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Tissue Injury (tissue + injury)
Kinds of Tissue Injury Selected AbstractsAlloimmune Activation Enhances Innate Tissue Inflammation/Injury in a Mouse Model of Liver Ischemia/Reperfusion InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010X. Shen The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these ,Ag-specific' cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo-Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF-,, IL-1, and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo-Ag sensitization in liver IRI. Furthermore, CD154, but not IFN-,, was the key mechanism in allo-Tx recipients to facilitate IR-triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag-nonspecific CD154-dependent but IFN-, independent mechanism. [source] Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in miceHEPATOLOGY, Issue 6 2000Olivier Le Moine M.D. Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-,) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-, were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-, release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-, release (,66% or ,41%, ,95% or ,94%, and ,70% or ,70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell, and macrophage-dependent cytokines. [source] Does l -carnitine have any effect on cold preservation injury of non-fatty liver in the University of Wisconsin solution?HEPATOLOGY RESEARCH, Issue 8 2007Abdurrahman Coskun Aim:, To evaluate the protective effect of l -carnitine on liver tissue preserved in University of Wisconsin (UW) solution. Methods:, Twenty Wistar Albino rats were divided into two groups, a control (UW) group and a UW plus l -carnitine group. Retrieved liver grafts were preserved in UW and UW plus l -carnitine solutions at +4°C. Preservation solution samples were assessed at 2, 24, 36, and 48 h to measure alanine aminotransferase and acid phosphatase activity. Tissue injury was scored on paraffin sections. Results:, No micro or macrovacuolar fat droplets were observed in the tissue slices. l -Carnitine effectively decreased enzyme release when added to UW solution (P < 0.05). Conclusion:, In addition to fatty liver, l -carnitine might be a metabolic adjunct in preservation solutions for non-fatty liver within UW solution. [source] Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2006Göksel Abstract:, Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU. [source] Trauma: physiology, pathophysiology, and clinical implicationsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2006DACVA, DACVECC, William Muir DVM Abstract Objective: To review the physiology, pathophysiology, and consequences of trauma. The therapeutic implications of hypovolemia, hypotension, hypothermia, tissue blood flow, oxygen delivery, and pain will be discussed. Data Sources: Human and veterinary clinical and research studies. Human and veterinary data synthesis: Trauma is defined as tissue injury that occurs more or less suddenly as a result of violence or accident and is responsible for initiating hyothalamic,pituitary,adrenal axis, immunologic and metabolic responses that are designed to restore homeostasis. Tissue injury, hemorrhage, pain, and fear are key components of any traumatic event. Trauma and blood loss result in centrally integrated autonomic-mediated cardiovascular responses that are designed to increase heart rate, systemic vascular resistance, and maintain arterial blood pressure (ABP) to vital organs at the expense of blood flow to the gut and skeletal muscle. Severe trauma elicits exuberant physiologic, immunologic, and metabolic changes predisposing the animal to organ malfunction, a systemic inflammatory response, infection, and multiple organ dysfunctions. The combination of both central and local influences produces regional redistribution of blood flow among and within tissue beds which, when combined with impaired vascular reactivity, leads to maldistribution of blood flow to tissues predisposing to tissue hypoperfusion and impaired oxygen delivery and extraction. Gut blood flow and viability may serve as a sentinel of patient survival. These consequences are magnified in animals suffering from pain or that become hypothermic. Successful treatment of traumatized animals goes beyond the restoration of blood pressure and urine output, is dependent on a fundamental understanding of the pathophysiologic processes responsible for the animals current physical status, and incorporates the reduction of pain, stress, and the systemic inflammatory response and methods that restore microcirculatory blood flow and tissue oxygenation. Conclusions: Severe trauma is a multifaceted event and is exacerbated by hypothermia, pain, and stress. Therapeutic approaches must go beyond the simple restoration of vascular volume and ABP by maintaining tissue blood flow, restoring tissue oxygenation, and preventing systemic inflammation. [source] ENDOPLASMIC RETICULUM STRESS INVOLVED IN HEART AND LIVER INJURY IN IRON-LOADED RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2009Li-Xia Lou SUMMARY 1Iron overload contributes to the pathogenesis of various diseases and directly induces tissue injury. In the present study, we investigated the relationship between heart and liver injury induced by iron overload and cellular endoplasmic reticulum (ER) stress to explore the molecular mechanism of iron overload-induced cellular injury. 2Iron overload in rats was generated by intraperitoneal injection of iron,dextran chronically (30 mg/kg per day for 9 weeks) or acutely (300 mg/kg once). Tissue injury was assessed by determining serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as malondialdehyde (MDA) content in the heart and liver. The ER stress response was analysed by expression of glucose-response protein 78 (GRP78) and activation of caspase 12. 3In chronic iron-loaded rats, iron levels in the heart and liver were higher, by approximately 2-and 7.8-fold, respectively (P < 0.01), compared with control. Serum LDH, ALT and AST activity, as well as MDA content, GRP78 expression and caspase 12 activity in the heart and liver, were upregulated in chronically iron-loaded rats. In acute iron-loaded rats, iron content in the heart and liver was 51% and 63% higher than in controls (both P < 0.01). Serum LDH, ALT and AST activity, MDA content in the heart and liver and levels of ER stress markers were all increased in acute iron-loaded rats. N -Acetylcysteine (150 mg/kg, s.c.) lowered the levels of these parameters in acute iron-loaded rats. 4The results of the present study indicate that ER stress may play an important role in iron-induced tissue injury and that reactive oxygen species may mediate the ER stress response in the pathogenesis of iron-overload cellular injury. [source] Oral trauma, mouthguard awareness, and use in two contact sports in TurkeyDENTAL TRAUMATOLOGY, Issue 5 2006Ibrahim Tulunoglu Abstract,,, The purpose of the present study was to evaluate the occurrence of dental hard and soft tissue injuries during participation in contact sports, and the awareness and use of mouthguards in a young adult sample of semi-professional or amateur boxers and tae kwon do participants in Turkey. The samples consisted of 274 young adults [174 male (63.5%) and 100 female (36.5%)] aged between 17 and 27 years of which 185 (67.5%) were tae kwon do practitioners, and 89 (32.5%) were boxers. The participants answered a standard questionnaire. All answers were evaluated and then statistical analyses were performed. Of the total sample, 61 of the subjects (22.3%) suffered dental trauma. Of these sufferers, 32 (17.3%) were boxers and 29 (32.6%) were tae kwon do practitioners. It was found that 19 (6.9%) athletes lost their teeth post-trauma. Of the 54 subjects (19.7%) suffering soft tissue injuries, 44 were female (81.5%), while only 10 were male (18.5%), of which 40 (74.1%) were tae kwon do practitioners and 14 (25.9%) were boxers. Of the total sample of 274 subjects, 228 (83.2%) were well informed about mouthguard usage. Of the total sample, 153 (55.8%) of the subjects used mouthguards, all of which were boil-and-bite type. The results of our study indicate that dentists and sports authorities in Turkey should promote the use of mouthguards in contact sports such as tae kwon do and boxing, which have a serious risk for dental and oral soft tissue trauma and tooth loss. [source] Dental emergencies presenting to a dental teaching hospital due to complications from traumatic dental injuriesDENTAL TRAUMATOLOGY, Issue 4 2002Suhad H. Al-JundiArticle first published online: 29 JUL 200 Abstract ,,,In Jordan, only two surveys of dental trauma have been carried out. The aim of this study was to determine the incidence and pattern of dental emergencies resulting from traumatic injuries, as well as treatment provided to children presenting with these dental emergencies. Over a 1-year period, 620 children presented to our pediatric dental clinics with dental emergencies; 195 (31%) of these emergencies were a consequence of dental trauma to 287 teeth and were included in the study. The average time between the trauma and the dental emergency was 5 months. Pain or sensitivity was the most frequent presenting symptom (31.3%) followed by swelling or sinus tract (17.4%). The age of these patients ranged from 15 months to 14 years, with an average age of 9.3 years. Males accounted for 75.4% of the children in the samples, whereas females accounted for only 24.6%. The main cause of dental trauma was falling during play (58.5%); the least common cause was motor vehicle accidents, accounting for only 1.5% of all injuries. Most of the dental injuries occurred at home (41.5%), around noon time. The most commonly involved teeth were permanent maxillary central incisors accounting for 79.5% of all teeth involved by dental trauma. The most frequently encountered type of trauma in this sample was crown fracture seen in 76.6% of the teeth . Soft tissue injuries were estimated to occur in 16.9% of the children. The treatment received by the children in the sample ranged from no active treatment (6.2%) to elaborate dental procedures such as pulp therapy (41.3%) and prosthetic replacement of missing teeth (5.1%). [source] Collateral desmitis of the distal interphalangeal joint in conjunction with concurrent ossification of the cartilages of the foot in nine horsesEQUINE VETERINARY EDUCATION, Issue 9 2008T. S. Mair Summary The purpose of this study was to describe the frequency of occurrence of severe ossification of the collateral cartilages (sidebone) coexistent with collateral desmitis of the distal interphalangeal joint (DIPJ) in lame horses. Sidebone was diagnosed and graded on standard radiographs and soft tissue injuries of the foot were diagnosed using standing low-field magnetic resonance imaging (MRI). Of 15 horses with forelimb lameness and severe sidebone, 9 had evidence of concurrent collateral desmitis of the DIPJ. All 15 horses had damage to other structures (including the deep digital flexor tendon, distal sesamoidean impar ligament, collateral sesamoidean ligament, navicular bone and distal phalanx) within the affected feet as identified on MRI. The clinical and pathophysiological significance of concurrent collateral desmitis of the DIPJ and sidebone is currently uncertain. However, this study shows that injuries to multiple structures within the foot are common and that collateral desmitis of the distal interphalangeal joint is frequently seen in lame horses in conjunction with severe ossification of the collateral cartilages. [source] Post mortem survey of dental disorders in 349 donkeys from an aged population (2005,2006).EQUINE VETERINARY JOURNAL, Issue 3 2008Part 1: Prevalence of specific dental disorders Summary Reasons for performing study: Donkey dental disorders are being recognised with increased frequency worldwide and have important welfare implications; however, no detailed investigations of dental disorders in donkeys appear to have been published. Objectives: To determine the prevalence of specified dental disorders in donkeys by performing a prospective post mortem study on donkeys that were subjected to euthanasia or died for other reasons at the Donkey Sanctuary, UK. Methods: Post mortem examinations were performed on 349 donkeys over an 18 month period, 2005,2006. The presence and extent of specified dental disorders were recorded and these data analysed to determine their prevalence and common locations. 45Results: A high prevalence (93%) of disorders was noted in the population with a median age of 31 years. In particular, cheek teeth diastemata (85% prevalence) were very common, often associated with advanced periodontal disease. Other disorders observed included missing teeth (in 55.6% of donkeys), displaced teeth (43%), worn teeth (34%), local overgrowths (15%), focal sharp overgrowths (3%) and dental-related soft tissue injuries (8%). Conclusions and potential relevance: Aged donkeys have a high prevalence of significant dental disease, especially cheek teeth diastemata. These findings highlight the importance of routine dental examinations and prophylactic dental treatments to improve the dental health and welfare of donkeys. [source] Proximal interphalangeal joint instability in the dogJOURNAL OF SMALL ANIMAL PRACTICE, Issue 9 2003M. J. Guilliard A prospective study into the use of transarticular external skeletal fixation in the treatment of proximal interphalangeal instability was undertaken. Only dogs with soft tissue injuries were included. All the dogs except one were greyhounds or related breeds. A hypothesis was proposed that if the articular surfaces were held in normal congruency for a period of time then the development of periarticular fibrosis would alone give sufficient joint support. Joint congruency was maintained by the application of a unilateral external skeletal fixator for approximately three weeks. Complications were common and were due to frame impingement on the neighbouring digit, pin tract infection and pin loosening, and all resolved following frame removal and antibiotic therapy. Careful pinplacement and prophylactic antibiotic treatment prevented complications in subsequent cases. All dogs returned to normal function with no lameness, with the exception of one racing greyhound which had a recurrence of the instability. [source] Relationship of age, injury severity, injury type, comorbid conditions, level of care, and survival among older motor vehicle trauma patients,RESEARCH IN NURSING & HEALTH, Issue 3 2005Linda J. Scheetz Abstract The purpose of this secondary data analysis was to compare age, injury severity, injury types, selected comorbidities, level of care (at trauma center [TC] and non,trauma center [NTC] hospitals), and survival among older motor vehicle trauma patients (N,=,1,478). Patients admitted to both levels of care had similar comorbid conditions. TC patients had a higher injury severity, whereas NTC patients had a greater proportion of soft tissue injuries. Results of logistic regression analyses subsequent to group comparisons revealed that higher injury severity was associated with TC admission. The likelihood of TC admission of severely injured patients decreased in the presence of spinal, internal, and head injuries. Internal injuries, liver, renal, and cardiovascular diseases were associated with non-survival while hypertension was associated with survival. Special attention is needed when triaging older trauma patients because their injuries may be covert, thus putting them at risk for admission to a level of care that may be inappropriate given the extent of their injuries. © 2005 Wiley Periodicals, Inc. Res Nurs Health 28: 198,209, 2005 [source] Baicalin attenuates air embolism-induced acute lung injury in rat isolated lungsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009Min-Hui Li Background and purpose:, Baicalin has been reported to have anti-inflammatory effects and protect against various tissue injuries. However, the effect of baicalin on air embolism-induced acute lung injury has not been tested yet. Experimental approach:, Acute lung injury was induced by infusion of air at a rate of 0.25 mL·min,1 for 1 min into the pulmonary artery of rat isolated lungs. At the end of the experiment, samples were collected for assessment of lung injury, biochemical analysis and histology. Different doses of baicalin (1, 2 and 4 mg·kg,1) were given into the perfusate before air infusion. Key results:, Air embolism elicited a significant increase in microvascular permeability (Kf), lung weight gain, wet/dry weight ratio, pulmonary artery pressure and protein concentration in the bronchoalveolar lavage fluid. Levels of the cytokines, tumour necrosis factor , and cytokine-induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels and myeloperoxidase activities in lung tissue were also significantly increased. In addition, histological examination showed increased neutrophil infiltration in lung tissues. Furthermore, nuclear factor-,B activity and degradation of I,B-, were significantly increased in lungs. Pretreatment of the lungs with baicalin (4 mg·kg,1) showed a statistically significant difference in all of the assessed parameters, except for alteration in the pulmonary artery pressure. Conclusions and implications:, Our study suggests that baicalin attenuated air embolism-induced acute lung injury and may be considered a useful adjunct drug therapy in this clinical condition. [source] Pluripotent plasticity of stem cells and liver repopulationCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2010Luisa Gennero Abstract Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver. Copyright © 2010 John Wiley & Sons, Ltd. [source] Big snake, small snake: which wound is worse when bitten?ACTA PAEDIATRICA, Issue 8 2009Kam-Lun Ellis Hon Abstract Snakebites in children and teenagers are relatively uncommon in the metropolitan city of Hong Kong. They are rarely fatal but may cause significant morbidity and fear. We report two cases of snakebites to illustrate that the spectrum of morbidity is independent of the size of the snakes. A 7-year-old boy was bitten in successions by a green snake. Envenomation occurred at the second bite site. He developed local and systemic signs that were promptly relieved with anti-venom therapy at the intensive care unit. An 18-year-old girl was bitten by a large python but only sustained minor local soft tissue injuries. This report serves to alert the public that snake may bite in successions and envenomation may occur with the subsequent bite. Conclusion:, A small snake may be venomous and a large snake may not be. Avoidable risk factors associated with snakebites (such as avoiding areas known to harbour snakes in the evening in summer and autumn and wearing protective footwear) are highlighted. [source] Clinical investigation of traumatic injuries in Yeditepe University, Turkey during the last 3 yearsDENTAL TRAUMATOLOGY, Issue 4 2005Nuket Sandalli Abstract,,, The aim of this study was to evaluate etiology, types of traumatic dental injuries, treatment and to determine the incidence of complications according to dental injuries in patients who referred to Yeditepe University, Faculty of Dentistry, Istanbul, Turkey. The study was based on the clinical data of the 161 traumatized teeth in 92 patients. WHO classification slightly modified by Andreasen & Andreasen for dental trauma was used. The causes and localization of trauma, traumatized teeth classification, treatment and complications were evaluated both primary and permanent teeth. The distribution of complications according to diagnosis and treatment of the injured teeth were evaluated. Of 35 (38%) girls and 56 (72%) boys with a mean age 7.6 ± 3.5 (ranging 1,14.2) participated to study and the mean followed up was 1.72 ± 1.28 years (ranging 0.10,3.8 years). From the 161 affected teeth, 69 (42.9%) were in primary teeth and 92 (57.1%) in permanent teeth. The highest frequency of trauma occurred in the 6,12 year age group. Overall boys significantly outnumbered girls by approximately 1:1.6. The most common type of injury in the primary and permanent teeth was seen as luxation (38%) and enamel fracture (20%) of the maxillary central incisors, respectively. Falls were the major sources of trauma both the primary (90%) and the permanent teeth (84%). In the primary dentition, the most common type of soft tissue injury is contusion (62.5%) and in the permanent dentition, it is laceration (49%). The most of the treatment choice was determined as examination only and extraction in primary teeth (58 and 24.6%, respectively) while it was applied as restoration and pulpectomy in permanent teeth (31.5 and 18.5%, respectively). Complications were recorded on 37 teeth (23%) with a most common type of necrosis (10.5%) and dental abscess (7.4%). Necrosis was more frequent in luxation whereas dental abscess were in crown fracture with pulpal involvement in both dentitions. The study showed that boys were more prone to dental traumas than girls. Falls were more frequent trauma type with a high complication risk. It reveals that the time of the immediate treatment showed the important predisposing factors that increase the success of treatment and decrease the risk of complication. The correct diagnosis of dental injuries is more important for eliminating the occurrence of complications. [source] Hypothermic insult to the periodontium: a model for the study of aseptic tooth resorptionDENTAL TRAUMATOLOGY, Issue 1 2000C. W. Dreyer Abstract , The aim of the current investigation was to define an animal model for the study of hard tissue resorption by examining the responses of the periodontal ligament (PDL) to both single and multiple episodes of hypothermic injury to the crowns of rat teeth. A group of 12 male rats weighing 200,250 g were anesthetized, and pellets of dry ice (CO2) were applied once to the crowns of the right first maxillary molars for continuous periods of 10 or 20 min. Animals were sacrificed at 2, 7, 14 and 28 days and tissues were processed for routine histological examination. A second group of eight animals and a third group of 12 animals were subjected to three applications of dry ice over a period of 1 week and sacrificed at 2 and 14 days respectively after the final application. In addition to thermal insult, the periodontium of teeth from a fourth group of six rats was subjected to mechanical trauma. Examination of the sections from the group undergoing a single freezing episode revealed that, by 1 week, shallow resorption lacunae had appeared on the root surface. These became more extensive after 14 days. At the same time hyaline degeneration was evident in the PDL. Within this group, teeth subjected to the longer 20-min application times generally showed more extensive injuries. By 28 days, evidence of repair was observed with reparative cementum beginning to line the resorption lacunae in the root dentin. Sections from animals subjected to multiple episodes of thermal trauma and those subjected to additional mechanical insult showed more extensive external root resorption than those from single-injury animals. It was concluded that low temperature stimuli applied to the crowns of rat molars were capable of eliciting a sterile degenerative response in the PDL which, in turn, resulted in external root resorption. Furthermore, the degree of this tissue injury was commensurate with the duration and number of exposures to the trauma. The results also indicated that progression of the resorptive process required periodic exposure to the injury, in the absence of which repair to the damaged root occurred. [source] Laser-Assisted Hair Transplantation: Histologic Comparison Between CO2 and Ho:YAG LasersDERMATOLOGIC SURGERY, Issue 4 2001Eugene A. Chu MD Background. Various laser wavelengths and devices have been advocated for use in the creation of recipient channels during hair transplant surgery, including flash-scanned CO2, Ho:YAG (, = 2.12 ,m), and Er:YAG (, = 2.94 ,m). Objective. To determine the tissue injury caused by flash-scanned CO2 and pulsed Ho:YAG lasers during the creation of hair transplant recipient channels and to assess the efficacy of the Ho:YAG laser. Methods. Recipient channels were created in vivo in human scalp tissue using both lasers, and were excised and prepared for histologic examination. Optical micrometry of tissue sections was used to assess thermal injury. Results. The Ho:YAG laser created jagged, irregular-shaped channels with larger zones of thermal injury (superficial deepithelialization, thermal necrosis, and thermal damage). In contrast, the CO2 laser produced well-defined cylindrically shaped channels free of cellular debris with minimal epithelial disruption and significantly less lateral thermal injury. Conclusion. Given that the Ho:YAG produced larger regions of thermal injury and recipient channels that were unacceptable for graft, the CO2 laser remains the better choice for the creation of recipient channels during hair transplant surgery. However, ongoing research will be necessary to determine the optimal laser wavelength and/or devices for this procedure. [source] Evaluation of systemic oxidative status and mononuclear leukocytes DNA damage in children with caustic esophageal strictureDISEASES OF THE ESOPHAGUS, Issue 4 2006M. Kaya SUMMARY., Esophageal stricture (ES) due to accidentally caustic digestions is a common problem in children. Mucosal damage and repeated dilatations lead to chronic inflammation and finally ES. We investigated the oxidative status and DNA damage of children with ES. Five children with ES were compared with the same age- and sex-matched healthy subjects. Oxidative status of plasma was evaluated by measuring myeloperoxidase (MPO) activity, and total peroxide (TP) level. Anti-oxidative status of the plasma was evaluated by measuring catalase (CAT) activity, and total antioxidant response (TAR). We used the Single Cell Gel Electrophoresis (also called Comet Assay) to measure DNA strand break in peripheral blood mononuclear leukocytes. Mean MPO activity and TP levels in the ES group were significantly higher than the control group (0.83 ± 0.35, 0.09 ± 0.03 and 0.98 ± 0.38, 0.34 ± 0.20, P = 0.009 and P = 0.047 respectively). There was no significant difference in CAT activity and TAR levels between the two groups (P = 0.347). DNA damage in patients with ES was increased compared to control subjects (108.8 ± 51.2 and 57.6 ± 31.2 arbitrary units, respectively), but this difference was not significant statistically (P= 0.09). This study shows that systemic oxidative stress and alteration at the nuclear level occur in patients with ES, as a result of multiple dilatations and tissue injury. On the other hand, these results support that patients with ES may benefit from antioxidant treatment. [source] White-eyed blowout fracture: Another lookEMERGENCY MEDICINE AUSTRALASIA, Issue 3 2009Patrick Mehanna Abstract Orbital floor fractures have the potential to cause significant morbidity both in the short and long terms and commonly present to the ED for initial assessment. Although treatment of the majority of these injuries involves clinic review and possible later surgery, there is a specific subset that present to emergency clinically suggestive of a head injury. This subset, ,white-eyed blowout', usually occurring under 18 years of age, with a history of trauma and little sign of soft tissue injury, describes a trap door orbital floor fracture with herniation and acute entrapment of orbital muscle and is regarded as a maxillofacial emergency. The injury presents with marked nausea, vomiting, headache and irritability suggestive of a head injury that commonly distracts from the true aetiology. It requires prompt diagnosis and treatment to avoid permanent morbidity. We present three cases and discuss their management. [source] Inflammatory nerve responses in the dental pulpENDODONTIC TOPICS, Issue 1 2007INGE FRISTAD Tooth pulp has a dense innervation and a rich vascular supply to maintain homeostasis and to preserve the integrity of the tissue. Function, trauma, and antigenic challenges make teeth and supporting tissues susceptible to tissue injury and inflammation, partially due to the lack of collateral blood and nerve supply and to their low compliance. This review focuses on dental nerve functions and adaptive changes in the pulpal nerve supply following inflammation and peripheral injury. Overviews of dental innervation and its development and of the peptidergic innervation of oral tissues are presented, followed by a discussion of peripheral and central changes after local insults to teeth and peripheral nerve injuries. The functional implications of these adaptive changes are considered. Received 13 February 2009; accepted 3 September 2009. [source] Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxideEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2004W. B. Borke Abstract Background, Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia,reoxygenation injury. Objective, To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O2 at different PaCO2 -levels. Methods, Newborn pigs (12,36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O2 at different PaCO2 levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay. Results, Matrix metalloproteinase-2 more than doubled from baseline values (P < 0·001), and was higher in piglets resuscitated with 100% O2 than with ambient air (P = 0·012). The ORAC value was considerably decreased (P < 0·001). In piglets with elevated PaCO2, total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0·008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO2 than in the piglets with elevated PaCO2 (P = 0·013). Conclusion, In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O2. Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO2 during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium. [source] Molecular mimicry in innate immunity?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008The viral RNA recognition receptor TLR7 accelerates murine lupus Abstract Toll-like receptors (TLR), such as TLR7, were first described as innate pathogen recognition receptors that trigger appropriate antimircrobial immune responses upon exposure to pathogen-associated molecules, e.g. viral ssRNA. In parallel to ongoing studies on TLR-biology, mounting experimental evidence suggests that endogenous RNA-related autoantigens may also activate dendritic cells (DC) and B cells through TLR7. TLR7-mediated DC activation, autoantibody secretion, lymphoproliferation, and autoimmune tissue injury, are frequently observed in various murine models of systemic lupus and lupus nephritis. A paper in the current issue of the European Journal of Immunology, provide striking experimental evidence for this concept; the authors show that the Y chromosome-linked autoimmune accelerating (Yaa) translocation from the X-chromosome, consisting of 16 genes including Tlr7, largely mediates the autoimmune phenotype via the duplication of Tlr7. This finding highlights the need to address the significance of TLR7 in human lupus in terms of both genetic risk and as a therapeutic option. See accompanying article: http://dx.doi.org/10.1002/eji.200838138 [source] Activation of the Nrf2/antioxidant response pathway increases IL-8 expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2005Xiaolan Zhang Abstract Oxidant stress can initiate or enhance inflammatory responses during tissue injury, possibly through activation of redox-sensitive chemokines. Because the transcription factor Nrf2 (NF-E2-related factor,2) is responsive to oxidative stress, and induces expression of cytoprotective and antioxidant genes that attenuate tissue injury, we postulated that Nrf2 may also regulate chemokine expression. To test this hypothesis, Nrf2 expression was directly increased in primary human kidney mesangial cells and aortic endothelial cells, or cell lines with an adenoviral construct, and the effects on the pro-inflammatory chemokine interleukin-8 (IL-8) were assessed. Nrf2 expression significantly increased IL-8 mRNA levels and protein secretion. Nrf2 caused only a weak induction of IL-8 transcription, but significantly increased the half-life of IL-8 mRNA. These data demonstrate that activation of the Nrf2/antioxidant response pathway induces expression of IL-8. The dominant mechanism of Nrf2-mediated IL-8 induction is through mRNA stabilization. Considering the evidence that Nrf2 activation is mainly cytoprotective, these observations raise the possibility that under certain circumstances IL-8 may serve an anti-inflammatory role and thereby contribute to the resolution of tissue injury. See accompanying commentary http://dx.doi.org/10.1002/eji.200535489 [source] Contribution of the Reelin signaling pathways to nociceptive processingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008Alin L. Akopians Abstract The reeler gene encodes Reelin, a secreted glycoprotein that binds to the very-low-density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer,2), and induces Src- and Fyn-mediated tyrosine phosphorylation of the intracellular adaptor protein Disabled-1 (Dab1). This Reelin,Dab1 signaling pathway regulates neuronal positioning during development. A second Reelin pathway acts through Apoer,2,exon 19 to modulate synaptic plasticity in adult mice. We recently reported positioning errors in reeler dorsal horn laminae I,II and V, and the lateral spinal nucleus. Behavioral correlates of these positioning errors include a decreased mechanical and increased thermal sensitivity in reeler mice. Here we examined mice with deletions or modifications of both the Reelin,Dab1 signaling pathway and the Reelin,Apoer,2,exon 19 pathway on a Vldlr-deficient background. We detected reeler -like dorsal horn positioning errors only in Dab1 mutant and Apoer,2/Vldlr double mutant mice. Although Dab1 mutants, like reeler, showed decreased mechanical and increased thermal sensitivity, neither the single Vldlr or Apoer,2 knockouts, nor the Apoer,2,exon 19 mutants differed in their acute pain sensitivity from controls. However, despite the dramatic alterations in acute ,pain' processing in reeler and Dab1 mutants, the exacerbation of pain processing after tissue injury (hindpaw carrageenan injection) was preserved. Finally, we recapitulated the reeler dorsal horn positioning errors by inhibiting Dab1 phosphorylation in organotypic cultures. We conclude that the Reelin,Dab1 pathway differentially contributes to acute and persistent pain, and that the plasticity associated with the Reelin,Apoer,2,exon 19 pathway is distinct from that which contributes to injury-induced enhancement of ,pain' processing. [source] Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skinEXPERIMENTAL DERMATOLOGY, Issue 3 2002László Virág Abstract: In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO,), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO, on various cellular processes may explain the ,double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing ,cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases. [source] Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidasesFEBS JOURNAL, Issue 5 2008Shoichiro Mukai Hepatocyte growth factor activator (HGFA) is a serine protease and a potent activator of prohepatocyte growth factor/scatter factor (pro-HGF/SF), a multifunctional growth factor that is critically involved in tissue morphogenesis, regeneration, and tumor progression. HGFA circulates as a zymogen (pro-HGFA) and is activated in response to tissue injury. Although thrombin is considered to be an activator of pro-HGFA, alternative pro-HGFA activation pathways in tumor microenvironments remain to be identified. In this study, we examined the effects of kallikrein 1-related peptidases (KLKs), a family of extracellular serine proteases, on the activation of pro-HGFA. Among the KLKs examined (KLK2, KLK3, KLK4 and KLK5), we identified KLK4 and KLK5 as novel activators of pro-HGFA. Using N-terminal sequencing, the cleavage site was identified as the normal processing site, Arg407,Ile408. The activation of pro-HGFA by KLK5 required a negatively charged substance such as dextran sulfate, whereas KLK4 could process pro-HGFA without dextran sulfate. KLK5 showed more efficient pro-HGFA processing than KLK4, and was expressed in 50% (13/25) of the tumor cell lines examined. HGFA processed by these KLKs efficiently activated pro-HGF/SF, and led to cellular scattering and invasion in vitro. The activities of both KLK4 and KLK5 were strongly inhibited by HGFA inhibitor type 1, an integral membrane Kunitz-type serine protease inhibitor that inhibits HGFA and other pro-HGF/SF-activating proteases. These data suggest that KLK4 and KLK5 mediate HGFA-induced activation of pro-HGF/SF within tumor tissue, which may thereafter trigger a series of events leading to tumor progression via the MET receptor. [source] Complement and its implications in cardiac ischemia/reperfusion: strategies to inhibit complementFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2001Tiphaine Monsinjon Although reperfusion of the ischemic myocardium is an absolute necessity to salvage tissue from eventual death, it is also associated with pathologic changes that represent either an acceleration of processes initiated during ischemia or new pathophysiological changes that were initiated after reperfusion. This so-called ,reperfusion injury' is accompanied by a marked inflammatory reaction, which contributes to tissue injury. In addition to the well known role of oxygen free radicals and white blood cells, activation of the complement system probably represents one of the major contributors of the inflammatory reaction upon reperfusion. The complement may be activated through three different pathways: the classical, the alternative, and the lectin pathway. During reperfusion, complement may be activated by exposure to intracellular components such as mitochondrial membranes or intermediate filaments. Two elements of the activated complement contribute directly or indirectly to damages: anaphylatoxins (C3a and C5a) and the membrane attack complex (MAC). C5a, the most potent chemotactic anaphylatoxin, may attract neutrophils to the site of inflammation, leading to superoxide production, while MAC is deposited over endothelial cells and smooth vessel cells, leading to cell injury. Experimental evidence suggests that tissue salvage may be achieved by inhibition of the complement pathway. As the complement is composed of a cascade of proteins, it provides numerous sites for pharmacological interventions during acute myocardial infarction. Although various strategies aimed at modulating the complement system have been tested, the ideal approach probably consists of maintaining the activity of C3 (a central protein of the complement cascade) and inhibiting the later events implicated in ischemia/reperfusion and also in targeting inhibition in a tissue-specific manner. [source] Activation of the complement system in human nonalcoholic fatty liver disease,HEPATOLOGY, Issue 6 2009Sander S. Rensen Activation of the innate immune system plays a major role in nonalcoholic fatty liver disease (NAFLD). The complement system is an important component of innate immunity that recognizes danger signals such as tissue injury. We aimed to determine whether activation of the complement system occurs in NAFLD, to identify initiating pathways, and to assess the relation between complement activation, NAFLD severity, apoptosis, and inflammatory parameters. Liver biopsies of 43 obese subjects with various degrees of NAFLD and of 10 healthy controls were analyzed for deposition of complement factors C1q, mannose-binding lectin (MBL), C4d, activated C3, and membrane attack complex (MAC)-associated C9. Furthermore, hepatic neutrophil infiltration, apoptosis, and pro-inflammatory cytokine expression were quantified. Whereas complement activation was undetectable in the liver of healthy subjects, 74% of the NAFLD patients showed hepatic deposition of activated C3 and C4d. C1q as well as MBL accumulation was found in most activated C3-positive patients. Strikingly, 50% of activated C3-positive patients also displayed MAC-associated C9 deposition. Deposition of complement factors was predominantly seen around hepatocytes with macrovesicular steatosis. Subjects showing accumulation of activated C3 displayed increased numbers of apoptotic cells. Importantly, hepatic neutrophil infiltration as well as interleukin (IL)-8 and IL-6 expression was significantly higher in patients showing activated C3 deposition, whereas patients with C9 deposition additionally had increased IL-1, expression. Moreover, nonalcoholic steatohepatitis (NASH) was more prevalent in patients showing hepatic C9 or activated C3 deposition. Conclusion: There is widespread activation of the complement system in NAFLD, which is associated with disease severity. This may have important implications for the pathogenesis and progression of NAFLD given the function of complement factors in clearance of apoptotic cells, hepatic fibrosis, and liver regeneration. (HEPATOLOGY 2009.) [source] Incubation phase of acute hepatitis B in man: Dynamic of cellular immune mechanismsHEPATOLOGY, Issue 5 2000George J.M. Webster After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease. [source] | ||||||||||||||||||||||||||||||||||||||||