentiation of TTS from malignancy, infection, or vasculitis is possible on the basis of clinical history, tissue biopsy, and serologic evaluation.

[Principles of management of high-energy injuries of the leg].

PubMed

Jovanović, Mladen; Janjić, Zlata; Marić, Dusan

2002-01-01

High-energy traumas are open or closed injuries caused by force (missile, traffic injuries, crush or blust injuries, falling from heights), affecting the body surface and transferring high amount of kinetic energy inducing great damage to the tissue. Management of such lower extremity injuries has evolved over past several decades, but still remains a difficult task for every surgical team. Specific anatomic and functional characteristics combined with extensive injuries demands specific treatment protocols. In a multiple injured patient the first priority is management of life-threatening trauma. Despite other injuries, surgical treatment of limb-threatening injuries must start as soon as life-threatening condition has been managed. Algorithms are especially beneficial in management of severely injured, but salvageable extremities and in making decision on amputation. Insight into mechanisms of injury, as well as systematic examination of the affected limb, should help us understand the extensiveness of trauma and make an adequate management plan. Prevention of wound infection and surgical approach to high-energy limb trauma, which includes wound extension, wound excision, skeletal stabilization and if necessary muscle compartment release, should be done in the first 6 hours after injury. Commonly used methods for soft tissue defects must provide wound coverage in less than five days following injury. Early passive and active mobilization and verticalization of patients is very important for successful treatment. Good and timely evaluation of the injured and collaboration between plastic and orthopaedic surgeons from the beginning of treatment, are crucial for final outcome.

Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid

PubMed Central

Anand David, Alexander Victor; Arulmoli, Radhakrishnan; Parasuraman, Subramani

2016-01-01

Antioxidants are substances that may protect cells from the damage caused by unstable molecules such as free radicals. Flavonoids are phenolic substances widely found in fruits and vegetables. The previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels. Free radicals are constantly generated resulting in extensive damage to tissues leading to various disease conditions such as cancer, Alzheimer's, renal diseases, cardiac abnormalities, etc., Medicinal plants with antioxidant properties play a vital functions in exhibiting beneficial effects and employed as an alternative source of medicine to mitigate the disease associated with oxidative stress. Flavonoids have existed over one billion years and possess wide spectrum of biological activities that might be able to influence processes which are dysregulated in a disease. Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities. PMID:28082789

Tumor control by hypoxia-specific chemotargeting of iron-oxide nanoparticle - Berberine complexes in a mouse model.

PubMed

Sreeja, S; Krishnan Nair, C K

2018-02-15

To evaluate the therapeutic efficacy of hypoxic cell-sensitizer Sanazole (SAN) -directed targeting of cytotoxic drug Berberine (BBN) and Iron-oxide nanoparticle (NP) complexes, to solid tumor in Swiss albino mice. NP-BBN-SAN complexes were characterized by FTIR, XRD, TEM and Nano-size analyzer. This complex was orally administered to mice-bearing solid tumor in hind limb. Tumor regression was analysed by measuring tumor volume. Cellular DNA damages were assessed by comet assay. Transcriptional expression of genes related to tumor hypoxia and apoptosis was evaluated by quantitative real-time PCR and morphological changes in tissues were analysed by histopathology. Also levels of antioxidants and tumor markers in tissues and serum biochemical parameters were analysed. Administration of NP-BBN-SAN complexes reduced tumor volume and studies were focussed on the underlying mechanisms. Extensive damage to cellular-DNA; down-regulated transcription of hif-1α, vegf, akt and bcl2; and up-regulated expression of bax and caspases, were observed in tumor. Results on tumor markers, antioxidant-status and serum parameters corroborated the molecular findings. Histopathology of tumor, liver and kidney revealed the therapeutic specificity of NP-BBN-SAN. Thus SAN and NP can be used for specific targeting of drugs, to hypoxic solid tumor, to improve therapeutic efficacy. Copyright © 2017. Published by Elsevier Inc.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

PubMed

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan; Subbiah, Suresh Kumar

2018-02-13

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

Safety and effectiveness of a polyvinyl alcohol barrier in reducing risks of vascular tissue damage during anterior spinal revision surgery.

PubMed

Jeffords, Paul; Li, Jinsheng; Panchal, Deepal; Denoziere, Guilhem; Fetterolf, Donald

2012-05-01

This study was conducted as a controlled, prospective investigation to show the safety and efficacy of a polyvinyl alcohol (PVA) device in a sheep model. To evaluate the ability of a permanent PVA hydrogel barrier to reduce the risk of potential vessel damage during anterior vertebral revision surgery, to provide a nonadhesive barrier at the surgical site, and to create a surgical revision plane of dissection. The development of scar tissue and adhesions presents a significant postoperative problem in spine surgery, where adhesion involvement of overlying structures can cause pain, neurovascular complications, and present a difficult surgical environment during revisions. The devices were implanted onto the ventral surface of exposed lumbar intervertebral discs using an anterolateral approach. One disc separated from the study site was also exposed to serve as a control. Three sheep each were then evaluated with an explant procedure at 30 and 90 days. Extensive sampling was undertaken to evaluate gross anatomic, micropathologic, and biochemical environments and properties of the device. The structural properties and appearance of the device remained intact at both 30 and 90 days. The material remained flexible, hydrophilic, and soft, without visible resorption or decomposition. The material was well tolerated by the animal, with minimal histologic signs of inflammation or rejection. Tissue planes were easily able to be localized by the surgeon attempting to locate the prior surgical site at the time of resection. The PVA vessel shield effectively protected the structures overlying the sheep spine during revision, providing a clear dissection plane for resection at repeat surgery. The overlying structures separated from the previous surgical site with no adhesion, and allowed safe separation of adjacent tissues without the use of sharp dissection.

Magnetic resonance image guided transurethral ultrasound prostate ablation: a preclinical safety and feasibility study with 28-day followup.

PubMed

Burtnyk, Mathieu; Hill, Tracy; Cadieux-Pitre, Heather; Welch, Ian

2015-05-01

We determine the safety and feasibility of magnetic resonance image guided transurethral ultrasound prostate ablation using active temperature feedback control in a preclinical canine model with 28-day followup. After a long acclimatization period we performed ultrasound treatment in 8 subjects using the magnetic resonance image guided TULSA-PRO™ transurethral ultrasound prostate ablation system. Comprehensive examinations and observations were done before and throughout the 28-day followup, including assessment of clinically significant treatment related adverse events. In addition to gross pathology evaluation, extensive histopathological analysis was done to assess cell kill inside and outside the prostate. We evaluated prostate conformal heating by comparing the spatial difference between the treatment plan and the 55C isotherm measured on magnetic resonance imaging thermometry acquired during treatment. These findings were confirmed on contrast enhanced magnetic resonance imaging immediately after treatment and at 28 days. Clinically there were no adverse events in any of the 8 subjects throughout the 28-day followup. All subjects had normal urinary and bowel function. Gross necropsy and histology confirmed that the intended thermal cell kill was confined to the prostate. No surrounding tissue was damaged, including the rectum and the external urinary sphincter. Conformal heating was achieved with an average -0.9 mm accuracy and 0.9 mm precision. Contrast enhanced magnetic resonance imaging and histological analysis confirmed tissue ablation in targeted areas of the prostate. Urethral tissue was spared from thermal damage. Magnetic resonance image guided transurethral ultrasound is a safe, feasible procedure for accurate and precise conformal thermal ablation of prostate tissue, as demonstrated in a preclinical model with 28-day followup. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

PubMed Central

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan

2018-01-01

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections. PMID:29438279

Electric Ablation with Irreversible Electroporation (IRE) in Vital Hepatic Structures and Follow-up Investigation

PubMed Central

Chen, Xinhua; Ren, Zhigang; Zhu, Tongyin; Zhang, Xiongxin; Peng, Zhiyi; Xie, Haiyang; Zhou, Lin; Yin, Shengyong; Sun, Junhui; Zheng, Shusen

2015-01-01

Irreversible electroporation (IRE) with microsecond-pulsed electric fields (μsPEFs) can effectively ablate hepatocellular carcinomas in animal models. This preclinical study evaluates the feasibility and safety of IRE on porcine livers. Altogether, 10 pigs were included. Computed tomography (CT) was used to guide two-needle electrodes that were inserted near the hilus hepatis and gall bladder. Animals were followed-up at 2 hours and at 2, 7 and 14 days post-treatment. During and after μsPEF ablation, electrocardiographs found no cardiovascular events, and contrast CT found no portal vein thrombosis. There was necrosis in the ablation zone. Mild cystic oedema around the gall bladder was found 2 hours post-treatment. Pathological studies showed extensive cell death. There was no large vessel damage, but there was mild endothelial damage in some small vessels. Follow-up liver function tests and routine blood tests showed immediate liver function damage and recovery from the damage, which correlated to the pathological changes. These results indicate that μsPEF ablation affects liver tissue and is less effective in vessels, which enable μsPEFs to ablate central tumour lesions close to the hilus hepatis and near large vessels and bile ducts, removing some of the limitations and contraindications of conventional thermal ablation. PMID:26549662

Electric Ablation with Irreversible Electroporation (IRE) in Vital Hepatic Structures and Follow-up Investigation.

PubMed

Chen, Xinhua; Ren, Zhigang; Zhu, Tongyin; Zhang, Xiongxin; Peng, Zhiyi; Xie, Haiyang; Zhou, Lin; Yin, Shengyong; Sun, Junhui; Zheng, Shusen

2015-11-09

Irreversible electroporation (IRE) with microsecond-pulsed electric fields (μsPEFs) can effectively ablate hepatocellular carcinomas in animal models. This preclinical study evaluates the feasibility and safety of IRE on porcine livers. Altogether, 10 pigs were included. Computed tomography (CT) was used to guide two-needle electrodes that were inserted near the hilus hepatis and gall bladder. Animals were followed-up at 2 hours and at 2, 7 and 14 days post-treatment. During and after μsPEF ablation, electrocardiographs found no cardiovascular events, and contrast CT found no portal vein thrombosis. There was necrosis in the ablation zone. Mild cystic oedema around the gall bladder was found 2 hours post-treatment. Pathological studies showed extensive cell death. There was no large vessel damage, but there was mild endothelial damage in some small vessels. Follow-up liver function tests and routine blood tests showed immediate liver function damage and recovery from the damage, which correlated to the pathological changes. These results indicate that μsPEF ablation affects liver tissue and is less effective in vessels, which enable μsPEFs to ablate central tumour lesions close to the hilus hepatis and near large vessels and bile ducts, removing some of the limitations and contraindications of conventional thermal ablation.

Effects of soft X-ray radiation damage on paraffin-embedded rat tissues supported on ultralene: a chemical perspective.

PubMed

Bedolla, Diana E; Mantuano, Andrea; Pickler, Arissa; Mota, Carla Lemos; Braz, Delson; Salata, Camila; Almeida, Carlos Eduardo; Birarda, Giovanni; Vaccari, Lisa; Barroso, Regina Cély; Gianoncelli, Alessandra

2018-05-01

Radiation damage is an important aspect to be considered when analysing biological samples with X-ray techniques as it can induce chemical and structural changes in the specimens. This work aims to provide new insights into the soft X-ray induced radiation damage of the complete sample, including not only the biological tissue itself but also the substrate and embedding medium, and the tissue fixation procedure. Sample preparation and handling involves an unavoidable interaction with the sample matrix and could play an important role in the radiation-damage mechanism. To understand the influence of sample preparation and handling on radiation damage, the effects of soft X-ray exposure at different doses on ultralene, paraffin and on paraffin-embedded rat tissues were studied using Fourier-transform infrared (FTIR) microspectroscopy and X-ray microscopy. Tissues were preserved with three different commonly used fixatives: formalin, glutaraldehyde and Karnovsky. FTIR results showed that ultralene and paraffin undergo a dose-dependent degradation of their vibrational profiles, consistent with radiation-induced oxidative damage. In addition, formalin fixative has been shown to improve the preservation of the secondary structure of proteins in tissues compared with both glutaraldehyde and Karnovsky fixation. However, conclusive considerations cannot be drawn on the optimal fixation protocol because of the interference introduced by both substrate and embedding medium in the spectral regions specific to tissue lipids, nucleic acids and carbohydrates. Notably, despite the detected alterations affecting the chemical architecture of the sample as a whole, composed of tissue, substrate and embedding medium, the structural morphology of the tissues at the micrometre scale is essentially preserved even at the highest exposure dose.

Development of novel force-limiting grasping forceps with a simple mechanism.

PubMed

Sakaguchi, Yasuto; Sato, Toshihiko; Yutaka, Yojiro; Muranishi, Yusuke; Komatsu, Teruya; Yoshizawa, Akihiko; Nakajima, Naoki; Nakamura, Tatsuo; Date, Hiroshi

2018-06-06

In endoscopic surgery, fragile tissues may be damaged by the application of excessive force. Thus, we developed novel endoscopic forceps with a simple force-limiting mechanism. The novel forceps were constructed with a leaf spring, and the spring thickness determines grasping pressure. We established an evaluation system (maximum score is 11 points) for lung tissue damage leading to complications. We tested the conventional forceps (186.8 kPa) and 3 novel spring forceps with the following thicknesses: 1.3 mm (53.0 kPa), 2.2 mm (187.7 kPa) and 2.8 mm (369.2 kPa). After grasping, peripheral canine lung tissues were microscopically examined for acute- and late-phase damages. In the acute phase (20 sites), the novel forceps caused capillary congestion and haemorrhage in the subpleural tissue, whereas the conventional forceps caused deep tissue and pleural damages. In the late phase (30 sites), both forceps caused fibroblast formation and interstitial thickening, which progressed to the deeper tissues as grasping pressure increased. In the acute phase, the median scores were 2.0 and 6.0 for the novel and conventional forceps, respectively (P = 0.003). In the late phase, the median scores were 2.0, 2.5 and 5.0 for 1.3-, 2.2- and 2.8-mm thick forceps, respectively, and 5.0 for the conventional forceps (P < 0.001). In both phases, the novel forceps with grasping pressure set below 187.7 kPa (2.2 mm) caused significantly less lung tissue damage than the conventional forceps. The novel endoscopic forceps are able to regulate the tissue-grasping pressure and induce less damage in lung tissues than conventional forceps.

Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo

PubMed Central

Brönnimann, Daniel; Bouchet, Audrey; Schneider, Christoph; Potez, Marine; Serduc, Raphaël; Bräuer-Krisch, Elke; Graber, Werner; von Gunten, Stephan; Laissue, Jean Albert; Djonov, Valentin

2016-01-01

Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25–100 μm wide) and minibeams (200–800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a+ thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool. PMID:27640676

Survival mechanisms of vertebrate ectotherms at subfreezing temperatures: applications in cryomedicine.

PubMed

Costanzo, J P; Lee, R E; DeVries, A L; Wang, T; Layne, J R

1995-03-01

Various marine fishes, amphibians, and reptiles survive at temperatures several degrees below the freezing point of their body fluids by virtue of adaptive mechanisms that promote freeze avoidance or freeze tolerance. Freezing is avoided by a colligative depression of the blood freezing point, supercooling of the body fluids, or the biosynthesis of unique antifreeze proteins that inhibit the propagation of ice within body fluids. Conversely, freeze tolerance is an adaptation for the survival of tissue freezing under ecologically relevant thermal and temporal conditions that is conferred by the biosynthesis of permeating carbohydrate cryoprotectants and an extensive dehydration of tissues and organs. Such cryoprotective responses, invoked by the onset of freezing, mitigate the osmotic stress associated with freeze-concentration of cytoplasm, attendant metabolic perturbations, and physical damage. Cryomedical research has historically relied on mammalian models for experimentation even though endotherms do not naturally experience subfreezing temperatures. Some vertebrate ectotherms have "solved" not only the problem of freezing individual tissues and organs, but also that of simultaneously freezing all organ systems. An emerging paradigm in cryomedicine is the application of principles governing natural cold hardiness to the development of protocols for the cryopreservation of mammalian tissues and organs.

Nonpharmaceutical approaches to pain management.

PubMed

Corti, Lisa

2014-03-01

A nonpharmaceutical approach to managing pain is one that does not employ a medication. The use of such approaches, in conjunction with pharmaceuticals as part of multimodal methods to managing pain, is becoming more popular as evidence is emerging to support their use. Cold therapy, for one, is used to reduce the inflammation and tissue damage seen in acute injuries and can be very effective at reducing acute pain. Incorporating the use of superficial heat therapy when treating pain associated with chronic musculoskeletal conditions is often employed as heat increases blood flow, oxygen delivery, and tissue extensibility. Acupuncture is gaining acceptance in veterinary medicine. Research is confirming that release of endogenous endorphins and enkephalins from the application of needles at specific points around the body can effectively control acute and chronic pain. The use of 2 newer therapies-extracorporeal shockwave therapy and platelet-rich plasma-represent an attempt to eliminate the causes of pain at the tissue level by promoting tissue healing and regeneration. Reviewed in this article, these therapies are intended to be used in conjunction with pharmaceuticals as part of a multimodal approach to pain management. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.

PubMed

Zitnay, Jared L; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P; Buehler, Markus J; Yu, S Michael; Weiss, Jeffrey A

2017-03-22

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage.

PubMed

Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C; Lin, Yinan; Kaplan, David L; Kumamoto, Carol A; Mecsas, Joan

2018-04-01

Endospore-forming Clostridioides difficile is a causative agent of antibiotic-induced diarrhea, a major nosocomial infection. Studies of its interactions with mammalian tissues have been hampered by the fact that C. difficile requires anaerobic conditions to survive after spore germination. We recently developed a bioengineered 3D human intestinal tissue model and found that low O 2 conditions are produced in the lumen of these tissues. Here, we compared the ability of C. difficile spores to germinate, produce toxin and cause tissue damage in our bioengineered 3D tissue model versus in a 2D transwell model in which human cells form a polarized monolayer. 3D tissue models or 2D polarized monolayers on transwell filters were challenged with the non-toxin producing C. difficile CCUG 37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in the presence of the germinant, taurocholate. Spores germinated in both the 3D tissue model as well as the 2D transwell system, however toxin activity was significantly higher in the 3D tissue models compared to the 2D transwells. Moreover, the epithelium damage in the 3D tissue model was significantly more severe than in 2D transwells and damage correlated significantly with the level of toxin activity detected but not with the amount of germinated spores. Combined, these results show that the bioengineered 3D tissue model provides a powerful system with which to study early events leading to toxin production and tissue damage of C. difficile with mammalian cells under anaerobic conditions. Furthermore, these systems may be useful for examining the effects of microbiota, novel drugs and other potential therapeutics directed towards C. difficile infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

A polarization sensitive hyperspectral imaging system for detection of differences in tissue properties

NASA Astrophysics Data System (ADS)

Peller, Joseph A.; Ceja, Nancy K.; Wawak, Amanda J.; Trammell, Susan R.

2018-02-01

Polarized light imaging and optical spectroscopy can be used to distinguish between healthy and diseased tissue. In this study, the design and testing of a single-pixel hyperspectral imaging system that uses differences in the polarization of light reflected from tissue to differentiate between healthy and thermally damaged tissue is discussed. Thermal lesions were created in porcine skin (n = 8) samples using an IR laser. The damaged regions were clearly visible in the polarized light hyperspectral images. Reflectance hyperspectral and white light imaging was also obtained for all tissue samples. Sizes of the thermally damaged regions as measured via polarized light hyperspectral imaging are compared to sizes of these regions as measured in the reflectance hyperspectral images and white light images. Good agreement between the sizes measured by all three imaging modalities was found. Hyperspectral polarized light imaging can differentiate between healthy and damaged tissue. Possible applications of this imaging system include determination of tumor margins during cancer surgery or pre-surgical biopsy.

TNFα-Mediated Liver Destruction by Kupffer Cells and Ly6Chi Monocytes during Entamoeba histolytica Infection

PubMed Central

Ernst, Thomas; Ittrich, Harald; Jacobs, Thomas; Heeren, Joerg; Tacke, Frank; Tannich, Egbert; Lotter, Hannelore

2013-01-01

Amebic liver abscess (ALA) is a focal destruction of liver tissue due to infection by the protozoan parasite Entamoeba histolytica (E. histolytica). Host tissue damage is attributed mainly to parasite pathogenicity factors, but massive early accumulation of mononuclear cells, including neutrophils, inflammatory monocytes and macrophages, at the site of infection raises the question of whether these cells also contribute to tissue damage. Using highly selective depletion strategies and cell-specific knockout mice, the relative contribution of innate immune cell populations to liver destruction during amebic infection was investigated. Neutrophils were not required for amebic infection nor did they appear to be substantially involved in tissue damage. In contrast, Kupffer cells and inflammatory monocytes contributed substantially to liver destruction during ALA, and tissue damage was mediated primarily by TNFα. These data indicate that besides direct antiparasitic drugs, modulating innate immune responses may potentially be beneficial in limiting ALA pathogenesis. PMID:23300453

Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds.

PubMed

Serpooshan, Vahid; Mahmoudi, Morteza; Zhao, Mingming; Wei, Ke; Sivanesan, Senthilkumar; Motamedchaboki, Khatereh; Malkovskiy, Andrey V; Gladstone, Andrew B; Cohen, Jeffrey E; Yang, Phillip C; Rajadas, Jayakumar; Bernstein, Daniel; Woo, Y Joseph; Ruiz-Lozano, Pilar

2015-07-22

Biomaterials are extensively used to restore damaged tissues, in the forms of implants (e.g. tissue engineered scaffolds) or biomedical devices (e.g. pacemakers). Once in contact with the physiological environment, nanostructured biomaterials undergo modifications as a result of endogenous proteins binding to their surface. The formation of this macromolecular coating complex, known as 'protein corona', onto the surface of nanoparticles and its effect on cell-particle interactions are currently under intense investigation. In striking contrast, protein corona constructs within nanostructured porous tissue engineering scaffolds remain poorly characterized. As organismal systems are highly dynamic, it is conceivable that the formation of distinct protein corona on implanted scaffolds might itself modulate cell-extracellular matrix interactions. Here, we report that corona complexes formed onto the fibrils of engineered collagen scaffolds display specific, distinct, and reproducible compositions that are a signature of the tissue microenvironment as well as being indicative of the subject's health condition. Protein corona formed on collagen matrices modulated cellular secretome in a context-specific manner ex-vivo , demonstrating their role in regulating scaffold-cellular interactions. Together, these findings underscore the importance of custom-designing personalized nanostructured biomaterials, according to the biological milieu and disease state. We propose the use of protein corona as in situ biosensor of temporal and local biomarkers.

Pediatric Tubular Pulmonary Heart Valve from Decellularized Engineered Tissue Tubes

PubMed Central

Reimer, Jay M.; Syedain, Zeeshan H.; Haynie, Bee H.T.; Tranquillo, Robert T.

2015-01-01

Pediatric patients account for a small portion of the heart valve replacements performed, but a pediatric pulmonary valve replacement with growth potential remains an unmet clinical need. Herein we report the first tubular heart valve made from two decellularized, engineered tissue tubes attached with absorbable sutures, which can meet this need, in principle. Engineered tissue tubes were fabricated by allowing ovine dermal fibroblasts to replace a sacrificial fibrin gel with an aligned, cell-produced collagenous matrix, which was subsequently decellularized. Previously, these engineered tubes became extensively recellularized following implantation into the sheep femoral artery. Thus, a tubular valve made from these tubes may be amenable to recellularization and, ideally, somatic growth. The suture line pattern generated three equi-spaced “leaflets” in the inner tube, which collapsed inward when exposed to back pressure, per tubular valve design. Valve testing was performed in a pulse duplicator system equipped with a secondary flow loop to allow for root distention. All tissue-engineered valves exhibited full leaflet opening and closing, minimal regurgitation (< 5%), and low systolic pressure gradients (< 2.5 mmHg) under pulmonary conditions. Valve performance was maintained under various trans-root pressure gradients and no tissue damage was evident after 2 million cycles of fatigue testing. PMID:26036175

A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

PubMed

Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

2010-12-01

Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Glycerophospholipid Profiles of Bats with White-Nose Syndrome.

PubMed

Pannkuk, Evan L; McGuire, Liam P; Warnecke, Lisa; Turner, James M; Willis, Craig K R; Risch, Thomas S

2015-01-01

Pseudogymnoascus destructans is an ascomycetous fungus responsible for the disease dubbed white-nose syndrome (WNS) and massive mortalities of cave-dwelling bats. The fungus infects bat epidermal tissue, causing damage to integumentary cells and pilosebaceous units. Differences in epidermal lipid composition caused by P. destructans infection could have drastic consequences for a variety of physiological functions, including innate immune efficiency and water retention. While bat surface lipid and stratum corneum lipid composition have been described, the differences in epidermal lipid content between healthy tissue and P. destructans-infected tissue have not been documented. In this study, we analyzed the effect of wing damage from P. destructans infection on the epidermal polar lipid composition (glycerophospholipids [GPs] and sphingomyelin) of little brown bats (Myotis lucifugus). We hypothesized that infection would lead to lower levels of total lipid or higher oxidized lipid product proportions. Polar lipids from three damaged and three healthy wing samples were profiled by electrospray ionization tandem mass spectrometry. We found lower total broad lipid levels in damaged tissue, specifically ether-linked phospholipids, lysophospholipids, phosphatidylcholine, and phosphatidylethanolamine. Thirteen individual GP species from four broad GP classes were present in higher amounts in healthy tissue. Six unsaturated GP species were absent in damaged tissue. Our results confirm that P. destructans infection leads to altered lipid profiles. Clinical signs of WNS may include lower lipid levels and lower proportions of unsaturated lipids due to cellular and glandular damage.

Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions

PubMed Central

Weber, Daniela; Davies, Michael J.; Grune, Tilman

2015-01-01

Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples. PMID:26141921

Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions.

PubMed

Weber, Daniela; Davies, Michael J; Grune, Tilman

2015-08-01

Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples. © 2015 Published by Elsevier Ltd.

Thermal damage control of dye-assisted laser tissue welding: effect of dye concentration

NASA Astrophysics Data System (ADS)

Xie, Hua; Buckley, Lisa A.; Prahl, Scott A.; Shaffer, Brian S.; Gregory, Kenton W.

2001-05-01

Successful laser-assisted tissue welding was implemented to provide proper weld strength with minimized tissue thermal injury. We investigated and compared the weld strengths and morphologic changes in porcine small intestinal submucose (SIS) and porcine ureteral tissues with various concentration of indocyanine green (ICG) and with a solid albumin sheet. The study showed that the tissues were welded at lower ICG concentration (0.05 mM) with minimized tissue thermal damage using an 800-nm wavelength diode laser.

Application of immunohistochemical staining to detect antigen destruction as a measure of tissue damage.

PubMed

Onul, Abdullah; Colvard, Michael D; Paradise, William A; Elseth, Kim M; Vesper, Benjamin J; Gouvas, Eftychia; Deliu, Zane; Garcia, Kelly D; Pestle, William J; Radosevich, James A

2012-09-01

Electrocautery and directed energy devices (DEDs) such as lasers, which are used in surgery, result in tissue damage that cannot be readily detected by traditional histological methods, such as hematoxylin and eosin staining. Alternative staining methods, including 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to stain live tissue, have been reported. Despite providing superior detection of damaged tissue relative to the hematoxylin and eosin (H&E) method, the MTT method possesses a number of drawbacks, most notably that it must be carried out on live tissue samples. Herein, we report the development of a novel staining method, "antigen destruction immunohistochemistry" (ADI), which can be carried out on paraffin-embedded tissue. The ADI method takes advantage of epitope loss to define the area of tissue damage and provides many of the benefits of live tissue MTT staining without the drawbacks inherent to that method. In addition, the authors provide data to support the use of antibodies directed at a number of gene products for use in animal tissue for which there are no species-specific antibodies commercially available, as well as an example of a species-specific direct antibody. Data are provided that support the use of this method in many tissue models, as well as evidence that ADI is comparable to the live tissue MTT method.

Application of Immunohistochemical Staining to Detect Antigen Destruction as a Measure of Tissue Damage

PubMed Central

Onul, Abdullah; Colvard, Michael D.; Paradise, William A.; Elseth, Kim M.; Vesper, Benjamin J.; Gouvas, Eftychia; Deliu, Zane; Garcia, Kelly D.; Pestle, William J.

2012-01-01

Electrocautery and directed energy devices (DEDs) such as lasers, which are used in surgery, result in tissue damage that cannot be readily detected by traditional histological methods, such as hematoxylin and eosin staining. Alternative staining methods, including 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to stain live tissue, have been reported. Despite providing superior detection of damaged tissue relative to the hematoxylin and eosin (H&E) method, the MTT method possesses a number of drawbacks, most notably that it must be carried out on live tissue samples. Herein, we report the development of a novel staining method, “antigen destruction immunohistochemistry” (ADI), which can be carried out on paraffin-embedded tissue. The ADI method takes advantage of epitope loss to define the area of tissue damage and provides many of the benefits of live tissue MTT staining without the drawbacks inherent to that method. In addition, the authors provide data to support the use of antibodies directed at a number of gene products for use in animal tissue for which there are no species-specific antibodies commercially available, as well as an example of a species-specific direct antibody. Data are provided that support the use of this method in many tissue models, as well as evidence that ADI is comparable to the live tissue MTT method. PMID:22723525

Analysis of plastic deformation in cortical bone after insertion of coated and non-coated self-tapping orthopaedic screws.

PubMed

Koistinen, A P; Korhonen, H; Kiviranta, I; Kröger, H; Lappalainen, R

2011-07-01

Insertion of internal fracture fixation devices, such as screws, mechanically weakens the bone. Diamond-like carbon has outstanding tribology properties which may decrease the amount of damage in tissue. The purpose of this study was to investigate methods for quantification of cortical bone damage after orthopaedic bone screw insertion and to evaluate the effect of surface modification on tissue damage. In total, 48 stainless steel screws were inserted into cadaver bones. Half of the screws were coated with a smooth amorphous diamond coating. Geometrical data of the bones was determined by peripheral quantitative computed tomography. Thin sections of the bone samples were prepared after screw insertion, and histomorphometric evaluation of damage was performed on images obtained using light microscopy. Micro-computed tomography and scanning electron microscopy were also used to examine tissue damage. A positive correlation was found between tissue damage and the geometric properties of the bone. The age of the cadaver significantly affected the bone mineral density, as well as the damage perimeter and diameter of the screw hole. However, the expected positive effect of surface modification was probably obscured by large variations in the results and, thus, statistically significant differences were not found in this study. This can be explained by natural variability in bone tissue, which also made automated image analysis difficult.

Arterial embolism

MedlinePlus

... This can result in damage or tissue death ( necrosis ). Arterial emboli often occur in the legs and ... sloughing) of skin Skin erosion ( ulcer ) Tissue death (necrosis; skin is dark and damaged) Symptoms of a ...

Reconstruction with a 180-degree Rotationally Divided Latissimus-dorsi-musculocutaneous Flap after the Removal of Locally Advanced Breast Cancer

PubMed Central

Kirita, Miho; Sakurai, Hiroyuki

2014-01-01

Summary: This study described a technique for reconstruction of a large lateral thoracic region defect after locally advanced breast cancer resection that allows for full coverage of the defect and primary closure of the flap donor site. The authors performed reconstruction using the newly designed 180-degree rotationally-divided latissimus-dorsi-musculocutaneous flap in a 42-year-old woman for coverage of a large skin defect (18 × 15 cm) following extensive tissue resection for locally advanced breast cancer. The latissimus-dorsi-musculocutaneous flap, consisting of two rotated skin islands (18 × 7.5 cm each) that were sutured to form a large skin island, was used for coverage of the defect. The flap was sutured without causing excessive tension in the recipient region and the donor site was closed with simple reefing. No skin grafting was necessary. The flap survived completely, shoulder joint function was intact, and esthetic outcome was satisfactory. Quick wound closure allowed postoperative irradiation to be started 1 month after surgery. The technique offered advantages over the conventional pedicled latissimus-dorsi-musculocutaneous flap, but the flap was unable to be used, when the thoracodorsal artery and vein were damaged during extensive tissue removal. Detailed planning before surgery with breast surgeons would be essential. PMID:25426400

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo.

PubMed

De Francesco, Francesco; Guastafierro, Antonio; Nicoletti, Gianfranco; Razzano, Sergio; Riccio, Michele; Ferraro, Giuseppe A

2017-05-12

Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here.

A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue

NASA Astrophysics Data System (ADS)

Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

2013-04-01

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here inspired by the endoparasite Pomphorhynchus laevis, which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~3.5-fold increase in adhesion strength compared with staples in skin graft fixation, and removal force of ~4.5 N cm-2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue

PubMed Central

Yang, Seung Yun; O'Cearbhaill, Eoin D.; Sisk, Geoffroy C.; Park, Kyeng Min; Cho, Woo Kyung; Villiger, Martin; Bouma, Brett E.; Pomahac, Bohdan; Karp, Jeffrey M.

2013-01-01

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics. PMID:23591869

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

PubMed Central

Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

2014-01-01

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

Stromal regulation of vessel stability by MMP14 and TGFβ

PubMed Central

Sounni, Nor E.; Dehne, Kerstin; van Kempen, Leon; Egeblad, Mikala; Affara, Nesrine I.; Cuevas, Ileana; Wiesen, Jane; Junankar, Simon; Korets, Lidiya; Lee, Jake; Shen, Jennifer; Morrison, Charlotte J.; Overall, Christopher M.; Krane, Stephen M.; Werb, Zena; Boudreau, Nancy; Coussens, Lisa M.

2010-01-01

Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGFβ1). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFβ1, or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGFβ bioavailability are chronically elevated, or in mice that ectopically express TGFβ in the epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if the fibrotic mice are pretreated with metalloproteinase inhibitors or TGFβ signaling antagonists. Neoplastic tissues, however, are in a constant state of tissue damage and exhibit altered hemodynamics owing to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into the interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGFβ that mediates vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery. PMID:20223936

Does prolonged radiofrequency radiation emitted from Wi-Fi devices induce DNA damage in various tissues of rats?

PubMed

Akdag, Mehmet Zulkuf; Dasdag, Suleyman; Canturk, Fazile; Karabulut, Derya; Caner, Yusuf; Adalier, Nur

2016-09-01

Wireless internet (Wi-Fi) providers have become essential in our daily lives, as wireless technology is evolving at a dizzying pace. Although there are different frequency generators, one of the most commonly used Wi-Fi devices are 2.4GHz frequency generators. These devices are heavily used in all areas of life but the effect of radiofrequency (RF) radiation emission on users is generally ignored. Yet, an increasing share of the public expresses concern on this issue. Therefore, this study intends to respond to the growing public concern. The purpose of this study is to reveal whether long term exposure of 2.4GHz frequency RF radiation will cause DNA damage of different tissues such as brain, kidney, liver, and skin tissue and testicular tissues of rats. The study was conducted on 16 adult male Wistar-Albino rats. The rats in the experimental group (n=8) were exposed to 2.4GHz frequency radiation for over a year. The rats in the sham control group (n=8) were subjected to the same experimental conditions except the Wi-Fi generator was turned off. After the exposure period was complete the possible DNA damage on the rat's brain, liver, kidney, skin, and testicular tissues was detected through the single cell gel electrophoresis assay (comet) method. The amount of DNA damage was measured as percentage tail DNA value. Based on the DNA damage results determined by the single cell gel electrophoresis (Comet) method, it was found that the% tail DNA values of the brain, kidney, liver, and skin tissues of the rats in the experimental group increased more than those in the control group. The increase of the DNA damage in all tissues was not significant (p>0.05). However the increase of the DNA damage in rat testes tissue was significant (p<0.01). In conclusion, long-term exposure to 2.4GHz RF radiation (Wi-Fi) does not cause DNA damage of the organs investigated in this study except testes. The results of this study indicated that testes are more sensitive organ to RF radiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion.

PubMed

Mailänder-Sánchez, Daniela; Braunsdorf, Christina; Grumaz, Christian; Müller, Christoph; Lorenz, Stefan; Stevens, Philip; Wagener, Jeanette; Hebecker, Betty; Hube, Bernhard; Bracher, Franz; Sohn, Kai; Schaller, Martin

2017-01-01

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

Renal denervation by intravascular ultrasound: Preliminary in vivo study

NASA Astrophysics Data System (ADS)

Sinelnikov, Yegor; McClain, Steve; Zou, Yong; Smith, David; Warnking, Reinhard

2012-10-01

Ultrasound denervation has recently become a subject of intense research in connection with the treatment of complex medical conditions including neurological conditions, development of pain management, reproduction of skin sensation, neuropathic pain and spasticity. The objective of this study is to investigate the use of intravascular ultrasound to produce nerve damage in renal sympathetic nerves without significant injury to the renal artery. This technique may potentially be used to treat various medical conditions, such as hypertension. The study was approved by the Institutional Animal Care and Use Committee. Ultrasound was applied to renal nerves of the swine model for histopathological evaluation. Therapeutic ultrasound energy was delivered circumferentially by an intravascular catheter maneuvered into the renal arteries. Fluoroscopic imaging was conducted pre-and post-ultrasound treatment. Animals were recovered and euthanized up to 30 hours post procedure, followed by necropsy and tissue sample collection. Histopathological examination showed evidence of extensive damage to renal nerves, characterized by nuclear pyknosis, hyalinization of stroma and multifocal hemorrhages, with little or no damage to renal arteries. This study demonstrates the feasibility of intravascular ultrasound as a minimally invasive renal denervation technique. Further studies are necessary to evaluate the long-term safety and efficacy of this technique and its related clinical significance.

Adjustable patella grapple versus cannulated screw and cable technique for treatment of transverse patellar fractures.

PubMed

Yan, Ning; Yang, Anli; Liu, Xiaodong; Cai, Feng; Liu, Liang; Chang, Shimin

2014-03-01

Although the cannulated screw and cable (CSC) tension band technique is an effective method for fixation of transverse patellar fractures, it has shortcomings, such as extensive soft tissue damage, osseous substance damage, and complex manipulation. We conducted a retrospective comparison of the adjustable patella grapple (APG) technique and the CSC tension band technique. We retrospectively reviewed 78 patients with transverse patellar fractures (45 in the APG group and 33 in the CSC group). Follow-up was 18 months. Comparison criteria were operation time, fracture reduction, fracture healing time, the knee injury and osteoarthritis outcome score for knee function, and complications. The APG group showed shorter operation time and equal fracture reduction, fracture healing time, and knee function compared with the CSC group. Eleven patients in the APG group experienced skin irritation generated by implants. There was no complication in the CSC group. The APG technique should be considered as an alternative method for treatment of transverse patellar fractures.

75 FR 52710 - Notice of Request for Extension of Approval of an Information Collection; National Management...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

...] Notice of Request for Extension of Approval of an Information Collection; National Management Information... approval of an information collection associated with cooperative wildlife damage management programs...: For information on the national management information system for cooperative wildlife damage...

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

PubMed Central

Taeger, Christian D.; Friedrich, Oliver; Dragu, Adrian; Weigand, Annika; Hobe, Frieder; Drechsler, Caroline; Geppert, Carol I.; Arkudas, Andreas; Münch, Frank; Buchholz, Rainer; Pollmann, Charlotte; Schramm, Axel; Birkholz, Torsten; Horch, Raymund E.; Präbst, Konstantin

2015-01-01

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID:26145230

Wound ballistics of firearm-related injuries--part 1: missile characteristics and mechanisms of soft tissue wounding.

PubMed

Stefanopoulos, P K; Filippakis, K; Soupiou, O T; Pazarakiotis, V C

2014-12-01

Firearm-related injuries are caused by a wide variety of weapons and projectiles. The kinetic energy of the penetrating projectile defines its ability to disrupt and displace tissue, whereas the actual tissue damage is determined by the mode of energy release during the projectile-tissue interaction and the particular characteristics of the tissues and organs involved. Certain projectile factors, namely shape, construction, and stability, greatly influence the rate of energy transfer to the tissues along the wound track. Two zones of tissue damage can be identified, the permanent cavity created by the passage of the bullet and a potential area of contused tissue surrounding it, produced mainly by temporary cavitation which is a manifestation of effective high-energy transfer to tissue. Due to the complex nature of these injuries, wound assessment and the type and extent of treatment required should be based on an understanding of the various mechanisms contributing to tissue damage. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Radioprotective effect of a metalloporphyrin compound in rat eye model.

PubMed

Mao, X W; Crapo, J D; Mekonnen, T; Lindsey, N; Martinez, P; Gridley, D S; Slater, J M

2009-01-01

The purpose of this study was to evaluate the efficacy of the antioxidant Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) in protecting ocular tissue and retinal microvasculature from radiation damage. 75 rats were treated with Mn TE-2-PyP at 2.5 micro g/injection into one eye an hour before proton irradiation. The radiation was delivered in a single fraction to total doses of 8 Gray (Gy) or 28 Gy; Rats were sacrificed 3 days and 3, 6, 9, and 12 months thereafter for histology and quantification of photoreceptor cell populations and retinal capillary changes. By 6 months following radiation, there was significant loss of retinal outer and inner nuclear layers in eyes receiving radiation only (8 and 28 Gy) (p < 0.05) compared to their controls and to the eyes of rats treated with radiation plus metalloporphyrin. Retinal microvessel length density decreased significantly 6 months following 28 Gy (p < 0.05) compared to their controls and to MnTE-2-PyP treated rats. By 12 months following irradiation, irradiated eyes showed extensive damage to the photoreceptor layer, whereas the eyes of animals receiving radiation plus MnTE-2-PyP showed almost no morphological damage. MnTE-2-PyP treatment also suppressed radiation-induced apoptosis in our study. These results demonstrated that MnTE-2-PyP protected both photoreceptors and retinal capillaries from radiation damage, suggesting that this metalloporphyrin antioxidant is effective in regulating the damage induced by proton radiation.

77 FR 37344 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... reports of extensive damage to engine air intake cowls as a result of acoustic panel collapse. This proposed AD would require repetitive inspections of the three inner acoustic panels of both engine air... finding extensive damage to engine air intake cowls as a result of acoustic panel collapse, most probably...

Microbial pathogens trigger host DNA double-strand breaks whose abundance is reduced by plant defense responses.

PubMed

Song, Junqi; Bent, Andrew F

2014-04-01

Immune responses and DNA damage repair are two fundamental processes that have been characterized extensively, but the links between them remain largely unknown. We report that multiple bacterial, fungal and oomycete plant pathogen species induce double-strand breaks (DSBs) in host plant DNA. DNA damage detected by histone γ-H2AX abundance or DNA comet assays arose hours before the disease-associated necrosis caused by virulent Pseudomonas syringae pv. tomato. Necrosis-inducing paraquat did not cause detectable DSBs at similar stages after application. Non-pathogenic E. coli and Pseudomonas fluorescens bacteria also did not induce DSBs. Elevation of reactive oxygen species (ROS) is common during plant immune responses, ROS are known DNA damaging agents, and the infection-induced host ROS burst has been implicated as a cause of host DNA damage in animal studies. However, we found that DSB formation in Arabidopsis in response to P. syringae infection still occurs in the absence of the infection-associated oxidative burst mediated by AtrbohD and AtrbohF. Plant MAMP receptor stimulation or application of defense-activating salicylic acid or jasmonic acid failed to induce a detectable level of DSBs in the absence of introduced pathogens, further suggesting that pathogen activities beyond host defense activation cause infection-induced DNA damage. The abundance of infection-induced DSBs was reduced by salicylic acid and NPR1-mediated defenses, and by certain R gene-mediated defenses. Infection-induced formation of γ-H2AX still occurred in Arabidopsis atr/atm double mutants, suggesting the presence of an alternative mediator of pathogen-induced H2AX phosphorylation. In summary, pathogenic microorganisms can induce plant DNA damage. Plant defense mechanisms help to suppress rather than promote this damage, thereby contributing to the maintenance of genome integrity in somatic tissues.

Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

NASA Astrophysics Data System (ADS)

Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

2014-01-01

Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague

PubMed Central

Guinet, Françoise; Avé, Patrick; Filali, Sofia; Huon, Christèle; Savin, Cyril; Huerre, Michel; Fiette, Laurence; Carniel, Elisabeth

2015-01-01

Activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. Yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease Pla, which activates plasmin and inactivates fibrinolysis inhibitors. Pla is encoded by the pPla plasmid. Following intradermal inoculation, Y. pestis has the capacity to multiply in and cause destruction of the lymph node (LN) draining the entry site. The closely related, pPla-negative, Y. pseudotuberculosis species lacks this capacity. We hypothesized that tissue damage and bacterial multiplication occurring in the LN during bubonic plague were linked and both driven by pPla. Using a set of pPla-positive and pPla-negative Y. pestis and Y. pseudotuberculosis strains in a mouse model of intradermal injection, we found that pPla is not required for bacterial translocation to the LN. We also observed that a pPla-cured Y. pestis caused the same extensive histological lesions as the wild type strain. Furthermore, the Y. pseudotuberculosis histological pattern, characterized by infectious foci limited by inflammatory cell infiltrates with normal tissue density and follicular organization, was unchanged after introduction of pPla. However, the presence of pPla enabled Y. pseudotuberculosis to increase its bacterial load up to that of Y. pestis. Similarly, lack of pPla strongly reduced Y. pestis titers in LNs of infected mice. This pPla-mediated enhancing effect on bacterial load was directly dependent on the proteolytic activity of Pla. Immunohistochemistry of Pla-negative Y. pestis-infected LNs revealed extensive bacterial lysis, unlike the numerous, apparently intact, microorganisms seen in wild type Y. pestis-infected preparations. Therefore, our study demonstrates that tissue destruction and bacterial survival/multiplication are dissociated in the bubo and that the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Y. pestis propagation in the host. PMID:26484539

Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague.

PubMed

Guinet, Françoise; Avé, Patrick; Filali, Sofia; Huon, Christèle; Savin, Cyril; Huerre, Michel; Fiette, Laurence; Carniel, Elisabeth

2015-10-01

Activation and/or recruitment of the host plasmin, a fibrinolytic enzyme also active on extracellular matrix components, is a common invasive strategy of bacterial pathogens. Yersinia pestis, the bubonic plague agent, expresses the multifunctional surface protease Pla, which activates plasmin and inactivates fibrinolysis inhibitors. Pla is encoded by the pPla plasmid. Following intradermal inoculation, Y. pestis has the capacity to multiply in and cause destruction of the lymph node (LN) draining the entry site. The closely related, pPla-negative, Y. pseudotuberculosis species lacks this capacity. We hypothesized that tissue damage and bacterial multiplication occurring in the LN during bubonic plague were linked and both driven by pPla. Using a set of pPla-positive and pPla-negative Y. pestis and Y. pseudotuberculosis strains in a mouse model of intradermal injection, we found that pPla is not required for bacterial translocation to the LN. We also observed that a pPla-cured Y. pestis caused the same extensive histological lesions as the wild type strain. Furthermore, the Y. pseudotuberculosis histological pattern, characterized by infectious foci limited by inflammatory cell infiltrates with normal tissue density and follicular organization, was unchanged after introduction of pPla. However, the presence of pPla enabled Y. pseudotuberculosis to increase its bacterial load up to that of Y. pestis. Similarly, lack of pPla strongly reduced Y. pestis titers in LNs of infected mice. This pPla-mediated enhancing effect on bacterial load was directly dependent on the proteolytic activity of Pla. Immunohistochemistry of Pla-negative Y. pestis-infected LNs revealed extensive bacterial lysis, unlike the numerous, apparently intact, microorganisms seen in wild type Y. pestis-infected preparations. Therefore, our study demonstrates that tissue destruction and bacterial survival/multiplication are dissociated in the bubo and that the primary action of Pla is to protect bacteria from destruction rather than to alter the tissue environment to favor Y. pestis propagation in the host.

[Scanning electron microscopy of heat-damaged bone tissue].

PubMed

Harsanyl, L

1977-02-01

Parts of diaphyses of bones were exposed to high temperature of 200-1300 degrees C. Damage to the bone tissue caused by the heat was investigated. The scanning electron microscopic picture seems to be characteristic of the temperature applied. When the bones heated to the high temperature of 700 degrees C characteristic changes appear on the periostal surface, higher temperatura on the other hand causes damage to the compact bone tissue and can be observed on the fracture-surface. Author stresses the importance of this technique in the legal medicine and anthropology.

Neurosurgical patties: adhesion and damage mitigation.

PubMed

Stratton-Powell, Ashley A; Anderson, Ian A; Timothy, Jake; Kapur, Nikil; Culmer, Peter

2015-07-01

Neurosurgical patties are textile pads used during most neurosurgical operations to protect tissues, manage the fluid environment, control hemostasis, and aid tissue manipulation. Recent research has suggested that, contrary to their aim, patties adhere to brain tissue and cause damage during removal. This study aimed to characterize and quantify the degree of and consequences resulting from adhesion between neurosurgical patties and brain tissue. Using a customized peel apparatus, the authors performed 90° peel tests on 5 patty products: Policot, Telfa, Americot, Delicot, and Ray-Cot (n = 247) from American Surgical Company. They tested 4 conditions: wet patty on glass (control), wet patty on wet brain peeled at 5 mm/sec (wet), dry patty on wet brain peeled at 5 mm/sec (dry), and wet patty on wet brain peeled at 20 mm/sec (speed). The interaction between patty and tissue was analyzed using peel-force traces and pre-peel histological analysis. Adhesion strength differed between patty products (p < 0.001) and conditions (p < 0.001). Adhesion strength was greatest for Delicot patties under wet (2.22 mN/mm) and dry (9.88 mN/mm) conditions. For all patties, damage at the patty-tissue interface was proportional to the degree of fiber contact. When patties were irrigated, mechanical adhesion was reduced by up to 550% compared with dry usage. For all patty products, mechanical (destructive) and liquid-mediated (nondestructive) adhesion caused damage to neural tissue. The greatest adhesion occurred with Delicot patties. To mitigate patty adhesion and neural tissue damage, surgeons should consider regular irrigation to be essential during neurosurgical procedures.

Optical monitoring of spinal cord subcellular damage after acute spinal cord injury

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Fong, Allan; Streijger, Femke; Macnab, Andrew; Kwon, Brian K.

2018-02-01

Introduction: Sudden physical trauma to the spinal cord results in acute spinal cord injury (SCI), leading to spinal cord (SC) tissue destruction, acute inflammation, increased SC intraparenchymal pressure, and tissue ischemia, hypoxia, and cellular necrosis. The ability to monitor SC tissue viability at subcellular level, using a real-time noninvasive method, would be extremely valuable to clinicians for estimating acute SCI damage, and adjusting and monitoring treatment in the intensive care setting. This study examined the feasibility and sensitivity of a custommade near infrared spectroscopy (NIRS) sensor to monitor the oxidation state of SC mitochondrial cytochrome aa3 (CCO), which reflects the subcellular damage of SC tissue in an animal model of SCI. Methods: Six anesthetized Yorkshire pigs were studied using a custom-made multi-wavelength NIRS system with a miniaturized optical sensor applied directly on the surgically exposed SC at T9. The oxidation states of SC tissue hemoglobin and CCO were monitored before, during and after acute SCI, and during mean arterial pressure alterations. Results: Non-invasive NIRS monitoring reflected changes in SC tissue CCO, simultaneous but independent of changes in hemoglobin saturation following acute SCI. A consistent decrease in SC tissue CCO chromophore concentration (-1.98 +/- 2.1 ab, p<0.05) was observed following SCI, indicating progressive SC cellular damage at the injury site. Elevation of mean arterial pressure can reduce SC tissue damage as suggested by different researchers and observed by significant increase in SC tissue CCO concentration (1.51 +/- 1.7 ab, p<0.05) in this study. Conclusions: This pilot study indicates that a novel miniaturized multi-wave NIRS sensor has the potential to monitor post-SCI changes of SC cytochrome aa3 oxygenation state in real time. Further development of this method may offer new options for improved SCI care.

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-11-30

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

Controlled-Release Personal Use Arthropod Repellent Formulation. Phase 2

DTIC Science & Technology

1986-09-15

damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS...M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS -Positive...Corneal epithelial damage, piling L - Corneal epithelial damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to

Validity of reciprocity rule on mouse skin thermal damage due to CO2 laser irradiation

NASA Astrophysics Data System (ADS)

Parvin, P.; Dehghanpour, H. R.; Moghadam, M. S.; Daneshafrooz, V.

2013-07-01

CO2 laser (10.6 μm) is a well-known infrared coherent light source as a tool in surgery. At this wavelength there is a high absorbance coefficient (860 cm-1), because of vibration mode resonance of H2O molecules. Therefore, the majority of the irradiation energy is absorbed in the tissue and the temperature of the tissue rises as a function of power density and laser exposure duration. In this work, the tissue damage caused by CO2 laser (1-10 W, ˜40-400 W cm-2, 0.1-6 s) was measured using 30 mouse skin samples. Skin damage assessment was based on measurements of the depth of cut, mean diameter of the crater and the carbonized layer. The results show that tissue damage as assessed above parameters increased with laser fluence and saturated at 1000 J cm-2. Moreover, the damage effect due to high power density at short duration was not equivalent to that with low power density at longer irradiation time even though the energy delivered was identical. These results indicate the lack of validity of reciprocity (Bunsen-Roscoe) rule for the thermal damage.

Tissue damage negatively regulates LPS-induced macrophage necroptosis.

PubMed

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-09-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules.

Tissue damage negatively regulates LPS-induced macrophage necroptosis

PubMed Central

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-01-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules. PMID:26943325

Tissue damage-induced intestinal stem cell division in Drosophila

PubMed Central

Amcheslavsky, Alla; Jiang, Jin; Ip, Y. Tony

2009-01-01

SUMMARY Stem cell division is essential for tissue integrity during growth, aging, and pathogenic assaults. Adult gastrointestinal tract encounters numerous stimulations and impaired tissue regeneration may lead to inflammatory diseases and cancer. Intestinal stem cells in adult Drosophila have recently been identified and shown to replenish the various cell types within the midgut. However, it is not known whether these intestinal stem cells can respond to environmental challenges. By feeding dextran sulfate sodium and bleomycin to flies and by expressing apoptotic proteins, we show that Drosophila intestinal stem cells can increase the rate of division in response to tissue damage. Moreover, if tissue damage results in epithelial cell loss, the newly formed enteroblasts can differentiate into mature epithelial cells. By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division. PMID:19128792

The DNA damage checkpoint pathway promotes extensive resection and nucleotide synthesis to facilitate homologous recombination repair and genome stability in fission yeast.

PubMed

Blaikley, Elizabeth J; Tinline-Purvis, Helen; Kasparek, Torben R; Marguerat, Samuel; Sarkar, Sovan; Hulme, Lydia; Hussey, Sharon; Wee, Boon-Yu; Deegan, Rachel S; Walker, Carol A; Pai, Chen-Chun; Bähler, Jürg; Nakagawa, Takuro; Humphrey, Timothy C

2014-05-01

DNA double-strand breaks (DSBs) can cause chromosomal rearrangements and extensive loss of heterozygosity (LOH), hallmarks of cancer cells. Yet, how such events are normally suppressed is unclear. Here we identify roles for the DNA damage checkpoint pathway in facilitating homologous recombination (HR) repair and suppressing extensive LOH and chromosomal rearrangements in response to a DSB. Accordingly, deletion of Rad3(ATR), Rad26ATRIP, Crb2(53BP1) or Cdc25 overexpression leads to reduced HR and increased break-induced chromosome loss and rearrangements. We find the DNA damage checkpoint pathway facilitates HR, in part, by promoting break-induced Cdt2-dependent nucleotide synthesis. We also identify additional roles for Rad17, the 9-1-1 complex and Chk1 activation in facilitating break-induced extensive resection and chromosome loss, thereby suppressing extensive LOH. Loss of Rad17 or the 9-1-1 complex results in a striking increase in break-induced isochromosome formation and very low levels of chromosome loss, suggesting the 9-1-1 complex acts as a nuclease processivity factor to facilitate extensive resection. Further, our data suggest redundant roles for Rad3ATR and Exo1 in facilitating extensive resection. We propose that the DNA damage checkpoint pathway coordinates resection and nucleotide synthesis, thereby promoting efficient HR repair and genome stability. © The Author(s) 2014. Published by Oxford University Press.

Biochemical and pharmacological characterization of Trimersurus malabaricus snake venom.

PubMed

Gowda, Raghavendra; Rajaiah, Rajesh; Angaswamy, Nataraj; Krishna, Sharath; Bannikuppe Sannanayak, Vishwanath

2018-07-01

Trimeresurus malabaricus is a venomous pit viper species endemic to southwestern part of India. In earlier reports, we have shown that envenomation by T. malabaricus venom leading to strong local tissue damage but the mechanism of action is not clearly revealed. Local tissue damage affected by T. malabaricus venom is of great importance since the poison has serious systemic effects including death in the case of multiple attacks. The present study details the major manifestations of T. malabaricus venom and the induction of local tissue damage, which suggests that most toxins are present in the form of hydrolytic enzymes. Hydrolytic activity of the enzymes was measured and the data indicated that protease and phospholipase A 2 activity was high which is responsible for local tissue damage. Furthermore, the role of hydrolytic enzymes in the induction of pathological events such as hemorrhage, edema, myotoxicity, and blood coagulation examination were assessed through animal models. © 2018 Wiley Periodicals, Inc.

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in themore » low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.« less

Pathogenesis of Infection by Clinical and Environmental Strains of Vibrio vulnificus in Iron-Dextran-Treated Mice

PubMed Central

Starks, Angela M.; Schoeb, Trenton R.; Tamplin, Mark L.; Parveen, Salina; Doyle, Thomas J.; Bomeisl, Philip E.; Escudero, Gloria M.; Gulig, Paul A.

2000-01-01

Vibrio vulnificus is an opportunistic pathogen that contaminates oysters harvested from the Gulf of Mexico. In humans with compromising conditions, especially excess levels of iron in plasma and tissues, consumption of contaminated seafood or exposure of wounds to contaminated water can lead to systemic infection and disfiguring skin infection with extremely high mortality. V. vulnificus-associated diseases are noted for the rapid replication of the bacteria in host tissues, with extensive tissue damage. In this study we examined the virulence attributes of three virulent clinical strains and three attenuated oyster or seawater isolates in mouse models of systemic disease. All six V. vulnificus strains caused identical skin lesions in subcutaneously (s.c.) inoculated iron dextran-treated mice in terms of numbers of recovered CFU and histopathology; however, the inocula required for identical frequency and magnitude of infection were at least 350-fold higher for the environmental strains. At lethal doses, all strains caused s.c. skin lesions with extensive edema, necrosis of proximate host cells, vasodilation, and as many as 108 CFU/g, especially in perivascular regions. These data suggest that the differences between these clinical and environmental strains may be related to growth in the host or susceptibility to host defenses. In non-iron dextran-treated mice, strains required 105-fold-higher inocula to cause an identical disease process as with iron dextran treatment. These results demonstrate that s.c. inoculation of iron dextran-treated mice is a useful model for studying systemic disease caused by V. vulnificus. PMID:10992486

The relation of microdamage to fracture and material property degradation in human cortical bone tissue

NASA Astrophysics Data System (ADS)

Akkus, Ozan

This dissertation investigates the relation of microdamage to fracture and material property degradation of human cortical bone tissue. Fracture resistance and fatigue crack growth of microcracks were examined experimentally and material property degradation was examined through theoretical modeling. To investigate the contribution of microdamage to static fracture resistance, fracture toughness tests were conducted in the transverse and longitudinal directions to the osteonal orientation of normal bone tissue. Damage accumulation was monitored by acoustic emission during testing and was spatially observed by histological observation following testing. The results suggested that the propagation of the main crack involved weakening of the tissue by diffuse damage at the fracture plane and by formation of linear microcracks away from the fracture plane for the transverse specimens. For the longitudinal specimens, growth of the main crack occurred in the form of separations at lamellar interfaces. Acoustic emission results supported the histological observations. To investigate the contribution of ultrastructure to static fracture resistance, fracture toughness tests were conducted after altering the collagen phase of the bone tissue by gamma radiation. A significant decrease in the fracture toughness, Work-to-Fracture and the amount damage was observed due to irradiation in both crack growth directions. For cortical bone irradiated at 27.5kGy, fracture toughness is reduced due to the inhibition of damage formation at and near the crack tip. Microcrack fatigue crack growth and arrest were investigated through observations of surface cracks during cyclic loading. At the applied cyclic stresses, the microcracks propagated and arrested in less than 10,000 cycles. In addition, the microcracks were observed not to grow beyond a length of 150mum and a DeltaK of 0.5MNm-3/2, supporting a microstructural barrier concept. Finally, the contribution of linear microcracks to material property degradation was examined by developing a theoretical micromechanical damage model. The model was compared to experimentally induced damage in bone tissue. The percent contribution of linear microcracks to the total degradation was predicted to be less than 5%, indicating that diffuse damage or an unidentified form of damage is primarily responsible for material property degradation in human cortical bone tissue.

Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application.

PubMed

Iseli, Hans Peter; Körber, Nicole; Karl, Anett; Koch, Christian; Schuldt, Carsten; Penk, Anja; Liu, Qing; Huster, Daniel; Käs, Josef; Reichenbach, Andreas; Wiedemann, Peter; Francke, Mike

2015-10-01

Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might induce tissue damage, dependent on the light intensity used. Therefore, we characterized the damage threshold and mechanical stiffening effect in rabbit eyes after application of riboflavin combined with various blue light intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5 %) and varying blue light (450 ± 50 nm) dosages from 18 to 780 J/cm(2) (15 to 650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were detected by means of light microscopy, electron microscopy and immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological changes in ocular tissues; the damage threshold was defined by the light intensities which induced cellular degeneration and/or massive collagen structure changes. At such high dosages, we observed alterations of the collagen structure in scleral tissue, as well as pigment aggregation, internal hemorrhages, and collapsed blood vessels. Additionally, photoreceptor degenerations associated with microglia activation and macroglia cell reactivity in the retina were detected. These pathological alterations were locally restricted to the treated areas. Pigmentation of rabbit eyes did not change the damage threshold after a treatment with riboflavin and blue light but seems to influence the vulnerability for blue light irradiations. Increased biomechanical stiffness of scleral tissue could be achieved with blue light intensities below the characterized damage threshold. We conclude that riboflavin and blue light application increased the biomechanical stiffness of scleral tissue at blue light energy levels below the damage threshold. Therefore, applied blue light intensities below the characterized damage threshold might define a therapeutic blue light tolerance range. Copyright © 2015 Elsevier Ltd. All rights reserved.

Infestation of gill copepod Lernanthropus latis (Copepoda: Lernanthropidae) and its effect on cage-cultured Asian sea bass Lates calcarifer.

PubMed

Kua, B C; Noraziah, M R; Nik Rahimah, A R

2012-09-01

Twenty Asian sea bass Lates calcarifer from a floating cage in Bt. Tambun, Penang were examined for the presence of parasitic gill copepod, Lernanthropus latis. The prevalence of L. latis was 100% with the intensity of infection ranging from 1 to 18 parasites per host or 3.75 of mean intensity. Female parasites having oblong cephalothorax and egg-strings were seen mainly on the entire gill of examined Asian sea bass. The infected gill of Asian sea bass was pale and had eccessive mucus production. Under light and scanning electron microscopies (SEM), L. latis was seen grasping or holding tightly to the gill filament using their antenna, maxilla and maxilliped. These structures are characteristically prehensile and uncinate for the parasite to attach onto the host tissue. The damage was clearly seen under SEM as the hooked end of the antenna was embedded into the gill filament. The parasite also has the mandible which is styliform with eight teeth on the inner margin. The pathological effects such as erosion, haemorrhages, hyperplasia and necrosis along the secondary lamellae of gill filaments were seen and more severe at the attachment site. The combined actions of the antenna, maxilla and maxilliped together with the mandible resulted in extensive damage as L. latis attached and fed on the host tissues.

Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis

PubMed Central

Rivas-Santiago, C E; Rivas-Santiago, B; León, D A; Castañeda-Delgado, J; Hernández Pando, R

2011-01-01

Tuberculosis is a worldwide health problem, and multidrug-resistant (MDR) and extensively multidrug-resistant (XMDR) strains are rapidly emerging and threatening the control of this disease. These problems motivate the search for new treatment strategies. One potential strategy is immunotherapy using cationic anti-microbial peptides. The capacity of l-isoleucine to induce beta-defensin expression and its potential therapeutic efficiency were studied in a mouse model of progressive pulmonary tuberculosis. BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv or with a MDR clinical isolate by the intratracheal route. After 60 days of infection, when disease was in its progressive phase, mice were treated with 250 µg of intratracheal l-isoleucine every 48 h. Bacillary loads were determined by colony-forming units, protein and cytokine gene expression were determined by immunohistochemistry and reverse transcription–quantitative polymerase chain reaction (RT–qPCR), respectively, and tissue damage was quantified by automated morphometry. Administration of l-isoleucine induced a significant increase of beta-defensins 3 and 4 which was associated with decreased bacillary loads and tissue damage. This was seen in animals infected with the antibiotic-sensitive strain H37Rv and with the MDR clinical isolate. Thus, induction of beta-defensins might be a potential therapy that can aid in the control of this significant infectious disease. PMID:21235540

Infrared laser damage thresholds in corneal tissue phantoms using femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Boretsky, Adam R.; Clary, Joseph E.; Noojin, Gary D.; Rockwell, Benjamin A.

2018-02-01

Ultrafast lasers have become a fixture in many biomedical, industrial, telecommunications, and defense applications in recent years. These sources are capable of generating extremely high peak power that can cause laser-induced tissue breakdown through the formation of a plasma upon exposure. Despite the increasing prevalence of such lasers, current safety standards (ANSI Z136.1-2014) do not include maximum permissible exposure (MPE) values for the cornea with pulse durations less than one nanosecond. This study was designed to measure damage thresholds in corneal tissue phantoms in the near-infrared and mid-infrared to identify the wavelength dependence of laser damage thresholds from 1200-2500 nm. A high-energy regenerative amplifier and optical parametric amplifier outputting 100 femtosecond pulses with pulse energies up to 2 mJ were used to perform exposures and determine damage thresholds in transparent collagen gel tissue phantoms. Three-dimensional imaging, primarily optical coherence tomography, was used to evaluate tissue phantoms following exposure to determine ablation characteristics at the surface and within the bulk material. The determination of laser damage thresholds in the near-IR and mid-IR for ultrafast lasers will help to guide safety standards and establish the appropriate MPE levels for exposure sensitive ocular tissue such as the cornea. These data will help promote the safe use of ultrafast lasers for a wide range of applications.

Developing a toolbox for analysis of warrior wound biopsies: vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Crane, Nicole J.; O'Brien, Frederick P.; Forsberg, Jonathan A.; Potter, Benjamin K.; Elster, Eric A.

2011-03-01

The management of modern traumatic war wounds remains a significant challenge for clinicians. This is a reflection of the extensive osseous and soft-tissue damage caused by blasts and high-energy projectiles. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjectively based. Some wounds require an extended period of time to close or fail to remain closed, despite the use and application of novel wound-specific treatment modalities. Aside from impaired wound healing, additional wound complications include wound infection, biofilm formation, and heterotopic ossification (the pathological mineralization of soft tissues). An understanding of the molecular environment of acute wounds throughout the debridement process can provide valuable insight into the mechanisms associated with the eventual wound outcome. The analysis of Raman spectra of ex vivo wound biopsy tissue obtained from serial traumatic wound debridements reveals a decreased 1665 cm-1/1445 cm-1 band area ratio in impaired healing wounds, indicative of an impaired remodeling process, in addition to a decreased 1240 cm-1/1270cm-1. The examination of debrided tissue exhibits mineralization during the early development of heterotopic ossification. Finally, preliminary results suggest that Fourier transform infrared (FT-IR) images of wound effluent may be able to provide early microbiological information about the wound.

Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established solid tumors and increase nanoparticle delivery.

PubMed

Fu, Xinping; Rivera, Armando; Tao, Lihua; Zhang, Xiaoliu

2013-11-15

Converting T cells into tumor cell killers by grafting them with a chimeric antigen receptor (CAR) has shown promise as a cancer immunotherapeutic. However, the inability of these cells to actively migrate and extravasate into tumor parenchyma has limited their effectiveness in vivo. Here we report the construction of a CAR containing an echistatin as its targeting moiety (eCAR). As echistatin has high binding affinity to αvβ3 integrin that is highly expressed on the surface of endothelial cells of tumor neovasculature, T cells engrafted with eCAR (T-eCAR) can efficiently lyse human umbilical vein endothelial cells and tumor cells that express αvβ3 integrin when tested in vitro. Systemic administration of T-eCAR led to extensive bleeding in tumor tissues with no evidence of damage to blood vessels in normal tissues. Destruction of tumor blood vessels by T-eCAR significantly inhibited the growth of established bulky tumors. Moreover, when T-eCAR was codelivered with nanoparticles in a strategically designed temporal order, it dramatically increased nanoparticle deposition in tumor tissues, pointing to the possibility that it may be used together with nanocarriers to increase their capability to selectively deliver antineoplastic drugs to tumor tissues. Copyright © 2013 UICC.

T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning

PubMed Central

Gaylo, Alison; Schrock, Dillon C.; Fernandes, Ninoshka R. J.; Fowell, Deborah J.

2016-01-01

Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell’s antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function. PMID:27790220

T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning.

PubMed

Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J; Fowell, Deborah J

2016-01-01

Effector T cells exit the inflamed vasculature into an environment shaped by tissue-specific structural configurations and inflammation-imposed extrinsic modifications. Once within interstitial spaces of non-lymphoid tissues, T cells migrate in an apparent random, non-directional, fashion. Efficient T cell scanning of the tissue environment is essential for successful location of infected target cells or encounter with antigen-presenting cells that activate the T cell's antimicrobial effector functions. The mechanisms of interstitial T cell motility and the environmental cues that may promote or hinder efficient tissue scanning are poorly understood. The extracellular matrix (ECM) appears to play an important scaffolding role in guidance of T cell migration and likely provides a platform for the display of chemotactic factors that may help to direct the positioning of T cells. Here, we discuss how intravital imaging has provided insight into the motility patterns and cellular machinery that facilitates T cell interstitial migration and the critical environmental factors that may optimize the efficiency of effector T cell scanning of the inflamed tissue. Specifically, we highlight the local micro-positioning cues T cells encounter as they migrate within inflamed tissues, from surrounding ECM and signaling molecules, as well as a requirement for appropriate long-range macro-positioning within distinct tissue compartments or at discrete foci of infection or tissue damage. The central nervous system (CNS) responds to injury and infection by extensively remodeling the ECM and with the de novo generation of a fibroblastic reticular network that likely influences T cell motility. We examine how inflammation-induced changes to the CNS landscape may regulate T cell tissue exploration and modulate function.

Effective melanin depigmentation of human and murine ocular tissues: an improved method for paraffin and frozen sections.

PubMed

Manicam, Caroline; Pitz, Susanne; Brochhausen, Christoph; Grus, Franz H; Pfeiffer, Norbert; Gericke, Adrian

2014-01-01

The removal of excessive melanin pigments that obscure ocular tissue morphology is important to address scientific questions and for differential diagnosis of ocular tumours based on histology. Thus, the goal of the present study was to establish an effective and fast melanin bleaching method for paraffin and frozen mouse and human ocular tissues. Paraffin-embedded and frozen ocular specimens from mice and human donors were subjected to bleaching employing two methods. The first employed potassium permanganate (KMnO4) with oxalic acid, and the second 10% hydrogen peroxide (H2O2). To determine optimal bleaching conditions, depigmentation was carried out at various incubation times. The effect of diluents used for 10% H2O2 was assessed using phosphate-buffered saline (PBS), and deionized water. Three different slide types and two fixatives, which were ice-cold acetone with 80% methanol, and 4% paraformaldehyde (PFA) were used to determine the optimal conditions for better tissue adherence during bleaching. All tissues were stained in hematoxylin and eosin for histological evaluation. Optimal bleaching was achieved using warm 10% H2O2 diluted in PBS at 65°C for 120 minutes. Chromium-gelatin-coated slides prevented tissue detachment. Adherence of cryosections was also improved with post-fixation using 4% PFA and overnight air-drying at RT after cryosectioning. Tissue morphology was preserved under these conditions. Conversely, tissues bleached in KMnO4/oxalic acid demonstrated poor depigmentation with extensive tissue damage. Warm dilute H2O2 at 65°C for 120 minutes rapidly and effectively bleached both cryo- and paraffin sections of murine and human ocular tissues.

CFTR expression and organ damage in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tizzano, E.; Chitayat, D.; Buchwald, M.

1994-09-01

To assist our understanding of the origin of organ damage caused by cystic fibrosis (CF) disease, we have analyzed the pattern of expression of the CF gene (CFTR). mRNA in situ hybridization analysis was carried out in human fetal, newborn, infant and adult tissues and the abundance of the mRNA was correlated with the known pathology at the various stages of human development. Analysis of the pattern of expression indicates a constitutive level of mRNA in gastrointestinal tissues starting during early development and maintained throughout life. Prenatal respiratory tissues show qualitative and quantitative major differences in comparison to postnatal lungmore » samples. Male reproductive tissues show high levels of expression in the head of the epididymis compared with the rest of the male ducts. Female reproductive tissues show a variable pattern of expression at different stages during fetal development and during puberty probably due to changes in hormonal levels. Gastrointestinal and male reproductive tissues have a consistent pathology at birth, whereas no lung abnormalities have been described in newborns affected by CF. Our results show that there is no exact correlations between organ damage present at birth and the degree of CFTR expression. To explain these observations, we hypothesize that the pathogenesis of organ damage in CF depend on at least three factors: the rate of CFTR-mediated fluid secretion, differences in genotype and environmental factors, such as the amount of macromolecules in the lumen of the ducts. This last element predicts that damage will occur in tissues with high protein loads and low flow rates (e.g. pancreas, epididymis), where the absence of CFTR function leads to obstruction and pathology. Organs that express CFTR but with no significant damage (e.g. prenatal lung, female reproductive tissues), will have a low protein load and a high flow rates.« less

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Preparation of a porous conductive scaffold from aniline pentamer-modified polyurethane/PCL blend for cardiac tissue engineering.

PubMed

Baheiraei, Nafiseh; Yeganeh, Hamid; Ai, Jafar; Gharibi, Reza; Ebrahimi-Barough, Somayeh; Azami, Mahmoud; Vahdat, Sadaf; Baharvand, Hossein

2015-10-01

A novel biodegradable electroactive polyurethane containing aniline pentamer (AP) was blended with polycaprolactone (PCL). The prepared blend (PB) and PCL were further fabricated in to scaffolds using a mixture of poly(ethylene glycol) and salt particles in a double porogen particulate leaching and compression molding methodology. Scaffolds held open and interconnected pores having pore size ranging from several μm to 150 µm. PB scaffolds had compression modulus and strength of 4.1 and 1.3 MPa, respectively. The conductivity of the scaffold was measured as 10(-5) ± 0.09 S .cm(-1) and preserved for at least 100 h post fabrication. Scaffolds supported neonatal cardiomyocytes adhesion and growth with PB showing more extensive effect on the expression of the cardiac genes involved in muscle contraction and relaxation (troponin-T) and cytoskeleton alignment (actinin-4). Our results highlight the potential of incorporation of AP as an electroactive moiety for induction of cardiomyocyte proliferation and repair of damaged heart tissue. © 2015 Wiley Periodicals, Inc.

Customized dynamic splinting: orthoses that promote optimal function and recovery after radial nerve injury: a case report.

PubMed

McKee, Pat; Nguyen, Cecilia

2007-01-01

Radial nerve injury is a relatively common occurrence and recovery depends on the level of injury and extent of connective tissue damage. Orthoses (splints) are often provided to compensate for lost motor power. This article chronicles the recovery, over 27 months, of a 76-year-old woman who sustained a high radial nerve injury of her dominant arm during surgery for total shoulder replacement (Delta Reverse). Customized, low-profile dynamic splints, unlike any previously published design, were developed to address her goals for functional independence and the biological needs of the tissues. Dynamic power was provided to the wrist, fingers, and thumb by elastic cords and thin, flexible thermoplastic, without the need of an outrigger, thus avoiding the need for wire bending and cutting. At the outset, the splint was forearm-based and when wrist extension power was recovered, a hand-based splint was designed. Eventually, a circumferential hand-based thumb-stabilizing splint fulfilled most of the remaining orthotic requirements.

Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis.

PubMed

Liu, Ting Xi; Howlett, Niall G; Deng, Min; Langenau, David M; Hsu, Karl; Rhodes, Jennifer; Kanki, John P; D'Andrea, Alan D; Look, A Thomas

2003-12-01

Mechanisms underlying the multiple developmental defects observed in Fanconi anemia (FA) patients are not well defined. We have identified the zebrafish homolog of human FANCD2, which encodes a nuclear effector protein that is monoubiquitinated in response to DNA damage, targeting it to nuclear foci where it preserves chromosomal integrity. Fancd2-deficient zebrafish embryos develop defects similar to those found in children with FA, including shortened body length, microcephaly, and microophthalmia, which are due to extensive cellular apoptosis. Developmental defects and increased apoptosis in Fancd2-deficient zebrafish were corrected by injection of human FANCD2 or zebrafish bcl2 mRNA, or by knockdown of p53, indicating that in the absence of Fancd2, developing tissues spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during embryogenesis to prevent inappropriate apoptosis in neural cells and other tissues undergoing high levels of proliferative expansion, implicating this mechanism in the congenital abnormalities observed in human infants with FA.

Skin bioengineering: preclinical and clinical applications.

PubMed

Martínez-Santamaría, L; Guerrero-Aspizua, S; Del Río, M

2012-01-01

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

A bio-ballistic micro-jet for drug injection into animal skin using a Nd:YAG laser

NASA Astrophysics Data System (ADS)

Yoh, J. J.; Jang, H.; Park, M.; Han, T.; Hah, J.

2016-01-01

Imaging of the abdominal skin of a guinea pig after injecting a fluorescent probe and biotin via the laser-induced ballistic technique revealed the epidermal and dermal layers which were stained well below 60 \\upmu m underneath the outer layer of the skin. An extensive network of cells was evident in the deeper layer of the stained dermis as the distributed fluorescein isothiocyanate dose was administered by repeated injection using a laser-based micro-jet. We performed optically controlled release of the drug by breaching the guinea pig's skin tissue targeting the region 10-400 \\upmu m beneath the outermost layer. Tissue damage was minimized by reducing the injection volume to approximately 100 nl per pulse. This was done using a micro-jet diameter equal to half of that of a conventional 200 \\upmu m syringe needle. Thus, the optimally controlled delivery of liquid drugs using an irradiated laser pulse was shown to be possible.

Using electrolyte leakage tests to determine lifting windows and detect tissue damage

Treesearch

Richard W. Tinus

2002-01-01

Physiological testing is rapidly coming into use as a means to determine the condition of nursery stock and predict how it will respond to treatment or use. One such test, the electrolyte leakage test, can be used to measure cold hardiness and detect tissue damage. The principle of this test is that when cell membranes are damaged, electrolytes leak out into the water...

Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats.

PubMed

Altintas, Ramazan; Parlakpinar, Hakan; Beytur, Ali; Vardi, Nigar; Polat, Alaadin; Sagir, Mustafa; Odabas, Gul Pelin

2012-01-01

This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time. Copyright © 2012 S. Karger AG, Basel.

Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 2: intratracheal instillation and intravenous injection.

PubMed

Guichard, Yves; Maire, Marie-Aline; Sébillaud, Sylvie; Fontana, Caroline; Langlais, Cristina; Micillino, Jean-Claude; Darne, Christian; Roszak, Joanna; Stępnik, Maciej; Fessard, Valérie; Binet, Stéphane; Gaté, Laurent

2015-03-01

Synthetic amorphous silica nanomaterials (SAS) are extensively used in food and tire industries. In many industrial processes, SAS may become aerosolized and lead to occupational exposure of workers through inhalation in particular. However, little is known about the in vivo genotoxicity of these particulate materials. To gain insight into the toxicological properties of four SAS (NM-200, NM-201, NM-202, and NM-203), rats are treated with three consecutive intratracheal instillations of 3, 6, or 12 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection (cumulative doses of 9, 18, and 36 mg/kg). Deoxyribonucleic acid (DNA) damage was assessed using erythrocyte micronucleus test and the standard and Fpg-modified comet assays on cells from bronchoalveolar lavage fluid (BALF), lung, blood, spleen, liver, bone marrow, and kidney. Although all of the SAS caused increased dose-dependent changes in lung inflammation as demonstrated by BALF neutrophilia, they did not induce any significant DNA damage. As the amount of SAS reaching the blood stream and subsequently the internal organs is probably to be low following intratracheal instillation, an additional experiment was performed with NM-203. Rats received three consecutive intravenous injections of 5, 10, or 20 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection. Despite the hepatotoxicity, thrombocytopenia, and even animal death induced by this nanomaterial, no significant increase in DNA damage or micronucleus frequency was observed in SAS-exposed animals. It was concluded that under experimental conditions, SAS induced obvious toxic effects but did cause any genotoxicity following intratracheal instillation and intravenous injection. © 2014 Wiley Periodicals, Inc.

Behavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat.

PubMed

Jin, Ying; Bouyer, Julien; Haas, Christopher; Fischer, Itzhak

2014-07-01

Moderate and severe spinal cord contusion injuries have been extensively studied, yet much less is known about mild injuries. Mild contusions result in transient functional deficits, proceeding to near-complete recovery, but they may render the spinal cord vulnerable to future injuries. However, to date there have been no appropriate models to study the behavioral consequences, anatomical changes, and susceptibility of a mild contusion to repeated injuries, which may occur in children as well as adults during competitive sport activities. We have developed a novel mild spinal cord contusion injury model characterized by a sequence of transient functional deficits after the first injury and restoration to near-complete motor and sensory function, which is then followed up by a second injury. This model can serve not only to study the effects of repeated injuries on behavioral and anatomical changes, but also to examine the relationship between successive tissue damage and recovery of function. In the present study, we confirmed that mild thoracic spinal cord contusion, utilizing the NYU impactor device, resulted in localized tissue damage, characterized by a cystic cavity and peripheral rim of spared white matter at the injury epicenter, and rapid functional recovery to near-normal levels utilizing several behavioral tests. Repeated injury after 3weeks, when functional recovery has been completed, resulted in worsening of both motor and sensory function, which did not recover to prior levels. Anatomical analyses showed no differences in the volumes of spared white matter, lesion, or cyst, but revealed modest extension of lesion area rostral to the injury epicenter as well as an increase in inflammation and apoptosis. These studies demonstrate that a mild injury model can be used to test efficacy of treatments for repeated injuries and may serve to assist in the formulation of policies and clinical practice regarding mild SCI injury and spinal concussion. Copyright © 2014 Elsevier Inc. All rights reserved.

Compound mechanism of fatal neck injury: A case report of a tiger attack in a zoo.

PubMed

Szleszkowski, Łukasz; Thannhäuser, Agata; Jurek, Tomasz

2017-08-01

Fatal injuries caused by attacks by large wild cats are extremely rare in forensic medical practice in Europe. There are very few cases described in the forensic medical literature concerning incidents in zoos similar to the tiger attack on a 58-year-old male zoo employee that we present here. While preparing a runway for tigers, the man was attacked by a male Sumatran tiger. Another zoo employee was an eyewitness to the accident; in his testimony he described the sequence of events in detail. The autopsy showed the injuries typical of a tiger attack: traces of claws and canine teeth indicating that the victim of the attack was knocked down from behind, along with deep and extensive fatal wounds to the neck. The injuries were inflicted by means of a compound mechanism: tissues were penetrated by the animal's canines, crushed with great force (transfixing injury), and violently distended. The skin revealed four characteristic deep wounds caused by canines as well as bite marks resulting from the action of six incisors. The neck area revealed extensive damage, including torn muscles, the esophagus and trachea, large blood vessels of the neck, and fractures of vertebrae C2 and C5 with internal channels resulting directly from penetration by the animal's canines. The mechanism of distension, as a result of the animal jerking its head after biting the victim in the neck, produced a complete tear of the spine and the vertebral arteries, as well as an intramural rupture of the carotid arteries which has never been described before. In the interests of a detailed assessment of bone damage, the cervical spine was macerated. The applied autopsy techniques and detailed analysis of injuries enabled us to demonstrate the compound mechanism that inflicted them, combining penetration of tissues by the canines, crushing, and distension. Copyright © 2017. Published by Elsevier B.V.

Ultra-high Speed Optical Imaging of Ultrasound-activated Microbubbles in Mesenteric Microvessels

NASA Astrophysics Data System (ADS)

Chen, Hong

Ultrasound contrast agent microbubbles have gained widespread applications in diagnostic and therapeutic ultrasound. Animal studies of bioeffects induced by ultrasound-activated microbubbles have demonstrated that microbubbles can cause microvessel damage. Much scientific attention has been attracted to such microvascular bioeffects, not only because of the related safety concerns, but also because of the potential useful applications of microbubbles in the intravascular delivery of drugs and genetic materials into target tissues. A significant challenge in using microbubbles in medical ultrasound is the lack of knowledge about how the microbubbles behave in blood vessels when exposed to ultrasound and how their interactions with ultrasound cause vascular damage. Although extensive studies were performed in the past to study the dynamics of microbubbles, most of those studies were performed in vitro and did not directly address the clinical environment in which microbubbles are injected into blood vessels. In this thesis work, a synchronized optical-acoustic system was set up for ultrahigh speed imaging of insonated microbubbles in microvessels. The recorded images revealed the formation of microjets penetrating the microbubbles, as well as vessel distention (motion outward against the surrounding tissue) and vessel invagination (motion inward toward the lumen) caused by the expansion and collapse of the microbubbles, respectively. Contrary to current paradigms which propose that microbubbles damage vessels either by distending them or by forming liquid jets impinging on them, microbubbles translation and jetting were in the direction away from the nearest vessel wall; furthermore, invagination typically exceeded distention in arterioles and venules. Vessel invagination was found to be associated with vascular damage. These studies suggest that vessel invagination may be a newly discovered potential mechanism for vascular damage by ultrasound-activated microbubbles. The dynamics of bubble-vessel interactions are coupled intimately with the viscoelastic properties of the microvessels. To probe these properties, a method based on the relaxation times of the invaginated microvessels was used to estimate the relaxation time constants of the microvessels. It was found that the time constants were on microsecond time scales, which provided insight into the unique and unknown viscoelastic properties of the microvessels.

[Physical and chemical emergencies in dermatology].

PubMed

Malisiewicz, B; Meissner, M; Kaufmann, R; Valesky, E

2018-05-01

Physical and chemical emergencies are often caused by household or work accidents. Regardless of the medical field and outside specialized clinics, the physician may be confronted with the situation for first or secondary care. The identification of the causing agent and a rapid assessment of the extent and severity of the tissue damage are essential to initiate early transfer to a specialized burn clinic. Grade 2b tissue damage is usually surgically treated. Smaller and superficial injuries can often be conservatively treated. Even supposedly safe and over-the-counter medicines can also lead to serious tissue damage.

A quantitative and non-contact technique to characterise microstructural variations of skin tissues during photo-damaging process based on Mueller matrix polarimetry.

PubMed

Dong, Yang; He, Honghui; Sheng, Wei; Wu, Jian; Ma, Hui

2017-10-31

Skin tissue consists of collagen and elastic fibres, which are highly susceptible to damage when exposed to ultraviolet radiation (UVR), leading to skin aging and cancer. However, a lack of non-invasive detection methods makes determining the degree of UVR damage to skin in real time difficult. As one of the fundamental features of light, polarization can be used to develop imaging techniques capable of providing structural information about tissues. In particular, Mueller matrix polarimetry is suitable for detecting changes in collagen and elastic fibres. Here, we demonstrate a novel, quantitative, non-contact and in situ technique based on Mueller matrix polarimetry for monitoring the microstructural changes of skin tissues during UVR-induced photo-damaging. We measured the Mueller matrices of nude mouse skin samples, then analysed the transformed parameters to characterise microstructural changes during the skin photo-damaging and self-repairing processes. Comparisons between samples with and without the application of a sunscreen showed that the Mueller matrix-derived parameters are potential indicators for fibrous microstructure in skin tissues. Histological examination and Monte Carlo simulations confirmed the relationship between the Mueller matrix parameters and changes to fibrous structures. This technique paves the way for non-contact evaluation of skin structure in cosmetics and dermatological health.

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo

PubMed Central

De Francesco, Francesco; Guastafierro, Antonio; Nicoletti, Gianfranco; Razzano, Sergio; Riccio, Michele; Ferraro, Giuseppe A.

2017-01-01

Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here. PMID:28498335

Manipulation of mechanical compliance of elastomeric PGS by incorporation of halloysite nanotubes for soft tissue engineering applications.

PubMed

Chen, Qi-Zhi; Liang, Shu-Ling; Wang, Jiang; Simon, George P

2011-11-01

Poly (glycerol sebacate) (PGS) is a promising elastomer for use in soft tissue engineering. However, it is difficult to achieve with PGS a satisfactory balance of mechanical compliance and degradation rate that meet the requirements of soft tissue engineering. In this work, we have synthesised a new PGS nanocomposite system filled with halloysite nanotubes, and mechanical properties, as well as related chemical characters, of the nanocomposites were investigated. It was found that the addition of nanotubular halloysite did not compromise the extensibility of material, compared with the pure PGS counterpart; instead the elongation at rupture was increased from 110 (in the pure PGS) to 225% (in the 20 wt% composite). Second, Young's modulus and resilience of 3-5 wt% composites were ∼0.8 MPa and >94% respectively, remaining close to the level of pure PGS which is desired for applications in soft tissue engineering. Third, an important feature of the 1-5 wt% composites was their stable mechanical properties over an extended period, which could allow the provision of reliable mechanical support to damaged tissues during the lag phase of the healing process. Finally, the in vitro study indicated that the addition of halloysite slowed down the degradation rate of the composites. In conclusion, the good compliance, enhanced stretchability, stable mechanical behavior over an extended period, and reduced degradation rates make the 3-5 wt% composites promising candidates for application in soft tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Specificities in children wound healing].

PubMed

Sanchez, J; Antonicelli, F; Tuton, D; Mazouz Dorval, S; François, C

2016-10-01

Children have specific characteristics of wound healing. The aim of this study was to describe the specific clinical characteristics of wounds healing in children and to present the current knowledge on the specific mechanisms with regard to infant age. The tissue insult or injury in fetus can heal without scar, mainly due to reduced granulation tissue associated to diminished or even no inflammatory phase, modified extracellular matrix such as the concentration of hyaluronic acid in amniotic liquid, expression and arrangement of collagen and tenascin. Thickness of children skin is a serious negative factor in case of trauma, whereas poor co-morbidities and efficient growth tissue mechanisms are beneficial to good evolution, even in cases of extensive damage and loss of tissue. The subsequent tissue mechanical forces, wound healing during childhood, spanning from the age of 2 until the end of puberty, is associated with more hypertrophic scars, both in duration and in intensity. Consequently, unnecessary surgery has to be avoided during this period when possible, and children with abnormal or pathologic wound healing should benefit from complementary treatments (hydration, massage, brace, silicone, hydrotherapy…), which represent efficient factors to minimize tissue scarring. After wound healing, the growth body rate can be responsible for specific complications, such as contractures, alopecia, and scar intussusceptions. Its evolutionary character implies the need of an attentive follow-up until adult age. Psychologic repercussions, as a consequence of pathologic scars, must be prevented and investigated by the surgeon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The comparison of thermal tissue injuries caused by ultrasonic scalpel and electrocautery use in rabbit tongue tissue

PubMed Central

Beriat, Guclu Kaan; Akmansu, Sefik Halit; Ezerarslan, Hande; Dogan, Cem; Han, Unsal; Saglam, Mehmet; Senel, Oytun Okan; Kocaturk, Sinan

2012-01-01

The aim of this study compares to the increase in tissue temperature and the thermal histological effects of ultrasonic scalpel, bipolar and unipolar electrosurgery incisions in the tongue tissue of rabbits. This study evaluates the histopathological changes related to thermal change and the maximum temperature values in the peripheral tissue brought about by the incisions carried out by the three methods in a comparative way. To assess thermal tissue damage induced by the three instruments, maximum tissue temperatures were measured during the surgical procedure and tongue tissue samples were examined histopathologically following the surgery. The mean maximum temperature values of the groups were 93.93±2.76 C° for the unipolar electrocautery group, whereas 85.07±5.95 C° for the bipolar electrocautery group, and 108.23±7.64 C° for the ultrasonic scalpel group. There was a statistically significant relationship between the increase in maximum temperature values and the separation among tissue layers, edema, congestion, necrosis, hemorrhage, destruction in blood vessel walls and fibrin accumulation, and between the existence of fibrin thrombus and tissue damage depth (p<0.05). It was concluded that the bipolar electrocautery use gives way to less temperature increase in the tissues and less thermal tissue damage in comparison to the other methods. PMID:22938541

The Role of Direct and Visual Force Feedback in Suturing Using a 7-DOF Dual-Arm Teleoperated System.

PubMed

Talasaz, Ali; Trejos, Ana Luisa; Patel, Rajni V

2017-01-01

The lack of haptic feedback in robotics-assisted surgery can result in tissue damage or accidental tool-tissue hits. This paper focuses on exploring the effect of haptic feedback via direct force reflection and visual presentation of force magnitudes on performance during suturing in robotics-assisted minimally invasive surgery (RAMIS). For this purpose, a haptics-enabled dual-arm master-slave teleoperation system capable of measuring tool-tissue interaction forces in all seven Degrees-of-Freedom (DOFs) was used. Two suturing tasks, tissue puncturing and knot-tightening, were chosen to assess user skills when suturing on phantom tissue. Sixteen subjects participated in the trials and their performance was evaluated from various points of view: force consistency, number of accidental hits with tissue, amount of tissue damage, quality of the suture knot, and the time required to accomplish the task. According to the results, visual force feedback was not very useful during the tissue puncturing task as different users needed different amounts of force depending on the penetration of the needle into the tissue. Direct force feedback, however, was more useful for this task to apply less force and to minimize the amount of damage to the tissue. Statistical results also reveal that both visual and direct force feedback were required for effective knot tightening: direct force feedback could reduce the number of accidental hits with the tissue and also the amount of tissue damage, while visual force feedback could help to securely tighten the suture knots and maintain force consistency among different trials/users. These results provide evidence of the importance of 7-DOF force reflection when performing complex tasks in a RAMIS setting.

Milk phospholipid's protective effects against UV damage in skin equivalent models

NASA Astrophysics Data System (ADS)

Dargitz, Carl; Russell, Ashley; Bingham, Michael; Achay, Zyra; Jimenez-Flores, Rafael; Laiho, Lily H.

2012-03-01

Exposure of skin tissue to UV radiation has been shown to cause DNA photodamage. If this damaged DNA is allowed to replicate, carcinogenesis may occur. DNA damage is prevented from being passed on to daughter cells by upregulation of the protein p21. p21 halts the cells cycle allowing the cell to undergo apoptosis, or repair its DNA before replication. Previous work suggested that milk phospholipids may possess protective properties against UV damage. In this study, we observed cell morphology, cell apoptosis, and p21 expression in tissue engineered epidermis through the use of Hematoxylin and Eosin staining, confocal microscopy, and western blot respectively. Tissues were divided into four treatment groups including: a control group with no UV and no milk phospholipid treatment, a group exposed to UV alone, a group incubated with milk phospholipids alone, and a group treated with milk phospholipids and UV. All groups were incubated for twenty-four hours after treatment. Tissues were then fixed, processed, and embedded in paraffin. Performing western blots resulted in visible p21 bands for the UV group only, implying that in every other group, p21 expression was lesser. Numbers of apoptotic cells were determined by observing the tissues treated with Hoechst dye under a confocal microscope, and counting the number of apoptotic and total cells to obtain a percentage of apoptotic cells. We found a decrease in apoptotic cells in tissues treated with milk phospholipids and UV compared to tissues exposed to UV alone. Collectively, these results suggest that milk phospholipids protect cell DNA from damage incurred from UV light.

PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.

PubMed

Cho, John S; Fang, Terry C; Reynolds, Taylor L; Sofia, Daniel J; Hamann, Stefan; Burkly, Linda C

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated.

Original and regenerating lizard tail cartilage contain putative resident stem/progenitor cells.

PubMed

Alibardi, Lorenzo

2015-11-01

Regeneration of cartilaginous tissues is limited in mammals but it occurs with variable extension in lizards (reptiles), including in their vertebrae. The ability of lizard vertebrae to regenerate cartilaginous tissue that is later replaced with bone has been analyzed using tritiated thymidine autoradiography and 5BrdU immunocytochemistry after single pulse or prolonged-pulse and chase experiments. The massive cartilage regeneration that can restore broad vertebral regions and gives rise to a long cartilaginous tube in the regenerating tail, depends from the permanence of some chondrogenic cells within adult vertebrae. Few cells that retain tritiated thymidine or 5-bromodeoxy-uridine for over 35 days are mainly localized in the inter-vertebral cartilage and in sparse chondrogenic regions of the neural arch of the vertebrae, suggesting that they are putative resident stem/progenitor cells. The study supports previous hypothesis indicating that the massive regeneration of the cartilaginous tissue in damaged vertebrae and in the regenerating tail of lizards derive from resident stem cells mainly present in the cartilaginous areas of the vertebrae including in the perichondrium that are retained in adult lizards as growing centers for most of their lifetime. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer hyperthermia using magnetic nanoparticles.

PubMed

Kobayashi, Takeshi

2011-11-01

Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Néel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43°C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite-nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat-shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extracerebral Tissue Damage in the Intraluminal Filament Mouse Model of Middle Cerebral Artery Occlusion

PubMed Central

Vaas, Markus; Ni, Ruiqing; Rudin, Markus; Kipar, Anja; Klohs, Jan

2017-01-01

Middle cerebral artery occlusion is the most common model of focal cerebral ischemia in the mouse. In the surgical procedure, the external carotid artery (ECA) is ligated; however, its effect on the tissue supplied by the vessel has not been described so far. C57BL/6 mice underwent 1 h of transient MCAO (tMCAO) or sham surgery. Multi-spectral optoacoustic tomography was employed at 30 min after surgery to assess oxygenation in the temporal muscles. Microstructural changes were assessed with magnetic resonance imaging and histological examination at 24 h and 48 h after surgery. Ligation of the ECA resulted in decreased oxygenation of the left temporal muscle in most sham-operated and tMCAO animals. Susceptible mice of both groups exhibited increased T2 relaxation times in the affected muscle with histological evidence of myofibre degeneration, interstitial edema, and neutrophil influx. Ligatures had induced an extensive neutrophil-dominated inflammatory response. ECA ligation leads to distinct hypoxic degenerative changes in the tissue of the ECA territory and to ligature-induced inflammatory processes. An impact on outcome needs to be considered in this stroke model. PMID:28348545

Complement component C5a mediates hemorrhage-induced intestinal damage

PubMed Central

Fleming, Sherry D.; Phillips, Lauren M.; Lambris, John D.; Tsokos, George C.

2008-01-01

Background Complement has been implicated in the pathogenesis of intestinal damage and inflammation in multiple animal models. Although the exact mechanism is unknown, inhibition of complement prevents hemodynamic alterations in hemorrhage. Materials/Methods C57Bl/6, complement 5 deficient (C5−/−) and sufficient (C5+/+) mice were subjected to 25% blood loss. In some cases, C57Bl/6 mice were treated with C5a receptor antagonist (C5aRa) post-hemorrhage. Intestinal injury, leukotriene B4, and myeloperoxidase production were assessed for each treatment group of mice. Results Mice subjected to significant blood loss without major trauma develop intestinal inflammation and tissue damage within two hours. We report here that complement 5 (C5) deficient mice are protected from intestinal tissue damage when subjected to hemorrhage (Injury score = 0.36 compared to wildtype hemorrhaged animal injury score = 2.89; p<0.05). We present evidence that C5a represents the effector molecule because C57Bl/6 mice treated with a C5a receptor antagonist displayed limited intestinal injury (Injury score = 0.88), leukotriene B4 (13.16 pg/mg tissue) and myeloperoxidase (115.6 pg/mg tissue) production compared to hemorrhaged C57Bl/6 mice (p<0.05). Conclusion Complement activation is important in the development of hemorrhage-induced tissue injury and C5a generation is critical for tissue inflammation and damage. Thus, therapeutics targeting C5a may be useful therapeutics for hemorrhage-associated injury. PMID:18639891

A study on thermal damage during hyperthermia treatment based on DPL model for multilayer tissues using finite element Legendre wavelet Galerkin approach.

PubMed

Kumar, Dinesh; Rai, K N

2016-12-01

Hyperthermia is a process that uses heat from the spatial heat source to kill cancerous cells without damaging the surrounding healthy tissues. Efficacy of hyperthermia technique is related to achieve temperature at the infected cells during the treatment process. A mathematical model on heat transfer in multilayer tissues in finite domain is proposed to predict the control temperature profile at hyperthermia position. The treatment technique uses dual-phase-lag model of heat transfer in multilayer tissues with modified Gaussian distribution heat source subjected to the most generalized boundary condition and interface at the adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved using finite element Legendre wavelet Galerkin approach. The present solution has been verified with exact solution in a specific case and provides a good accuracy. The effect of the variability of different parameters such as lagging times, external heat source, metabolic heat source and the most generalized boundary condition on temperature profile in multilayer tissues is analyzed and also discussed the effective approach of hyperthermia treatment. Furthermore, we studied the modified thermal damage model with regeneration of healthy tissues as well. For viewpoint of thermal damage, the least thermal damage has been observed in boundary condition of second kind. The article concludes with a discussion of better opportunities for future clinical application of hyperthermia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thermomechanical testing of high-temperature composites - Thermomechanical fatigue (TMF) behavior of SiC(SCS-6)/Ti-15-3

NASA Technical Reports Server (NTRS)

Castelli, Michael G.; Bartolotta, Paul; Ellis, John R.

1992-01-01

Thermomechanical testing techniques recently developed for monolithic structural alloys were successfully extended to continuous fiber reinforced composite materials in plate form. The success of this adaptation was verified on a model metal matrix composite (MMC) material, namely SiC(SCS-6)/Ti-15V-3Cr-3Al-3Sn. Effects of heating system type and specimen preparation are also addressed. Cyclic lives determined under full thermomechanical conditions were shown to be significantly reduced from those obtained under comparable isothermal and in-phase bi-thermal conditions. Fractography and metallography from specimens subjected to isothermal, out-of-phase and in-phase conditions reveal distinct differences in damage-failure modes. Isothermal metallography revealed extensive matrix cracking associated with fiber damage throughout the entire cross-section of the specimen. Out-of-phase metallography revealed extensive matrix damage associated with minimal (if any) fiber cracking. However, the damage was located exclusively at surface and near-surface locations. In-phase conditions produced extensive fiber cracking throughout the entire cross-section, associated with minimal (if any) matrix damage.

Thermomechanical testing techniques for high-temparature composites: TMF behavior of SiC(SCS-6)/Ti-15-3

NASA Technical Reports Server (NTRS)

Castelli, Michael G.; Ellis, J. Rodney; Bartolotta, Paul A.

1990-01-01

Thermomechanical testing techniques recently developed for monolithic structural alloys were successfully extended to continuous fiber reinforced composite materials in plate form. The success of this adaptation was verified on a model metal matrix composite (MMC) material, namely SiC(SCS-6)/Ti-15V-3Cr-3Al-3Sn. Effects of heating system type and specimen preparation are also addressed. Cyclic lives determined under full thermo-mechanical conditions were shown to be significantly reduced from those obtained under comparable isothermal and in-phase bi-thermal conditions. Fractography and metallography from specimens subjected to isothermal, out-of-phase and in-phase conditions reveal distinct differences in damage-failure modes. Isothermal metallography revealed extensive matrix cracking associated with fiber damage throughout the entire cross-section of the specimen. Out-of-phase metallography revealed extensive matrix damage associated with minimal (if any) fiber cracking. However, the damage was located exclusively at surface and near-surface locations. In-phase conditions produced extensive fiber cracking throughout the entire cross-section, associated with minimal (if any) matrix damage.

Modeling of skin cooling, blood flow, and optical properties in wounds created by electrical shock

NASA Astrophysics Data System (ADS)

Nguyen, Thu T. A.; Shupp, Jeffrey W.; Moffatt, Lauren T.; Jordan, Marion H.; Jeng, James C.; Ramella-Roman, Jessica C.

2012-02-01

High voltage electrical injuries may lead to irreversible tissue damage or even death. Research on tissue injury following high voltage shock is needed and may yield stage-appropriate therapy to reduce amputation rate. One of the mechanisms by which electricity damages tissue is through Joule heating, with subsequent protein denaturation. Previous studies have shown that blood flow had a significant effect on the cooling rate of heated subcutaneous tissue. To assess the thermal damage in tissue, this study focused on monitoring changes of temperature and optical properties of skin next to high voltage wounds. The burns were created between left fore limb and right hind limb extremities of adult male Sprague-Dawley rats by a 1000VDC delivery shock system. A thermal camera was utilized to record temperature variation during the exposure. The experimental results were then validated using a thermal-electric finite element model (FEM).

Suppression of Neutrophil-Mediated Tissue Damage—A Novel Skill of Mesenchymal Stem Cells

PubMed Central

Jiang, Dongsheng; Muschhammer, Jana; Qi, Yu; Kügler, Andrea; De Vries, Juliane C.; Saffarzadeh, Mona; Sindrilaru, Anca; Beken, Seppe Vander; Wlaschek, Meinhard; Kluth, Mark A.; Ganss, Christoph; Frank, Natasha Y.; Frank, Markus H.; Preissner, Klaus T.; Scharffetter-Kochanek, Karin

2017-01-01

Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and regeneration. Though of prime interest, their potentially protective role on neutrophil-induced tissue damage, associated with high morbidity and mortality, has not been explored in sufficient detail. Here we report the therapeutic skill of MSCs to suppress unrestrained neutrophil activation and to attenuate severe tissue damage in a murine immune-complex mediated vasculitis model of unbalanced neutrophil activation. MSC-mediated neutrophil suppression was due to intercellular adhesion molecule 1-dependent engulfment of neutrophils by MSCs, decreasing overall neutrophil numbers. Similar to MSCs in their endogenous niche of murine and human vasculitis, therapeutically injected MSCs via upregulation of the extracellular superoxide dismutase (SOD3), reduced super-oxide anion concentrations and consequently prevented neutrophil death, neutrophil extracellular trap formation and spillage of matrix degrading neutrophil elastase, gelatinase and myeloperoxidase. SOD3-silenced MSCs did not exert tissue protective effects. Thus, MSCs hold substantial therapeutic promise to counteract tissue damage in conditions with unrestrained neutrophil activation. PMID:27299700

Regenerative Repair of Damaged Meniscus with Autologous Adipose Tissue-Derived Stem Cells

PubMed Central

Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

2014-01-01

Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee. PMID:24592390

Deep tissue penetration of nanoparticles using pulsed-high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

You, Dong Gil; Yoon, Hong Yeol; Jeon, Sangmin; Um, Wooram; Son, Sejin; Park, Jae Hyung; Kwon, Ick Chan; Kim, Kwangmeyung

2017-11-01

Recently, ultrasound (US)-based drug delivery strategies have received attention to improve enhanced permeation and retention (EPR) effect-based passive targeting efficiency of nanoparticles in vitro and in vivo conditions. Among the US treatment techniques, pulsed-high intensity focused ultrasound (pHIFU) have specialized for improving tissue penetration of various macromolecules and nanoparticles without irreversible tissue damages. In this study, we have demonstrated that pHIFU could be utilized to improve tissue penetration of fluorescent dye-labeled glycol chitosan nanoparticles (FCNPs) in femoral tissue of mice. pHIFU could improve blood flow of the targeted-blood vessel in femoral tissue. In addition, tissue penetration of FCNPs was specifically increased 5.7-, 8- and 9.3-folds than that of non-treated (0 W pHIFU) femoral tissue, when the femoral tissue was treated with 10, 20 and 50 W of pHIFU, respectively. However, tissue penetration of FCNPs was significantly reduced after 3 h post-pHIFU treatment (50 W). Because overdose (50 W) of pHIFU led to irreversible tissue damages, including the edema and chapped red blood cells. These overall results support that pHIFU treatment can enhance the extravasation and tissue penetration of FCNPs as well as induce irreversible tissue damages. We expect that our results can provide advantages to optimize pHIFU-mediated delivery strategy of nanoparticles for further clinical applications.

Reduction of thermal damage in photodynamic therapy by laser irradiation techniques.

PubMed

Lim, Hyun Soo

2012-12-01

General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per 10 J/cm2 was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within ± 0.2%, and specific wavelength shift was limited to ± 3 nm. Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.

Collateral damage-free debridement using 193nm ArF laser

NASA Astrophysics Data System (ADS)

Wynne, James J.; Felsenstein, Jerome M.; Trzcinski, Robert; Zupanski-Nielsen, Donna; Connors, Daniel P.

2011-03-01

Burn eschar and other necrotic areas of the skin and soft tissue are anhydrous compared to the underlying viable tissue. A 193 nm ArF excimer laser, emitting electromagnetic radiation at 6.4 eV at fluence exceeding the ablation threshold, will debride such necrotic areas. Because such radiation is strongly absorbed by aqueous chloride ions through the nonthermal process of electron photodetachment, debridement will cease when hydrated (with chloride ions) viable tissue is exposed, avoiding collateral damage to this tissue. Such tissue will be sterile and ready for further treatment, such as a wound dressing and/or a skin graft.

Mechanical and histological characterization of trachea tissue subjected to blast-type pressures

NASA Astrophysics Data System (ADS)

Butler, B. J.; Bo, C.; Tucker, A. W.; Jardine, A. P.; Proud, W. G.; Williams, A.; Brown, K. A.

2014-05-01

Injuries to the respiratory system can be a component of polytrauma in blast-loading injuries. Tissues located at air-liquid interfaces, including such tissues in the respiratory system, are particularly vulnerable to damage by blast overpressures. There is a lack of information about the mechanical and cellular responses that contribute to the damage of this class of tissues subjected to the high strain rates associated with blast loading. Here, we describe the results of dynamic blast-like pressure loading tests at high strain rates on freshly harvested ex vivo trachea tissue specimens.

[Electrohydraulic intracorporeal lithotripsy of salivary calculi. In vitro and animal experiment studies].

PubMed

Iro, H; Zenk, J; Hosemann, W G; Benzel, W

1993-08-01

Extracorporeal lithotripsy is now used routinely for the treatment of salivary duct stones. The question arose whether electrohydraulic intracorporeal lithotripsy, which is applied in urology and gastroenterology, might also be useful in the treatment of this disease. Before its possible clinical application the influence of electrohydraulic intracorporeal shock waves on salivary stones in vitro and any influence on the tissue in the head and neck region (in vivo) had to be investigated. In vitro experiments. Fifty-eight salivary stones and 11 extirpated human submandibular glands were treated by three different electrohydraulic devices. Animal experiments. Electrohydraulic shock waves were applied to the dilated Stensen's duct and other tissues (muscle, parotid gland, facial nerve) of six rabbits. Of 58 salivary stones, 53 (91%) were fragmented, 39 (67%) with a remaining size of less than 1.5 mm and 14 (24%) more than 1.5 mm. In 5 cases (9%) no effects were seen at all. Fragmentation occurred independent of the mineralogical components of the stone and independent of the different lithotriptors used. The smaller the probe diameter and the larger the stone, the more shock waves were needed to achieve fragmentation. With the smaller probes the stones could not be fragmented completely. In human submandibular glands, extensive tissue lesions could be evidenced macroscopically and histologically after application of electrohydraulic shock waves in vitro. Application of electrohydraulic shock waves to the dilated parotid gland duct of rabbits led to perforations of the duct after 1-5 single pulses. Lesions of nerves and blood vessels could also be observed within the duct environment. This occurred with all of the different electrohydraulic devices, probe diameters and intensities used. In our opinion the damage produced is probably the result of both the direct effect of the plasma as well as the resultant stress wave. In view of the severe damage caused to different tissues, use of the described method for the treatment of stones in the narrow human salivary ducts should be greatly restricted.

Upregulated epidermal growth factor receptor expression following near-infrared irradiation simulating solar radiation in a three-dimensional reconstructed human corneal epithelial tissue culture model.

PubMed

Tanaka, Yohei; Nakayama, Jun

2016-01-01

Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues. DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000-1,800 nm wavelengths and excluded 1,400-1,500 nm wavelengths. A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm(2) irradiation (P<0.05). We found that NIR irradiation induced the upregulated expression of EGFR in human corneal cells. Since over half of the solar energy reaching the Earth is in the NIR region, which cannot be adequately blocked by eyewear and thus can induce eye damage with intensive or long-term exposure, protection from both UV and NIR radiation may prevent changes in gene expression and in turn eye damage.

Exercise promotes alpha7 integrin gene transcription and protection of skeletal muscle.

PubMed

Boppart, Marni D; Volker, Sonja E; Alexander, Nicole; Burkin, Dean J; Kaufman, Stephen J

2008-11-01

The alpha7beta1 integrin is increased in skeletal muscle in response to injury-producing exercise, and transgenic overexpression of this integrin in mice protects against exercise-induced muscle damage. The present study investigates whether the increase in the alpha7beta1 integrin observed in wild-type mice in response to exercise is due to transcriptional regulation and examines whether mobilization of the integrin at the myotendinous junction (MTJ) is a key determinant in its protection against damage. A single bout of downhill running exercise selectively increased transcription of the alpha7 integrin gene in 5-wk-old wild-type mice 3 h postexercise, and an increased alpha7 chain was detected in muscle sarcolemma adjacent to tendinous tissue immediately following exercise. The alpha7B, but not alpha7A isoform, was found concentrated and colocalized with tenascin-C in muscle fibers lining the MTJ. To further validate the importance of the integrin in the protection against muscle damage following exercise, muscle injury was quantified in alpha7(-/-) mice. Muscle damage was extensive in alpha7(-/-) mice in response to both a single and repeated bouts of exercise and was largely restricted to areas of high MTJ concentration and high mechanical force near the Achilles tendon. These results suggest that exercise-induced muscle injury selectively increases transcription of the alpha7 integrin gene and promotes a rapid change in the alpha7beta integrin at the MTJ. These combined molecular and cellular alterations are likely responsible for integrin-mediated attenuation of exercise-induced muscle damage.

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

PubMed Central

Braunsdorf, Christina; Grumaz, Christian; Müller, Christoph; Lorenz, Stefan; Stevens, Philip; Wagener, Jeanette; Hebecker, Betty; Hube, Bernhard; Bracher, Franz; Sohn, Kai; Schaller, Martin

2017-01-01

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG. PMID:29023454

Neuritogenesis: A model for space radiation effects on the central nervous system

NASA Technical Reports Server (NTRS)

Vazquez, M. E.; Broglio, T. M.; Worgul, B. V.; Benton, E. V.

1994-01-01

Pivotal to the astronauts' functional integrity and survival during long space flights are the strategies to deal with space radiations. The majority of the cellular studies in this area emphasize simple endpoints such as growth related events which, although useful to understand the nature of primary cell injury, have poor predictive value for extrapolation to more complex tissues such as the central nervous system (CNS). In order to assess the radiation damage on neural cell populations, we developed an in vitro model in which neuronal differentiation, neurite extension, and synaptogenesis occur under controlled conditions. The model exploits chick embryo neural explants to study the effects of radiations on neuritogenesis. In addition, neurobiological problems associated with long-term space flights are discussed.

Wound ballistics 101: the mechanisms of soft tissue wounding by bullets.

PubMed

Stefanopoulos, P K; Pinialidis, D E; Hadjigeorgiou, G F; Filippakis, K N

2017-10-01

The mechanisms of soft tissue injury by bullets are reviewed, in the belief that the current incidence of firearm injuries in many urban areas necessitates an understanding of wound ballistics on the part of trauma surgeons who may not be familiar with the wounding factors involved. Review of the literature, with technical information obtained from appropriate non-medical texts. Despite numerous publications concerning the treatment of gunshot wounds, relatively few papers contain details on the mechanisms of ballistic trauma, with the main body of evidence derived from previous laboratory and animal studies which have only recently been systematically appraised. These studies have shown that in rifle injuries the main wound tract is surrounded by an area of damaged tissue as a result of the temporary cavitation induced once the bullet becomes destabilized or deformed. On the other hand, the more commonly encountered non-deforming handgun bullets cause damage limited to the bullet's path, mainly as a result of localized crush injury. The bullet's construction and ballistic behavior within tissue determine to what extent the previously overestimated velocity factor may influence wound severity. The damage produced from temporary cavitation depends on the tensile properties of the tissues involved, and in high-energy injuries may lead to progressive muscle tissue necrosis. Therefore, the term "high-energy" should be reserved for those injuries with substantial tissue damage extending beyond the visible wound tract.

Dietary supplementation with the microalga Galdieria sulphuraria (Rhodophyta) reduces prolonged exercise-induced oxidative stress in rat tissues.

PubMed

Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Pollio, Antonino; Venditti, Paola

2015-01-01

We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion.

Clinical effects of the use of a bipolar vessel sealing device for soft palate resection and tonsillectomy in dogs, with histological assessment of resected tonsillar tissue.

PubMed

Cook, D A; Moses, P A; Mackie, J T

2015-12-01

To investigate whether soft palate resection and tonsillectomy with a bipolar vessel sealing device (BVSD) improves clinical respiratory score. To document histopathological changes to tonsillar tissue following removal with a BVSD. Case series of 22 dogs with clinical signs of upper respiratory obstruction related to brachycephalic airway syndrome. Soft palate and tonsils were removed using a BVSD. Alarplasty and saccullectomy were also performed if indicated. A clinical respiratory score was assigned preoperatively, 24-h postoperatively and 5 weeks postoperatively. Excised tonsillar samples were measured and then assessed histologically for depth of tissue damage deemed to be caused by the device. Depth of tissue damage was compared between two power settings of the device. Soft palate resection and tonsillectomy with a BVSD lead to a significant improvement in respiratory scores following surgery. Depth of tissue damage was significantly less for power setting 1 compared with power setting 2. Using power setting 1, median calculated depth of tonsillar tissue damage was 3.4 mm (range 1.2-8.0). One dog experienced major complications. Soft palate resection and tonsillectomy with a BVSD led to significant improvement in clinical respiratory score. © 2015 Australian Veterinary Association.

Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues

PubMed Central

Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Venditti, Paola

2015-01-01

We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

Life extending control: An interdisciplinary engineering thrust

NASA Technical Reports Server (NTRS)

Lorenzo, Carl F.; Merrill, Walter C.

1991-01-01

The concept of Life Extending Control (LEC) is introduced. Possible extensions to the cyclic damage prediction approach are presented based on the identification of a model from elementary forms. Several candidate elementary forms are presented. These extensions will result in a continuous or differential form of the damage prediction model. Two possible approaches to the LEC based on the existing cyclic damage prediction method, the measured variables LEC and the estimated variables LEC, are defined. Here, damage estimates or measurements would be used directly in the LEC. A simple hydraulic actuator driven position control system example is used to illustrate the main ideas behind LEC. Results from a simple hydraulic actuator example demonstrate that overall system performance (dynamic plus life) can be maximized by accounting for component damage in the control design.

A common carcinogen benzo[a]pyrene causes p53 overexpression in mouse cervix via DNA damage.

PubMed

Gao, Meili; Li, Yongfei; Sun, Ying; Long, Jiangang; Kong, Yu; Yang, Shuiyun; Wang, Yili

2011-09-18

Benzo[a]pyrene (BaP) is cytotoxic and/or genotoxic to lung, stomach and skin tissue in the body. However, the effect of BaP on cervical tissue remains unclear. The present study detected DNA damage and the expression of the p53 gene in BaP-induced cervical tissue in female mice. Animals were intraperitoneally injected and orally gavaged with BaP at the doses of 2.5, 5, and 10mg/kg twice a week for 14 weeks. The single-cell gel electrophoresis (SCGE) assay was used to detect the DNA damage. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to detect the expression of p53 protein and p53 mRNA, respectively. The results showed that BaP induced a significant and dose-dependent increase of the number of cells with DNA damaged and the tail length as well as Comet tail moment in cervical tissue. The expression level of p53 protein and mRNA was increased. The results demonstrate that BaP may show toxic effect on the cervix by increasing DNA damage and the expression of the p53 gene. Copyright © 2011 Elsevier B.V. All rights reserved.

Histopomorphic Evaluation of Radiofrequency Mediated Débridement Chondroplasty

PubMed Central

Ganguly, Kumkum; McRury, Ian D; Goodwin, Peter M; Morgan, Roy E; Augé II, Wayne K

2010-01-01

The use of radiofrequency devices has become widespread for surgical ablation procedures. When ablation devices have been deployed in treatment settings requiring tissue preservation like débridement chondroplasty, adoption has been limited due to the collateral damage caused by these devices in healthy tissue surrounding the treatment site. Ex vivo radiofrequency mediated débridement chondroplasty was performed on osteochondral specimens demonstrating surface fibrillation obtained from patients undergoing knee total joint replacement. Three radiofrequency systems designed to perform débridement chondroplasty were tested each demonstrating different energy delivery methods: monopolar ablation, bipolar ablation, and non-ablation energy. Treatment outcomes were compared with control specimens as to clinical endpoint and histopomorphic characteristics. Fibrillated cartilage was removed in all specimens; however, the residual tissue remaining at the treatment site displayed significantly different characteristics attributable to radiofrequency energy delivery method. Systems that delivered ablation-based energies caused tissue necrosis and collateral damage at the treatment site including corruption of cartilage Superficial and Transitional Zones; whereas, the non-ablation system created a smooth articular surface with Superficial Zone maintenance and without chondrocyte death or tissue necrosis. The mechanism of radiofrequency energy deposition upon tissues is particularly important in treatment settings requiring tissue preservation. Ablation-based device systems can cause a worsened state of articular cartilage from that of pre-treatment. Non-ablation energy can be successful in modifying/preconditioning tissue during débridement chondroplasty without causing collateral damage. Utilizing a non-ablation radiofrequency system provides the ability to perform successful débridement chondroplasty without causing additional articular cartilage tissue damage and may allow for other cartilage intervention success. PMID:20721322

Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

NASA Astrophysics Data System (ADS)

Sulmartiwi, Laksmi; Triastuti, Juni; Andriyono, Sapto; Umami, Mardiah Rahma

2017-02-01

Many procedures continuously in aquaculture and scientific research like tagging and vaccinating cause pain, involving damaging tissue and also cause stress responses in fish. Stress responses in fish influence liver because liver have vital role to supply energy and metabolism. Histology alteration in liver is caused by stress response like changes of vacuolation hepatocyte and characteristic colour. Triterpenoid was known had hepatoprotective activity. One of marine organism contained triterpenoid was sea cucumber. Result of research showed that liver tissue in fish with injected acetic acid 5 % (in upper lip) as pain stimulus have histopathology damages such as pyknosis (medium damage level) and oedema (heavy damage level) after 8 hour injection. Injected Lidocaine 1mg/fish as analgesic drug have histopathology damages such as oedema (heavy damages level), necrosis and pyknosis (low damages level). Injected acetic acid 5 % (in upper lip) and ethanolic extract of sea cucumber Phyllophorus sp. dose 5 mg/50 gr body weight shown histopathology damages such as necrosis, edema (medium damage level) and pyknosis (low damage level).

Study on the Protective Effect of a New Manganese Superoxide Dismutase on the Microvilli of Rabbit Eyes Exposed to UV Radiation.

PubMed

Grumetto, Lucia; Del Prete, Antonio; Ortosecco, Giovanni; Barbato, Francesco; Del Prete, Salvatore; Borrelli, Antonella; Schiattarella, Antonella; Mancini, Roberto; Mancini, Aldo

2015-01-01

We present a study on the protective effects against UV radiation of a gel formulation containing a new recombinant form of manganese superoxide dismutase on the conjunctiva and corneal epithelia of rabbit eyes. The integrity of the microvilli of both ocular tissues has been considered as an indicator of the health of the tissues. Samples, collected by impression cytology technique, were added of 80 µL of a gel formulation containing superoxide dismutase (2.0 µg/mL) and irradiated with UV rays for 30 minutes and were evaluated with scanning electron microscopy. Wilcoxon test was used to verify the possible occurrence of statistically significant differences between damage for treated and nontreated tissues. Application of gel produces a significant reduction of damage by UV irradiation of ocular epithelia; both epithelia present a significant reduction of damaged microvilli number if treated with the superoxide dismutase gel formulation: the p values (differences between damage found for treated and nontreated both ocular tissues) for conjunctiva and cornea samples were p ≪ 0.01 and p ≪ 0.0001, respectively, at confidence level of 95%. The administration of this gel formulation before UV exposure plays a considerable protective role in ocular tissues of rabbit eye with a significant reduction of the damage.

The effect of predator exposure and reproduction on oxidative stress parameters in the Catarina scallop Argopecten ventricosus.

PubMed

Guerra, C; Zenteno-Savín, T; Maeda-Martínez, A N; Abele, D; Philipp, E E R

2013-05-01

Predation is known to impact growth and reproduction, and the physiological state of the prey, including its susceptibility to oxidative stress. In this study, we investigated how prolonged exposure to predators modulates tissue specific antioxidant defense and oxidative damage in the short-lived epibenthic scallop Argopecten ventricosus (2years maximum lifespan). Scallops that were experimentally exposed to predators had not only lower antioxidant capacities (superoxide dismutase and catalase), but also lower oxidative damage (protein carbonyls and TBARS=thiobarbituric acid reactive substances including lipid peroxides) in gills and mantle compared to individuals not exposed to predators. In contrast, oxidative damage in the swimming muscle was higher in predator-exposed scallops. When predator-exposed scallops were on the verge of spawning, levels of oxidative damage increased in gills and mantle in spite of a parallel increase in antioxidant defense in both tissues. Levels of oxidative damage increased also in the swimming muscle whereas muscle antioxidant capacities decreased. Interestingly, post-spawned scallops restored antioxidant capacities and oxidative damage to immature levels, suggesting they can recover from spawning-related oxidative stress. Our results show that predator exposure and gametogenesis modulate oxidative damage in a tissue specific manner and that high antioxidant capacities do not necessarily coincide with low oxidative damage. Copyright © 2013 Elsevier Inc. All rights reserved.

DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

PubMed

Schuler, Nadine; Palm, Jan; Kaiser, Mareike; Betten, Dominik; Furtwängler, Rhoikos; Rübe, Christian; Graf, Norbert; Rübe, Claudia E

2014-01-01

In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA) suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

Seismic vulnerability assessment to earthquake at urban scale: A case of Mostaganem city in Algeria

PubMed Central

Benanane, Abdelkader; Boutaraa, Zohra

2018-01-01

The focus of this study was the seismic vulnerability assessment of buildings constituting Mostaganem city in Algeria. Situated 320 km to the west of Algiers, Mostaganem city encompasses a valuable cultural and architectural built heritage. The city has suffered several moderate earthquakes in recent years; this has led to extensive structural damage to old structures, especially unreinforced historical buildings. This study was divided into two essential steps, the first step being to establish fragility curves based on a non-linear static pushover analysis for each typology and height of buildings. Twenty-seven pushover analyses were performed by means of SAP2000 software (three analyses for each type of building). The second step was to adopt the US HAZUS software and to modify it to suit the typical setting and parameters of the city of Mostaganem. A seismic vulnerability analysis of Mostaganem city was conducted using HAZUS software after inputting the new parameters of the fragility curves established within the first step. The results indicated that the number of poor-quality buildings expected to be totally destroyed under a 5.5 Mw earthquake scenario could reach more than 28 buildings. Three percent of unreinforced masonry (URM) buildings were completely damaged and 10% were extensively damaged. Of the concrete frame buildings, 6% were extensively damaged and 19% were moderately damaged. According to the built year, 6% of both concrete frame and URM buildings built before 1980 are estimated to be collapsing. Buildings constructed between 1980 and 1999 are more resistant; 8% of those structures were extensively damaged and 18% were moderately damaged. Only 10% of buildings constructed after 1999 were moderately damaged. The results also show that the main hospital of the city, built before 1960, will be extensively damaged during an earthquake of 5.5 Mw. The number of human casualties could reach several hundreds – 10.5% of residents of URM buildings are injured or dead. Compared with the URM buildings, concrete frame buildings have lower casualty rates of 1.5% and 0.5% for those built before and after 1980, respectively. It was concluded that Mostaganem city belongs to seismic vulnerable zones in Algeria; in this regard, an action plan is needed for the rehabilitation of old constructions. In addition, the effectiveness of establishing and introducing new and appropriate fragility curves was demonstrated.

A flexible microneedle array as low-voltage electroporation electrodes for in vivo DNA and siRNA delivery.

PubMed

Wei, Zewen; Zheng, Shuquan; Wang, Renxin; Bu, Xiangli; Ma, Huailei; Wu, Yidi; Zhu, Ling; Hu, Zhiyuan; Liang, Zicai; Li, Zhihong

2014-10-21

In vivo electroporation is an appealing method to deliver nucleic acid into living tissues, but the clinical application of such a method was limited due to severe tissue damage and poor coverage of the tissue surface. Here we present the validation of a novel flexible microneedle array electrode (MNAE) chip, in which the microneedle array and the flexible substrate are integrated together to simultaneously facilitate low-voltage electroporation and accomplish good coverage of the tissue surface. The efficient delivery of both DNA and siRNA was demonstrated on mice. Upon penetrating the high-resistance stratum corneum, the electroporation voltage was reduced to about 35 V, which was generally recognized safe for humans. Also, a pathological analysis of the microneedle-electroporated tissues was carried out to thoroughly assess the skin damage, which is an important consideration in pre-clinical studies of electroporation devices. This MNAE constitutes a novel way of in vivo delivery of siRNA and DNA to certain tissues or organs with satisfactory efficiency and good adaptation to the tissue surface profile as well as minimum tissue damage, thus avoiding the disadvantages of existing electroporation methods.

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

PubMed

Jones, D A; Prior, S L; Barry, J D; Caplin, S; Baxter, J N; Stephens, J W

2014-12-01

In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (P<0.05). Lower MDA concentration and longer telomere length were seen in subjects with diabetes compared to those without (P<0.05). DNA damage, analysed via Comet assay, was significantly lower in subjects with diabetes compared to those without (P<0.05). A paradoxical decrease in oxidative stress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Balancing repair and tolerance of DNA damage caused by alkylating agents.

PubMed

Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

2012-01-12

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

PubMed Central

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

2013-01-01

Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

46 CFR 188.10-23 - Corrosive liquids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... tissues, will cause severe damage of such tissues, by chemical action; or in case of leakage, will materially damage or destroy other freight by chemical action, or are liable to cause fire when in contact with organic matter or with certain chemicals. (b) A corrosive substance may be: (1) Solid, such as...

46 CFR 188.10-23 - Corrosive liquids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... tissues, will cause severe damage of such tissues, by chemical action; or in case of leakage, will materially damage or destroy other freight by chemical action, or are liable to cause fire when in contact with organic matter or with certain chemicals. (b) A corrosive substance may be: (1) Solid, such as...

Width of thermal damage after using the YAG contact laser for cutting biological tissue: animal experimental investigation.

PubMed

Mecke, H; Schünke, M; Schnaidt, S; Freys, I; Semm, K

1991-01-01

At the University Women's Clinic in Kiel, the YAG contact laser has been used as a cutting instrument in pelviscopic operations since 1987. When the laser cuts, it produces only a scant amount of mechanical trauma. The determining factor is the amount of thermal damage produced along the wound margins and in direct neighboring tissue. The extent of the tissue change seen in the uterus and liver parenchyma of rats and the striated muscle of rabbits after application of the YAG contact laser was demonstrated using various staining techniques and stains. Liver parenchyma proved to be the most sensitive to thermal damage. In the uterine horn, enzyme-histochemical ATPase and alkaline phosphatase demonstrations showed a significantly wider zone of thermal damage after laser incision than did hematoxylin-eosin and Goldner staining techniques. A good understanding of the extent of thermal damage is essential for atraumatic pelviscopic operations using the YAG contact laser and also for the preventing of complications.

Numerical models of laser fusion of intestinal tissues.

PubMed

Pearce, John A

2009-01-01

Numerical models of continuous wave Tm:YAG thermal fusion in rat intestinal tissues were compared to experiment. Optical and thermal FDM models that included tissue damage based on Arrhenius kinetics were used to predict birefringence loss in collagen as the standard of comparison. The models also predicted collagen shrinkage, jellification and water loss. The inclusion of variable optical and thermal properties is essential to achieve favorable agreement between predicted and measured damage boundaries.

Photothermal effects of laser tissue soldering.

PubMed

McNally, K M; Sorg, B S; Welch, A J; Dawes, J M; Owen, E R

1999-04-01

Low-strength anastomoses and thermal damage of tissue are major concerns in laser tissue welding techniques where laser energy is used to induce thermal changes in the molecular structure of the tissues being joined, hence allowing them to bond together. Laser tissue soldering, on the other hand, is a bonding technique in which a protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. The addition of protein solders to augment tissue repair procedures significantly reduces the problems of low strength and thermal damage associated with laser tissue welding techniques. Investigations were conducted to determine optimal solder and laser parameters for tissue repair in terms of tensile strength, temperature rise and damage and the microscopic nature of the bonds formed. An in vitro study was performed using an 808 nm diode laser in conjunction with indocyanine green (ICG)-doped albumin protein solders to repair bovine aorta specimens. Liquid and solid protein solders prepared from 25% and 60% bovine serum albumin (BSA), respectively, were compared. The efficacy of temperature feedback control in enhancing the soldering process was also investigated. Increasing the BSA concentration from 25% to 60% greatly increased the tensile strength of the repairs. A reduction in dye concentration from 2.5 mg ml(-1) to 0.25 mg ml(-1) was also found to result in an increase in tensile strength. Increasing the laser irradiance and thus surface temperature resulted in an increased severity of histological injury. Thermal denaturation of tissue collagen and necrosis of the intimal layer smooth muscle cells increased laterally and in depth with higher temperatures. The strongest repairs were produced with an irradiance of 6.4 W cm(-2) using a solid protein solder composed of 60% BSA and 0.25 mg ml(-1) ICG. Using this combination of laser and solder parameters, surface temperatures were observed to reach 85+/-5 degrees C with a maximum temperature difference through the 150 microm thick solder strips of about 15 degrees C. Histological examination of the repairs formed using these parameters showed negligible evidence of collateral thermal damage to the underlying tissue. Scanning electron microscopy suggested albumin intertwining within the tissue collagen matrix and subsequent fusion with the collagen as the mechanism for laser tissue soldering. The laser tissue soldering technique is shown to be an effective method for producing repairs with improved tensile strength and minimal collateral thermal damage over conventional laser tissue welding techniques.

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

PubMed

Klein, H C; Krop-Van Gastel, W; Go, K G; Korf, J

1993-02-01

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

Pre- vs. post-treatment with melatonin in CCl4-induced liver damage: Oxidative stress inferred from biochemical and pathohistological studies.

PubMed

Ničković, Vanja P; Novaković, Tatjana; Lazarević, Slavica; Šulović, Ljiljana; Živković, Zorica; Živković, Jovan; Mladenović, Bojan; Stojanović, Nikola M; Petrović, Vladmir; Sokolović, Dušan T

2018-06-01

The present study was designed to compare the ameliorating potential of pre- and post-treatments with melatonin, a potent natural antioxidant, in the carbon tetrachloride-induced rat liver damage model by tracking changes in enzymatic and non-enzymatic liver tissue defense parameters, as well as in the occurring pathohistological changes. Rats from two experimental groups were treated with melatonin before and after CCl 4 administration, while the controls, negative and positive, received vehicle/melatonin and CCl 4 , respectively. Serum levels of transaminases, alkaline phosphates, γ-GT, bilirubin, and albumin, as well as a wide panel of oxidative stress-related parameters in liver tissue, were determined in all experimental animals. Liver tissue specimens were stained with hematoxylin and eosin and further evaluated for morphological changes. Both pre- and post-treatment with melatonin prevented a CCl 4 -induced increase in serum (ALT, AST, and γ-GT) and tissue (MDA and XO) liver damage markers and a decrease in the tissue total antioxidant capacity, in both enzymatic and non-enzymatic systems. The intensity of pathological changes, hepatocyte vacuolar degeneration, necrosis and inflammatory cell infiltration, was suppressed by the treatment with melatonin. In conclusion, melatonin, especially as a post-intoxication treatment, attenuated CCl 4 -induced liver oxidative damage, increased liver antioxidant capacities and improved liver microscopic appearance. The results are of interest due to the great protective potential of melatonin that was even demonstrated to be stronger if applied after the tissue damage. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of tissue damage in whiplash associated disorders: Discussion paper 1

PubMed Central

Bogduk, Nikolai; Ivancic, Paul C.; McLean, Samuel A.; Siegmund, Gunter P.; Winkelstein, Beth

2011-01-01

STUDY DESIGN Non-systematic review of cervical spine lesions in whiplash-associated disorders (WAD). OBJECTIVE To describe whiplash injury models in terms of basic and clinical science, to summarize what can and cannot be explained by injury models, and to highlight future research areas to better understand the role of tissue damage in WAD. SUMMARY OF BACKGROUND DATA The frequent lack of detectable tissue damage has raised questions about whether tissue damage is necessary for WAD and what role it plays in the clinical context of WAD. METHODS Non-systematic review. RESULTS Lesions of various tissues have been documented by numerous investigations conducted in animals, cadavers, healthy volunteers and patients. Most lesions are undetected by imaging techniques. For zygapophysial (facet) joints, lesions have been predicted by bioengineering studies and validated through animal studies; for zygapophysial joint pain, a valid diagnostic test and a proven treatment are available. Lesions of dorsal root ganglia, discs, ligaments, muscles and vertebral artery have been documented in biomechanical and autopsy studies, but no valid diagnostic test is available to assess their clinical relevance. The proportion of WAD patients in whom a persistent lesion is the major determinant of ongoing symptoms is unknown. Psychosocial factors, stress reactions and generalized hyperalgesia have also been shown to predict WAD outcomes. CONCLUSION There is evidence supporting a lesion-based model in WAD. Lack of macroscopically identifiable tissue damage does not rule out the presence of painful lesions. The best available evidence concerns zygapophysial joint pain. The clinical relevance of other lesions needs to be addressed by future research. PMID:22020601

Variation in damage from growing-season frosts among open-pollinated families of red alder.

Treesearch

Kevin C. Peeler; Dean S. DeBell

1987-01-01

Repeated growing-season frosts during late April and early May 1985 caused extensive damage to red alder (Alnus rubra Bong.) seedlings in a newly planted research trial in western Washington. About two-thirds of the seedlings were severely damaged (entire stem damaged or necrotic). Such damage varied by family, from 50 percent of seedlings in the...

Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis.

PubMed

Rivas-Santiago, C E; Rivas-Santiago, B; León, D A; Castañeda-Delgado, J; Hernández Pando, R

2011-04-01

Tuberculosis is a worldwide health problem, and multidrug-resistant (MDR) and extensively multidrug-resistant (XMDR) strains are rapidly emerging and threatening the control of this disease. These problems motivate the search for new treatment strategies. One potential strategy is immunotherapy using cationic anti-microbial peptides. The capacity of l-isoleucine to induce beta-defensin expression and its potential therapeutic efficiency were studied in a mouse model of progressive pulmonary tuberculosis. BALB/c mice were infected with Mycobacterium tuberculosis strain H37Rv or with a MDR clinical isolate by the intratracheal route. After 60 days of infection, when disease was in its progressive phase, mice were treated with 250 µg of intratracheal l-isoleucine every 48 h. Bacillary loads were determined by colony-forming units, protein and cytokine gene expression were determined by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively, and tissue damage was quantified by automated morphometry. Administration of l-isoleucine induced a significant increase of beta-defensins 3 and 4 which was associated with decreased bacillary loads and tissue damage. This was seen in animals infected with the antibiotic-sensitive strain H37Rv and with the MDR clinical isolate. Thus, induction of beta-defensins might be a potential therapy that can aid in the control of this significant infectious disease. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Acute administration of ucf-101 ameliorates the locomotor impairments induced by a traumatic spinal cord injury.

PubMed

Reigada, D; Nieto-Díaz, M; Navarro-Ruiz, R; Caballero-López, M J; Del Águila, A; Muñoz-Galdeano, T; Maza, R M

2015-08-06

Secondary death of neural cells plays a key role in the physiopathology and the functional consequences of traumatic spinal cord injury (SCI). Pharmacological manipulation of cell death pathways leading to the preservation of neural cells is acknowledged as a main therapeutic goal in SCI. In the present work, we hypothesize that administration of the neuroprotective cell-permeable compound ucf-101 will reduce neural cell death during the secondary damage of SCI, increasing tissue preservation and reducing the functional deficits. To test this hypothesis, we treated mice with ucf-101 during the first week after a moderate contusive SCI. Our results reveal that ucf-101 administration protects neural cells from the deleterious secondary mechanisms triggered by the trauma, reducing the extension of tissue damage and improving motor function recovery. Our studies also suggest that the effects of ucf-101 may be mediated through the inhibition of HtrA2/OMI and the concomitant increase of inhibitor of apoptosis protein XIAP, as well as the induction of ERK1/2 activation and/or expression. In vitro assays confirm the effects of ucf-101 on both pathways as well as on the reduction of caspase cascade activation and apoptotic cell death in a neuroblastoma cell line. These results suggest that ucf-101 can be a promising therapeutic tool for SCI that deserves more detailed analyses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in Wistar rats.

PubMed

Faria, Juliana; Barbosa, Joana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Moreira, Roxana; Queirós, Odília; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

2017-06-15

Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively). 24h after intraperitoneal administration, biochemical and oxidative stress analyses were performed in blood, and specimens from brain, lung and heart were taken for histopathological and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio, in LDH, CK and CK-MB activities in serum samples, and an increase in lactate levels in serum and brain samples. Oxidative damage, namely protein oxidation, was found in heart and lung tissues. In histological analyses, tramadol and tapentadol were found to cause alterations in cell morphology, inflammatory cell infiltrates and cell death in all tissues under study, although tapentadol caused more damage than tramadol. Our results confirmed the risks of tramadol exposure, and demonstrated the higher risk of tapentadol, especially at high doses. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental study of delivery of humidified-warm carbon dioxide during open abdominal surgery.

PubMed

Carpinteri, S; Sampurno, S; Malaterre, J; Millen, R; Dean, M; Kong, J; Chittleborough, T; Heriot, A; Lynch, A C; Ramsay, R G

2018-04-01

The aim of this study was to monitor the effect of humidified-warm carbon dioxide (HWCO 2 ) delivered into the open abdomen of mice, simulating laparotomy. Mice were anaesthetized, ventilated and subjected to an abdominal incision followed by wound retraction. In the experimental group, a diffuser device was used to deliver HWCO 2 ; the control group was exposed to passive air flow. In each group of mice, surgical damage was produced on one side of the peritoneal wall. Vital signs and core temperature were monitored throughout the 1-h procedure. The peritoneum was closed and mice were allowed to recover for 24 h or 10 days. Tumour cells were delivered into half of the mice in each cohort. Tissue was then examined using scanning electron microscopy and immunohistochemistry. Passive air flow generated ultrastructural damage including mesothelial cell bulging/retraction and loss of microvilli, as assessed at 24 h. Evidence of surgical damage was still measurable on day 10. HWCO 2 maintained normothermia, whereas open surgery alone led to hypothermia. The degree of tissue damage was significantly reduced by HWCO 2 compared with that in controls. Peritoneal expression of hypoxia inducible factor 1α and vascular endothelial growth factor A was lowered by HWCO 2 . These effects were also evident at the surgical damage sites, where protection from tissue trauma extended to 10 days. HWCO 2 did not reduce tumorigenesis in surgically damaged sites compared with passive air flow. HWCO 2 diffusion into the abdomen in the context of open surgery afforded tissue protection and accelerated tissue repair in mice, while preserving normothermia. Surgical relevance Damage to the peritoneum always occurs during open abdominal surgery, by exposure to desiccating air and by mechanical trauma/damage owing to the surgical intervention. Previous experimental studies showed that humidified-warm carbon dioxide (HWCO 2 ) reduced peritoneal damage during laparoscopic insufflation. Additionally, this intervention decreased experimental peritoneal carcinomatosis compared with the use of conventional dry-cold carbon dioxide. In the present experimental study, the simple delivery of HWCO 2 into the open abdomen reduced the amount of cellular damage and inflammation, and accelerated tissue repair. Sites of surgical intervention serve as ideal locations for cancer cell adhesion and subsequent tumour formation, but this was not changed measurably by the delivery of HWCO 2 . © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

PubMed

Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

2016-10-22

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. Deutsche Arthrose-Hilfe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Autoxidation and toxicant-induced oxidation of lipid and DNA in monkey liver: reduction of molecular damage by melatonin.

PubMed

Cabrer, J; Burkhardt, S; Tan, D X; Manchester, L C; Karbownik, M; Reiter, R J

2001-11-01

Melatonin, the main secretory product of the pineal gland, is a free radical scavenger and antioxidant which protects against oxidative damage due to a variety of toxicants. However, there is little information regarding melatonin's antioxidative capacity in tissues of primates. In this study we examined the protective effects of melatonin in monkey liver homogenates against lipid damage that occurred as a result of autoxidation or that induced by exogenous addition of H202 and ferrous iron (Fe2+). Additionally, we tested melatonin's protective effect against oxidative damage to DNA induced by chromium(III) (CrIII) plus H202. The levels of malondialdehyde and 4-hydroxyalkenals were assayed as an index of lipid peroxidation, and the concentrations of 8-hydroxydeoxyguanosine (8-OHdG) as an endpoint of oxidative DNA damage. The increases in malondialdehyde+4-hydroxyalkenals concentrations as a consequence of autoxidation or after the addition of H202 plus Fe2+ to the homogenates were time-dependent. The accumulation of these damaged products due to either auto-oxidative processes or induced by H202 and Fe2+ were significantly reduced by melatonin in a concentration-dependent-manner. The levels of 8-OHdG were elevated in purified monkey liver DNA incubated with a combination of CrCl3 plus H2O2. This rise in oxidatively damaged DNA was prevented by 10 microM concentration of melatonin. Also, melatonin reduced the damage to DNA that was caused by auto-oxidative processes. These findings in monkey liver tissue document the ability of melatonin to protect against oxidative damage to both lipid and DNA in primate tissue, as observed previously in rodent tissue. The findings provide support for the use of melatonin as suitable agent to reduce damage inflicted by free radical species in primates.

1954 hurricane damage on Penobscot Experimental Forest

Treesearch

T. J. Grisez

1954-01-01

The two hurricanes "Carol" and "Edna" that struck inland over New England this summer caused some timber losses. But the damage was neither so extensive nor so severe as the damage done by the hurricane of 1938 and the storms of 1950.

Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

PubMed

Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

2018-02-17

The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

PubMed Central

Holley, Aaron K.; Miao, Lu; St. Clair, Daret K.

2014-01-01

Abstract Significance: Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. Recent Advances: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. Critical Issues: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. Future Directions: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation. Antioxid. Redox Signal. 20, 1567–1589. PMID:24094070

A Review of Current Regenerative Medicine Strategies that Utilize Nanotechnology to Treat Cartilage Damage

PubMed Central

Kumar, R.; Griffin, M.; Butler, P.E.

2016-01-01

Background: Cartilage is an important tissue found in a variety of anatomical locations. Damage to cartilage is particularly detrimental, owing to its intrinsically poor healing capacity. Current reconstructive options for cartilage repair are limited, and alternative approaches are required. Biomaterial science and Tissue engineering are multidisciplinary areas of research that integrate biological and engineering principles for the purpose of restoring premorbid tissue function. Biomaterial science traditionally focuses on the replacement of diseased or damaged tissue with implants. Conversely, tissue engineering utilizes porous biomimetic scaffolds, containing cells and bioactive molecules, to regenerate functional tissue. However, both paradigms feature several disadvantages. Faced with the increasing clinical burden of cartilage defects, attention has shifted towards the incorporation of Nanotechnology into these areas of regenerative medicine. Methods: Searches were conducted on Pubmed using the terms “cartilage”, “reconstruction”, “nanotechnology”, “nanomaterials”, “tissue engineering” and “biomaterials”. Abstracts were examined to identify articles of relevance, and further papers were obtained from the citations within. Results: The content of 96 articles was ultimately reviewed. The literature yielded no studies that have progressed beyond in vitro and in vivo experimentation. Several limitations to the use of nanomaterials to reconstruct damaged cartilage were identified in both the tissue engineering and biomaterial fields. Conclusion: Nanomaterials have unique physicochemical properties that interact with biological systems in novel ways, potentially opening new avenues for the advancement of constructs used to repair cartilage. However, research into these technologies is in its infancy, and clinical translation remains elusive. PMID:28217211

Detection of vesicant-induced upper airway mucosa damage in the hamster cheek pouch model using optical coherence tomography.

PubMed

Hammer-Wilson, Marie J; Nguyen, Vi; Jung, Woong-Gyu; Ahn, Yehchen; Chen, Zhongping; Wilder-Smith, Petra

2010-01-01

Hamster cheek pouches were exposed to 2-chloroethyl ethyl sulfide [CEES, half-mustard gas (HMG)] at a concentration of 0.4, 2.0, or 5.0 mg/ml for 1 or 5 min. Twenty-four hours post-HMG exposure, tissue damage was assessed by both stereomicrography and optical coherence tomography (OCT). Damage that was not visible on gross visual examination was apparent in the OCT images. Tissue changes were found to be dependent on both HMG concentration and exposure time. The submucosal and muscle layers of the cheek pouch tissue showed the greatest amount of structural alteration. Routine light microscope histology was performed to confirm the OCT observations.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior.

PubMed

Rajan, Alexander T; Boback, Jessica L; Dammann, John F; Tenore, Francesco V; Wester, Brock A; Otto, Kevin J; Gaunt, Robert A; Bensmaia, Sliman J

2015-12-01

One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal's ability to use their hand--the cortical representation of which is targeted by the ICMS--as a further assay of possible neuronal damage. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

NASA Astrophysics Data System (ADS)

Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

2015-12-01

Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

NASA Technical Reports Server (NTRS)

Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

2011-01-01

Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

Subepidermal moisture detection of pressure induced tissue damage on the trunk: The pressure ulcer detection study outcomes.

PubMed

Bates-Jensen, Barbara M; McCreath, Heather E; Patlan, Anabel

2017-05-01

We examined the relationship between subepidermal moisture measured using surface electrical capacitance and visual skin assessment of pressure ulcers at the trunk location (sacral, ischial tuberosities) in 417 nursing home residents residing in 19 facilities. Participants were on average older (mean age of 77 years), 58% were female, over half were ethnic minorities (29% African American, 12% Asian American, and 21% Hispanic), and at risk for pressure ulcers (mean score for Braden Scale for Predicting Pressure Ulcer Risk of 15.6). Concurrent visual assessments and subepidermal moisture were obtained at the sacrum and right and left ischium weekly for 16 weeks. Visual assessment was categorized as normal, erythema, stage 1 pressure ulcer, Deep Tissue Injury or stage 2+ pressure ulcer using the National Pressure Ulcer Advisory Panel 2009 classification system. Incidence of any skin damage was 52%. Subepidermal moisture was measured with a dermal phase meter where higher readings indicate greater moisture (range: 0-70 tissue dielectric constant), with values increasing significantly with the presence of skin damage. Elevated subepidermal moisture values co-occurred with concurrent skin damage in generalized multinomial logistic models (to control for repeated observations) at the sacrum, adjusting for age and risk. Higher subepidermal moisture values were associated with visual damage 1 week later using similar models. Threshold values for subepidermal moisture were compared to visual ratings to predict skin damage 1 week later. Subepidermal moisture of 39 tissue dielectric constant units predicted 41% of future skin damage while visual ratings predicted 27%. Thus, this method of detecting early skin damage holds promise for clinicians, especially as it is objective and equally valid for all groups of patients. © 2017 by the Wound Healing Society.

Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation.

PubMed

Sakakura, Kenichi; Ladich, Elena; Fuimaono, Kristine; Grunewald, Debby; O'Fallon, Patrick; Spognardi, Anna-Maria; Markham, Peter; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Shen, Kai; Kolodgie, Frank D; Joner, Michael; Virmani, Renu

2015-01-01

The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (P<0.001 for circumference; P=0.003 for thinning). Severe collagen damage such as denatured collagen was also significantly less in the irrigated compared with the conventional radiofrequency group (P<0.001). Nerve damage although not statistically different between the irrigated radiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (P<0.001). Saline irrigation significantly reduces arterial and periarterial tissue damage during radiofrequency ablation, and there is a trend toward less nerve damage. © 2014 American Heart Association, Inc.

Histological evaluation and optimization of surgical vessel sealing systems

NASA Astrophysics Data System (ADS)

Lathrop, Robert; Ryan, Thomas; Gaspredes, Jonathan; Woloszko, Jean; Coad, James E.

2017-02-01

Surgical vessel sealing systems are widely used to achieve hemostasis and dissection in open surgery and minimally invasive, laparoscopic surgery. This enabling technology was developed about 17 years ago and continues to evolve with new devices and systems achieving improved outcomes. Histopathological assessment of thermally sealed tissues is a valuable tool for refining and comparing performance among surgical vessel sealing systems. Early work in this field typically assessed seal time, burst rate, and failure rate (in-situ). Later work compared histological staining methods with birefringence to assess the extent of thermal damage to tissues adjacent to the device. Understanding the microscopic architecture of a sealed vessel is crucial to optimizing the performance of power delivery algorithms and device design parameters. Manufacturers rely on these techniques to develop new products. A system for histopathological evaluation of vessels and sealing performance was established, to enable the direct assessment of a treatment's tissue effects. The parameters included the commonly used seal time, pressure burst rate and failure rate, as well as extensions of the assessment to include its likelihood to form steam vacuoles, adjacent thermal effect near the device, and extent of thermally affected tissue extruded back into the vessel lumen. This comprehensive assessment method provides an improved means of assessing the quality of a sealed vessel and understanding the exact mechanisms which create an optimally sealed vessel.

Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury

NASA Astrophysics Data System (ADS)

Coburn, Luke; Lopez, Hender; Schouwenaar, Irin-Maya; Yap, Alpha S.; Lobaskin, Vladimir; Gomez, Guillermo A.

2018-03-01

Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.

Optical coherence tomography (OCT) guided smart laser knife for cancer surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Katta, Nitesh; Mcelroy, Austin; Estrada, Arnold; Milner, Thomas E.

2017-02-01

Neurological cancer surgeries require specialized tools that enhance imaging for precise cutting and removal of tissue without damaging adjacent neurological structures. The novel combination of high-resolution fast optical coherence tomography (OCT) alongside short pulsed nanosecond thulium (Tm) lasers offers stark advantages utilizing the superior beam quality, high volumetric tissue removal rates of thulium lasers with minimal residual thermal footprint in the tissue and avoiding damage to delicate sub-surface structures (e.g., nerves and microvessels); which has not been showcased before. A bench-top system is constructed, using a 15W 1940nm nanosecond pulsed Tm fiber laser (500uJ pulse energy, 100ns pulse duration, 30kHz repetition rate) for removing tissue and a swept source laser (1310±70nm, 100kHz sweep rate) is utilized for OCT imaging, forming a combined Tm/OCT system - a smart laser knife. The OCT image-guidance informs the Tm laser for cutting/removal of targeted tissue structures. Tissue phantoms were constructed to demonstrate surgical incision with blood vessel avoidance on the surface where 2mm wide 600um deep cuts are executed around the vessel using OCT to guide the procedure. Cutting up to delicate subsurface blood vessels (2mm deep) is demonstrated while avoiding damage to their walls. A tissue removal rate of 5mm^3/sec is obtained from the bench-top system. We constructed a blow-off model to characterize Tm cut depths taking into account the absorption coefficients and beam delivery systems to compute Arrhenius damage integrals. The model is used to compare predicted tissue removal rate and residual thermal injury with experimental values in response to Tm laser-tissue modification.

Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

PubMed

Vinatier, C; Guicheux, J

2016-06-01

Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Thermal injury models for optical treatment of biological tissues: a comparative study.

PubMed

Fanjul-Velez, Felix; Ortega-Quijano, Noe; Salas-Garcia, Irene; Arce-Diego, Jose L

2010-01-01

The interaction of optical radiation with biological tissues causes an increase in the temperature that, depending on its magnitude, can provoke a thermal injury process in the tissue. The establishment of laser irradiation pathological limits constitutes an essential task, as long as it enables to fix and delimit a range of parameters that ensure a safe treatment in laser therapies. These limits can be appropriately described by kinetic models of the damage processes. In this work, we present and compare several models for the study of thermal injury in biological tissues under optical illumination, particularly the Arrhenius thermal damage model and the thermal dosimetry model based on CEM (Cumulative Equivalent Minutes) 43°C. The basic concepts that link the temperature and exposition time with the tissue injury or cellular death are presented, and it will be shown that they enable to establish predictive models for the thermal damage in laser therapies. The results obtained by both models will be compared and discussed, highlighting the main advantages of each one and proposing the most adequate one for optical treatment of biological tissues.

Effects of C1 Inhibitor on Tissue Damage in a Porcine Model of Controlled Hemorrhage

DTIC Science & Technology

2012-07-01

and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups...damage in a dose-dependent man- ner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis ... acidosis , reduced circulating tumor necrosis factor !, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on

Tm:fiber laser ablation with real-time temperature monitoring for minimizing collateral thermal damage: ex vivo dosimetry for ovine brain.

PubMed

Tunc, Burcu; Gulsoy, Murat

2013-01-01

The thermal damage of the surrounding tissue can be an unwanted result of continuous-wave laser irradiations. In order to propose an effective alternative to conventional surgical techniques, photothermal damage must be taken under control by a detailed dose study. Real-time temperature monitoring can be also an effective way to get rid of these negative effects. The aim of the present study is to investigate the potential of a new laser-thermoprobe, which consists of a continuous-wave 1,940-nm Tm:fiber laser and a thermocouple measurement system for brain surgery in an ex vivo study. A laser-thermoprobe was designed for using the near-by tissue temperature as a real-time reference for the applicator. Fresh lamb brain tissues were used for experiments. 320 laser shots were performed on both cortical and subcortical tissue. The relationship between laser parameters, temperature changes, and ablation (removal of tissue) efficiency was determined. The correlation between rate of temperature change and ablation efficiency was calculated. Laser-thermoprobe leads us to understand the basic laser-tissue interaction mechanism in a very cheap and easy way, without making a change in the experimental design. It was also shown that the ablation and coagulation (thermally irreversible damage) diameters could be predicted, and carbonization can be avoided by temperature monitoring. Copyright © 2013 Wiley Periodicals, Inc.

The Cell Nucleus Serves as a Mechanotransducer of Tissue Damage-Induced Inflammation.

PubMed

Enyedi, Balázs; Jelcic, Mark; Niethammer, Philipp

2016-05-19

Tissue damage activates cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (AA), which is oxidized to proinflammatory eicosanoids by 5-lipoxygenase (5-LOX) on the nuclear envelope. How tissue damage is sensed to activate cPLA2 is unknown. We investigated this by live imaging in wounded zebrafish larvae, where damage of the fin tissue causes osmotic cell swelling at the wound margin and the generation of a chemotactic eicosanoid signal. Osmotic swelling of cells and their nuclei activates cPla2 by translocating it from the nucleoplasm to the nuclear envelope. Elevated cytosolic Ca(2+) was necessary but not sufficient for cPla2 translocation, and nuclear swelling was required in parallel. cPla2 translocation upon nuclear swelling was reconstituted in isolated nuclei and appears to be a simple physical process mediated by tension in the nuclear envelope. Our data suggest that the nucleus plays a mechanosensory role in inflammation by transducing cell swelling and lysis into proinflammatory eicosanoid signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Seasonal Liza aurata tissue-specific DNA integrity in a multi-contaminated coastal lagoon (Ria de Aveiro, Portugal).

PubMed

Oliveira, M; Maria, V L; Ahmad, I; Pacheco, M; Santos, M A

2010-10-01

In this study, the DNA integrity of golden grey mullet (Liza aurata) collected in differently contaminated sites of a coastal lagoon, Ria de Aveiro (Portugal), was assessed, over the period of 1 year, using the DNA alkaline unwinding assay, in four different tissues (gill, kidney, liver and blood) and compared to a reference site. The four tissues displayed different DNA integrity basal levels, clearly affected by seasonal factors. Gill and kidney were, respectively, the most and least sensitive tissues. All sites demonstrated the capacity to interfere with DNA integrity. The sites displaying the highest and lowest DNA damage capability were, respectively, Barra (subject to naval traffic) and Vagos (contaminated with polycyclic aromatic hydrocarbons). In terms of seasonal variability, autumn seems to be the more critical season (more DNA damage) unlike summer when no DNA damage was found in any tissue. Data recommend the continued monitoring of this aquatic system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Role of ROS and RNS Sources in Physiological and Pathological Conditions

PubMed Central

Victor, Victor Manuel

2016-01-01

There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis. PMID:27478531

Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

PubMed Central

Lu, Zhiyan; Wu, Jinwei; Cheng, Guangyuan; Tian, Jianying; Lu, Zeqing; Bi, Yongyi

2014-01-01

Previous studies have found that methylmercury can damage hippocampal neurons and accordingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmercury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride. PMID:25368649

Ceramide-1-phosphate regulates migration of multipotent stromal cells (MSCs) and endothelial progenitor cells (EPCs) – implications for tissue regeneration

PubMed Central

Kim, ChiHwa; Schneider, Gabriela; Abdel-Latif, Ahmed; Mierzejewska, Kasia; Sunkara, Manjula; Borkowska, Sylwia; Ratajczak, Janina; Morris, Andrew J.; Kucia, Magda; Ratajczak, Mariusz Z.

2012-01-01

Ceramide-1-phosphate (C1P) is a bioactive lipid that, in contrast to ceramide, is an anti-apoptotic molecule released from cells that are damaged and “leaky”. As reported recently, C1P promotes migration of hematopoietic cells. In the current paper, we tested the hypothesis that C1P released upon tissue damage may play an underappreciated role in chemoattraction of various types of stem cells and endothelial cells involved in tissue/organ regeneration. We show for a first time that C1P is upregulated in damaged tissues and chemoattracts BM-derived multipotent stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs). Furthermore, compared to other bioactive lipids, C1P more potently chemoattracted human umbilical vein endothelial cells (HUVECs) and stimulated tube formation by these cells. C1P also promoted in vivo vascularization of Matrigel implants and stimulated secretion of stromal derived factor-1 (SDF-1) from BM-derived fibroblasts. Thus, our data demonstrate, for the first time, that C1P is a potent bioactive lipid released from damaged cells that potentially plays an important and novel role in recruitment of stem/progenitor cells to damaged organs and may promote their vascularization. PMID:23193025

Impact of Hot Environment on Fluid and Electrolyte Imbalance, Renal Damage, Hemolysis, and Immune Activation Postmarathon

PubMed Central

Oliveira, Rodrigo Assunção; Sierra, Ana Paula Rennó; Benetti, Marino; Ghorayeb, Nabil; Sierra, Carlos A.; Kiss, Maria Augusta Peduti Dal Molin

2017-01-01

Previous studies have demonstrated the physiological changes induced by exercise exposure in hot environments. We investigated the hematological and oxidative changes and tissue damage induced by marathon race in different thermal conditions. Twenty-six male runners completed the São Paulo International Marathon both in hot environment (HE) and in temperate environment (TE). Blood and urine samples were collected 1 day before, immediately after, 1 day after, and 3 days after the marathon to analyze the hematological parameters, electrolytes, markers of tissue damage, and oxidative status. In both environments, the marathon race promotes fluid and electrolyte imbalance, hemolysis, oxidative stress, immune activation, and tissue damage. The marathon runner's performance was approximately 13.5% lower in HE compared to TE; however, in HE, our results demonstrated more pronounced fluid and electrolyte imbalance, renal damage, hemolysis, and immune activation. Moreover, oxidative stress induced by marathon in HE is presumed to be related to protein/purine oxidation instead of other oxidative sources. Fluid and electrolyte imbalance and protein/purine oxidation may be important factors responsible for hemolysis, renal damage, immune activation, and impaired performance after long-term exercise in HE. Nonetheless, we suggested that the impairment on performance in HE was not associated to the muscle damage and lipoperoxidation. PMID:29430287

Effect of T3 on metabolic response and oxidative stress in skeletal muscle from sedentary and trained rats.

PubMed

Venditti, Paola; Bari, Angela; Di Stefano, Lisa; Di Meo, Sergio

2009-02-01

We investigated whether swim training modifies the effect of T3-induced hyperthyroidism on metabolism and oxidative damage in rat muscle. Respiratory capacities, oxidative damage, levels of antioxidants, and susceptibility to oxidative challenge of homogenates were determined. Mitochondrial respiratory capacities, H2O2 release rates, and oxidative damage were also evaluated. T3-treated rats exhibited increases in muscle respiratory capacity, which were associated with enhancements in mitochondrial respiratory capacity and tissue mitochondrial protein content in sedentary and trained animals, respectively. Hormonal treatment induced muscle oxidative damage and GSH depletion. Both effects were reduced by training, which also attenuated tissue susceptibility to oxidative challenge. The changes in single antioxidant levels were slightly related to oxidative damage extent, but the examination of parameters affecting the susceptibility to oxidants indicated that training was associated with greater effectiveness of the muscle antioxidant system. Training also attenuated T3-induced increases in H2O2 production and, therefore, oxidative damage of mitochondria by lowering their content of autoxidizable electron carriers. The above results suggest that moderate training is able to reduce hyperthyroid state-linked tissue oxidative damage, increasing antioxidant protection and decreasing the ROS flow from the mitochondria to the cytoplasmic compartment.

The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading.

PubMed

Loerakker, S; Manders, E; Strijkers, G J; Nicolay, K; Baaijens, F P T; Bader, D L; Oomens, C W J

2011-10-01

Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. In the present study, the contributions of deformation, ischemia, and reperfusion to skeletal muscle damage development were examined in a rat model during a 6-h period. Magnetic resonance imaging (MRI) was used to study perfusion (contrast-enhanced MRI) and tissue integrity (T2-weighted MRI). The levels of tissue deformation were estimated using finite element models. Complete ischemia caused a gradual homogeneous increase in T2 (∼20% during the 6-h period). The effect of reperfusion on T2 was highly variable, depending on the anatomical location. In experiments involving deformation, inevitably associated with partial ischemia, a variable T2 increase (17-66% during the 6-h period) was observed reflecting the significant variation in deformation (with two-dimensional strain energies of 0.60-1.51 J/mm) and ischemia (50.8-99.8% of the leg) between experiments. These results imply that deformation, ischemia, and reperfusion all contribute to the damage process during prolonged loading, although their importance varies with time. The critical deformation threshold and period of ischemia that cause muscle damage will certainly vary between individuals. These variations are related to intrinsic factors, such as pathological state, which partly explain the individual susceptibility to the development of DTI and highlight the need for regular assessments of individual subjects.

Optoacoustic monitoring of cutting efficiency and thermal damage during laser ablation.

PubMed

Bay, Erwin; Douplik, Alexandre; Razansky, Daniel

2014-05-01

Successful laser surgery is characterized by a precise cut and effective hemostasis with minimal collateral thermal damage to the adjacent tissues. Consequently, the surgeon needs to control several parameters, such as power, pulse repetition rate, and velocity of movements. In this study we propose utilizing optoacoustics for providing the necessary real-time feedback of cutting efficiency and collateral thermal damage. Laser ablation was performed on a bovine meat slab using a Q-switched Nd-YAG laser (532 nm, 4 kHz, 18 W). Due to the short pulse duration of 7.6 ns, the same laser has also been used for generation of optoacoustic signals. Both the shockwaves, generated due to tissue removal, as well as the normal optoacoustic responses from the surrounding tissue were detected using a single broadband piezoelectric transducer. It has been observed that the rapid reduction in the shockwave amplitude occurs as more material is being removed, indicating decrease in cutting efficiency, whereas gradual decrease in the optoacoustic signal likely corresponds to coagulation around the ablation crater. Further heating of the surrounding tissue leads to carbonization accompanied by a significant shift in the optoacoustic spectra. Our results hold promise for real-time monitoring of cutting efficiency and collateral thermal damage during laser surgery. In practice, this could eventually facilitate development of automatic cut-off mechanisms that will guarantee an optimal tradeoff between cutting and heating while avoiding severe thermal damage to the surrounding tissues.

Tapered fiber optic applicator for laser ablation: Theoretical and experimental assessment of thermal effects on ex vivo model.

PubMed

Saccomandi, P; Di Matteo, F M; Schena, E; Quero, G; Massaroni, C; Giurazza, F; Costamagna, G; Silvestri, S

2017-07-01

Laser Ablation (LA) is a minimally invasive technique for tumor removal. The laser light is guided into the target tissue by a fiber optic applicator; thus the physical features of the applicator tip strongly influence size and shape of the tissue lesion. This study aims to verify the geometry of the lesion achieved by a tapered-tip applicator, and to investigate the percentage of thermally damaged cells induced by the tapered-tip fiber optic applicator. A theoretical model was implemented to simulate: i) the distribution of laser light fluence rate in the tissue through Monte Carlo method, ii) the induced temperature distribution, by means of the Bio Heat Equation, iii) the tissue injury, by Arrhenius integral. The results obtained by the implementation of the theoretical model were experimentally assessed. Ex vivo porcine liver underwent LA with tapered-tip applicator, at different laser settings (laser power of 1 W and 1.7 W, deposited energy equal to 330 J and 500 J, respectively). Almost spherical volume lesions were produced. The thermal damage was assessed by measuring the diameter of the circular-shaped lesion. The comparison between experimental results and theoretical prediction shows that the thermal damage discriminated by visual inspection always corresponds to a percentage of damaged cells of 96%. A tapered-tip applicator allows obtaining localized and reproducible damage close to spherical shape, whose diameter is related to the laser settings, and the simple theoretical model described is suitable to predict the effects, in terms of thermal damage, on ex vivo liver. Further trials should be addressed to adapt the model also on in vivo tissue, aiming to develop a tool useful to support the physician in clinical application of LA.

Histological alterations in gills of Macrobrachium amazonicum juveniles exposed to ammonia and nitrite.

PubMed

Dutra, Fabrício Martins; Rönnau, Milton; Sponchiado, Dircelei; Forneck, Sandra Carla; Freire, Carolina Arruda; Ballester, Eduardo Luis Cupertino

2017-06-01

Aquaculture has shown great growth in the last decades. Due to the restrictions on water use, production systems are becoming increasingly more intensive, raising concerns about the production water quality. Macrobrachium amazonicum is among the freshwater prawn species with favorable characteristics for production and possibility of intensification. Nitrogen compounds such as ammonia and nitrite affect the health of aquatic organisms since they quickly reach toxic concentrations. These compounds can also cause damage to the gill structure, leading to hypoxia in tissues, affecting acid-base balance, osmoregulation (salt absorption) and ammonia excretion, decreasing the immune capacity of the animal and, in extreme cases, cause death. The aim of this study was to assess histological changes in the gills of Macrobrachium amazonicum juveniles subjected to different concentrations of total ammonia and nitrite. The prawns were subjected to different concentrations of those compounds and their gills were removed and preserved for histological analysis. The gills were assessed for changes according to the Organ Index (I org ) and, for each change, an importance factor (w) was attributed according to the degree of reversibility and applied according to the degree of extension or frequency of the damage. The damage to the gills in the treatments with 100% mortality, both for ammonia and nitrite, corresponded to the high occurrence of progressive, regressive, circulatory, and inflammation damages. The other treatments (which caused less mortality) had mainly inflammation and regressive damages, whose occurrence increased according to the increase in ammonia and nitrite concentration. The histological analysis confirmed that the higher the total ammonia and nitrite concentrations, the larger the damages caused to the gill structure and that lower nitrite concentrations caused similar damages to those caused by higher total ammonia concentrations, which reflects the lower capacity M. amazonicum has to tolerate nitrite. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of captopril on the cysteamine-induced duodenal ulcer in the rat.

PubMed

Saghaei, Firoozeh; Karimi, Iraj; Jouyban, Abolghasem; Samini, Morteza

2012-05-01

Oxidative stress is important factor underlying in a variety of diseases. Antioxidative enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) are part of the physiological defenses against oxidative stress. Malondialdehyde (MDA) is a lipid peroxidation biomarker and its elevated level in various diseases is related to free radical damage. Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) and may decrease defense activity of antioxidative enzymes against ROS and induce duodenal ulcer. Captopril, acts as free radical scavengers and protect against injuries from oxidative damage to tissues.The aim of this study was the evaluation of the effect of captopril against cysteamine-induced duodenal ulcer by determining duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MAD level. This study was performed on 3 groups of 7 rats each: saline, cysteamine and cysteamine plus captopril treated groups. The effect of captopril against cysteamine-induced duodenal ulcer is determined by evaluating the duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MDA level. All animals were euthanized 24h after the last treatment and 2 ml blood and duodena samples were collected for calculation of ulcer index, histopathological assessment and measurement of tissue SOD, GSH-PX activities and plasma MDA level. Cysteamine produced severe duodenal damage, decreased the activity of duodenal tissue SOD and GSH-PX and increased the plasma MDA level compared with saline pretreated rats. Pretreatment with captopril decreased the cysteamine-induced duodenal damage and plasma level of MDA and increased the activities of SOD and GSH-PX in duodenal tissue compared with cysteamine pretreated animal. Our results suggest that captopril protects against cysteamine-induced duodenal ulcer and inhibits the decrease in SOD and GSH-PX activities and lipid peroxidation by increasing antioxidant defenses. Copyright © 2010 Elsevier GmbH. All rights reserved.

The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody staining and of biochemical assessments of tissue viability

PubMed Central

Tagboto, S; Griffiths, A Paul

2007-01-01

Background It is well recognised that there is often a disparity between the structural changes observed in the kidney following renal injury and the function of the organ. For this reason, we carried out studies to explore possible means of studying and quantifying the severity of renal ischaemic damage using a laboratory model. Methods To do this, freshly isolated rabbit kidney tissue was subjected to warm (37°C) or cold (1°C) ischaemia for 20 hours. Following this, the tissue was stained using Haematoxylin and Eosin (H+E), Periodic Schiff reagent (PAS) and the novel monoclonal antibody CD10 stain. Additionally, ischaemic damage to the kidneys was assessed by biochemical tests of tissue viability using formazan-based colorimetry. Results CD 10 antibody intensely stained the brush border of control kidney tissue with mild or no cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10 into the lumen and cell cytoplasm. There was good correlation between a score of histological damage using the CD 10 monoclonal antibody stain and the biochemical assessment of viability. Similarly, a score of histological damage using traditional PAS staining correlated well with that using the CD10 antibody stain. In particular, the biochemical assay and the monoclonal antibody staining techniques were able to demonstrate the efficacy of Soltran (this solution is used cold to preserve freshly isolated human kidneys prior to transplantation) in preserving renal tissue at cold temperatures compared to other randomly selected solutions. Conclusion We conclude that the techniques described using the CD10 monoclonal antibody stain may be helpful in the diagnosis and assessment of ischaemic renal damage. In addition, biochemical tests of viability may have an important role in routine histopathological work by giving additional information about cellular viability which may have implications on the function of the organ. PMID:17531101

Ultrasound-induced cavitation damage to external epithelia of fish skin.

PubMed

Frenkel, V; Kimmel, E; Iger, Y

1999-10-01

Transmission electron microscopy was used to show the effects of therapeutic ultrasound (< or = 1.0 W/cm2, 1 MHz) on the external epithelia of fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage.

PubMed

Vassallo, Christopher N; Wall, Daniel

2016-04-01

Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage-coping mechanism used by multicellular myxobacteria. We propose that cell-cell transfer of membrane material within a population serves as a wound-healing strategy and provide evidence for its utility. We suggest that--similar to how tissues in eukaryotes have evolved cooperative methods of damage repair--so too have some bacteria that live a multicellular lifestyle. © 2016 WILEY Periodicals, Inc.

Indocyanine green video angiography predicts outcome of extravasation injuries.

PubMed

Haslik, Werner; Pluschnig, Ursula; Steger, Günther G; Zielinski, Christoph C; Schrögendorfer, K F; Nedomansky, Jakob; Bartsch, Rupert; Mader, Robert M

2014-01-01

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention. Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome. The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001). In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.

Structural damage to periodontal tissues at varying rate of anesthetic injection.

PubMed

Sarapultseva, Maria; Sarapultsev, Alexey; Medvedeva, Svetlana; Danilova, Irina

2018-04-01

Incorrect administration of an anesthetic during local anesthesia is one of the most important causes of pain symptoms in patients scheduled for dental procedures. The current study assessed the severity of damage to periodontal tissue following different rates of anesthetic administration. The research was conducted on 50 outbred male rats with a body mass of 180-240 g. The anesthetic used was 1% articaine. The results showed that administration of the anesthetic at a rapid pace caused structural damage to the periodontal tissue. Further, signs of impaired microcirculation were noted at all rates of administration. Biochemical studies demonstrated changes in the level of glucose and enzymes with the rapid introduction of the anesthetic, indicating severe systemic stress response of the body. Injection of local anesthetic at any rate of introduction induces vascular congestion in the microcirculatory bloodstream and exudative reactions. Rapid introduction of an anesthetic causes progression of structural changes in the gingival tissue.

Adaptation of rat gastric tissue against indomethacin toxicity.

PubMed

Polat, Beyzagul; Suleyman, Halis; Alp, Hamit Hakan

2010-06-07

Indomethacin is used in the treatment of inflammatory diseases. But the drug toxicity limits its usage. This study investigated whether adaptation occurred after various dosages of repeated (chronic) indomethacin in rats to the gastro-toxic effects of indomethacin. It also examined whether the adaptation was related to oxidant-antioxidant mechanisms and oxidative DNA damage in gastric tissue. To illuminate the adaptation mechanism in the gastric tissue of rats given various dosages of chronic indomethacin, the levels of oxidants and antioxidants (GSH, MDA, NO, SOD and MPO), activities of COX-1 and COX-2 enzymes and oxidative DNA damage (8-OHd Gua/10(5) Gua) were measured. Results were compared to 25-mg/kg single-dose indomethacin group, and the role of oxidant and antioxidant parameters and oxidative DNA damage in the adaptation mechanism was evaluated. The average ulcer areas of gastric tissue of the 0.5-, 1-, 2-, 3-, 4-, and 5-mg/kg dosages of chronic indomethacin given to rats were 19.5+/-3.7, 12.5+/-3.3, 10+/-5.2, 4.5+/-3.6, 8.6+/-2.4, and 9.5+/-2.1mm(2), respectively. This rate was measured as 21.3+/-2.6mm(2) in the single-dose indomethacin group. Consequently, after various dosages of repeated (chronic) indomethacin administration in rats, it was observed that a clear adaptation developed against gastric damage and that gastric damage was reduced. The best adaptation was observed in the gastric tissue of the 3-mg/kg chronic indomethacin group. In parallel with the damage reduction, the oxidant parameters (MDA and MPO) and oxidative DNA damage (8-OHd Gua/10(5) Gua) were reduced, and the antioxidant parameters (GSH, NO and SOD) were increased. There is no relation between COX enzymes and adaptation mechanism. This circumstance shows that not COX-1 and COX-2 enzymes, oxidant and antioxidant parameters may play a role in the adaptation mechanism. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Segmentation of epidermal tissue with histopathological damage in images of haematoxylin and eosin stained human skin

PubMed Central

2014-01-01

Background Digital image analysis has the potential to address issues surrounding traditional histological techniques including a lack of objectivity and high variability, through the application of quantitative analysis. A key initial step in image analysis is the identification of regions of interest. A widely applied methodology is that of segmentation. This paper proposes the application of image analysis techniques to segment skin tissue with varying degrees of histopathological damage. The segmentation of human tissue is challenging as a consequence of the complexity of the tissue structures and inconsistencies in tissue preparation, hence there is a need for a new robust method with the capability to handle the additional challenges materialising from histopathological damage. Methods A new algorithm has been developed which combines enhanced colour information, created following a transformation to the L*a*b* colourspace, with general image intensity information. A colour normalisation step is included to enhance the algorithm’s robustness to variations in the lighting and staining of the input images. The resulting optimised image is subjected to thresholding and the segmentation is fine-tuned using a combination of morphological processing and object classification rules. The segmentation algorithm was tested on 40 digital images of haematoxylin & eosin (H&E) stained skin biopsies. Accuracy, sensitivity and specificity of the algorithmic procedure were assessed through the comparison of the proposed methodology against manual methods. Results Experimental results show the proposed fully automated methodology segments the epidermis with a mean specificity of 97.7%, a mean sensitivity of 89.4% and a mean accuracy of 96.5%. When a simple user interaction step is included, the specificity increases to 98.0%, the sensitivity to 91.0% and the accuracy to 96.8%. The algorithm segments effectively for different severities of tissue damage. Conclusions Epidermal segmentation is a crucial first step in a range of applications including melanoma detection and the assessment of histopathological damage in skin. The proposed methodology is able to segment the epidermis with different levels of histological damage. The basic method framework could be applied to segmentation of other epithelial tissues. PMID:24521154

Hippocampal damage causes retrograde but not anterograde memory loss for context fear discrimination in rats.

PubMed

Lee, Justin Q; Sutherland, Robert J; McDonald, Robert J

2017-09-01

There is a substantial body of evidence that the hippocampus (HPC) plays and essential role in context discrimination in rodents. Studies reporting anterograde amnesia (AA) used repeated, alternating, distributed conditioning and extinction sessions to measure context fear discrimination. In addition, there is uncertainty about the extent of damage to the HPC. Here, we induced conditioned fear prior to discrimination tests and rats sustained extensive, quantified pre- or post-training HPC damage. Unlike previous work, we found that extensive HPC damage spares context discrimination, we observed no AA. There must be a non-HPC system that can acquire long-term memories that support context fear discrimination. Post-training HPC damage caused retrograde amnesia (RA) for context discrimination, even when rats are fear conditioned for multiple sessions. We discuss the implications of these findings for understanding the role of HPC in long-term memory. © 2017 Wiley Periodicals, Inc.

Comparison of neural damage induced by electrical stimulation with faradaic and capacitor electrodes.

PubMed

McCreery, D B; Agnew, W F; Yuen, T G; Bullara, L A

1988-01-01

Arrays of platinum (faradaic) and anodized, sintered tantalum pentoxide (capacitor) electrodes were implanted bilaterally in the subdural space of the parietal cortex of the cat. Two weeks after implantation both types of electrodes were pulsed for seven hours with identical waveforms consisting of controlled-current, charge-balanced, symmetric, anodic-first pulse pairs, 400 microseconds/phase and a charge density of 80-100 microC/cm2 (microcoulombs per square cm) at 50 pps (pulses per second). One group of animals was sacrificed immediately following stimulation and a second smaller group one week after stimulation. Tissues beneath both types of pulsed electrodes were damaged, but the difference in damage for the two electrode types was not statistically significant. Tissue beneath unpulsed electrodes was normal. At the ultrastructural level, in animals killed immediately after stimulation, shrunken and hyperchromic neurons were intermixed with neurons showing early intracellular edema. Glial cells appeared essentially normal. In animals killed one week after stimulation most of the damaged neurons had recovered, but the presence of shrunken, vacuolated and degenerating neurons showed that some of the cells were damaged irreversibly. It is concluded that most of the neural damage from stimulations of the brain surface at the level used in this study derives from processes associated with passage of the stimulus current through tissue, such as neuronal hyperactivity rather than electrochemical reactions associated with current injection across the electrode-tissue interface, since such reactions occur only with the faradaic electrodes.

Xeroderma pigmentosum: a case report and review of the literature.

PubMed

Feller, L; Wood, N H; Motswaledi, M H; Khammissa, R A G; Meyer, M; Lemmer, J

2010-06-01

Inherited molecular defects in nucleotide excision repair genes cause the autosomal recessive condition xeroderma pigmentosum. Xeroderma pigmentosum is characterized by photo-hypersensitivity of sun-exposed tissues, and by a several thousand-fold increase in the risk of developing malignant neoplasms of the skin and of the eyes. Mutations in xeroderma pigmentosum genes that regulate nucleotide excision repair, not only predispose persons with xeroderma pigmentosum to multiple malignancies, but also promote premature cutaneous and ocular ageing, and in some cases promote progressive neurodegenerative changes. This paper describes a case of xeroderma pigmentosum with advanced cutaneous squamous cell carcinoma, actinic cheilitis and ocular lesions in a 19-year-old black woman. The extensive ultraviolet radiation-induced skin and eye damage are evidence of neglect of sun-protection and lack of appropriate medical care from childhood.

The role of the transcription factor Ets1 in lupus and other autoimmune diseases

PubMed Central

Garrett-Sinha, Lee Ann; Kearly, Alyssa; Satterthwaite, Anne B.

2017-01-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by excess B and T cell activation, the development of autoantibodies against self-antigens including nuclear antigens, and immune complex deposition in target organs which triggers an inflammatory response and tissue damage. The genetic and environmental factors that contribute to development of SLE have been extensively studied in both humans and mouse models of the disease. One of the important genetic contributions to SLE development is an alteration in the expression of the transcription factor Ets1, which regulates the functional differentiation of lymphocytes. Here we review the genetic, biochemical and immunological studies that have linked low levels of Ets1 to aberrant lymphocyte differentiation and to the pathogenesis of SLE. PMID:28845756

The pathogenesis of measles.

PubMed

de Vries, Rory D; Mesman, Annelies W; Geijtenbeek, Teunis B H; Duprex, W Paul; de Swart, Rik L

2012-06-01

Measles is an important cause of childhood morbidity and mortality in developing countries. Measles virus (MV) is transmitted via the respiratory route and causes systemic disease. Over the last decade, identification of new cellular receptors and studies in animal models have challenged the historic concepts of measles pathogenesis. It is thought that MV enters the host by infection of alveolar macrophages and/or dendritic cells in the airways, and is amplified in local lymphoid tissues. Viremia mediated by infected CD150+ lymphocytes results in systemic dissemination. Infection of lymphocytes and dendritic cells in the respiratory submucosa facilitates basolateral infection of epithelial cells via the newly identified receptor Nectin-4. Concomitant and extensive epithelial damage may contribute to efficient transmission to the next host. Copyright © 2012 Elsevier B.V. All rights reserved.

Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Read, David J.; Li Yong; Chao, Moses V.

2010-05-15

Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but maymore » incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.« less

The benefit of angiotensin AT1 receptor blockers for early treatment of hypertensive patients.

PubMed

Trimarco, Bruno; Santoro, Ciro; Pepe, Marco; Galderisi, Maurizio

2017-12-01

ESC guidelines for management of arterial hypertension allow one to choose among five classes of antihypertensive drugs indiscriminately. They are based on the principle that in the management of hypertensive patients, it is fundamental to reduce blood pressure (BP), independently of the utilized drug. However, it has been demonstrated that the renin-angiotensin system (RAS) plays a relevant role in the hypertensive-derived development and progression of organ damage. Thus, antihypertensive drugs interfering with the RAS should be preferred in preventing and reducing target organ damage. The availability of two classes of drugs, ACE-inhibitors and angiotensin AT1 receptor blockers (ARBs), both interfering with the RAS, makes the choice between them difficult. Both pharmacological strategies offer an effective BP control, and a substantial improvement of prognosis in different associated pathologies. Regarding cardiovascular prevention, ACE-inhibitors have an extensive scientific literature regarding utility in high-risk patients. Nevertheless, there is evidence to support the concept that in the early phases of organ tissue damage, the RAS is activated, but the ACE pathway producing angiotensin II is not always employed. Accordingly, ACE-inhibitors appear to be less effective, whereas ARBs have a greater beneficial action in the initial stages of atherosclerotic disease. Moreover, patients undergoing ARBs therapy show a substantially lower risk of therapy discontinuation when compared to those treated with ACE-inhibitors, because of a better tolerability. In conclusion, ACE-inhibitors should be used in patients who have already developed organ damage, but tolerate this drug well, while ARBs should be the first choice in naïve hypertensive patients without organ damage or at the initial stages of disease.

Complex Intraoral Reconstruction Using a Single Free Anterolateral Thigh Flap and Supermicrosurgery After Corrosive Ingestion in a 14-Month-Old Child.

PubMed

El Fahar, Mohammed H

2018-05-01

Oral chemical burn injuries induce more damage to the underlying tissues with extensive scarring. It is very well known that alkali causes severe liquefaction necrosis and injury to the deeper tissues. Pediatric facial burns must be managed thoroughly and always require complex reconstruction, which is a challenging process. So, any reconstructive surgeon must be aware of all the deformities that may have significant functional and aesthetic impact on the burn survivors especially children. Few medical studies addressed pediatric microsurgical reconstruction for oral burn injuries induced by chemical materials. Anterolateral thigh (ALT) free flap is a common flap with a multitude of indications. The purpose of this article is to present the youngest case in the medical literature of caustic intraoral scarring managed with a very thin free anterolateral thigh flap in a 14-month-old child who underwent reconstruction of his inner cheek, the angle of the mouth and tongue using supermicrosurgery techniques. Further development of the surgical techniques is required to establish early and safe intraoral pediatric microsurgery with a long-term follow-up.

Intraoperative radiotherapy. Literature updating with an overview of results presented at the 6th International Symposium of Intraoperative Radiation Therapy.

PubMed

Calvo, F A; Santos, M; Azinovic, I

1998-01-01

Intraoperative radiotherapy is a technique that can be integrated into multidisciplinary treatment strategies in oncology. A radiation boost delivered with high energy electron beams can intensify locoregional antitumor therapy in patients undergoing cancer surgery. Intraoperative radiotherapy can increase the therapeutic index of the conventional combination of surgery and radiotherapy by improving the precision of radiation dose location, while decreasing the normal tissue damage in mobile structures and enhancing the biological effect of radiation when combined with surgical debulking. Intraoperative radiotherapy has been extensively investigated in clinical oncology in the last 15 years. Commercially available linear accelerators require minimal changes to be suitable for intraoperative radiotherapy. Its successful implementation in clinical protocols depends on the support given by the single institutions and on a clinical research-oriented mentality. Tumors where intraoperative radiotherapy as a treatment component has shown promising rates of local control include locally advanced rectal, gastric and gynecologic cancer, bone and soft tissue sarcoma. Intraoperative radiotherapy can be applied to brain tumors, head and neck cancer, NSCLC and pancreatic carcinoma.

Lipidomic Analysis of Endocannabinoid Signaling: Targeted Metabolite Identification and Quantification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keereetaweep, Jantana; Chapman, Kent D.

The endocannabinoidsN-arachidonoylethanolamide (or anandamide, AEA) and 2-arachidonoylglycerol (2-AG) belong to the larger groups ofN-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Along with AEA, several NAEs, for example,N-palmitoylethanolamine (PEA),N-stearoylethanolamine (SEA), andN-oleoylethanolamine (OEA) are also present in tissues, usually at much larger concentrations than AEA. Any perturbation that involves the endocannabinoid pathway may subsequently alter basal level or metabolism of these lipid mediators. Further,more » the altered levels of these molecules often reflect pathological conditions associated with tissue damage. Robust and sensitive methodologies to analyze these lipid mediators are essential to understanding how they act as endocannabinoids. Lastly, the recent advances in mass spectrometry allow researchers to develop lipidomics approaches and several methodologies have been proposed to quantify endocannabinoids in various biological systems.« less

Angiopellosis as an Alternative Mechanism of Cell Extravasation.

PubMed

Allen, Tyler A; Gracieux, David; Talib, Maliha; Tokarz, Debra A; Hensley, M Taylor; Cores, Jhon; Vandergriff, Adam; Tang, Junnan; de Andrade, James B M; Dinh, Phuong-Uyen; Yoder, Jeffrey A; Cheng, Ke

2017-01-01

Stem cells possess the ability to home in and travel to damaged tissue when injected intravenously. For the cells to exert their therapeutic effect, they must cross the blood vessel wall and enter the surrounding tissues. The mechanism of extravasation injected stem cells employ for exit has yet to be characterized. Using intravital microscopy and a transgenic zebrafish line Tg(fli1a:egpf) with GFP-expressing vasculature, we documented the detailed extravasation processes in vivo for injected stem cells in comparison to white blood cells (WBCs). While WBCs left the blood vessels by the standard diapedesis process, injected cardiac and mesenchymal stem cells underwent a distinct method of extravasation that was markedly different from diapedesis. Here, the vascular wall undergoes an extensive remodeling to allow the cell to exit the lumen, while the injected cell remains distinctively passive in activity. We termed this process Angio-pello-sis, which represents an alternative mechanism of cell extravasation to the prevailing theory of diapedesis. Stem Cells 2017;35:170-180 Video Highlight: https://youtu.be/i5EI-ZvhBps. © 2016 AlphaMed Press.

On the wetting properties of human stratum corneum epidermidis surface exposed to cold atmospheric-pressure pulsed plasma

NASA Astrophysics Data System (ADS)

Athanasopoulos, D.; Svarnas, P.; Ladas, S.; Kennou, S.; Koutsoukos, P.

2018-05-01

The Stratum corneum is the outermost layer of the skin, acting as a protective barrier of the epidermis, and its surface properties are directly related to the spreading of topically applied drugs and cosmetics. Numerous works have been devoted to the wettability of this layer over the past 70 years, but, despite the extensive application of atmospheric-pressure plasmas to dermatology, stratum corneum wettability with respect to plasma-induced species has never been considered. The present report assesses the treatment of human stratum corneum epidermidis by atmospheric-pressure pulsed cold plasma-jets for various time intervals and both chemical and morphological modifications are probed. The increase and saturation of the surface free energy due to functionalization are demonstrated, whereas prolonged treatment leads to tissue local disruption (tissue integrity is lost, and stratum corneum looks exfoliated, porous, and even thermally damaged). The latter point arises skepticism about the common practice of contacting atmospheric-pressure plasmas with skin without any previous precautions since the lost skin surface integrity may allow the penetration of pathogenic microorganisms.

Histochemical study of the elastic fibers in pathologic human temporomandibular joint discs.

PubMed

Leonardi, R; Villari, L; Bernasconi, G; Caltabiano, M

2001-10-01

This study investigated histochemically the elastic fibers in human temporomandibular joint (TMJ) discs with varying degrees of tissue degeneration/regeneration to determine whether there are differences that correlate with the histologic findings. Ten diseased human TMJ discs and 2 control specimens were studied histochemically by staining with Weigert's resorcin-fuchsin after oxidation with peracetic acid. This technique selectively stains elastic, elaunin, (pre-elastic), and oxytalan fibers. In TMJ discs with an abnormal collagen fiber arrangement, an increased number of oxytalan fibers could be observed, contrary to discs with scar-like tissue transformation in which oxytalan fibers were decreased in number. In discs showing tears and clefts, the oxytalan fibers run perpendicular to the defects, whereas elaunin and elastic fibers were mainly circumferentially arranged. In discs with chondroid metaplasia, elastic, elaunin, and oxytalan fibers were extensively detected. It is hypothesized that the elastic, elaunin, and oxytalan fibers found in severely damaged discs appear to ensure biomechanical compliance by reinforcing regions devoid of collagen bundles and thus function as shock absorbers of stretch and compression. Copyright 2001 American Association of Oral and Maxillofacial Surgeons

Lipidomic Analysis of Endocannabinoid Signaling: Targeted Metabolite Identification and Quantification

DOE PAGES

Keereetaweep, Jantana; Chapman, Kent D.

2016-01-01

The endocannabinoidsN-arachidonoylethanolamide (or anandamide, AEA) and 2-arachidonoylglycerol (2-AG) belong to the larger groups ofN-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Along with AEA, several NAEs, for example,N-palmitoylethanolamine (PEA),N-stearoylethanolamine (SEA), andN-oleoylethanolamine (OEA) are also present in tissues, usually at much larger concentrations than AEA. Any perturbation that involves the endocannabinoid pathway may subsequently alter basal level or metabolism of these lipid mediators. Further,more » the altered levels of these molecules often reflect pathological conditions associated with tissue damage. Robust and sensitive methodologies to analyze these lipid mediators are essential to understanding how they act as endocannabinoids. Lastly, the recent advances in mass spectrometry allow researchers to develop lipidomics approaches and several methodologies have been proposed to quantify endocannabinoids in various biological systems.« less

Lipidomic Analysis of Endocannabinoid Signaling: Targeted Metabolite Identification and Quantification

PubMed Central

Keereetaweep, Jantana; Chapman, Kent D.

2016-01-01

The endocannabinoids N-arachidonoylethanolamide (or anandamide, AEA) and 2-arachidonoylglycerol (2-AG) belong to the larger groups of N-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Along with AEA, several NAEs, for example, N-palmitoylethanolamine (PEA), N-stearoylethanolamine (SEA), and N-oleoylethanolamine (OEA) are also present in tissues, usually at much larger concentrations than AEA. Any perturbation that involves the endocannabinoid pathway may subsequently alter basal level or metabolism of these lipid mediators. Further, the altered levels of these molecules often reflect pathological conditions associated with tissue damage. Robust and sensitive methodologies to analyze these lipid mediators are essential to understanding how they act as endocannabinoids. The recent advances in mass spectrometry allow researchers to develop lipidomics approaches and several methodologies have been proposed to quantify endocannabinoids in various biological systems. PMID:26839710

A laser syringe aimed at delivering drug into the outer layer of human skin

NASA Astrophysics Data System (ADS)

Yoh, Jack J.; Jang, Hun-jae; Park, Mi-ae; Han, Tae-hee; Hah, Jung-moo

2012-07-01

A desire to eliminate hypodermic needle in transdermal drug delivery may now be realized. Imaging of the skin after injection of fluorescent probe and biotin via the bio-ballistic technique revealed the epidermal and dermal layers which were stained well below 60 μm underneath the abdominal skin of the guinea-pig. An extensive network of cells are shown in the deeper layer of the stained dermis as the distributed fluorescein isothiocyanate (FITC) dose is administered by repeated injection via the laser-based microjet. Here, we show our method of laser-based microjet drug delivery is capable of breaching guinea-pig's skin tissue and then delivering controlled dose of drug to the targeted region between 10 to 400 μm underneath the outermost layer of the skin. While minimizing pain and tissue damage by reducing the injection volume to ˜100 nl per pulse and the microjet diameter of half the conventional syringe needle in 100 μm, the optimally controlled delivery of liquid drug by the irradiated laser pulse is shown possible.

Nanobiotechnology promotes noninvasive high-intensity focused ultrasound cancer surgery.

PubMed

Chen, Yu; Chen, Hangrong; Shi, Jianlin

2015-01-07

The successful cancer eradication in a noninvasive manner is the ultimate objective in the fight against cancer. As a "bloodless scalpel," high-intensity focused ultrasound (HIFU) is regarded as one of the most promising and representative noninvasive therapeutic modalities for cancer surgery. However, large-scale clinical applications of HIFU are still in their infancy because of critical efficiency and safety issues which remain to be solved. Fortunately, recently developed nanobiotechnology provides an alternative efficient approach to improve such important issues in HIFU, especially for cancer therapy. This Research News presents the very recent exciting progresses on the elaborate design and fabrication of organic, inorganic, and organic/inorganic hybrid nanoparticles for enhancing the HIFU ablation efficiency against tumor tissues. It is highly expected that this Research News can arouse more extensive research enthusiasm on the development of functional nanomaterials for highly efficient HIFU-based synergistic therapy, which will give a promising noninvasive therapeutic modality for the successful cancer therapy with minimal damage to surrounding normal tissues, due to the noninvasive and site-specific therapeutic features of HIFU. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Defensive Armor of Potato Tubers: Nonpolar Metabolite Profiling, Antioxidant Assessment, and Solid-State NMR Compositional Analysis of Suberin-Enriched Wound-Healing Tissues

PubMed Central

Dastmalchi, Keyvan; Kallash, Linda; Wang, Isabel; Phan, Van C.; Huang, Wenlin; Serra, Olga; Stark, Ruth E.

2016-01-01

The cultivation, storage, and distribution of potato tubers are compromised by mechanical damage and suboptimal healing. To investigate wound-healing progress in cultivars with contrasting russeting patterns, metabolite profiles reported previously for polar tissue extracts were complemented by GC/MS measurements for nonpolar extracts and quantitative 13C NMR of interfacial solid suspensions. Potential marker compounds that distinguish cultivar type and wound-healing time point included fatty acids, fatty alcohols, alkanes, glyceryl esters, α,ω-fatty diacids, and hydroxyfatty acids. The abundant long-chain fatty acids in nonpolar extracts and solids from the smooth-skinned Yukon Gold cultivar suggested extensive suberin biopolymer formation; this hypothesis was supported by high proportions of arenes, alkenes, and carbonyl groups in the solid and among the polar markers. The absence of many potential marker classes in nonpolar Atlantic extracts and interfacial solids suggested a limited extent of suberization. Modest scavenging activities of all nonpolar extracts indicate that the majority of antioxidants produced in response to wounding are polar. PMID:26166447

Defensive Armor of Potato Tubers: Nonpolar Metabolite Profiling, Antioxidant Assessment, and Solid-State NMR Compositional Analysis of Suberin-Enriched Wound-Healing Tissues.

PubMed

Dastmalchi, Keyvan; Kallash, Linda; Wang, Isabel; Phan, Van C; Huang, Wenlin; Serra, Olga; Stark, Ruth E

2015-08-05

The cultivation, storage, and distribution of potato tubers are compromised by mechanical damage and suboptimal healing. To investigate wound-healing progress in cultivars with contrasting russeting patterns, metabolite profiles reported previously for polar tissue extracts were complemented by GC/MS measurements for nonpolar extracts and quantitative (13)C NMR of interfacial solid suspensions. Potential marker compounds that distinguish cultivar type and wound-healing time point included fatty acids, fatty alcohols, alkanes, glyceryl esters, α,ω-fatty diacids, and hydroxyfatty acids. The abundant long-chain fatty acids in nonpolar extracts and solids from the smooth-skinned Yukon Gold cultivar suggested extensive suberin biopolymer formation; this hypothesis was supported by high proportions of arenes, alkenes, and carbonyl groups in the solid and among the polar markers. The absence of many potential marker classes in nonpolar Atlantic extracts and interfacial solids suggested a limited extent of suberization. Modest scavenging activities of all nonpolar extracts indicate that the majority of antioxidants produced in response to wounding are polar.

TGF-.beta. antagonists as mitigators of radiation-induced tissue damage

DOEpatents

Barcellos-Hoff, Mary H.

1997-01-01

A method for treating tissue damage caused by radiation is described by use of a TGF-.beta. antagonist, such as an anti-TGF-.beta. antibody or a TGF-.beta. latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

TGF-{beta} antagonists as mitigators of radiation-induced tissue damage

DOEpatents

Barcellos-Hoff, M.H.

1997-04-01

A method for treating tissue damage caused by radiation is described by use of a TGF-{beta} antagonist, such as an anti-TGF-{beta} antibody or a TGF-{beta} latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

Divergent growth strategies between red algae and kelps influence biomechanical properties.

PubMed

Krumhansl, Kira A; Demes, Kyle W; Carrington, Emily; Harley, Christopher D G

2015-11-01

Morphology and material properties are the main components of the mechanical design of organisms, with species groups developing different optimization strategies in the context of their physical environment. For intertidal and subtidal seaweeds, possessing highly flexible and extensible tissues allows individuals to bend and reconfigure in flow, thereby reducing drag. Previous research has shown that aging may compromise these qualities. Tissue age increases with distance from the blade's meristem, which differs in its position on kelps and red algae. Here, we assess whether longitudinal patterns of blade material properties differ between these two algal groups according to tissue age. We performed tensile tests on tissues samples excised from various positions along the extent of blades in nine kelp species (basal growth) and 15 species of red algae (apical growth). We found that older tissues were less flexible and extensible than younger tissues in all species tested. As predicted, tissue near the basal meristem in kelp was more flexible and extensible than older tissue at the blade's distal end. The opposite pattern was observed for red algae, with the most flexible and extensible tissues found near the apical meristem at the distal ends of blades. We propose that divergent patterns in the distribution of material properties along blades may have different consequences for the performance of kelps and red algae. The positioning of younger tissues at the blade base for kelps may enable these species to attain larger body sizes in wave-swept habitats. © 2015 Botanical Society of America.

A novel minimal invasive mouse model of extracorporeal circulation.

PubMed

Luo, Shuhua; Tang, Menglin; Du, Lei; Gong, Lina; Xu, Jin; Chen, Youwen; Wang, Yabo; Lin, Ke; An, Qi

2015-01-01

Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.

A Novel Minimal Invasive Mouse Model of Extracorporeal Circulation

PubMed Central

Luo, Shuhua; Tang, Menglin; Du, Lei; Gong, Lina; Xu, Jin; Chen, Youwen; Wang, Yabo; Lin, Ke; An, Qi

2015-01-01

Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury. PMID:25705092

Collagen in Human Tissues: Structure, Function, and Biomedical Implications from a Tissue Engineering Perspective

NASA Astrophysics Data System (ADS)

Balasubramanian, Preethi; Prabhakaran, Molamma P.; Sireesha, Merum; Ramakrishna, Seeram

The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30-35% of the whole-body protein. "Collagen" is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5-3.5 nm wide), collagen fibers (50-70 nm wide), and collagen bundles (150-250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for which collagen scaffolds are currently being applied.

No post-no core approach to restore severely damaged posterior teeth: An up to 10-year retrospective study of documented endocrown cases.

PubMed

Belleflamme, Marcia M; Geerts, Sabine O; Louwette, Marie M; Grenade, Charlotte F; Vanheusden, Alain J; Mainjot, Amélie K

2017-08-01

The objectives of the present study were to (1) retrospectively evaluate documented cases of ceramic and composite endocrowns performed using immediate dentin sealing (IDS); (2) correlate failures with clinical parameters such as tooth preparation characteristics and occlusal parameters. 99 documented cases of endocrowns were evaluated after a mean observation period of 44.7±34.6months. A classification of restorations was established in function of the level of damage of residual tooth tissues after preparation, from 1 to 3. Evaluation was performed according to FDI criteria and endodontic outcomes were analyzed. Occlusal risk factors were examined and fractographic analysis was performed in case of fracture. 48.4% of patients were shown to present occlusal risk factors. 75.8% of restorations were Class 3 endocrowns. 56.6% were performed on molars, 41.4% on premolars and 2.0% on canines. 84.8% were performed in lithium-disilicate glass-ceramic and 12.1% in Polymer-Infiltrated Ceramic Network (PICN) material. The survival and success rates of endocrowns were 99.0% and 89.9% respectively, while the 10-year Kaplan-Meier estimated survival and success rates were 98.8% and 54.9% respectively. Ten failures were detected: periodontal disease (n=3), endocrown debonding (n=2), minor chipping (n=2), caries recurrence (n=2) and major fractures (n=1). Due to the reduced amount of failures, no statistical correlation could be established with clinical parameters. Endocrowns were shown to constitute a reliable approach to restore severely damaged molars and premolars, even in the presence of extensive coronal tissue loss or occlusal risk factors, such as bruxism or unfavorable occlusal relationships. Practitioners should consider the endocrown instead of the post and core approach to restore severely damaged non-vital posterior teeth. This minimally invasive solution reduces the risk of catastrophic failures and is easily performed. The use of IDS procedure and lithium-disilicate glass-ceramic as prosthesis material gave very good results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cartilage tissue engineering approaches applicable in orthopaedic surgery: the past, the present, and the future.

PubMed

Khan, Wasim S; Hardingham, Timothy E

2012-01-01

Tissue is frequently damaged or lost in injury and disease. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in cartilage repair. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells and cartilage being a relatively simpler tissue to engineer. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. In this paper we discuss the structure, function and embryology of cartilage and osteoarthritis. This is followed by a review of current treatment strategies for the repair of cartilage and the use of tissue engineering.

Activation of EGFR and ERBB2 by Helicobacter pylori results in survival of gastric epithelial cells with DNA damage.

PubMed

Chaturvedi, Rupesh; Asim, Mohammad; Piazuelo, M Blanca; Yan, Fang; Barry, Daniel P; Sierra, Johanna Carolina; Delgado, Alberto G; Hill, Salisha; Casero, Robert A; Bravo, Luis E; Dominguez, Ricardo L; Correa, Pelayo; Polk, D Brent; Washington, M Kay; Rose, Kristie L; Schey, Kevin L; Morgan, Douglas R; Peek, Richard M; Wilson, Keith T

2014-06-01

The gastric cancer-causing pathogen Helicobacter pylori up-regulates spermine oxidase (SMOX) in gastric epithelial cells, causing oxidative stress-induced apoptosis and DNA damage. A subpopulation of SMOX(high) cells are resistant to apoptosis, despite their high levels of DNA damage. Because epidermal growth factor receptor (EGFR) activation can regulate apoptosis, we determined its role in SMOX-mediated effects. SMOX, apoptosis, and DNA damage were measured in gastric epithelial cells from H. pylori-infected Egfr(wa5) mice (which have attenuated EGFR activity), Egfr wild-type mice, or in infected cells incubated with EGFR inhibitors or deficient in EGFR. A phosphoproteomic analysis was performed. Two independent tissue microarrays containing each stage of disease, from gastritis to carcinoma, and gastric biopsy specimens from Colombian and Honduran cohorts were analyzed by immunohistochemistry. SMOX expression and DNA damage were decreased, and apoptosis increased in H. pylori-infected Egfr(wa5) mice. H. pylori-infected cells with deletion or inhibition of EGFR had reduced levels of SMOX, DNA damage, and DNA damage(high) apoptosis(low) cells. Phosphoproteomic analysis showed increased EGFR and erythroblastic leukemia-associated viral oncogene B (ERBB)2 signaling. Immunoblot analysis showed the presence of a phosphorylated (p)EGFR-ERBB2 heterodimer and pERBB2; knockdown of ErbB2 facilitated apoptosis of DNA damage(high) apoptosis(low) cells. SMOX was increased in all stages of gastric disease, peaking in tissues with intestinal metaplasia, whereas pEGFR, pEGFR-ERBB2, and pERBB2 were increased predominantly in tissues showing gastritis or atrophic gastritis. Principal component analysis separated gastritis tissues from patients with cancer vs those without cancer. pEGFR, pEGFR-ERBB2, pERBB2, and SMOX were increased in gastric samples from patients whose disease progressed to intestinal metaplasia or dysplasia, compared with patients whose disease did not progress. In an analysis of gastric tissues from mice and patients, we identified a molecular signature (based on levels of pEGFR, pERBB2, and SMOX) for the initiation of gastric carcinogenesis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effect of damage on elastically tailored composite laminates

NASA Technical Reports Server (NTRS)

Armanios, Erian; Badir, Ashraf; Berdichevsky, Victor

1991-01-01

A variationally consistent theory is derived in order to predict the response of anisotropic thin-walled closed sections subjected to axial load, torsion and bending. The theory is valid for arbitrary cross-sections made of laminated composite materials with variable thickness and stiffness. Closed form expressions for the stiffness coefficients are provided as integrals in terms of lay-ups parameters and cross-sectional geometry. A comparison of stiffness coefficients and response with finite element predictions and a closed form solution is performed. The theory is applied to the investigation of the effect of damage on the extension-twist coupling in a thin-walled closed section beam. The damage is simulated as a progressive ply-by-ply failure. Results show that damage can have a significant effect on the extension-twist coupling.

Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

PubMed Central

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

2014-01-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage. PMID:25033386

Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

PubMed

Aihara, Eitaro; Closson, Chet; Matthis, Andrea L; Schumacher, Michael A; Engevik, Amy C; Zavros, Yana; Ottemann, Karen M; Montrose, Marshall H

2014-07-01

Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.

Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakker, Akke, E-mail: akke.bakker@amc.uva.nl; Kolff, M. Willemijn; Holman, Rebecca

Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79more » sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.« less

Mechanical factors relate to pain in knee osteoarthritis.

PubMed

Maly, Monica R; Costigan, Patrick A; Olney, Sandra J

2008-07-01

Pain experienced by people with knee osteoarthritis is related to psychosocial factors and damage to articular tissues and/or the pain pathway itself. Mechanical factors have been speculated to trigger this pain experience; yet mechanics have not been identified as a source of pain in this population. The purpose of this study was to identify whether mechanics could explain variance in pain intensity in people with knee osteoarthritis. Data from 53 participants with physician-diagnosed knee osteoarthritis (mean age=68.5 years; standard deviation=8.6 years) were analyzed. Pain intensity was reported on the Western Ontario and McMaster Universities Osteoarthritis Index. Mechanical measures included weight-bearing varus-valgus alignment, body mass index and isokinetic quadriceps torque. Gait analysis captured the range of adduction-abduction angle, range of flexion-extension angle and external knee adduction moment during level walking. Pain intensity was significantly related to the dynamic range of flexion-extension during gait and body mass index. A total of 29% of the variance in pain intensity was explained by mechanical variables. The range of flexion-extension explained 18% of variance in pain intensity. Body mass index added 11% to the model. The knee adduction moment was unrelated to pain intensity. The findings support that mechanical factors are related to knee osteoarthritis pain. Because limitations in flexion-extension range of motion and body size are modifiable factors, future research could examine whether interventions targeting these mechanics would facilitate pain management.

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress

PubMed Central

Antonucci, Laura; Fagman, Johan B.; Kim, Ju Youn; Todoric, Jelena; Gukovsky, Ilya; Mackey, Mason; Ellisman, Mark H.; Karin, Michael

2015-01-01

Pancreatic acinar cells possess very high protein synthetic rates as they need to produce and secrete large amounts of digestive enzymes. Acinar cell damage and dysfunction cause malnutrition and pancreatitis, and inflammation of the exocrine pancreas that promotes development of pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic neoplasm. The cellular and molecular mechanisms that maintain acinar cell function and whose dysregulation can lead to tissue damage and chronic pancreatitis are poorly understood. It was suggested that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis, but it is unknown whether impaired autophagy is a cause or a consequence of pancreatitis. To address this question, we generated Atg7Δpan mice that lack the essential autophagy-related protein 7 (ATG7) in pancreatic epithelial cells. Atg7Δpan mice exhibit severe acinar cell degeneration, leading to pancreatic inflammation and extensive fibrosis. Whereas ATG7 loss leads to the expected decrease in autophagic flux, it also results in endoplasmic reticulum (ER) stress, accumulation of dysfunctional mitochondria, oxidative stress, activation of AMPK, and a marked decrease in protein synthetic capacity that is accompanied by loss of rough ER. Atg7Δpan mice also exhibit spontaneous activation of regenerative mechanisms that initiate acinar-to-ductal metaplasia (ADM), a process that replaces damaged acinar cells with duct-like structures. PMID:26512112

Gadolinium-based nanoparticles to improve the hadrontherapy performances.

PubMed

Porcel, Erika; Tillement, Olivier; Lux, François; Mowat, Pierre; Usami, Noriko; Kobayashi, Katsumi; Furusawa, Yoshiya; Le Sech, Claude; Li, Sha; Lacombe, Sandrine

2014-11-01

Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

PubMed

Sanbe, Toshihiro; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Tamaki, Naofumi; Yamamoto, Tatsuo

2007-11-01

A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene.

PubMed

Bagchi, D; Bagchi, M; Stohs, S J

2001-06-01

Chromium (VI) is a widely used industrial chemical, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome, and wood treatment. On the contrary, chromium (III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been demonstrated to exhibit a significant number of health benefits in rodents and humans. However, the cause for the hexavalent chromium to induce cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that chromium (VI) induces an oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following chromium (VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. In this paper, we have demonstrated concentration- and time-dependent effects of sodium dichromate (chromium (VI) or Cr (VI)) on enhanced production of superoxide anion and hydroxyl radicals, changes in intracellular oxidized states as determined by laser scanning confocal microscopy, DNA fragmentation and apoptotic cell death (by flow cytometry) in human peripheral blood mononuclear cells. These results were compared with the concentration-dependent effects of chromium (VI) on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Chromium (VI)-induced enhanced production of ROS, as well as oxidative tissue and DNA damage were observed in these cells. More pronounced effect was observed on chronic myelogenous leukemic K562 cells and J774A.1 murine macrophage cells. Furthermore, we have assessed the effect of a single oral LD50 dose of chromium (VI) on female C57BL/6Ntac and p53-deficient C57BL/6TSG p53 mice on enhanced production of superoxide anion, lipid peroxidation and DNA fragmentation in the hepatic and brain tissues. Chromium (VI)-induced more pronounced oxidative damage in p53 deficient mice. This in vivo study highlighted that apoptotic regulatory protein p53 may play a major role in chromium (VI)-induced oxidative stress and toxicity. Taken together, oxidative stress and oxidative tissue damage, and a cascade of cellular events including modulation of apoptotic regulatory gene p53 are involved in chromium (VI)-induced toxicity and carcinogenesis.

It takes a tissue to make a tumor: epigenetics, cancer and the microenvironment

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

2001-01-01

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises its ability to suppress carcinogenesis.

Research progress on reconstruction of meniscus in tissue engineering.

PubMed

Zhang, Yu; Li, Pengsong; Wang, Hai; Wang, Yiwei; Song, Kedong; Li, Tianqing

2017-05-01

Meniscus damages are most common in sports injuries and aged knees. One third of meniscus lesions are known as white-white zone or nonvascular zones, which are composed of chondrocyte and extracellular matrix composition only. Due to low vascularization the ability of regeneration in such zones is inherently limited, leading to impossible self-regeneration post damage. Meniscus tissue engineering is known for emerging techniques for treating meniscus damage, but there are questions that need to be answered, including an optimal and suitable cell source, the usability of growth factor, the selectivity of optimal biomaterial scaffolds as well as the technology for improving partial reconstruction of meniscus tears. This review focuses on current research on the in vitro reconstruction of the meniscus using tissue engineering methods with the expectation to develop a series of tissue engineering meniscus products for the benefit of sports injuries. With rapid growth of clinical demand, the key breakthrough of meniscus tissue engineering research foundation is enlarged to a great extent. This review discusses aspects of meniscus tissue engineering, which is relative to the clinical treatment of meniscus injuries for further support and establishment of fundamental and clinical studies.

78 FR 77697 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

...; no future agency need; 800 sq. ft.; office; significant water damage; repairs a must; asbestos/lead... damage to Admin. bldg.; bathroom; major repairs required; contamination; asbestos; contact GSA for more... future agency USE; 1,014 sq. ft.; 108+ months vacant; extensive termite damage; asbestos; mold, lead...

Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial.

PubMed

Gagliano-Jucá, Thiago; Moreno, Ronilson A; Zaminelli, Tiago; Napolitano, Mauro; Magalhães, Antônio Frederico N; Carvalhaes, Aloísio; Trevisan, Miriam S; Wallace, John L; De Nucci, Gilberto

2016-06-04

Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen. Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers. ClinicalTrials.gov, NCT02632812 . Registered 14 December 2015.

Greater inadvertent muscle damage in direct anterior approach when compared with the direct superior approach for total hip arthroplasty.

PubMed

Amanatullah, D F; Masini, M A; Roger, D J; Pagnano, M W

2016-08-01

We wished to quantify the extent of soft-tissue damage sustained during minimally invasive total hip arthroplasty through the direct anterior (DA) and direct superior (DS) approaches. In eight cadavers, the DA approach was performed on one side, and the DS approach on the other, a single brand of uncemented hip prosthesis was implanted by two surgeons, considered expert in their surgical approaches. Subsequent reflection of the gluteus maximus allowed the extent of muscle and tendon damage to be measured and the percentage damage to each anatomical structure to be calculated. The DA approach caused substantially greater damage to the gluteus minimus muscle and tendon when compared with the DS approach (t-test, p = 0.049 and 0.003, respectively). The tensor fascia lata and rectus femoris muscles were damaged only in the DA approach. There was no difference in the amount of damage to the gluteus medius muscle and tendon, piriformis tendon, obturator internus tendon, obturator externus tendon or quadratus femoris muscle between approaches. The posterior soft-tissue releases of the DA approach damaged the gluteus minimus muscle and tendon, piriformis tendon and obturator internus tendon. The DS approach caused less soft-tissue damage than the DA approach. However the clinical relevance is unknown. Further clinical outcome studies, radiographic evaluation of component position, gait analyses and serum biomarker levels are necessary to evaluate and corroborate the safety and efficacy of the DS approach. Cite this article: Bone Joint J 2016;98-B1036-42. ©2016 The British Editorial Society of Bone & Joint Surgery.

Plant lesions promote the rapid multiplication of Escherichia coli O157:H7 on post-harvest lettuce

USDA-ARS?s Scientific Manuscript database

Several outbreaks of Escherichia coli O157:H7 (EcO157) infections have been associated with minimally processed leafy vegetables in the U.S. Harvesting and processing cause plant tissue damage. In order to assess the role of plant tissue damage in the contamination of leafy greens with EcO157, the e...

Observational analysis on inflammatory reaction to talc pleurodesis: Small and large animal model series review

PubMed Central

Vannucci, Jacopo; Bellezza, Guido; Matricardi, Alberto; Moretti, Giulia; Bufalari, Antonello; Cagini, Lucio; Puma, Francesco; Daddi, Niccolò

2018-01-01

Talc pleurodesis has been associated with pleuropulmonary damage, particularly long-term damage due to its inert nature. The present model series review aimed to assess the safety of this procedure by examining inflammatory stimulus, biocompatibility and tissue reaction following talc pleurodesis. Talc slurry was performed in rabbits: 200 mg/kg checked at postoperative day 14 (five models), 200 mg/kg checked at postoperative day 28 (five models), 40 mg/kg, checked at postoperative day 14 (five models), 40 mg/kg checked at postoperative day 28 (five models). Talc poudrage was performed in pigs: 55 mg/kg checked at postoperative day 60 (18 models). Tissue inspection and data collection followed the surgical pathology approach currently used in clinical practice. As this was an observational study, no statistical analysis was performed. Regarding the rabbit model (Oryctolagus cunicoli), the extent of adhesions ranged between 0 and 30%, and between 0 and 10% following 14 and 28 days, respectively. No intraparenchymal granuloma was observed whereas, pleural granulomas were extensively encountered following both talc dosages, with more evidence of visceral pleura granulomas following 200 mg/kg compared with 40 mg/kg. Severe florid inflammation was observed in 2/10 cases following 40 mg/kg. Parathymic, pericardium granulomas and mediastinal lymphadenopathy were evidenced at 28 days. At 60 days, from rare adhesions to extended pleurodesis were observed in the pig model (Sus Scrofa domesticus). Pleural granulomas were ubiquitous on visceral and parietal pleurae. Severe spotted inflammation among the adhesions were recorded in 15/18 pigs. Intraparenchymal granulomas were observed in 9/18 lungs. Talc produced unpredictable pleurodesis in both animal models with enduring pleural inflammation whether it was performed via slurry or poudrage. Furthermore, talc appeared to have triggered extended pleural damage, intraparenchymal nodules (porcine poudrage) and mediastinal migration (rabbit slurry). PMID:29403549

Microjet-assisted dye-enhanced diode laser ablation of cartilaginous tissue

NASA Astrophysics Data System (ADS)

Pohl, John; Bell, Brent A.; Motamedi, Massoud; Frederickson, Chris J.; Wallace, David B.; Hayes, Donald J.; Cowan, Daniel

1994-08-01

Recent studies have established clinical application of laser ablation of cartilaginous tissue. The goal of this study was to investigate removal of cartilaginous tissue using diode laser. To enhance the interaction of laser light with tissue, improve the ablation efficiency and localize the extent of laser-induced thermal damage in surrounding tissue, we studied the use of a novel delivery system developed by MicroFab Technologies to dispense a known amount of Indocyanine Green (ICG) with a high spatial resolution to alter the optical properties of the tissue in a controlled fashion. Canine intervertebral disks were harvested and used within eight hours after collection. One hundred forty nL of ICG was topically applied to both annulus and nucleus at the desired location with the MicroJet prior to each irradiation. Fiber catheters (600 micrometers ) were used and positioned to irradiate the tissue with a 0.8 mm spot size. Laser powers of 3 - 10 W (Diomed, 810 nm) were used to irradiate the tissue with ten pulses (200 - 500 msec). Discs not stained with ICG were irradiated as control samples. Efficient tissue ablation (80 - 300 micrometers /pulse) was observed using ICG to enhance light absorption and confine thermal damage while there was no observable ablation in control studied. The extent of tissue damage observed microscopically was limited to 50 - 100 micrometers . The diode laser/Microjet combination showed promise for applications involving removal of cartilaginous tissue. This procedure can be performed using a low power compact diode laser, is efficient, and potentially more economical compared to procedures using conventional lasers.

Tissue engineering in periodontal tissue.

PubMed

Iwata, Takanori; Yamato, Masayuki; Ishikawa, Isao; Ando, Tomohiro; Okano, Teruo

2014-01-01

Periodontitis, a recognized disease worldwide, is bacterial infection-induced inflammation of the periodontal tissues that results in loss of alveolar bone. Once it occurs, damaged tissue cannot be restored to its original form, even if decontaminating treatments are performed. For more than half a century, studies have been conducted to investigate true periodontal regeneration. Periodontal regeneration is the complete reconstruction of the damaged attachment apparatus, which contains both hard tissue (alveolar bone and cementum) and soft tissue (periodontal ligament). Several treatments, including bone grafts, guided tissue regeneration with physical barriers for epithelial cells, and growth factors have been approved for clinical use; however, their indications and outcomes are limited. To overcome these limitations, the concept of "tissue engineering" was introduced. Combination treatment using cells, growth factors, and scaffolds, has been studied in experimental animal models, and some studies have been translated into clinical trials. In this review, we focus on recent progressive tissue engineering studies and discuss future perspectives on periodontal regeneration. Copyright © 2013 Wiley Periodicals, Inc.

In situ FTIR microspectroscopy of extravasated blood-damaged brain tissue

NASA Astrophysics Data System (ADS)

Wetzel, David L.; Le Vine, Steven M.

1994-01-01

Fourier transform infrared (FT-IR) microspectroscopy enables the collection of infrared spectra from microscopic regions of tissue sections. The objectives of this study were to utilize FT-IR microspectroscopy to analyze the spatial distribution of chemical changes that result from the extravasation of blood into the brain and to determine if products of free radical damage are associated with the damaged areas. An animal model that involves the injection of blood into the white matter of rat brains was used. Maps depicting the relative concentrations of chemical functional groups of lesioned sites and surrounding areas were made. Significant decreases were observed for CH2, C equals O, P equals O, and HO-C-H functional groups at the lesioned site and penumbra regions compared to the neighboring normal tissue areas.

Effects of hydrogen-rich water on aging periodontal tissues in rats

PubMed Central

Tomofuji, Takaaki; Kawabata, Yuya; Kasuyama, Kenta; Endo, Yasumasa; Yoneda, Toshiki; Yamane, Mayu; Azuma, Tetsuji; Ekuni, Daisuke; Morita, Manabu

2014-01-01

Oxidative damage is involved in age-related inflammatory reactions. The anti-oxidative effects of hydrogen-rich water suppress oxidative damage, which may aid in inhibiting age-related inflammatory reactions. We investigated the effects of drinking hydrogen-rich water on aging periodontal tissues in healthy rats. Four-month-old male Fischer 344 rats (n = 12) were divided into two groups: the experimental group (hydrogen-rich water treatment) and the control group (distilled water treatment). The rats consumed hydrogen-rich water or distilled water until 16 months of age. The experimental group exhibited lower periodontal oxidative damage at 16 months of age than the control group. Although protein expression of interleukin-1β did not differ, gene expression of Nod-like receptor protein 3 inflammasomes was activated in periodontal tissues from the experimental group as compared with the control group. Drinking hydrogen-rich water is proposed to have anti-aging effects on periodontal oxidative damage, but not on inflammatory reactions in healthy rats. PMID:24985521

Lymphatic system of the pancreas.

PubMed

O'Morchoe, C C

A network of lymphatic vessels exists within the pancreas. The majority of vessels forming this network lie in the interlobular septa of connective tissue that subdivide the pancreas into lobes and lobules. Peripheral extensions of these interlobular lymphatics can be found within the lobules, but these intralobular lymphatics are relatively sparse. In the main, the intimate relationships of these internal pancreatic lymphatics are with the blood vessels and associated connective tissue. However in random areas, both intra- and interlobular lymphatics come into close relationship with acinar cells. Rarely are there lymphatics associated with islets of Langerhans, and then only where lymphatic vessels in connective tissue septa pass close to a pancreatic lobule that contains an islet at its periphery. Intra- and interlobular lymphatics are similar in structure. Both are thin walled having an endothelial lining and a delicate component of connective tissue. The pattern of interendothelial cell contacts and the sparsity of gaps between adjacent cells suggest that fluid movement through the intracytoplasmic system of vesicles is important in lymph formation in the pancreas. However intercellular transport is also likely to occur by a dynamic process involving fluid movement through dilatations between cells from interstitium to lymphatic lumen. Both exocrine and endocrine secretions of the pancreas may enter thoracic duct lymph directly in pancreatic lymph, but in normal circumstances this route of entry is not quantitatively important. The structural relationships between lymphatics and pancreatic parenchymal cells also make clear that lymph is not a significant pathway for their secretory products. Rather, the arrangement of lymphatics in the pancreas supports the view that lymph is primarily the drainage medium for substances that, for whatever reason, enter the interstitium. In addition, the low flow of lymph compared with that of plasma lends credence to the view that lymph is not a functionally important pathway for endocrine secretions from the pancreas to reach the blood. Both structural and functional evidence suggests that the proper functioning of the lymphatic system is of critical importance in the homeostasis of the pancreas. The lymphatic system of the pancreas, like that in other organs, is essential in the removal of excess fluid from the interstitium. In this sense, the lymphatics may be considered to serve as an overflow, protective, or safety system. When the system is inadequate or its capacity is exceeded, as in inflammation of the pancreas, exocrine secretions entering the interstitium are not cleared and the proteolytic enzymes cause major damage to the tissue. This, in turn, exacerbates the edema, accentuates the inability of lymphatics to drain the fluid, and results in further damage. The fibrosis that ensues damages the lymphatics either directly or through stricture of the surrounding connective tissue. In consequence, they become inadequate at an even earlier stage in subsequent attacks of inflammation and thereby predispose to chronic and recurrent pancreatitis. The larger interlobular lymphatics formed by the junction of their tributaries emerge upon the surface of the pancreas. There they travel primarily with blood vessels and stream toward a ring of lymph nodes that intimately surrounds the pancreas. A second system of nodes extensively involved in drainage from the pancreas is related to the front and sides of the aorta from the level of the celiac trunk to the origin of the superior mesenteric artery. This second set of nodes receives lymph either directly from the pancreas or indirectly from the first echelon of nodes that rings the organ. Although there is general agreement on the disposition of the groups within these sets of nodes, confusion results from the different classifications used by various authors. These classifications range from being purely descriptive, through an alpha and num

Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa.

PubMed

Lee, Yann-Leei; Obiako, Boniface; Gorodnya, Olena M; Ruchko, Mykhaylo V; Kuck, Jamie L; Pastukh, Viktor M; Wilson, Glenn L; Simmons, Jon D; Gillespie, Mark N

2017-07-01

Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal Pseudomonas aeruginosa (strain 103; PA103)-induced ALI and MOSF. Relative to controls, animals given PA103 displayed increases in lung vascular filtration coefficient accompanied by transient lung tissue oxidative mtDNA damage and variable changes in mtDNA copy number without evidence of nuclear DNA damage. The approximate 40% of animals surviving 24 h after bacterial administration exhibited multiple organ dysfunction, manifest as increased serum and tissue-specific indices of kidney and liver failure, along with depressed heart rate and blood pressure. While administration of mt-targeted Ogg1 to control animals was innocuous, the active fusion protein, but not a DNA repair-deficient mutant, prevented bacteria-induced increases in lung tissue oxidative mtDNA damage, failed to alter mtDNA copy number, and attenuated lung endothelial barrier degradation. These changes were associated with suppression of liver, kidney, and cardiovascular dysfunction and with decreased 24 h mortality. Collectively, the present findings indicate that oxidative mtDNA damage to lung tissue initiates PA103-induced ALI and MOSF in rats.

Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in partial-thickness scald burns in mice.

PubMed

Bayliss, Jill; Delarosa, Sara; Wu, Jianfeng; Peterson, Jonathan R; Eboda, Oluwatobi N; Su, Grace L; Hemmila, Mark; Krebsbach, Paul H; Cederna, Paul S; Wang, Stewart C; Xi, Chuanwu; Levi, Benjamin

2014-01-01

Extracellular adenosine triphosphate (ATP), present in thermally injured tissue, modulates the inflammatory response and causes significant tissue damage. The authors hypothesize that neutrophil infiltration and ensuing tissue necrosis would be mitigated by removing ATP-dependent signaling at the burn site. Mice were subjected to 30% TBSA partial-thickness scald burn by dorsal skin immersion in a water bath at 60 or 20°C (nonburn controls). In the treatment arm, an ATP hydrolyzing enzyme, apyrase, was applied directly to the site immediately after injury. Skin was harvested after 24 hours and 5 days for hematoxylin and eosin stain, elastase, and Ki-67 staining. Tumor necrosis factor (TNF)-α and interferon (IFN)-β expression were measured through quantitative real-time polymerase chain reaction. At 24 hours, the amount of neutrophil infiltration was different between the burn and burn + apyrase groups (P < .001). Necrosis was less extensive in the apyrase group when compared with the burn group at 24 hours and 5 days. TNF-α and IFN-β expression at 24 hours in the apyrase group was lower than in the burn group (P < .05). However, Ki-67 signaling was not significantly different among the groups. The results of this study support the role of extracellular ATP in neutrophil activity. The authors demonstrate that ATP hydrolysis at the burn site allays the neutrophil response to thermal injury and reduces tissue necrosis. This decrease in inflammation and tissue necrosis is at least partially because of TNF-α and IFN-β signaling. Apyrase could be used as topical inflammatory regulators to quell the injury caused by inflammation.

Neural tissue engineering: Bioresponsive nanoscaffolds using engineered self-assembling peptides.

PubMed

Koss, K M; Unsworth, L D

2016-10-15

Rescuing or repairing neural tissues is of utmost importance to the patient's quality of life after an injury. To remedy this, many novel biomaterials are being developed that are, ideally, non-invasive and directly facilitate neural wound healing. As such, this review surveys the recent approaches and applications of self-assembling peptides and peptide amphiphiles, for building multi-faceted nanoscaffolds for direct application to neural injury. Specifically, methods enabling cellular interactions with the nanoscaffold and controlling the release of bioactive molecules from the nanoscaffold for the express purpose of directing endogenous cells in damaged or diseased neural tissues is presented. An extensive overview of recently derived self-assembling peptide-based materials and their use as neural nanoscaffolds is presented. In addition, an overview of potential bioactive peptides and ligands that could be used to direct behaviour of endogenous cells are categorized with their biological effects. Finally, a number of neurotrophic and anti-inflammatory drugs are described and discussed. Smaller therapeutic molecules are emphasized, as they are thought to be able to have less potential effect on the overall peptide self-assembly mechanism. Options for potential nanoscaffolds and drug delivery systems are suggested. Self-assembling nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. The combination of the existing knowledge on bioactive motifs for neural engineering and the self-assembling propensity of peptides is discussed in specific reference to neural tissue engineering. Copyright © 2016. Published by Elsevier Ltd.

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

PubMed

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

Alternative erythropoietin-mediated signaling prevents secondary microvascular thrombosis and inflammation within cutaneous burns

PubMed Central

Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Vitalo, Antonia G.; Brines, Michael; Cerami, Anthony; Berthiaume, Francois; Yarmush, Martin L.

2013-01-01

Alternate erythropoietin (EPO)–mediated signaling via the heteromeric receptor composed of the EPO receptor and the β-common receptor (CD131) exerts the tissue-protective actions of EPO in various types of injuries. Herein we investigated the effects of the EPO derivative helix beta surface peptide (synonym: ARA290), which specifically triggers alternate EPO-mediated signaling, but does not bind the erythropoietic EPO receptor homodimer, on the progression of secondary tissue damage following cutaneous burns. For this purpose, a deep partial thickness cutaneous burn injury was applied on the back of mice, followed by systemic administration of vehicle or ARA290 at 1, 12, and 24 h postburn. With vehicle-only treatment, wounds exhibited secondary microvascular thrombosis within 24 h postburn, and subsequent necrosis of the surrounding tissue, thus converting to a full-thickness injury within 48 h. On the other hand, when ARA290 was systemically administered, patency of the microvasculature was maintained. Furthermore, ARA290 mitigated the innate inflammatory response, most notably tumor necrosis factor-alpha–mediated signaling. These findings correlated with long-term recovery of initially injured yet viable tissue components. In conclusion, ARA290 may be a promising therapeutic approach to prevent the conversion of partial- to full-thickness burn injuries. In a clinical setting, the decrease in burn depth and area would likely reduce the necessity for extensive surgical debridement as well as secondary wound closure by means of skin grafting. This use of ARA290 is consistent with its tissue-protective properties previously reported in other models of injury, such as myocardial infarction and hemorrhagic shock. PMID:23401545

Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

NASA Technical Reports Server (NTRS)

Torres, Samantha M.; Schreurs, Ann-Sofie; Truong, Tiffany A.; Tahimic, Candice; Globus, Ruth

2017-01-01

Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

Clinical Management of Salivary Gland Hypofunction and Xerostomia in Head-and-Neck Cancer Patients: Successes and Barriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vissink, Arjan; Mitchell, James B.; Baum, Bruce J.

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Design of optimal hyperthermia protocols for prostate cancer by controlling HSP expression through computer modeling (Invited Paper)

NASA Astrophysics Data System (ADS)

Rylander, Marissa N.; Feng, Yusheng; Diller, Kenneth; Bass, J.

2005-04-01

Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

INHIBITION OF FRIED MEAT-INDUCED DNA DAMAGE: A DIETARY INTERVENTION STUDY IN HUMANS

EPA Science Inventory

Dietary exposures have been implicated as risk factors in colorectal cancer. Such agents may act by causing DNA damage or may be protective against DNA damage. The effects of dietary exposures in causing or preventing damage have not been assessed directly in colon tissues. In th...

Regeneration of eye tissues is modulated by altered levels of gravity at 1g, 2g, and in microgravity during spaceflight

NASA Astrophysics Data System (ADS)

Grigoryan, Eleonora; Almeida, Eduardo; Mitashov, Victor

The pursuit of human space exploration requires detailed knowledge of microgravity-related changes in fundamental biological processes, and their effects on health. Normal regeneration of organs and tissues is one such fundamental process that allows maintenance of vitality and function of living organisms. Animal models of tissue regeneration include the newt (Pleurodeles waltl, Urodela) eye, which has been extensively used by our team in Russian Bion and Foton microgravity experiments since 1985, and in recent NASA 2.5 meter diameter centrifuge hypergravity experiments. In total, these experiments allow us to draw several broad conclusions: Newt lens regeneration is significantly altered in microgravity and hypergravity relative to 1g controls. Lenses formed in microgravity are larger and more developed than those regenerated in 1g controls; Microgravity alterations of lens regeneration can persist after spaceflight, and continue to affect repeated removal and regeneration of the lens after return to 1g; Microgravity increases the numbers of early stage regenerative proliferating BrdU-labeled cells in dorsal iris progenitors and in the lens regenerate. Regeneration under hypergravity conditions at 2g inhibits lens regeneration, and often causes retinal detachment. Molecular mechanisms regulating lens regeneration rate include FGF2 signaling, (a key pathway for eye tissue development and regeneration), and an expression of stress-related proteins - HSPs. In conclusion, regeneration of lens and other eye tissues in the newt is sensitive to, and regulated by the level of gravity mechanotransduction and developmental signaling pathways, with microgravity favoring stem cell progenitor proliferation, and gravity at 1g promoting terminal differentiation, while hypergravity at 2g often causes damage of delicate regenerating tissues.

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model.

PubMed

Jain, Sumeet V; Kollisch-Singule, Michaela; Satalin, Joshua; Searles, Quinn; Dombert, Luke; Abdel-Razek, Osama; Yepuri, Natesh; Leonard, Antony; Gruessner, Angelika; Andrews, Penny; Fazal, Fabeha; Meng, Qinghe; Wang, Guirong; Gatto, Louis A; Habashi, Nader M; Nieman, Gary F

2017-12-01

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH 2 O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H DS , n = 6) and (2) over-distension + low dynamic strain (OD + L DS , n = 6). OD was caused by setting the inspiratory pressure at 40 cmH 2 O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (N T ), OD + L DS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H DS . In acutely injured tissue (ALI T ), OD + L DS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H DS . Both N T and ALI T are resistant to VILI caused by OD alone, but when combined with a H DS , significant tissue injury develops.

Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response.

PubMed

Brines, M; Cerami, A

2008-11-01

In its classic hormonal role, erythropoietin (EPO) is produced by the kidney and regulates the number of erythrocytes within the circulation to provide adequate tissue oxygenation. EPO also mediates other effects directed towards optimizing oxygen delivery to tissues, e.g. modulating regional blood flow and reducing blood loss by promoting thrombosis within damaged vessels. Over the past 15 years, many unexpected nonhaematopoietic functions of EPO have been identified. In these more recently appreciated nonhormonal roles, locally-produced EPO signals through a different receptor isoform and is a major molecular component of the injury response, in which it counteracts the effects of pro-inflammatory cytokines. Acutely, EPO prevents programmed cell death and reduces the development of secondary, pro-inflammatory cytokine-induced injury. Within a longer time frame, EPO provides trophic support to enable regeneration and healing. As the region immediately surrounding damage is typically relatively deficient in endogenous EPO, administration of recombinant EPO can provide increased tissue protection. However, effective use of EPO as therapy for tissue injury requires higher doses than for haematopoiesis, potentially triggering serious adverse effects. The identification of a tissue-protective receptor isoform has facilitated the engineering of nonhaematopoietic, tissue-protective EPO derivatives, e.g. carbamyl EPO, that avoid these complications. Recently, regions within the EPO molecule mediating tissue protection have been identified and this has enabled the development of potent tissue-protective peptides, including some mimicking EPO's tertiary structure but unrelated in primary sequence.

Enhancement of the Feature Extraction Capability in Global Damage Detection Using Wavelet Theory

NASA Technical Reports Server (NTRS)

Saleeb, Atef F.; Ponnaluru, Gopi Krishna

2006-01-01

The main objective of this study is to assess the specific capabilities of the defect energy parameter technique for global damage detection developed by Saleeb and coworkers. The feature extraction is the most important capability in any damage-detection technique. Features are any parameters extracted from the processed measurement data in order to enhance damage detection. The damage feature extraction capability was studied extensively by analyzing various simulation results. The practical significance in structural health monitoring is that the detection at early stages of small-size defects is always desirable. The amount of changes in the structure's response due to these small defects was determined to show the needed level of accuracy in the experimental methods. The arrangement of fine/extensive sensor network to measure required data for the detection is an "unlimited" ability, but there is a difficulty to place extensive number of sensors on a structure. Therefore, an investigation was conducted using the measurements of coarse sensor network. The white and the pink noises, which cover most of the frequency ranges that are typically encountered in the many measuring devices used (e.g., accelerometers, strain gauges, etc.) are added to the displacements to investigate the effect of noisy measurements in the detection technique. The noisy displacements and the noisy damage parameter values are used to study the signal feature reconstruction using wavelets. The enhancement of the feature extraction capability was successfully achieved by the wavelet theory.

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

PubMed

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases. Besides intrinsic cellular mechanisms architectural, and microenvironmental factors relevantly limitate the effect of intensive locoregional therapy.

Laser treatment of female stress urinary incontinence: optical, thermal, and tissue damage simulations

NASA Astrophysics Data System (ADS)

Hardy, Luke A.; Chang, Chun-Hung; Myers, Erinn M.; Kennelly, Michael J.; Fried, Nathaniel M.

2016-02-01

Treatment of female stress urinary incontinence (SUI) by laser thermal remodeling of subsurface tissues is studied. Light transport, heat transfer, and thermal damage simulations were performed for transvaginal and transurethral methods. Monte Carlo (MC) provided absorbed photon distributions in tissue layers (vaginal wall, endopelvic fascia, urethral wall). Optical properties (n,μa,μs,g) were assigned to each tissue at λ=1064 nm. A 5-mm-diameter laser beam and power of 5 W for 15 s was used, based on previous experiments. MC output was converted into absorbed energy, serving as input for ANSYS finite element heat transfer simulations of tissue temperatures over time. Convective heat transfer was simulated with contact cooling probe set at 0 °C. Thermal properties (κ,c,ρ) were assigned to each tissue layer. MATLAB code was used for Arrhenius integral thermal damage calculations. A temperature matrix was constructed from ANSYS output, and finite sum was incorporated to approximate Arrhenius integral calculations. Tissue damage properties (Ea,A) were used to compute Arrhenius sums. For the transvaginal approach, 37% of energy was absorbed in endopelvic fascia layer with 0.8% deposited beyond it. Peak temperature was 71°C, treatment zone was 0.8-mm-diameter, and almost all of 2.7-mm-thick vaginal wall was preserved. For transurethral approach, 18% energy was absorbed in endopelvic fascia with 0.3% deposited beyond it. Peak temperature was 80°C, treatment zone was 2.0-mm-diameter, and only 0.6 mm of 2.4-mm-thick urethral wall was preserved. A transvaginal approach is more feasible than transurethral approach for laser treatment of SUI.

Temporal changes in the tensile strength of ultra-high-molecular-weight polyethylene cable embedded in muscle tissue.

PubMed

Matsumori, Hiroaki; Ueda, Yurito; Koizumi, Munehisa; Miyazaki, Kiyoshi; Shigematsu, Hideki; Satoh, Nobuhisa; Oshima, Takuya; Tanaka, Masato; Tanaka, Yasuhito; Takakura, Yoshinori

2010-02-01

Wires and cables have been used extensively for spinal sublaminar wiring, but damages to the spinal cord due to compression by metal wires have been reported. We have used more flexible ultra-high-molecular-weight polyethylene cable (Tekmilon tape) instead of metal wires since 1999 and have obtained good clinical outcomes. Although the initial strength of Tekmilon tape is equivalent to metal wires, the temporal changes in the strength of Tekmilon tape in the body should be investigated to show that sufficient strength is maintained over time until bone union is complete. Tekmilon tape was embedded into the paravertebral muscle of 10-week-old male Japanese white rabbits. Samples were embedded for 0, 1, 3, 6 or 12 months. At the end of each period, sequential straight tensile strength and sequential knot-pull tensile strength were measured. The initial strength of Tekmilon tape in muscle tissue was maintained over time, with 92% straight tensile strength and 104% knot-pull tensile strength at 6months, and values of 77% and 100% at 12 months, respectively. Since single knot is clinically relevant, it is very important that the knot-pull tensile strength did not decrease over a 12-month period. This suggests that temporal changes in the tensile strength of Tekmilon tape are negligible at 1 year. Tekmilon tape maintains sufficient strength in vivo until bone union has occurred. It is useful for sublaminar wiring instead of metal materials due to its flexibility and strength and may reduce the risk of neurological damage. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

CCR5 Controls Immune and Metabolic Functions during Toxoplasma gondii Infection

PubMed Central

Bonfá, Giuliano; Benevides, Luciana; Souza, Maria do Carmo; Fonseca, Denise Morais; Mineo, Tiago Wilson Patriarca; Rossi, Marcos Antônio; Silva, Neide Maria; Silva, João Santana; de Barros Cardoso, Cristina Ribeiro

2014-01-01

CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5-/- mice with a sub lethal dose of the parasite by oral route. CCR5-/- mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5-/- mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5-/- infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5-/- infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases. PMID:25119429

Environmental monitoring of brominated flame retardants

NASA Astrophysics Data System (ADS)

Vagula, Mary C.; Kubeldis, Nathan; Nelatury, Charles F.

2011-06-01

Brominated flame retardants (BFRs) are synthetic organobromide compounds which inhibit ignition and combustion processes. Because of their immense ability to retard fire and save life and property, they have been extensively used in many products such as TVs, computers, foam, plastics etc. The five major classes of BFRs are tetrabromobisphenol-A (TBBPA), hexabromocyclododecane (HBCD), pentabromodiphenyl ether, octabromodiphenyl ether, and decabromodiphenyl ether. The last three are also commonly called PBDEs. BDE-85 and BDE-209 are the two prominent congeners of PBDEs and this study reports the adverse effects of these congeners in rodents. Exposure of rat sciatic nerves to 5 μg/mL and 20 μg/mL of BDE-85 and BDE-209 respectively lead to significant, concentration dependent reduction in nerve conduction function. Glucose absorption in the rat intestinal segments exposed to 5 μg/mL of BDE-85 and BDE-209 was significantly reduced for both the compounds tested. Lastly, mice when exposed to 0.25 mg/kg body weight for four days showed a disruption in oxidant and antioxidant equilibrium. The tissues namely liver and brain have shown increase in the levels of lipid hydroperoxides indicating oxidative stress. Moreover, all the protective enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and glutathione S transferase (GST) have shown tissue specific alterations indicating the induction of damaging oxidative stress and setting in of lipid peroxidation in exposed animals. The results indicate monitoring of PBDEs in the environment is essential because levels as low as 5 μg/mL and 0.25 mg/kg body weight were able to cause damage to the functions of rodents.

Damage Tolerance of Composites

NASA Technical Reports Server (NTRS)

Hodge, Andy

2007-01-01

Fracture control requirements have been developed to address damage tolerance of composites for manned space flight hardware. The requirements provide the framework for critical and noncritical hardware assessment and testing. The need for damage threat assessments, impact damage protection plans, and nondestructive evaluation are also addressed. Hardware intended to be damage tolerant have extensive coupon, sub-element, and full-scale testing requirements in-line with the Building Block Approach concept from the MIL-HDBK-17, Department of Defense Composite Materials Handbook.

A finite element method model to simulate laser interstitial thermo therapy in anatomical inhomogeneous regions

PubMed Central

Mohammed, Yassene; Verhey, Janko F

2005-01-01

Background Laser Interstitial ThermoTherapy (LITT) is a well established surgical method. The use of LITT is so far limited to homogeneous tissues, e.g. the liver. One of the reasons is the limited capability of existing treatment planning models to calculate accurately the damage zone. The treatment planning in inhomogeneous tissues, especially of regions near main vessels, poses still a challenge. In order to extend the application of LITT to a wider range of anatomical regions new simulation methods are needed. The model described with this article enables efficient simulation for predicting damaged tissue as a basis for a future laser-surgical planning system. Previously we described the dependency of the model on geometry. With the presented paper including two video files we focus on the methodological, physical and mathematical background of the model. Methods In contrast to previous simulation attempts, our model is based on finite element method (FEM). We propose the use of LITT, in sensitive areas such as the neck region to treat tumours in lymph node with dimensions of 0.5 cm – 2 cm in diameter near the carotid artery. Our model is based on calculations describing the light distribution using the diffusion approximation of the transport theory; the temperature rise using the bioheat equation, including the effect of microperfusion in tissue to determine the extent of thermal damage; and the dependency of thermal and optical properties on the temperature and the injury. Injury is estimated using a damage integral. To check our model we performed a first in vitro experiment on porcine muscle tissue. Results We performed the derivation of the geometry from 3D ultrasound data and show for this proposed geometry the energy distribution, the heat elevation, and the damage zone. Further on, we perform a comparison with the in-vitro experiment. The calculation shows an error of 5% in the x-axis parallel to the blood vessel. Conclusions The FEM technique proposed can overcome limitations of other methods and enables an efficient simulation for predicting the damage zone induced using LITT. Our calculations show clearly that major vessels would not be damaged. The area/volume of the damaged zone calculated from both simulation and in-vitro experiment fits well and the deviation is small. One of the main reasons for the deviation is the lack of accurate values of the tissue optical properties. In further experiments this needs to be validated. PMID:15631630

Damage tolerance in filament-wound graphite/epoxy pressure vessels

NASA Technical Reports Server (NTRS)

Simon, William E.; Ngueyen, Vinh D.; Chenna, Ravi K.

1995-01-01

Graphite/epoxy composites are extensively used in the aerospace and sporting goods industries due to their superior engineering properties compared to those of metals. However, graphite/epoxy is extremely susceptible to impact damage which can cause considerable and sometimes undetected reduction in strength. An inelastic impact model was developed to predict damage due to low-velocity impact. A transient dynamic finite element formulation was used in conjunction with the 3D Tsai-Wu failure criterion to determine and incorporate failure in the materials during impact. Material degradation can be adjusted from no degradation to partial degradation to full degradation. The developed software is based on an object-oriented implementation framework called Extensible Implementation Framework for Finite Elements (EIFFE).

Combined use of transcranial magnetic stimulation and metal electrode implants: a theoretical assessment of safety considerations

NASA Astrophysics Data System (ADS)

Golestanirad, Laleh; Rouhani, Hossein; Elahi, Behzad; Shahim, Kamal; Chen, Robert; Mosig, Juan R.; Pollo, Claudio; Graham, Simon J.

2012-12-01

This paper provides a theoretical assessment of the safety considerations encountered in the simultaneous use of transcranial magnetic stimulation (TMS) and neurological interventions involving implanted metallic electrodes, such as electrocorticography. Metal implants are subject to magnetic forces due to fast alternating magnetic fields produced by the TMS coil. The question of whether the mechanical movement of the implants leads to irreversible damage of brain tissue is addressed by an electromagnetic simulation which quantifies the magnitude of imposed magnetic forces. The assessment is followed by a careful mechanical analysis determining the maximum tolerable force which does not cause irreversible tissue damage. Results of this investigation provide useful information on the range of TMS stimulator output powers which can be safely used in patients having metallic implants. It is shown that conventional TMS applications can be considered safe when applied on patients with typical electrode implants as the induced stress in the brain tissue remains well below the limit of tissue damage.

Accumulation of senescent cells in mitotic tissue of aging primates.

PubMed

Jeyapalan, Jessie C; Ferreira, Mark; Sedivy, John M; Herbig, Utz

2007-01-01

Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over 40 years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event.

Biological Effects of Protracted Exposure to Ionizing Radiation: Review, Analysis, and Model Development

DTIC Science & Technology

1991-11-01

dynamics, physiological changes, morphologi- cal changes, cell/tissue damage and recovery mechanisms, and existing radiobiological injury and recovery...humans and the ferret. The gut injury model (GIM) is a three-compartment hierarchial- type tissue model to simulate radiation-induced changes in the...Prodromal Symptoms Diarrhea Gastrointestinal Symptoms Dose Rate Cell Survival Intestinal Injury Fatigability Cell Damage Cell Repair Cell Proliferation

76 FR 54453 - Request for Comments on the Notice of Intent To Prepare a Draft Environmental Impact Statement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... Investigation Study (Previously Advertised as the Skagit River Flood Damage Reduction Study), Skagit County, WA... advertised as the Skagit River Flood Damage Reduction Study), Skagit County, Washington. This extension will... Investigation Study (previously advertised as the Skagit River Flood Damage Reduction Study), Skagit County...

Peripheral intravenous and central catheter algorithm: a proactive quality initiative.

PubMed

Wilder, Kerry A; Kuehn, Susan C; Moore, James E

2014-12-01

Peripheral intravenous (PIV) infiltrations causing tissue damage is a global issue surrounded by situations that make vascular access decisions difficult. The purpose of this quality improvement project was to develop an algorithm and assess its effectiveness in reducing PIV infiltrations in neonates. The targeted subjects were all infants in our neonatal intensive care unit (NICU) with a PIV catheter. We completed a retrospective chart review of the electronic medical record to collect 4th quarter 2012 baseline data. Following adoption of the algorithm, we also performed a daily manual count of all PIV catheters in the 1st and 2nd quarters 2013. Daily PIV days were defined as follows: 1 patient with a PIV catheter equals 1 PIV day. An infant with 2 PIV catheters in place was counted as 2 PIV days. Our rate of infiltration or tissue damage was determined by counting the number of events and dividing by the number of PIV days. The rate of infiltration or tissue damage was reported as the number of events per 100 PIV days. The number of infiltrations and PIV catheters was collected from the electronic medical record and also verified manually by daily assessment after adoption of the algorithm. To reduce the rate of PIV infiltrations leading to grade 4 infiltration and tissue damage by at least 30% in the NICU population. Incidence of PIV infiltrations/100 catheter days. The baseline rate for total infiltrations increased slightly from 5.4 to 5.68/100 PIV days (P = .397) for the NICU. We attributed this increase to heightened awareness and better reporting. Grade 4 infiltrations decreased from 2.8 to 0.83/100 PIV catheter days (P = .00021) after the algorithm was implemented. Tissue damage also decreased from 0.68 to 0.3/100 PIV days (P = .11). Statistical analysis used the Fisher exact test and reported as statistically significant at P < .05. Our findings suggest that utilization of our standardized decision pathway was instrumental in providing guidance for problem solving related to vascular access decisions. We feel this contributed to the overall reduction in grade 4 intravenous infiltration and tissue damage rates. Grade 4 infiltration reductions were highly statistically significant (P = .00021).

Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

PubMed

Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

2017-09-01

Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

[Anterior lumbar interbody fusion. Indications, technique, advantages and disadvantages].

PubMed

Richter, M; Weidenfeld, M; Uckmann, F P

2015-02-01

Anterior lumbar interbody fusion (ALIF) for lumbar interbody fusion from L2 to the sacrum has been an established technique for decades. The advantages and disadvantages of ALIF compared to posterior interbody fusion techniques are discussed. The operative technique is described in detail. Complications and avoidance strategies are discussed. This article is based on a selective literature search using PubMed and the experience of the authors in this medical field. The advantages of ALIF compared to posterior fusion techniques are the free approach to the anterior disc space without opening of the spinal canal or the neural foramina. This gives the possibility of an extensive anterior release and placement of the largest possible cages without the risk of neural structure damage. The disadvantages of ALIF are the additional anterior approach and the related complications. The most frequent complication is due to damage of vessels. The rate of complications is significantly increased in revision surgery. The ALIF technique meaningfully expands the repertoire of the spinal surgeon especially for the treatment of non-union after interbody fusion, in patients with epidural scar tissue at the index level and spinal infections. Advantages and disadvantages should be considered when evaluating the indications for ALIF.

Upregulated epidermal growth factor receptor expression following near-infrared irradiation simulating solar radiation in a three-dimensional reconstructed human corneal epithelial tissue culture model

PubMed Central

Tanaka, Yohei; Nakayama, Jun

2016-01-01

Background and objective Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues. Materials and methods DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000–1,800 nm wavelengths and excluded 1,400–1,500 nm wavelengths. Results A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm2 irradiation (P<0.05). Conclusion We found that NIR irradiation induced the upregulated expression of EGFR in human corneal cells. Since over half of the solar energy reaching the Earth is in the NIR region, which cannot be adequately blocked by eyewear and thus can induce eye damage with intensive or long-term exposure, protection from both UV and NIR radiation may prevent changes in gene expression and in turn eye damage. PMID:27536083

Uncovering dental implants using a new thermo-optically powered (TOP) technology with tissue air-cooling.

PubMed

Romanos, Georgios E; Belikov, Andrey V; Skrypnik, Alexei V; Feldchtein, Felix I; Smirnov, Michael Z; Altshuler, Gregory B

2015-07-01

Uncovering implants with lasers, while bloodless, has been associated with a risk of implant and bone overheating. The present study evaluated the effect of using a new generation of high-power diode lasers on the temperature of a dental implant and the surrounding tissues using an in vitro model. The implant temperature was measured at three locations using micro thermocouples. Collateral thermal damage of uncovered soft tissues was evaluated using NTBC stain. Implant temperature rise during and collateral thermal soft-tissue damage following implant uncovering with and without tissue air-cooling was studied using both the classic operational mode and the new thermo-optically powered (TOP) technology. For the classic surgical mode using a cork-initiated tip and constant laser power set at 3.4 W, the maximum temperature rise in the coronal and apical parts of the implant was 23.2 ± 4.1°С and 9.5 ± 1.8°С, respectively, while 1.5 ± 0.5 mm of collateral thermal damage of the soft tissue surrounding the implant model occurred. Using the TOP surgical tip with constant laser power reduced implant overheating by 30%; collateral thermal soft-tissue damage was 0.8 ± 0.2 mm. Using the TOP surgical mode with a tip temperature setting of 800°C and air-cooling reduced the implant temperature rise by more than 300%, and only 0.2 ± 0.1 mm of collateral thermal soft-tissue damage occurred, typical for optimized CO2 laser surgery. Furthermore, use of the new generation diode technology (TOP surgical mode) appeared to reduce the time required for implant uncovering by a factor of two, compared to the standard surgical mode. Use of the new generation diode technology (TOP surgical mode) may significantly reduce overheating of dental implants during uncovering and seems to be safer for the adjacent soft and hard tissues. Use of such diode lasers with air-cooling can radically reduce the rise in implant temperatures (by more than three times), potentially making this technology safe and effective for implant uncovering. © 2015 Wiley Periodicals, Inc.

The influence of parotid gland sparing on radiation damages of dental hard tissues.

PubMed

Hey, Jeremias; Seidel, Johannes; Schweyen, Ramona; Paelecke-Habermann, Yvonne; Vordermark, Dirk; Gernhardt, Christian; Kuhnt, Thomas

2013-07-01

The aim of the present study was to evaluate whether radiation damage on dental hard tissue depends on the mean irradiation dose the spared parotid gland is subjected to or on stimulated whole salivary flow rate. Between June 2002 and October 2008, 70 patients with neck and cancer curatively irradiated were included in this study. All patients underwent dental treatment referring to the guidelines and recommendations of the German Society of Dental, Oral and Craniomandibular Sciences prior, during, and after radiotherapy (RT). During the follow-up period of 24 months, damages on dental hard tissues were classified according to the RTOG/EORTC guidelines. The mean doses (D(mean)) during spared parotid gland RT were determined. Stimulated whole saliva secretion flow rates (SFR) were measured before RT and 1, 6, 12, 24 months after RT. Thirty patients showed no carious lesions (group A), 18 patients developed sporadic carious lesions (group B), and 22 patients developed general carious lesions (group C). Group A patients received a D mean of 21.2 ± 11.04 Gy. Group B patients received a D(mean) of 26.5 ± 11.59 Gy and group C patients received a D(mean) of 33.9 ± 9.93 Gy, respectively. The D(mean) of group A was significantly lower than the D(mean) of group C (p < 0.001). Additionally, the mean SFR 6 months after RT of group A was significantly higher than the mean SFR of group C (p < 0.01). Irradiation damage on dental hard tissue correlates with increased mean irradiation doses as well as decreased salivary flow rates. Parotid gland sparing resulting in a dose below 20 Gy reduces radiation damage on dental hard tissues, and therefore, the dose may act as a predictor for the damage to be expected.

Experimental evaluation of a new system for laser tissue welding applied on damaged lungs.

PubMed

Schiavon, Marco; Marulli, Giuseppe; Zuin, Andrea; Lunardi, Francesca; Villoresi, Paolo; Bonora, Stefano; Calabrese, Fiorella; Rea, Federico

2013-05-01

Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding. The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH2O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features. After applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen. This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.

Quantitatively characterizing microstructural variations of skin tissues during ultraviolet radiation damaging process based on Mueller matrix polarimetry

NASA Astrophysics Data System (ADS)

Sheng, Wei; He, Honghui; Dong, Yang; Ma, Hui

2018-02-01

As one of the most fundamental features of light, polarization can be used to develop imaging techniques which can provide insight into the optical and structural properties of tissues. Especially, the Mueller matrix polarimetry is suitable to detect the changes in collagen and elastic fibres, which are the main compositions of skin tissue. Here we demonstrate a novel quantitative, non-contact and in situ technique to monitor the microstructural variations of skin tissue during ultraviolet radiation (UVR) induced photoaging based on Mueller matrix polarimetry. Specifically, we measure the twodimensional (2D) backscattering Mueller matrices of nude mouse skin samples, then calculate and analyze the Mueller matrix derived parameters during the skin photoaging and self-repairing processes. To induce three-day skin photoaging, the back skin of each mouse is irradiated with UVR (0.05J/cm2) for five minutes per day. After UVR, the microstructures of the nude mouse skin are damaged. During the process of UV damage, we measure the backscattering Mueller matrices of the mouse skin samples and examine the relationship between the Mueller matrix parameters and the microstructural variations of skin tissue quantitatively. The comparisons between the UVR damaged groups with and without sunscreens show that the Mueller matrix derived parameters are potential indicators for fibrous microstructure variation in skin tissue. The pathological examinations and Monte Carlo simulations confirm the relationship between the values of Mueller matrix parameters and the changes of fibrous structures. Combined with smart phones or wearable devices, this technique may have a good application prospect in the fields of cosmetics and dermatological health.

It takes a tissue to make a tumor: Epigenetics, cancer and the microenvironment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barcellos-Hoff, Mary Helen

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises itsmore » ability to suppress carcinogenesis.« less

The Role of Public Extension in Introducing Environment-Friendly Farming Methods in Turkey.

ERIC Educational Resources Information Center

Kumuk, T.; Akgungor, S.

1995-01-01

Currently, the Turkish extension service plays a minimal role in reducing adverse environmental effects of farming methods. Public investment in research and extension on sustainable agriculture is needed to ensure long-term production practices that maintain the food supply without damaging the environment. (SK)

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

PubMed

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

2015-11-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse after 1 month of implantation. We reported a method for preparing autologous extracellular matrix scaffolds, murine collagen-Ph hydrogels, and demonstrated its suitability for use in supporting human progenitor cell-based formation of 3D vascular networks in vitro and in vivo. Results showed extensive human vascular networks can be generated within 7 days, engineered vascular density inside collagen-Ph constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with existing vasculature to further support the survival of host muscle tissues. Moreover, optimized conditions of cell-laden collagen-Ph hydrogel resulted in not only improving the long-term differentiation of transplanted MSCs into mineralized osteoblasts, but the collagen-Ph hydrogel also improved an increased of adipocytes within the vascularized bioengineered tissue in a mouse. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Investigation of retinal damage during refractive eye surgery

NASA Astrophysics Data System (ADS)

Schumacher, S.; Sander, M.; Dopke, C.; Grone, A.; Ertmer, W.; Lubatschowski, H.

2005-04-01

Ultrashort laser pulses are increasingly used in refractive eye surgery to cut inside transparent corneal tissue. This is exploited by the fs-LASIK procedure which affords the opportunity to correct ametropia without any mechanical effects. The cutting process is caused by the optical breakdown occurring in the laser focus. During this process only a certain amount of the pulse energy is deposited into the tissue. The remaining pulse energy propagates further through the eye and interacts with the retina and the strong absorbing tissue layers behind. Therefore this investigation shall clarify if the intensity of the remaining laser pulse and the resulting temperature field can damage the retina and the surrounding tissue. Threshold values of the retinal tissue and theoretical calculations of the temperature field will be presented.

Tissue repair

PubMed Central

2010-01-01

As living beings that encounter every kind of traumatic event from paper cut to myocardial infarction, we must possess ways to heal damaged tissues. While some animals are able to regrow complete body parts following injury (such as the earthworm who grows a new head following bisection), humans are sadly incapable of such feats. Our means of recovery following tissue damage consists largely of repair rather than pure regeneration. Thousands of times in our lives, a meticulously scripted but unseen wound healing drama plays, with cells serving as actors, extracellular matrix as the setting and growth factors as the means of communication. This article briefly reviews the cells involved in tissue repair, their signaling and proliferation mechanisms and the function of the extracellular matrix, then presents the actors and script for the three acts of the tissue repair drama. PMID:21220961

Estrogen protects the liver and intestines against sepsis-induced injury in rats.

PubMed

Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

2005-09-01

Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P < 0.01 to P < 0.001), suggesting oxidative organ damage, which was also verified histologically. In the estradiol-treated sepsis group, all of these oxidant responses were reversed significantly (P < 0.05 to P < 0.01). Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

Diode laser (808 nm) applied to oral soft tissue lesions: a retrospective study to assess histopathological diagnosis and evaluate physical damage.

PubMed

Angiero, Francesca; Parma, Luisa; Crippa, Rolando; Benedicenti, Stefano

2012-03-01

The diode laser is today widely used in oral pathology to excise lesions; however, some controversy surrounds laser surgery, specifically the accuracy of pathological diagnosis and the control over thermal tissue damage. This study aimed to establish if physical damage induced by the diode laser could affect the histopathological diagnosis and to evaluate the damage caused to the resection margins. Between 2005 and 2010, at S. Gerardo Hospital, Milan, 608 cases of soft tissue lesions localized in the oral cavity (cheek, gingiva, buccal mucosa, tongue, and lips) were examined. Specimens were excised with an 808-nm diode laser, output 1.6-2.7 W, in continuous-wave mode with fibers of 320 μm. Specimens were fixed in 10% buffered formalin solution and examined separately under an optical microscope by two pathologists. In all of the specimens, changes to the epithelium, connective tissue and blood vessels, shape of incision damage, and overall width of modified tissues were evaluated. The data for specimens larger than 3 mm excised with the diode laser were not significant in terms of stromal changes or vascular stasis, while epithelial and stromal changes were significantly more frequent in specimens with a mean size below 3 mm; the diagnosis was not achievable in 46.15%. Our data show that the diode laser is a valid therapeutic instrument for excising oral lesions larger than 3 mm in diameter, but induces serious thermal effects in small lesions (mean size below 3 mm). However, from a clinical standpoint, it is suggested necessary that the specimens taken have in vivo a diameter of at least 5 mm in order to have a reliable reading of the histological sample.

Non-damaging laser therapy of the macula: Titration algorithm and tissue response

NASA Astrophysics Data System (ADS)

Palanker, Daniel; Lavinsky, Daniel; Dalal, Roopa; Huie, Philip

2014-02-01

Retinal photocoagulation typically results in permanent scarring and scotomata, which limit its applicability to the macula, preclude treatments in the fovea, and restrict the retreatments. Non-damaging approaches to laser therapy have been tested in the past, but the lack of reliable titration and slow treatment paradigms limited their clinical use. We developed and tested a titration algorithm for sub-visible and non-damaging treatments of the retina with pulses sufficiently short to be used with pattern laser scanning. The algorithm based on Arrhenius model of tissue damage optimizes the power and duration for every energy level, relative to the threshold of lesion visibility established during titration (and defined as 100%). Experiments with pigmented rabbits established that lesions in the 50-75% energy range were invisible ophthalmoscopically, but detectable with Fluorescein Angiography and OCT, while at 30% energy there was only very minor damage to the RPE, which recovered within a few days. Patients with Diabetic Macular Edema (DME) and Central Serous Retinopathy (CSR) have been treated over the edematous areas at 30% energy, using 200μm spots with 0.25 diameter spacing. No signs of laser damage have been detected with any imaging modality. In CSR patients, subretinal fluid resolved within 45 days. In DME patients the edema decreased by approximately 150μm over 60 days. After 3-4 months some patients presented with recurrence of edema, and they responded well to retreatment with the same parameters, without any clinically visible damage. This pilot data indicates a possibility of effective and repeatable macular laser therapy below the tissue damage threshold.

Quantitation of Cellular Dynamics in Growing Arabidopsis Roots with Light Sheet Microscopy

PubMed Central

Birnbaum, Kenneth D.; Leibler, Stanislas

2011-01-01

To understand dynamic developmental processes, living tissues have to be imaged frequently and for extended periods of time. Root development is extensively studied at cellular resolution to understand basic mechanisms underlying pattern formation and maintenance in plants. Unfortunately, ensuring continuous specimen access, while preserving physiological conditions and preventing photo-damage, poses major barriers to measurements of cellular dynamics in growing organs such as plant roots. We present a system that integrates optical sectioning through light sheet fluorescence microscopy with hydroponic culture that enables us to image, at cellular resolution, a vertically growing Arabidopsis root every few minutes and for several consecutive days. We describe novel automated routines to track the root tip as it grows, to track cellular nuclei and to identify cell divisions. We demonstrate the system's capabilities by collecting data on divisions and nuclear dynamics. PMID:21731697

Histologic changes associated with talaporfin sodium-mediated photodynamic therapy in rat skin.

PubMed

Moy, Wesley J; Yao, Jonathan; de Feraudy, Sébastien M; White, Sean M; Salvador, Jocelynda; Kelly, Kristen M; Choi, Bernard

2017-10-01

Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a promising alternative treatment. To this end, we previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to understand treatment tissue effects to design a protocol that will achieve selective vascular injury without ulceration and scarring. The objective of this work is to assess skin changes associated with TS-mediated PDT with clinically relevant treatment parameters. We performed TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures were varied between 15 and 100 J/cm 2 . We took skin biopsies from subjects at 9 hours following PDT. We assessed the degree and depth of vascular and surrounding tissue injury using histology and immunohistochemical staining. TS-mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm 2 light doses resulted in vascular injury with minimal epidermal damage. At light dose of 50 J/cm 2 , epidermal damage was noted with vascular injury. At light doses >50 J/cm 2 , both vascular and surrounding tissue injury were observed in the forms of vasculitis, extravasated red blood cells, and coagulative necrosis. Extensive coagulative necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm 2 light doses. Observed depth of injury increased with increasing radiant exposure, although this relationship was not linear. TS-mediated PDT can cause selective vascular injury; however, at higher light doses, significant extra-vascular injury was observed. This information can be used to contribute to design of safe protocols to be used for treatment of cutaneous vascular lesions. Lasers Surg. Med. 49:767-772, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

PubMed Central

2012-01-01

Background Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs), a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation. Method The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100) DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100) tumor model. Results Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells. Conclusion Together, our findings suggest that shikonin can effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site. PMID:22494696

Microfluidic Actuation of Carbon Nanotube Fibers for Neural Recordings

NASA Astrophysics Data System (ADS)

Vercosa, Daniel G.

Implantable devices to record and stimulate neural circuits have led to breakthroughs in neuroscience; however, technologies capable of electrical recording at the cellular level typically rely on rigid metals that poorly match the mechanical properties of soft brain tissue. As a result these electrodes often cause extensive acute and chronic injury, leading to short electrode lifetime. Recently, flexible electrodes such as Carbon Nanotube fibers (CNTf) have emerged as an attractive alternative to conventional electrodes and studies have shown that these flexible electrodes reduce neuro-inflammation and increase the quality and longevity of neural recordings. Insertion of these new compliant electrodes, however, remains challenge. The stiffening agents necessary to make the electrodes rigid enough to be inserted increases device footprint, which exacerbates brain damage during implantation. To overcome this challenge we have developed a novel technology to precisely implant and actuate high-performance, flexible carbon nanotube fiber (CNTf) microelectrodes without using a stiffening agents or shuttles. Instead, our technology uses drag forces within a microfluidic device to drive electrodes into tissue while minimizing the amount of fluid that is ejected into the tissue. In vitro experiments in brain phantoms, show that microfluidic actuated CNTf can be implanted at least 4.5 mm depth with 30 microm precision, while keeping the total volume of fluid ejected below 0.1 microL. As proof of concept, we inserted CNTfs in the small cnidarian Hydra littoralis and observed compound action potentials corresponding to contractions and in agreement with the literature. Additionally, brain slices extracted from transgenic mice were used to show that our device can be used to record spontaneous and light evoked activity from the cortex and deep brain regions such as the thalamic reticular nucleus (TRN). Overall our microfluidic actuation technology provides a platform for implanting and actuating flexible electrodes that significantly reduces damage during insertion.

ESTUARINE HABITAT RESTORATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thom, Ronald M.; Borde, Amy B.

2015-09-01

Restoring estuarine habitats generally means repairing damages caused by humans and natural forces. Because of the extensive human occupation, development, and use of coastal areas for centuries, the extensive estuarine habitats have been either destroyed or significantly impaired.

77 FR 35304 - Airworthiness Directives; Costruzioni Aeronautiche Tecnam srl Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-13

... the LG emergency accumulator and the LG retraction/extension system. You may obtain further... 300 hours TIS, inspect the LG emergency accumulator and the LG retraction/extension system for damage...

77 FR 56991 - Airworthiness Directives; Costruzioni Aeronautiche Tecnam srl Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... as to inspect after the installation the LG emergency accumulator and the LG retraction/extension... the LG emergency accumulator and the LG retraction/extension system for damage and leakage following...

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

PubMed Central

Mitchell, David; Paniker, Lakshmi; Sanchez, Guillermo; Bella, Zsolt; Garaczi, Edina; Szell, Marta; Hamid, Qutayba; Kemeny, Lajos; Koreck, Andrea

2010-01-01

Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. PMID:18671762

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varma, S.D.; Mooney, J.M.

Studies have been conducted to examine the implications of photochemical generation of O2- and its derivatization to H/sub 2/O/sub 2/ and OH in the physiology of the lens in vitro. Physiological status was determined by measuring the uptake of rubidium by the intact tissue when cultured in riboflavin-containing medium, in dark and light, and in the presence and absence of various scavengers. In the presence of light, the uptake of rubidium in the lens was greatly diminished; this suggests photodamage to the tissue. MnSOD and ferricyanide protected against this photochemical damage. The damaging process was thus initiated by the generationmore » of O2-. The tissue damage was also attenuated by catalase, ferrocyanide, and mannitol. These results, therefore, suggest the participation of hydrogen peroxide and the subsequent Haber-Weiss reaction in the photodamaging process.« less

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

PubMed Central

Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

2017-01-01

ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

Tissue Damage, Temperature, and pH Induced by Different Electrode Arrays on Potato Pieces (Solanum tuberosum L.).

PubMed

González, Maraelys Morales; Aguilar, Claudia Hernández; Pacheco, Flavio Arturo Domínguez; Cabrales, Luis Enrique Bergues; Reyes, Juan Bory; Nava, Juan José Godina; Ambrosio, Paulo Eduardo; Domiguez, Dany Sanchez; Sierra González, Victoriano Gustavo; Pupo, Ana Elisa Bergues; Ciria, Héctor Manuel Camué; Alemán, Elizabeth Issac; García, Francisco Monier; Rivas, Clara Berenguer; Reina, Evelyn Chacón

2018-01-01

One of the most challenging problems of electrochemical therapy is the design and selection of suitable electrode array for cancer. The aim is to determine how two-dimensional spatial patterns of tissue damage, temperature, and pH induced in pieces of potato ( Solanum tuberosum L., var. Mondial) depend on electrode array with circular, elliptical, parabolic, and hyperbolic shape. The results show the similarity between the shapes of spatial patterns of tissue damage and electric field intensity, which, like temperature and pH take the same shape of electrode array. The adequate selection of suitable electrodes array requires an integrated analysis that involves, in a unified way, relevant information about the electrochemical process, which is essential to perform more efficiently way the therapeutic planning and the personalized therapy for patients with a cancerous tumor.

Dynamic relationship between the VOC emissions from a Scots pine stem and the tree water relations

NASA Astrophysics Data System (ADS)

Vanhatalo, Anni; Chan, Tommy; Aalto, Juho; Kolari, Pasi; Rissanen, Kaisa; Hakola, Hannele; Hölttä, Teemu; Bäck, Jaana

2013-04-01

The stems of coniferous trees contain huge storages of oleoresin. The composition of oleoresin depends on e.g. tree species, age, provenance, health status, and environmental conditions. Oleoresin is under pressure in the extensive network of resin ducts in wood and needles. It flows out from a mechanically damaged site to protect the tree by sealing the wounded site. Once in contact with air, volatile parts of oleoresin evaporate, and the residual compounds harden to make a solid protective seal over damaged tissues. The hardening time of the resin depends on evaporation rate of the volatiles which in turn depends on temperature. The storage is also toxic to herbivores and attracts predators that restrict the herbivore damage. Despite abundant knowledge on emissions of volatile isoprenoids from foliage, very little is known about their emissions from woody plant parts. We set up an experiment to measure emissions of isoprene and monoterpenes as well as two oxygenated VOCs, methanol and acetone, from a Scots pine (Pinus sylvestris) stem and branches. The measurements were started in early April and continued until mid-June, 2012. Simultaneously, we measured the dynamics of whole stem and xylem diameter changes, stem sap flow rate and foliage transpiration rate. These measurements were used to estimate A) pressure changes inside the living stem tissue and the water conducting xylem, B) the refilling of stem water stores after winter dehydration (the ratio of sap flow at the stem base to water loss by foliage), and C) the increase in tree water transport capacity (the ratio of maximum daily sap flow rate to the diurnal variation in xylem pressure) during spring due to winter embolism refilling and/or the temperature dependent root water uptake capacity. The results show that already very early in spring, significant VOC emissions from pine stem can be detected, and that they exhibit a diurnal cycle similar to that of ambient temperature. During the highest emission period a sudden decrease in stem diameter was observed, which we hypothesize could either indicate a decrease in the pressure of living cells in connection with stem VOC emissions, or result mechanically from exudation of oleoresin from the stem. We also found that the stem water stores and xylem water transport capacity increased during periods of VOC emissions, which indicates xylem embolism refilling during times of VOC emissions. A qualitative difference was found between VOC emissions from pine stem and thick branches, the stem emissions containing more sesquiterpenes. Most of the tree biomass is in the lower part of the stem, and as stem tissues are lacking green photosynthesizing tissue the emissions are supposed to be related to damage. Our results show that emissions from tree stems are connected to the tree water relations and that they are important during the period when the foliage still is rather inactive.

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis

PubMed Central

Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-01-01

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia. PMID:25650663

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis.

PubMed

Lin, Runhua; Xiao, Dejun; Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-02-20

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.

[In vitro examination of the influence of lipase and amylase on dog's pancreas tissue incubated with endotoxins, phospholipase A2 or cytokines].

PubMed

Kerekes, László; Antal-Szalmás, Péter; Dezso, Balázs; Sipka, Sándor; Furka, Andrea; Mikó, Irén; Sápy, Péter

2005-04-01

Proinflammatory cytokines are elevated during acute pancreatitis. The endotoxins and Phospholipase A2 (PLA2) also have important role in acute pancreatitis. The aim of this study was to determine, what factors are responsible for the tissue damage in acute pancreatitis. The examinations were performed on fixed and frozen sections of healthy dog's pancreas tissue. Direct effects of endotoxins, PLA2, and proinflammatory cytokines together with pancreas enzymes were examined on pancreatic tissue. Pancreas enzymes themselves did not cause any change in the structure of pancreas. The common influence of endotoxins, PLA2 and pancreas enzymes was examined, and finally the effect of proinflammatory cytokines and enzymes was examined on pancreas tissue. Our results show, that besides enzymes many other factors are necessary to inflict tissue damage in acute pancreatitis, but for necrosis the presence of TNF alfa is a must.

A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues

PubMed Central

Gasser, T. Christian; Bellomo, Facundo J.

2016-01-01

Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data. PMID:27009177

A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues.

PubMed

Comellas, Ester; Gasser, T Christian; Bellomo, Facundo J; Oller, Sergio

2016-03-01

Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data. © 2016 The Author(s).

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard

PubMed Central

Joseph, Laurie B.; Composto, Gabriella; Heck, Diane E.

2016-01-01

In mouse skin, sulfur mustard is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of sulfur mustard and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and progrowth/pro–wound healing mediators, including cyclooxygenase-2 (COX-2), which generates prostanoids, inducible nitric oxide synthase (iNOS), which generates nitric oxide, fibroblast growth factor receptor 2 (FGFR2), and galectin-3. Characterization of the mediators regulating structural changes in the skin during sulfur mustard–induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. PMID:27371823

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard.

PubMed

Joseph, Laurie B; Composto, Gabriella M; Heck, Diane E

2016-08-01

In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes. © 2016 New York Academy of Sciences.

Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

PubMed

Weinberg, Kerstin; Ortiz, Michael

2009-08-01

In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

Internalization of Escherichia coli O157:H7 gfp+ in rocket and Swiss chard baby leaves as affected by abiotic and biotic damage.

PubMed

Hartmann, R; Fricke, A; Stützel, H; Mansourian, S; Dekker, T; Wohanka, W; Alsanius, B

2017-07-01

Internalization of human pathogens in edible parts of vegetables eaten raw is a major concern, since once internalized they are protected from sanitizing treatments. In this study, we examined the invasion of gfp-labelled Escherichia coli O157:H7 into intact and biotically (infection with Xanthomonas campestris/Pseudomonas syringae) and abiotically (grating with silicon carbide) damaged leaves of wild rocket (Diplotaxis tenuifolia) and Swiss chard (Beta vulgaris subsp. cicla) using laser scanning confocal microscopy. Bacterial cells were found in internal locations of the tissue, irrespective of tissue health status. Contaminated leaf sections of biotically and abiotically damaged wild rocket leaves showed higher susceptibility to microbial invasion, while the pathogen was internalized in greater numbers into intact Swiss chard leaf sections when abiotically, but not biotically, damaged. The greatest differences were observed between the plant species; after surface sanitization, E. coli O157:H7 was still detected in wild rocket leaves, but not in Swiss chard leaves. Contamination of leafy vegetables with Escherichia coli O157:H7 is a growing problem, as reported outbreaks are increasing. However, establishment of this human pathogen in the phyllosphere is not completely understood. Using laser scanning confocal microscopy, we demonstrated that E. coli O157:H7gfp+ can invade plant tissue of Swiss chard and wild rocket leaves and that the bacterium is more sensitive to surface sanitization of Swiss chard leaves. Damage to leaf tissue promoted leaf invasion, but the nature of the damage (abiotic or biotic) and plant species had an impact. © 2017 The Society for Applied Microbiology.

Pronation-Supination Motion Is Altered in a Rat Model of Post-Traumatic Elbow Contracture.

PubMed

Dunham, Chelsey L; Castile, Ryan M; Chamberlain, Aaron M; Galatz, Leesa M; Lake, Spencer P

2017-07-01

The elbow joint is highly susceptible to joint contracture, and treating elbow contracture is a challenging clinical problem. Previously, we established an animal model to study elbow contracture that exhibited features similar to the human condition including persistent decreased range of motion (ROM) in flexion-extension and increased capsule thickness/adhesions. The objective of this study was to mechanically quantify pronation-supination in different injury models to determine if significant differences compared to control or contralateral persist long-term in our animal elbow contracture model. After surgically inducing soft tissue damage in the elbow, Injury I (anterior capsulotomy) and Injury II (anterior capsulotomy with lateral collateral ligament transection), limbs were immobilized for 6 weeks (immobilization (IM)). Animals were evaluated after the IM period or following an additional 6 weeks of free mobilization (FM). Total ROM for pronation-supination was significantly decreased compared to the uninjured contralateral limb for both IM and FM, although not different from control limbs. Specifically, for both IM and FM, total ROM for Injury I and Injury II was significantly decreased by ∼20% compared to contralateral. Correlations of measurements from flexion-extension and pronation-supination divulged that FM did not affect these motions in the same way, demonstrating that joint motions need to be studied/treated separately. Overall, injured limbs exhibited persistent motion loss in pronation-supination when comparing side-to-side differences, similar to human post-traumatic joint contracture. Future work will use this animal model to study how elbow periarticular soft tissues contribute to contracture.

MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

PubMed

Weihmuller, F B; O'Dell, S J; Marshall, J F

1992-06-01

Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Atmospheric Pressure Plasmas on Isolated and Cellular DNA—A Review

PubMed Central

Arjunan, Krishna Priya; Sharma, Virender K.; Ptasinska, Sylwia

2015-01-01

Atmospheric Pressure Plasma (APP) is being used widely in a variety of biomedical applications. Extensive research in the field of plasma medicine has shown the induction of DNA damage by APP in a dose-dependent manner in both prokaryotic and eukaryotic systems. Recent evidence suggests that APP-induced DNA damage shows potential benefits in many applications, such as sterilization and cancer therapy. However, in several other applications, such as wound healing and dentistry, DNA damage can be detrimental. This review reports on the extensive investigations devoted to APP interactions with DNA, with an emphasis on the critical role of reactive species in plasma-induced damage to DNA. The review consists of three main sections dedicated to fundamental knowledge of the interactions of reactive oxygen species (ROS)/reactive nitrogen species (RNS) with DNA and its components, as well as the effects of APP on isolated and cellular DNA in prokaryotes and eukaryotes. PMID:25642755

Effects of atmospheric pressure plasmas on isolated and cellular DNA-a review.

PubMed

Arjunan, Krishna Priya; Sharma, Virender K; Ptasinska, Sylwia

2015-01-29

Atmospheric Pressure Plasma (APP) is being used widely in a variety of biomedical applications. Extensive research in the field of plasma medicine has shown the induction of DNA damage by APP in a dose-dependent manner in both prokaryotic and eukaryotic systems. Recent evidence suggests that APP-induced DNA damage shows potential benefits in many applications, such as sterilization and cancer therapy. However, in several other applications, such as wound healing and dentistry, DNA damage can be detrimental. This review reports on the extensive investigations devoted to APP interactions with DNA, with an emphasis on the critical role of reactive species in plasma-induced damage to DNA. The review consists of three main sections dedicated to fundamental knowledge of the interactions of reactive oxygen species (ROS)/reactive nitrogen species (RNS) with DNA and its components, as well as the effects of APP on isolated and cellular DNA in prokaryotes and eukaryotes.

Clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients: successes and barriers*

PubMed Central

Vissink, Arjan; Mitchell, James B; Baum, Bruce J; Limesand, Kirsten H; Jensen, Siri Beier; Fox, Philip C; Elting, Linda S; Langendijk, Johannes A; Coppes, Robert P; Reyland, Mary E

2010-01-01

The most significant long-term complication of radiotherapy in the head and neck region is hyposalivation and its related complaints, particularily xerostomia. This paper addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to: (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy. PMID:20970030

Strength loss in southern pine poles damaged by woodpeckers

Treesearch

R.W. Rumsey; G.E. Woodson

1973-01-01

Woodpecker damage caused extensive reductions in strength of 50-foot, class-2 utility poles, the amount depending on the cross-sectional area of wood removed and its distance from the apex. Two methods for estimating when damaged poles should be replaced proved to be conservative when applied to results of field tests. Such conservative predictions of falling loads...

Strength loss in southern pine poles damaged by woodpeckers

Treesearch

R.L. Rumsey; George E. Woodson

1973-01-01

Woodpecker damage caused extensive reductions in strength of 50-foot, class-2 utility poles, the amount depending on the cross-sectional area of wood removed and its distance from the apex. Two methods for estimating when damaged poles should be replaced proved to be conservative when applied to results of field rests. Such conservative predictions of failing loads...

Efficacy and predictability of soft tissue ablation using a prototype Raman-shifted alexandrite laser

NASA Astrophysics Data System (ADS)

Kozub, John A.; Shen, Jin-H.; Joos, Karen M.; Prasad, Ratna; Shane Hutson, M.

2015-10-01

Previous research showed that mid-infrared free-electron lasers could reproducibly ablate soft tissue with little collateral damage. The potential for surgical applications motivated searches for alternative tabletop lasers providing thermally confined pulses in the 6- to-7-μm wavelength range with sufficient pulse energy, stability, and reliability. Here, we evaluate a prototype Raman-shifted alexandrite laser. We measure ablation thresholds, etch rates, and collateral damage in gelatin and cornea as a function of laser wavelength (6.09, 6.27, or 6.43 μm), pulse energy (up to 3 mJ/pulse), and spot diameter (100 to 600 μm). We find modest wavelength dependence for ablation thresholds and collateral damage, with the lowest thresholds and least damage for 6.09 μm. We find a strong spot-size dependence for all metrics. When the beam is tightly focused (˜100-μm diameter), ablation requires more energy, is highly variable and less efficient, and can yield large zones of mechanical damage (for pulse energies >1 mJ). When the beam is softly focused (˜300-μm diameter), ablation proceeded at surgically relevant etch rates, with reasonable reproducibility (5% to 12% within a single sample), and little collateral damage. With improvements in pulse-energy stability, this prototype laser may have significant potential for soft-tissue surgical applications.

Efficacy and predictability of soft tissue ablation using a prototype Raman-shifted alexandrite laser

PubMed Central

Kozub, John A.; Shen, Jin-H.; Joos, Karen M.; Prasad, Ratna; Shane Hutson, M.

2015-01-01

Abstract. Previous research showed that mid-infrared free-electron lasers could reproducibly ablate soft tissue with little collateral damage. The potential for surgical applications motivated searches for alternative tabletop lasers providing thermally confined pulses in the 6- to-7-μm wavelength range with sufficient pulse energy, stability, and reliability. Here, we evaluate a prototype Raman-shifted alexandrite laser. We measure ablation thresholds, etch rates, and collateral damage in gelatin and cornea as a function of laser wavelength (6.09, 6.27, or 6.43  μm), pulse energy (up to 3  mJ/pulse), and spot diameter (100 to 600  μm). We find modest wavelength dependence for ablation thresholds and collateral damage, with the lowest thresholds and least damage for 6.09  μm. We find a strong spot-size dependence for all metrics. When the beam is tightly focused (∼100-μm diameter), ablation requires more energy, is highly variable and less efficient, and can yield large zones of mechanical damage (for pulse energies >1  mJ). When the beam is softly focused (∼300-μm diameter), ablation proceeded at surgically relevant etch rates, with reasonable reproducibility (5% to 12% within a single sample), and little collateral damage. With improvements in pulse-energy stability, this prototype laser may have significant potential for soft-tissue surgical applications. PMID:26456553

Amniotic fluid stem cells: a promising therapeutic resource for cell-based regenerative therapy.

PubMed

Antonucci, Ivana; Pantalone, Andrea; Tete, Stefano; Salini, Vincenzo; Borlongan, Cesar V; Hess, David; Stuppia, Liborio

2012-01-01

Stem cells have been proposed as a powerful tool in the treatment of several human diseases, both for their ability to represent a source of new cells to replace those lost due to tissue injuries or degenerative diseases, and for the ability of produce trophic molecules able to minimize damage and promote recovery in the injured tissue. Different cell types, such as embryonic, fetal or adult stem cells, human fetal tissues and genetically engineered cell lines, have been tested for their ability to replace damaged cells and to restore the tissue function after transplantation. Amniotic fluid -derived Stem cells (AFS) are considered a novel resource for cell transplantation therapy, due to their high renewal capacity, the "in vitro" expression of embryonic cell lineage markers, and the ability to differentiate in tissues derived from all the three embryonic layers. Moreover, AFS do not produce teratomas when transplanted into animals and are characterized by a low antigenicity, which could represent an advantage for cell transplantation or cell replacement therapy. The present review focuses on the biological features of AFS, and on their potential use in the treatment of pathological conditions such as ischemic brain injury and bone damages.

Effects of boron on structure and antioxidative activities of spleen in rats.

PubMed

Hu, Qianqian; Li, Shenghe; Qiao, Enmei; Tang, Zhongtao; Jin, Erhui; Jin, Guangming; Gu, Youfang

2014-04-01

In order to determine the relationship between boron and development of the spleen, especially in the promoting biological effects, we examined the effects of different levels of boron on weight, organ index, microstructure, and antioxidative activities of the spleen in rats. Sprague-Dawley (SD) rats were selected and treated with different concentrations of boron, and then, the organs were resected and weighed. One half of the tissue was fixed and embedded in paraffin to observe tissue structure changes. The other half of the tissue was homogenated for determining the antioxidant activities. The results showed that 40 mg/L of boron could increase weight, organ indexes, and antioxidant capacity of spleens and improve the spleen tissue structure, while the boron concentration above 80 mg/L could decrease weight, organ indexes, and antioxidant capacity of spleens and damage the spleen tissue structure. The higher the concentration, the more serious the damage was. Especially at the concentration of 640 mg/L, it could significantly inhibit the development of the spleen and even exhibit toxic effect. Hence, low boron concentration played a protective role in the development of the spleen, while high boron concentration could damage the organs and even produce toxic effect.

3D-analysis of plant microstructures: advantages and limitations of synchrotron X-ray microtomography

NASA Astrophysics Data System (ADS)

Matsushima, U.; Graf, W.; Zabler, S.; Manke, I.; Dawson, M.; Choinka, G.; Hilger, A.; Herppich, W. B.

2013-01-01

Synchrotron X-ray computer microtomography was used to analyze the microstructure of rose peduncles. Samples from three rose cultivars, differing in anatomy, were scanned to study the relation between tissue structure and peduncles mechanical strength. Additionally, chlorophyll fluorescence imaging and conventional light microscopy was applied to quantify possible irradiation-induced damage to plant physiology and tissue structure. The spatial resolution of synchrotron X-ray computer microtomography was sufficiently high to investigate the complex tissues of intact rose peduncles without the necessity of any preparation. However, synchrotron X-radiation induces two different types of damage on irradiated tissues. First, within a few hours after first X-ray exposure, there is a direct physical destruction of cell walls. In addition, a slow and delayed destruction of chlorophyll and, consequently, of photosynthetic activity occurred within hours/ days after the exposure. The results indicate that synchrotron X-ray computer microtomography is well suited for three-dimensional visualization of the microstructure of rose peduncles. However, in its current technique, synchrotron X-ray computer microtomography is not really non-destructive but induce tissue damage. Hence, this technique needs further optimization before it can be applied for time-series investigations of living plant materials

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage.

PubMed

Velalopoulou, Anastasia; Chatterjee, Shampa; Pietrofesa, Ralph A; Koziol-White, Cynthia; Panettieri, Reynold A; Lin, Liyong; Tuttle, Stephen; Berman, Abigail; Koumenis, Constantinos; Christofidou-Solomidou, Melpo

2017-11-25

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

PubMed Central

Velalopoulou, Anastasia; Chatterjee, Shampa; Pietrofesa, Ralph A.; Koziol-White, Cynthia; Panettieri, Reynold A.; Lin, Liyong; Tuttle, Stephen; Berman, Abigail; Koumenis, Constantinos; Christofidou-Solomidou, Melpo

2017-01-01

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung. PMID:29186841

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models.

PubMed

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.

Tissue Damage Characterization Using Non-invasive Optical Modalities

NASA Astrophysics Data System (ADS)

Diaz, David

The ability to determine the degree of cutaneous and subcutaneous tissue damage is essential for proper wound assessment and a significant factor for determining patient treatment and morbidity. Accurate characterization of tissue damage is critical for a number of medical applications including surgical removal of nonviable tissue, severity assessment of subcutaneous ulcers, and depth assessment of visually open wounds. The main objective of this research was to develop a non-invasive method for identifying the extent of tissue damage underneath intact skin that is not apparent upon visual examination. This work investigated the relationship between tissue optical properties, blood flow, and tissue viability by testing the hypotheses that (a) changes in tissue oxygenation and/or microcirculatory blood flow measurable by Diffuse Near Infrared Spectroscopy (DNIRS) and Diffuse Correlation Spectroscopy (DCS) differ between healthy and damaged tissue and (b) the magnitude of those changes differs for different degrees of tissue damage. This was accomplished by developing and validating a procedure for measuring microcirculatory blood flow and tissue oxygenation dynamics at multiple depths (up to 1 centimeter) using non-invasive DCS and DNIRS technologies. Due to the lack of pressure ulcer animal models that are compatible with our optical systems, a proof of concept was conducted in a porcine burn model prior to conducting clinical trials in order to assess the efficacy of the system in-vivo. A reduction in total hemoglobin was observed for superficial (5%) and deep burns (35%) along with a statistically significant difference between the optical properties of superficial and deep burns (p < 0.05). Burn depth and viable vessel density were estimated via histological samples. 42% of vessels in the dermal layer were viable for superficial burns, compared to 25% for deep burns. The differences detected in optical properties and hemoglobin content by optical measurements correlated with the extent of tissue injury observed in histological stains. After proof of concept in animals, a human study was conducted and optical data was collected from 20 healthy subjects and 8 patients at risk of developing pressure ulcers. Blood flow index (BFI) values from the sacral region of patients were compared with those of healthy volunteers. Prior to loading measurements, baseline BFI values were measured in subjects in lateral position. These values were systematically higher for patients who developed open ulcers than for the other research subjects. While under the loading position, patients who developed a pressure ulcer had a decrease in BFI from baseline values an order of magnitude larger than healthy subjects (p < 0.01) and patients whose redness dissipated (p < 0.01). The hyperemic response, when pressure was released as the patient was moved back to a lateral position, showed a decreasing trend from one session to the next for patients who developed open ulcers. Overall, this work presents a novel non-invasive method of pressure ulcer assessment and provides an improvement over current assessment methods. The obtained results suggest the system may potentially predict whether non-blanchable redness will develop into an advanced pressure ulcer within four weeks from initial observation.

Polyphenols as Modulators of Aquaporin Family in Health and Disease.

PubMed

Fiorentini, Diana; Zambonin, Laura; Dalla Sega, Francesco Vieceli; Hrelia, Silvana

2015-01-01

Polyphenols are bioactive molecules widely distributed in fruits, vegetables, cereals, and beverages. Polyphenols in food sources are extensively studied for their role in the maintenance of human health and in the protection against development of chronic/degenerative diseases. Polyphenols act mainly as antioxidant molecules, protecting cell constituents against oxidative damage. The enormous number of polyphenolic compounds leads to huge different mechanisms of action not fully understood. Recently, some evidence is emerging about the role of polyphenols, such as curcumin, pinocembrin, resveratrol, and quercetin, in modulating the activity of some aquaporin (AQP) isoforms. AQPs are integral, small hydrophobic water channel proteins, extensively expressed in many organs and tissues, whose major function is to facilitate the transport of water or glycerol over cell plasma membranes. Here we summarize AQP physiological functions and report emerging evidence on the implication of these proteins in a number of pathophysiological processes. In particular, this review offers an overview about the role of AQPs in brain, eye, skin diseases, and metabolic syndrome, focusing on the ability of polyphenols to modulate AQP expression. This original analysis can contribute to elucidating some peculiar effects exerted by polyphenols and can lead to the development of an innovative potential preventive/therapeutic strategy.

Excimer laser debridement of necrotic erosions of skin without collateral damage

NASA Astrophysics Data System (ADS)

Wynne, James J.; Felsenstein, Jerome M.; Trzcinski, Robert; Zupanski-Nielsen, Donna; Connors, Daniel P.

2011-07-01

Pulsed ArF excimer laser radiation at 6.4 eV, at fluence exceeding the ablation threshold, will debride burn eschar and other dry necrotic erosions of the skin. Debridement will cease when sufficiently moist viable tissue is exposed, due to absorption by aqueous chloride ions (Cl-) through the non-thermal process of electron photodetachment, thereby inhibiting collateral damage to the viable tissue. ArF excimer laser radiation debrides/ablates ~1 micron of tissue with each pulse. While this provides great precision in controlling the depth of debridement, the process is relatively time-consuming. In contrast, XeCl excimer laser radiation debrides ~8 microns of tissue with each pulse. However the 4.0 eV photon energy of the XeCl excimer laser is insufficient to photodetach an electron from a Cl- ion, so blood or saline will not inhibit debridement. Consequently, a practical laser debridement system should incorporate both lasers, used in sequence. First, the XeCl excimer laser would be used for accelerated debridement. When the necrotic tissue is thinned to a predetermined thickness, the ArF excimer laser would be used for very precise and well-controlled debridement, removing ultra-thin layers of material with each pulse. Clearly, the use of the ArF laser is very desirable when debriding very close to the interface between necrotic tissue and viable tissue, where the overall speed of debridement need not be so rapid and collateral damage to viable tissue is undesirable. Such tissue will be sterile and ready for further treatment, such as a wound dressing and/or a skin graft.

Long-term treatment with a Yang-invigorating Chinese herbal formula produces generalized tissue protection against oxidative damage in rats.

PubMed

Chiu, Po Yee; Leung, Hoi Yan; Siu, Ada Hoi Ling; Chen, Na; Poon, Michel K T; Ko, Kam Ming

2008-02-01

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were examined in female rats. The results indicated that long-term VI-28 treatment invariably protected against oxidative tissue damage in the rat models of cerebral/myocardial ischemia-reperfusion injury, CCl4 hepatotoxicity, and gentamicin nephrotoxicity. The tissue protection was associated with increases in the levels and activities of mitochondrial antioxidant components as well as with the preservation of mitochondrial structural integrity. This was evidenced by decreases in the sensitivity of mitochondria to Ca2+-induced permeability transition, and in the levels of mitochondrial malondialdehyde production, Ca2+ loading, and cytochrome c release in the tissues examined. Interestingly, the VI-28 treatment increased red cell CuZn-superoxide dismutase (CuZn-SOD) levels, and these levels correlated positively with the degree of tissue protection afforded by long-term VI-28 treatment in rats. The generalized tissue protection afforded by long-term VI-28 treatment may have clinical implications in the prevention of age-related diseases, and VI-28 treatment may possibly delay the aging process.

Melt electrowriting below the critical translation speed to fabricate crimped elastomer scaffolds with non-linear extension behaviour mimicking that of ligaments and tendons.

PubMed

Hochleitner, Gernot; Chen, Fei; Blum, Carina; Dalton, Paul D; Amsden, Brian; Groll, Jürgen

2018-05-01

Ligaments and tendons are comprised of aligned, crimped collagen fibrils that provide tissue-specific mechanical properties with non-linear extension behaviour, exhibiting low stress at initial strain (toe region behaviour). To approximate this behaviour, we report fibrous scaffolds with sinusoidal patterns by melt electrowriting (MEW) below the critical translation speed (CTS) by exploitation of the natural flow behaviour of the polymer melt. More specifically, we synthesised photopolymerizable poly(L-lactide-co-ε-caprolactone-co-acryloyl carbonate) (p(LLA-co-ε-CL-co-AC)) and poly(ε-caprolactone-co-acryloyl carbonate) (p(ε-CL-co-AC)) by ring-opening polymerization (ROP). Single fibre (fØ = 26.8 ± 1.9 µm) tensile testing revealed a customisable toe region with Young's Moduli ranging from E = 29 ± 17 MPa for the most crimped structures to E = 314 ± 157 MPa for straight fibres. This toe region extended to scaffolds containing multiple fibres, while the sinusoidal pattern could be influenced by printing speed. The synthesized polymers were cytocompatible and exhibited a tensile strength of σ = 26 ± 7 MPa after 10 4 cycles of preloading at 10% strain while retaining the distinct toe region commonly observed in native ligaments and tendon tissue. Damaged tendons and ligaments are serious and frequently occurring injuries worldwide. Recent therapies, including autologous grafts, still have severe disadvantages leading to a demand for synthetic alternatives. Materials envisioned to induce tendon and ligament regeneration should be degradable, cytocompatible and mimic the ultrastructural and mechanical properties of the native tissue. Specifically, we utilised photo-cross-linkable polymers for additive manufacturing (AM) with MEW. In this way, we were able to direct-write cytocompatible fibres of a few micrometres thickness into crimp-structured elastomer scaffolds that mimic the non-linear biomechanical behaviour of tendon and ligament tissue. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The environmental implications of intensified land use in developing countries

PubMed Central

Tinker, P. B.

1997-01-01

The major agricultural intensifications in the developed world over the last half century have produced a range of important environmental problems. These include pollution, damage to wildlife and landscape and other issues, both on- and off-site. These are largely being controlled by scientific investigation and Government regulation. As developing countries increase agricultural production over the next 30 years, this may also cause even more serious environmental damage.
The paper distinguishes between production-related on-site damage, and off-site and more extensive effects. Both may involve soil and water effects, such as soil erosion, salinization, siltation, eutrophication and loss of water quality. The use of more agrochemicals can damage water quality, health, wildlife and biodiversity. Loss of habitat from the extension of farming is particularly damaging to biodiversity. A developing off-site problem is the production of greenhouse gases by farming systems, including the conversion of forests to farmland. In the future the introduction of genetically engineered species of plants, animals or microbes will need secure control.
Work, probably on a catchment basis, is necessary to understand and control these problems. The three main requirements are much better environmental information from the developing world; the selection of environmental indicators to be monitored; and the support of local farmers in protecting the environment. There are encouraging indications of farmer concern and action over obvious on-site damage, but this may not extend to extensive off-site issues. The main danger is that developing food scarcity would cause the environmental issues to be ignored in a race for production.

Real-time optical coherence tomography observation of retinal tissue damage during laser photocoagulation therapy on ex-vivo porcine samples

NASA Astrophysics Data System (ADS)

Steiner, P.; Považay, B.; Stoller, M.; Morgenthaler, P.; Inniger, D.; Arnold, P.; Sznitman, R.; Meier, Ch.

2015-07-01

Retinal laser photocoagulation represents a widely used treatment for retinal pathologies such as diabetic chorioretinopathy or diabetic edema. For effective treatment, an appropriate choice of the treatment energy dose is crucial to prevent excessive tissue damage caused by over-irradiation of the retina. In this manuscript we investigate simultaneous and time-resolved optical coherence tomography for its applicability to provide feedback to the ophthalmologist about the introduced retinal damage during laser photocoagulation. Time-resolved and volumetric optical coherence tomography data of 96 lesions on ex-vivo porcine samples, set with a 577 nm laser prototype and irradiance of between 300 and 8800 W=cm2 were analyzed. Time-resolved scans were compared to volumetric scans of the lesion and correlated with ophthalmoscopic visibility. Lastly, image parameters extracted from optical coherence tomography Mscans, suitable for lesion classification were identified. Results presented in this work support the hypothesis that simultaneous optical coherence tomography provides valuable information about the extent of retinal tissue damage and may be used to guide retinal laser photocoagulation in the future.

Biotechnological Management of Skin Burn Injuries: Challenges and Perspectives in Wound Healing and Sensory Recovery.

PubMed

Girard, Dorothée; Laverdet, Betty; Buhé, Virginie; Trouillas, Marina; Ghazi, Kamélia; Alexaline, Maïa M; Egles, Christophe; Misery, Laurent; Coulomb, Bernard; Lataillade, Jean-Jacques; Berthod, François; Desmoulière, Alexis

2017-02-01

Many wound management protocols have been developed to improve wound healing after burn with the primordial aim to restore the barrier function of the skin and also provide a better esthetic outcome. Autologous skin grafts remain the gold standard in the treatment of skin burn, but this treatment has its limitation especially for patients presenting limited donor sites due to extensive burn areas. Deep burn injuries also alter the integrity of skin-sensitive innervation and have an impact on patient's quality of life by compromising perceptions of touch, temperature, and pain. Thus, patients can suffer from long-term disabilities ranging from cutaneous sensibility loss to chronic pain. The cellular mechanisms involved in skin reinnervation following injury are not elucidated yet. Depending on the depth of the burn, nerve sprouting can occur from the wound bed or the surrounding healthy tissue, but somehow this process fails to provide correct reinnervation of the wound during scarring. In addition, several clinical observations indicate that damage to the peripheral nervous system influences wound healing, resulting in delayed wound healing or chronic wounds, underlining the role of innervation and neuromediators for normal cutaneous tissue repair development. Promising tissue engineering strategies, including the use of biomaterials, skin substitutes, and stem cells, could provide novel alternative treatments in wound healing and help in improving patient's sensory recovery.

[Arthroscopy-guided fracture management. Ankle joint and calcaneus].

PubMed

Schoepp, C; Rixen, D

2013-04-01

Arthroscopic fracture management of the ankle and calcaneus requires a differentiated approach. The aim is to minimize surgical soft tissue damage and to visualize anatomical fracture reduction arthroscopically. Moreover, additional cartilage damage can be detected and treated. The arthroscopic approach is limited by deep impressions of the joint surface needing cancellous bone grafting, by multiple fracture lines on the articular side and by high-grade soft tissue damage. An alternative to the minimally invasive arthroscopic approach is open arthroscopic reduction in conventional osteosynthesis. This facilitates correct assessment of surgical reduction of complex calcaneal fractures, otherwise remaining non-anatomical reduction might not be fluoroscopically detected during surgery.

Development and recovery of laser-induced retinal injury in rats

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Epstein, Yoram; Rosner, Mordechai

2005-04-01

Retinal photocoagulation lesions undergo primary and secondary degeneration followed by partial healing. This study follows the sequential changes in laser-induced retinal lesion over a time span of 60 days. Argon laser lesions were created in 36 pigmented rats. Sections of the retinal lesions were evaluated by light microscopy 1, 24, 48, 72 hours, and 20, and 60 days after the injury (six animals at each time point). The diameter of the lesion was equal to that of the laser spot 1h after irradiation and increased by 24h. It decreased later, slightly during the following 48h and significantly by 20 days. The destruction of photoreceptors was most severe after 24-48h. The nuclei in the outer-nuclear layer were pyknotic at the lesion site at 1h and disappeared later. Healing processes began 72h after the irradiation and was completed by 60 days. Filling-in by sliding of near nuclei was observed by the 60th day. Reversible changes were seen also in the retinal pigment epithelium (with formation of a plaque at 72h and its degradation later on) and in the choroid (disorganization of capillaries by 48h with later reorganization). Conclusions: The development of a laser-induced injury is gradual. The photoreceptors are damaged first and than the damage spreads to other layers of retina and to areas adjacent the primary injury site. The extension of the damage is later stopped and the adjacent tissues tend to fill the lesion and remodel the retina.

Hippocampus and Retrograde Amnesia in the Rat Model: A Modest Proposal for the Situation of Systems Consolidation

PubMed Central

Sutherland, Robert J.; Sparks, Fraser; Lehmann, Hugo

2010-01-01

The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that hippocampal retrograde amnesia normally exhibits a temporal gradient, affecting recent, but sparing remote memories. Surprisingly, the evidence does not provide much support for the idea that there is a lengthy process of systems consolidation following a learning episode. Instead, recent and remote memories tend to be equally affected. The extent of damage to the hippocampus is a significant factor in this work since it is likely that spared hippocampal tissue can support at least partial memory retrieval. With extensive hippocampal damage gradients are flat or, in the case of memory tasks with flavour/odour retrieval cues, the retrograde amnesia covers a period of about 1 – 3 days. There is consistent evidence that at the time of learning the hippocampus interferes with or overshadows memory acquisition by other systems. This contributes to the breadth and severity of retrograde amnesia relative to anterograde amnesia in the rat. The fact that multiple, distributed learning episodes can overcome this overshadowing is consistent with a parallel dual-store theory or a Distributed Reinstatement Theory in which each learning episode triggers a short period of memory replay that provides a brief hippocampal-dependent systems consolidation. PMID:20430043

Piezosurgery as a further technical adjunct in minimally invasive supraorbital keyhole approach and lateral orbitotomy.

PubMed

Iacoangeli, Maurizio; Di Rienzo, Alessandro; Nocchi, Niccolo; Balercia, Paolo; Lupi, Ettore; Regnicolo, Luana; Di Somma, Lucia Giovanna Maria; Alvaro, Lorenzo; Scerrati, Massimo

2015-03-01

One of the problems in neurosurgery is how to perform rapid and effective craniotomies that minimize the risk of injury to underlying eloquent structures. The traditional high-powered pneumatic tools and saws are efficient in terms of speed and penetration, but they can provoke bone necrosis and sometimes damage neurovascular structures. As an alternative, we evaluated the piezoelectric bone scalpel (piezosurgery), a device that potentially allows thinner and more precise bone cutting without lesioning neighboring delicate structures, even in the case of accidental contact. From January 2009 to December 2011, 20 patients (8 men and 12 women), 19 to 72 years of age (mean: 49.3 years) were treated using piezosurgery. Surgery was performed for the removal of anterior cranial fossa meningiomas, orbital tumors, and sinonasal lesions with intracranial extension. The time required to perform craniotomy using piezosurgery is a few minutes longer than with traditional drills. No damage was observed using the piezoelectric device. Follow-up clinical and neuroradiologic evaluation showed a faster and better ossification of the bone flap with good esthetic results. Piezosurgery is a new promising technique for selective bone cutting with soft tissue preservation. This instrument seems suitable to perform precise thin osteotomies while limiting damage to the bone itself and to the underlying delicate structures even in the case of unintentional contact. These advantages make the piezoelectric bone scalpel a particularly attractive instrument in neurosurgery. Georg Thieme Verlag KG Stuttgart · New York.

Effects of ion beam irradiation on size of mutant sector and genetic damage in Arabidopsis

NASA Astrophysics Data System (ADS)

Hase, Yoshihiro; Nozawa, Shigeki; Narumi, Issay; Oono, Yutaka

2017-01-01

Size of mutant sector and genetic damage were evaluated in Arabidopsis to further our understanding of effective ion beam use in plant mutation breeding. Arabidopsis seeds, heterozygous for the GLABRA1 (GL1) gene (GL1/gl1-1), were irradiated with 15.8 MeV/u neon ions (mean linear energy transfer (LET): 352 keV/μm), 17.3 MeV/u carbon ions (113 keV/μm), or 60Co gamma rays. The frequency and size of glabrous sectors generated because of inactivation of the GL1 allele were examined. The frequency and overall size of large deletions were evaluated based on the loss of heterozygosity of DNA markers using DNA isolated from glabrous tissue. Irrespective of the radiation properties, plants with mutant sectors were obtained at similar frequencies at the same effective dosage necessary for survival reduction. Ion beams tended to induce larger mutant sectors than gamma rays. The frequency of large deletions (>several kbp) increased as the LET value increased, with chromosome regions larger than 100 kbp lost in most large deletions. The distorted segregation ratio of glabrous plants in the progenies of irradiated GL1/gl1-1 plants suggested frequent occurrence of chromosome rearrangement, especially those subjected to neon ions. Exposure to ion beams with moderate LET values (30-110 keV/μm) is thought effective for inducing mutant sectors without causing extensive genetic damage.

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

PubMed Central

Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

2017-01-01

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

Propagation Effects in the Assessment of Laser Damage Thresholds to the Eye and Skin

DTIC Science & Technology

2007-01-01

Conference on Optical Interactions with Tissue and Cells [18th] Held in San Jose, California on January 22-24, 2007 To order the complete compilation report...evaluation of the role of propagation with regard to laser damage to tissues. Regions of the optical spectrum, where linear and non-linear propagation...photo-chemical toxicity. Exposure limits commonly address skin and eye hazards through separate definitions. Differing optical absorption and scattering

Tissue Damage, Temperature, and pH Induced by Different Electrode Arrays on Potato Pieces (Solanum tuberosum L.)

PubMed Central

González, Maraelys Morales; Aguilar, Claudia Hernández; Pacheco, Flavio Arturo Domínguez; Cabrales, Luis Enrique Bergues; Reyes, Juan Bory; Nava, Juan José Godina; Ambrosio, Paulo Eduardo; Domiguez, Dany Sanchez; Sierra González, Victoriano Gustavo; Pupo, Ana Elisa Bergues; Ciria, Héctor Manuel Camué; Alemán, Elizabeth Issac; García, Francisco Monier; Rivas, Clara Berenguer; Reina, Evelyn Chacón

2018-01-01

One of the most challenging problems of electrochemical therapy is the design and selection of suitable electrode array for cancer. The aim is to determine how two-dimensional spatial patterns of tissue damage, temperature, and pH induced in pieces of potato (Solanum tuberosum L., var. Mondial) depend on electrode array with circular, elliptical, parabolic, and hyperbolic shape. The results show the similarity between the shapes of spatial patterns of tissue damage and electric field intensity, which, like temperature and pH take the same shape of electrode array. The adequate selection of suitable electrodes array requires an integrated analysis that involves, in a unified way, relevant information about the electrochemical process, which is essential to perform more efficiently way the therapeutic planning and the personalized therapy for patients with a cancerous tumor. PMID:29725584

Precision machining of pig intestine using ultrafast laser pulses

NASA Astrophysics Data System (ADS)

Beck, Rainer J.; Góra, Wojciech S.; Carter, Richard M.; Gunadi, Sonny; Jayne, David; Hand, Duncan P.; Shephard, Jonathan D.

2015-07-01

Endoluminal surgery for the treatment of early stage colorectal cancer is typically based on electrocautery tools which imply restrictions on precision and the risk of harm through collateral thermal damage to the healthy tissue. As a potential alternative to mitigate these drawbacks we present laser machining of pig intestine by means of picosecond laser pulses. The high intensities of an ultrafast laser enable nonlinear absorption processes and a predominantly nonthermal ablation regime. Laser ablation results of square cavities with comparable thickness to early stage colorectal cancers are presented for a wavelength of 1030 nm using an industrial picosecond laser. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue. The depth of the ablation can be controlled precisely by means of the pulse energy. Overall, the application of ultrafast lasers to ablate pig intestine enables significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional techniques.

Co:MgF2 laser ablation of tissue: effect of wavelength on ablation threshold and thermal damage.

PubMed

Schomacker, K T; Domankevitz, Y; Flotte, T J; Deutsch, T F

1991-01-01

The wavelength dependence of the ablation threshold of a variety of tissues has been studied by using a tunable pulsed Co:MgF2 laser to determine how closely it tracks the optical absorption length of water. The Co:MgF2 laser was tuned between 1.81 and 2.14 microns, a wavelength region in which the absorption length varies by a decade. For soft tissues the ablation threshold tracks the optical absorption length; for bone there is little wavelength dependence, consistent with the low water content of bone. Thermal damage vs. wavelength was also studied for cornea and bone. Thermal damage to cornea has a weak wavelength dependence, while that to bone shows little wavelength dependence. Framing-camera pictures of the ablation of both cornea and liver show explosive removal of material, but differ as to the nature of the explosion.

Use of a Piezosurgery Technique to Remove a Deeply Impacted Supernumerary Tooth in the Anterior Maxilla

PubMed Central

Sukegawa, Shintaro; Kanno, Takahiro; Kawakami, Kiyokazu; Shibata, Akane; Takahashi, Yuka; Furuki, Yoshihiko

2015-01-01

Deeply impacted supernumerary teeth in the anterior maxillary cannot be generally removed by the conventional labial or palatal surgical approach because of the risk of damaging the surrounding soft tissues and the possibility of injuring the roots of adjacent permanent teeth. In piezosurgery, bony tissues are selectively cut, thereby avoiding the soft tissue damage caused by rotary cutting instruments. We report the case of a 15-year-old Japanese boy from whom a deeply impacted supernumerary tooth in the anterior maxillary was safely removed through the floor of the nasal cavity. The surgical extraction was performed without damaging the nasal mucosa or adjacent structures such as the roots of the adjacent permanent teeth. Considering that piezosurgery limits the extent of surgical invasion, this technique can be practiced as a minimally invasive and safe surgical procedure for treating suitably selected cases with a deeply impacted supernumerary tooth. PMID:26779355

75 FR 24737 - Extension of the Designation of Nicaragua for Temporary Protected Status and Automatic Extension...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... global economic crisis. Economic development has also been hindered and disrupted by electoral fraud and... damaged water supplies, leaving whole communities lacking potable water. According to the United Nations...

Carotid rupture following electrical injury: a report of two cases.

PubMed

Toy, Jonathan; Ball, Brandon J; Tredget, Edward E

2012-01-01

Electrical injuries often result in extensive tissue damage where vascular damage may occur and result in thrombosis and spontaneous rupture of blood vessels. Rupture of the brachial, radial, ulnar, internal mammary, and obturator arteries has been reported in the literature. The authors present two cases of carotid artery rupture following high-voltage electrical injuries. The first case is a 21-year-old man who was climbing a fence near a high-voltage power line when a gold chain he was wearing around his neck caught on the power line, resulting in a 10% circumferential electrical injury to his neck. He presented with visible arterial bleeding from the large neck wound and was taken to the operating room, where a 1-cm laceration to the carotid artery was repaired with a vein patch. On the second postoperative day, the patch dislodged, and a spontaneous rupture of the common carotid artery occurred. The damaged artery was subsequently ligated. The patient recovered with no neurological sequelae. The second case is a 43-year-old man who suffered a high-voltage injury while working on an electrical panel, resulting in a 50% TBSA full-thickness burn to the face, scalp, trunk, and extremities. Four weeks after admission, a latissimus dorsi myocutaneous free flap was used for coverage of exposed outer table of the skull. Intraoperatively, the carotid artery spontaneously ruptured proximal to where the dissection was being carried out. The patient recovered with no neurological sequelae. High-voltage electrical injury results in significant damage to blood vessels via a number of mechanisms. Rupture of a major vessel is a rare, life-threatening sequelae of electrical injury.

Evaluation of a biomimetic 3D substrate based on the Human Elastin-like Polypeptides (HELPs) model system for elastolytic activity detection.

PubMed

Corich, Lucia; Busetti, Marina; Petix, Vincenzo; Passamonti, Sabina; Bandiera, Antonella

2017-08-10

Elastin is a fibrous protein that confers elasticity to tissues such as skin, arteries and lung. It is extensively cross-linked, highly hydrophobic and insoluble. Nevertheless, elastin can be hydrolysed by bacterial proteases in infectious diseases, resulting in more or less severe tissue damage. Thus, development of substrates able to reliably and specifically detect pathogen-secreted elastolytic activity is needed to improve the in vitro evaluation of the injury that bacterial proteases may provoke. In this work, two human biomimetic elastin polypeptides, HELP and HELP1, as well as the matrices derived from HELP, have been probed as substrates for elastolytic activity detection. Thirty strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients were analyzed in parallel with standard substrates, to detect proteolytic and elastolytic activity. Results point to the HELP-based 3D matrix as an interesting biomimetic model of elastin to assess bacterial elastolytic activity in vitro. Moreover, this model substrate enables to further elucidate the mechanism underlying elastin degradation at molecular level, as well as to develop biomimetic material-based devices responsive to external stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis, characterization and in vivo evaluation of biocompatible ferrogels

NASA Astrophysics Data System (ADS)

Lopez-Lopez, M. T.; Rodriguez, I. A.; Rodriguez-Arco, L.; Carriel, V.; Bonhome-Espinosa, A. B.; Campos, F.; Zubarev, A.; Duran, J. D. G.

2017-06-01

A hydrogel is a 3-D network of polymer chains in which water is the dispersion medium. Hydrogels have found extensive applications in the biomedical field due to their resemblance to living tissues. Furthermore, hydrogels can be endowed with exceptional properties by addition of synthetic materials. For example, magnetic field-sensitive gels, called ferrogels, are obtained by embedding magnetic particles in the polymer network. Novel living tissues with unique magnetic field-sensitive properties were recently prepared by 3-D cell culture in biocompatible ferrogels. This paper critically reviews the most recent progress and perspectives in their synthesis, characterization and biocompatibility evaluation. Optimization of ferrogels for this novel application requires low-density, strongly magnetic, multi-domain particles. Interestingly, the rheological properties of the resulting ferrogels in the absence of field were largely enhanced with respect to nonmagnetic hydrogels, which can only be explained by the additional cross-linking imparted by the embedded magnetic particles. Remarkably, rheological measurements under an applied magnetic field demonstrated that ferrogels presented reversibly tunable mechanical properties, which constitutes a unique advantage with respect to nonmagnetic hydrogels. In vivo evaluation of ferrogels showed good biocompatibility, with only some local inflammatory response, and no particle migration or damage to distant organs.

Antibiotic penetration into bone in relation to the immediate management of open fractures: a review.

PubMed

Hughes, S P

1992-01-01

Bone is a vascular structure, which is capable of responding to changes in the systemic circulation. Antibiotics carried within the systemic circulation reach the capillaries in bone, and depending on molecular size, pass through the capillary walls to enter the fluid space. Following an open fracture, contamination with pathogenic organisms can occur both at the moment of injury, but also in the hospital, which is a particular problem in grade III fractures in which extensive soft tissue damage can occur in combination with an exposed wound. Antibiotics administered intravenously can be measured in bone by both bioassay and radioactive isotope techniques and are shown to reach bone in effective concentrations. It is apparent that short-course high-dose antibiotic therapy is appropriate for open fractures, and need not be continued as long as the normal fracture-healing process continues. However if infection in bone develops, further surgery is important to remove new dead tissue to allow adequate antibiotic penetration into bone. Thus antibiotics are useful when combined with effective surgical management, but do not on their own offer the only answer to management of the patient.

The Pathogenesis of Ebola Virus Disease.

PubMed

Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

2017-01-24

For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.