Hardware Removal in Maxillofacial Trauma: A Retrospective Study.

BACKGROUND: Miniplates are commonly used for the fixation of maxillofacial fracture segments. Removal of the hardware is controversial. A retrospective study of medical records was performed to observe the reasons for plate removal. MATERIALS AND METHODS: A 10-year retrospective study of medical records was performed. Demographics, type of fracture, location, type of miniplate used, the time gap between the insertion and removal, and causes of hardware removal were assessed. RESULTS: About 1472 patients had undergone internal fixation for the facial fractures. Stainless steel miniplate was used in 489 patients, and titanium was used in 983 patients. Out of the 42 cases, 22 cases involved the removal of titanium hardware and 20 patients involved the removal of stainless steel hardware. Infection/osteomyelitis was the main cause of hardware removal. The maximum amount of hardware failure was in the mandible. 78.6% of hardware removal was performed in males. CONCLUSION: Based on our study, routine removal of titanium miniplates can be performed in children to avoid growth disturbances, not indicated in adult patients unless symptomatic.

Interspecific differences in the effects of masking and distraction on anti-predator behavior in suburban anthropogenic noise.

Predation is a common threat to animal survival. The detection of predators or anti-predator communication signals can be disrupted by anthropogenic noise; however, the mechanism by which responses are affected is unclear. Masking and distraction are the two hypotheses that have emerged as likely explanations for changes in behavior in noise. Masking occurs when the signal and noise fall within the same sensory domain; noise overlapping the energy in the signal reduces signal detection. Distraction can occur when noise in any sensory domain contributes to a greater cognitive load, thereby reducing signal detection. Here, we used a repeated measures field experiment to determine the relative contributions of masking and distraction in mediating reduced anti-predator responses in noise. We recorded the approaches and vocalizations of black-capped chickadees (Poecile atricapillus), tufted titmice (Baeolophus bicolor), and white-breasted nuthatches (Sitta carolinensis) to both visual and acoustic cues of predator presence, either with or without simultaneous exposure to anthropogenic noise. Titmice increased their calling to both visual and acoustic cues of predator presence. However, there was no significant effect of noise on the calling responses of titmice regardless of stimulus modality. Noise appeared to produce a distraction effect in chickadees; however, this effect was small, suggesting that chickadees may be relatively unaffected by low levels of anthropogenic noise in suburban environments. White-breasted nuthatch calling behavior was affected by the interaction of the modality of the predator stimulus and the noise condition. Nuthatches had a delayed response to the predator presentations, with a greater calling rate following the presentation of the acoustic stimulus in quiet compared to the presentation of the acoustic stimulus in noise. However, there was no difference in calling rate between the quiet and noise conditions for the visual stimulus. Together this suggests that even moderate levels of noise have some masking effect for white-breasted nuthatches. We suggest that the mechanisms through which noise influences anti-predator behavior may depend on the social roles, foraging ecology and auditory capabilities of each species.

Isocytosine-based inhibitors of xanthine oxidase: design, synthesis, SAR, PK and in vivo efficacy in rat model of hyperuricemia.

Structure-activity relationship studies were carried out for lead generation following structure-guided design approach from an isocytosine scaffold identified earlier for xanthine oxidase inhibition. A 470-fold improvement in in vitro IC(50) was obtained in the process. Five most potent compounds with nanomolar IC(50) values were selected for pharmacokinetics and in vivo experiments. The best compound showed good in vivo activity when administered intraperitoneally but was not active by oral route. The results suggest that improvement in oral exposure could improve the in vivo efficacy of this series.

Thoughts and beliefs of healthcare workers regarding the coronavirus disease 2019 (COVID-19) vaccine and which messaging themes might affect vaccine confidence and recommendation of the vaccine.

We surveyed healthcare workers within the Duke Antimicrobial Stewardship Outreach Network (DASON) to describe beliefs regarding coronavirus disease 2019 (COVID-19) vaccination and their decision-making process behind vaccination recommendations. In contrast to the type of messaging that appealed most on a personal level to the healthcare workers, they preferred a more generic message emphasizing safety and efficacy when making vaccination recommendations.

Employing the Forced Oscillation Technique for the Assessment of Respiratory Mechanics in Adults.

There is increasing interest in the use of the forced oscillation technique (FOT) or oscillometry to characterize respiratory mechanics in healthy and diseased individuals. FOT, a complementary method to traditional pulmonary function testing, utilizes a range of oscillatory frequencies superimposed on tidal breathing to measure the functional relationship between airway pressure and flow. This passive assessment provides an estimate of respiratory system resistance (Rrs) and reactance (Xrs) that reflect airway caliber and energy storage and dissipation, respectively. Despite the recent increase in popularity and updated Technical Standards, clinical adoption has been slow which relates, in part, to the lack of standardization regarding the acquisition and reporting of FOT data. The goal of this article is to address the lack of standardization across laboratories by providing a comprehensive written protocol for FOT and an accompanying video. To illustrate that this protocol can be utilized irrespective of a particular device, three separate FOT devices have been employed in the case examples and video demonstration. This effort is intended to standardize the use and interpretation of FOT, provide practical suggestions, as well as highlight future questions that need to be addressed.

Evaluation of Opioid Overdose Reports in Patients Treated with Extended-Release Naltrexone: Postmarketing Data from 2006 to 2018.

INTRODUCTION: After treatment with naltrexone extended-release injectable suspension (XR-NTX), a µ-opioid receptor antagonist, opioid tolerance is reduced from pretreatment baseline. Patients may be vulnerable to opioid overdose if they attempt to override the blockade during treatment, at the end of a dosing interval, after missing a dose, or after discontinuing treatment. OBJECTIVE: We analyzed postmarketing data to characterize reporting rates of opioid overdose during treatment with and after discontinuation of XR-NTX. METHODS: Postmarketing adverse event reports within the XR-NTX safety database, received 2006-2018, for patients treated with XR-NTX for any indication were reviewed for opioid overdose cases. Assessable cases were categorized by timing of the event from the last dose of XR-NTX (latency): ≤28 days (on treatment), 29-56 days, and >56 days from last dose of XR-NTX. Within each latency group, cases were further classified as serious and, of those, cases that had a fatal outcome. RESULTS: During the 12-year period, an estimated 495,602 patients received XR-NTX. Opioid overdose was reported in 161 cases; of these, 66 contained sufficient information to determine latency. Reporting rates of opioid overdose per 10,000 patients treated were similar among latency groups: 0.54 for ≤28 days (0.24 fatal), 0.34 for 29-56 days (0.16 fatal), and 0.44 for >56 days (0.40 fatal) from the last dose of XR-NTX. CONCLUSIONS: Over the 12-year period, the reporting rates of opioid overdose were similar during treatment with or after discontinuation of XR-NTX and <10/10,000 patients exposed. Our findings are limited by the nature of spontaneously reported safety data.

Comparison of linezolid and daptomycin for the treatment of vancomycin-resistant enterococcal bacteremia.

Vancomycin-resistant enterococcal bacteremia (VRE-B) is a common nosocomial infection associated with significant morbidity and mortality. Daptomycin and linezolid are primary treatment options although definitive clinical data to assess comparative therapeutic effectiveness are lacking. This study assessed the outcomes of patients with VRE-B treated with linezolid or daptomycin. This was a single-center, retrospective cohort study evaluating adult patients with VRE-B treated with either daptomycin or linezolid admitted between January 2012 and August 2016 at a tertiary care, academic medical center. The primary outcome was clinical failure, a composite outcome defined as 14-day in-hospital mortality, microbiologic failure, or relapse of VRE-B. Secondary outcomes included 14-day in-hospital mortality, microbiologic failure, relapse of VRE-B, duration of VRE-B, and antibiotic failure. A multivariate logistic regression model was performed to adjust for potential confounding variables. A total of 93 patients were included (n = 62 for linezolid and n = 31 for daptomycin). All blood isolates were Enterococcus faecium. Overall clinical failure was 55.9% and 14-day in-hospital mortality was 21.5%. There was a significantly higher rate of clinical failure in the daptomycin group as compared with the linezolid-treated patients (74.2% versus 46.8%; p = 0.01; respectively). In multivariate logistic regression analysis, there was a significantly higher odds of clinical failure for patients treated with daptomycin as compared with linezolid (adjusted odds ratio 2.89; 95% confidence interval 1.08-7.75) after adjusting for confounders. Secondary outcomes were not statistically significantly different between study groups. Standard-dose (6 mg/kg) daptomycin treatment was associated with a higher rate of clinical failure as compared with linezolid treatment.

Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury.

Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single-cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the submucosal glands (SMGs) proliferate and migrate to repopulate the airway surface epithelium (SE) in multiple injury models. Specifically, SMG-derived cells display multipotency and contribute to basal and luminal cell types of the SMGs and SE. Ex vivo expanded MECs have the potential to repopulate and differentiate into SE cells when grafted onto denuded airway scaffolds. Significantly, we find that SMG-like cells appear on the SE of both extra- and intra-lobular airways of large animal lungs following severe injury. We find that the transcription factor SOX9 is necessary for MEC plasticity in airway regeneration. Because SMGs are abundant and present deep within airways, they may serve as a reserve cell source for enhancing human airway regeneration.

Oral trimethoprim/sulfamethoxazole in the treatment of acne vulgaris.

Oral trimethoprim/sulfamethoxazole (TMP-SMX) is approved by the US Food and Drug Administration for the treatment of urinary tract infections, shigellosis, acute otitis media in pediatric patients, and Pneumocystis carinii pneumonia. TMP-SMX has been used off label in dermatology to treat various skin conditions, including acne vulgaris and other skin and soft tissue infections, especially those infections caused by methicillin-resistant Staphylococcus aureus.

Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis.

1. Adenosine is a potent endogenous regulator of inflammation and tissue repair. Adenosine, which is released from injured and hypoxic tissue or in response to toxins and medications, may induce pulmonary fibrosis in mice, presumably via interaction with a specific adenosine receptor. We therefore determined whether adenosine and its receptors contribute to the pathogenesis of hepatic fibrosis. 2. As in other tissues and cell types, adenosine is released in vitro in response to the fibrogenic stimuli ethanol (40 mg dl(-1)) and methotrexate (100 nM). 3. Adenosine A(2A) receptors are expressed on rat and human hepatic stellate cell lines and adenosine A(2A) receptor occupancy promotes collagen production by these cells. Liver sections from mice treated with the hepatotoxins carbon tetrachloride (CCl(4)) (0.05 ml in oil, 50 : 50 v : v, subcutaneously) and thioacetamide (100 mg kg(-1) in PBS, intraperitoneally) released more adenosine than those from untreated mice when cultured ex vivo. 4. Adenosine A(2A) receptor-deficient, but not wild-type or A(3) receptor-deficient, mice are protected from development of hepatic fibrosis following CCl(4) or thioacetamide exposure. 5. Similarly, caffeine (50 mg kg(-1) day(-1), po), a nonselective adenosine receptor antagonist, and ZM241385 (25 mg kg(-1) bid), a more selective antagonist of the adenosine A(2A) receptor, diminished hepatic fibrosis in wild-type mice exposed to either CCl(4) or thioacetamide. 6. These results demonstrate that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis, and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis.

Evaluating pharmacy leader development through the seven action logics.

PURPOSE: Pharmacy leader development over time was analyzed using the seven action logics. METHODS: As part of an ongoing leadership seminar series, students were required to select a visionary pharmacy leader and conduct a structured interview to evaluate pharmacy leaders' action logics. A standardized questionnaire comprising 13 questions was created by the class. Questions addressed leadership qualities during the leaders' early years, education years, and work years. Transcripts were then coded by two separate trained investigators based on the leader's stage of life to provide a score for each action logic individually over time. Kappa coefficient was used to evaluate interrater agreement. RESULTS: A total of 14 leaders were interviewed. All leaders were currently employed and had won national awards for their contributions to pharmacy practice. Overall, there was 82% agreement between the two evaluators' scores for the various characteristics. Action logics changed based on the leaders' life stage. Using aggregate data from all leader interviews, a progression from lower-order action logics (opportunist, diplomat, expert) to higher-order action logics (strategist, alchemist) was found. Ten leaders (71%) were diplomats during their early years. Six leaders (43%) were experts during their education years, and 4 (29%) were strategists or alchemists. During the third life stage analyzed (the work years), 6 leaders (43%) were strategists, and 2 were alchemists. During their work years, all leaders had a percentage of their answers coded as alchemist (range, 5-22%). CONCLUSION: Throughout their professional careers, pharmacy leaders continually develop skills through formal education and mentorship that follow action logics.

Pharmacy Practice Model Initiative task force report: Improving participation in a survey on hospital pharmacy practices in Texas.

PURPOSE: Results of an initiative to increase participation in a survey on hospital pharmacy practices are reported. METHODS: In an initiative led by pharmacy residents at the University of Houston College of Pharmacy, a task force was created to boost the rate of response to the Hospital-Assessment Survey (HSA), an online benchmarking tool developed as part of the ASHP-sponsored Pharmacy Practice Model Initiative (PPMI). Under the guidance of leaders from ASHP's Texas affiliate and state health-system pharmacy leaders, an 11-member team of residents targeted Texas hospitals that had not responded to the HSA as of December 2013 and used phone and e-mail methods to encourage survey participation. Data obtained from newly responding institutions were aggregated with previously collected data on Texas facilities and compared with national data. RESULTS: During the 11-week initiative, 66 new HSA responses were received from Texas hospitals, raising the total number of respondents to 89 and boosting the overall participation rate from 4.3% to 16.7% (p <0.001). Analysis of the survey data indicated broad similarities among small and large Texas hospitals with regard to six optimal practice characteristics. Pharmacy practice models and characteristics in Texas overall were largely consistent with national statistics. CONCLUSION: The involvement of the PPMI task force was associated with a substantial increase in the survey response rate. The survey results indicated that, with a few exceptions, practice models and the use of optimal practices were similar at Texas hospitals of various sizes and between Texas hospitals overall and sampled hospitals nationwide.

Adenosine A2A receptor agonists promote more rapid wound healing than recombinant human platelet-derived growth factor (Becaplermin gel).

Animal studies of the topical application of adenosine A2A receptor agonists show that it promotes wound closure. To further confirm the efficacy of adenosine A2A receptor agonists as promoters of wound healing, we compared the effect of MRE0094, a novel selective adenosine A2A receptor agonist, to CGS-21680, a reference selective adenosine A2A receptor agonist, as well as to recombinant human platelet-derived growth factor (0.01% Becaplermin gel), an agent currently used to promote healing of diabetic ulcers, on wound closure in healthy BALB/C mice. Wounds (approximately 12 mm diameter) were created on the dorsum of mice (two per mouse) and then treated daily with vehicle, 0.01% Becaplermin gel, or different doses of the adenosine A2A receptor agonists. The wound margins were traced onto plastic sheets, and the wound areas were digitized, quantitated, and compared. We found that application of MRE0094 (1 microg/wound and 10 microg/wound) and CGS-21680 (1 microg/wound and 5 microg/wound) achieved 50% wound closure significantly more rapidly than control application (day 1.9, 1.9, 3.5, 3.2, respectively, versus control day 4, p < 0.05 ANOVA). Surprisingly, neither higher nor lower concentrations of CGS-21680 affected the rate of wound closure, as compared to control. In contrast, Becaplermin gel did not increase the rate at which wounds closed (50% closure by day 7.2, p = NS versus control). These data confirm our prior observations that adenosine A2A receptor agonists promote wound closure, and they suggest that these agents may be as effective if not more effective than Becaplermin gel for the treatment of poorly healing wounds.

Dermatofibrosarcoma protuberans: a case report and review of the literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing fibrohistiocytic neoplasm that commonly favors young to middle-aged adults. It is most commonly seen on the trunk and frequently recurs locally after an incomplete excision, but distant metastasis is rare. Mohs micrographic surgery (MMS) is the treatment of choice for DFSP.

Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis.

Prior studies demonstrate that adenosine, acting at one or more of its receptors, mediates the anti-inflammatory effects of methotrexate in animal models of both acute and chronic inflammation. Both adenosine A2A and A3 receptors contribute to the anti-inflammatory effects of methotrexate treatment in the air pouch model of inflammation, and the regulation of inflammation by these two receptors differs at the cellular level. Because different factors may regulate inflammation at different sites we examined the effect of low-dose weekly methotrexate treatment (0.75 mg/kg/week) in a model of acute peritoneal inflammation in adenosine A2A receptor knockout mice and A3 receptor knockout mice and their wild-type littermates. Following intraperitoneal injection of thioglycollate there was no significant difference in the number or type of leukocytes, tumor necrosis factor alpha (TNF-alpha) and IL-10 levels that accumulated in the thioglycollate-induced peritoneal exudates in adenosine A2A knockout mice or wild-type control mice. In contrast, there were more leukocytes, TNF-alpha and IL-10 in the exudates of the adenosine A3 receptor-deficient mice. Low-dose, weekly methotrexate treatment increased the adenosine concentration in the peritoneal exudates of all mice studied, and reduced the leukocyte accumulation in the wild-type mice and A3 receptor knockout mice but not in the A2A receptor knockout mice. Methotrexate reduced exudate levels of TNF-alpha in the wild-type mice and A3 receptor knockout mice but not the A2A receptor knockout mice. More strikingly, IL-10, a critical regulator of peritoneal inflammation, was increased in the methotrexate-treated wild-type mice and A3 knockout mice but decreased in the A2A knockout mice. Dexamethasone, an agent that suppresses inflammation by a different mechanism, was similarly effective in wild-type mice, A2A mice and A3 knockout mice. These findings provide further evidence that adenosine is a potent regulator of inflammation that mediates the anti-inflammatory effects of methotrexate. Moreover, these data provide strong evidence that the anti-inflammatory effects of methotrexate and adenosine are mediated by different receptors in different inflammatory loci, an observation that may explain why inflammatory diseases of some organs but not of other organs respond to methotrexate therapy.

The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn.

Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord blood monocytes demonstrate severe impairment in TNF-alpha production in response to triacylated (TLR 2/1) and diacylated (TLR 2/6) bacterial lipopeptides (BLPs). We now demonstrate that in marked contrast, BLP-induced synthesis of IL-6, a cytokine with anti-inflammatory and Th2-polarizing properties, is actually greater in neonates than adults. Remarkably, newborn blood plasma confers substantially reduced BLP-induced monocyte synthesis of TNF-alpha, while preserving IL-6 synthesis, reflecting the presence in neonatal blood plasma of a soluble, low molecular mass inhibitory factor (<10 kDa) that we identify as adenosine, an endogenous purine metabolite with immunomodulatory properties. The neonatal adenosine system also inhibits TNF-alpha production in response to whole microbial particles known to express TLR2 agonist activity, including Listeria monocytogenes, Escherichia coli (that express BLPs), and zymosan particles. Selective inhibition of neonatal TNF-alpha production is due to the distinct neonatal adenosine system, including relatively high adenosine concentrations in neonatal blood plasma and heightened sensitivity of neonatal mononuclear cells to adenosine A3 receptor-mediated accumulation of cAMP, a second messenger that inhibits TLR-mediated TNF-alpha synthesis but preserves IL-6 production. We conclude that the distinct adenosine system of newborns polarizes TLR-mediated cytokine production during the perinatal period and may thereby modulate their innate and adaptive immune responses.

Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1.

Topical adenosine A2A receptor agonists promote wound healing by, among other effects, increasing microvessel formation. Results of representational display analysis of human umbilical vein endothelial cells suggested that A2A receptor occupancy modulates expression of the antiangiogenic matrix protein thrombospondin 1 (TSP1). We therefore determined whether A2A receptor occupation stimulates angiogenesis by modulating TSP1 secretion. Human microvascular endothelial cells (HMVEC) were treated with medium alone, 2-p-[2-carboxyethyl] phenethyl-amino-5'-N-ethylcarboxamido-adenosine (CGS-21680), or 2-[2-(4-chlorophenyl)ethoxy]adenosine (MRE0094), selective A2A receptor agonists. TSP1 protein secretion was down-regulated after treatment with the A2A agonists CGS-21680 or MRE0094 in a dose-dependent manner (EC50 = 6.65 nM and 0.23 microM respectively). The selective A2A receptor antagonist 4-[2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl]phenol (ZM241385) but not the A1 and A2B receptor antagonists diphenylcyclopentylxanthine, enprofylline, and N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamide (MRS1706) completely abrogated the A2A receptor agonist-mediated effect on TSP1. Vascular tube formation by HMVEC was increased by adenosine A2A receptor agonists in a dose-dependent fashion (EC50 = 0.1 microM for both), and this effect was reversed by the A2A antagonist. Moreover, in the presence of antibodies to TSP1 and CD36, the receptor for TSP1, the adenosine A2A receptor agonists stimulated no increase in vascular tube formation. These results indicate that the angiogenic effects of adenosine A2A receptor activation are, at least in part, caused by the suppression of TSP1 secretion.

Genetically based resistance to the antiinflammatory effects of methotrexate in the air-pouch model of acute inflammation.

OBJECTIVE: Low-dose methotrexate (MTX), a mainstay in the treatment of rheumatoid arthritis, is effective in only 60-70% of patients, a finding mirrored by poor antiinflammatory efficacy in some animal models, most notably collagen-induced arthritis. To determine whether genetic factors or the model itself is responsible for the poor response to MTX, we directly compared the responses of 4 inbred mouse strains to MTX in the air-pouch model of acute inflammation. METHODS: The exudate leukocyte count and adenosine concentration were determined in inbred mice treated with MTX (0.75 mg/kg intraperitoneally every week for 4 weeks) or vehicle 4 hours after injection of carrageenan into the air pouch using previously described methods. Quantitative trait locus mapping was performed using an in silico, or computer-based, method to identify loci potentially associated with each phenotype. RESULTS: MTX significantly reduced the exudate leukocyte count in C57BL/6J and BALB/cJ mice, but not DBA/1J (the strain used in the collagen-induced arthritis model) or DBA/2J mice. In a parallel manner, MTX increased adenosine concentration in inflammatory exudates of C57BL/6J and BALB/cJ mice, but not DBA/1J or DBA/2J mice. Antiinflammatory and adenosine responses to MTX in DBA/1J x C57BL/6J F(1) and F(2) offspring were most consistent with single genetic loci being responsible for each phenotype. In silico mapping identified partially overlapping loci containing candidate genes involved in both responses. CONCLUSION: Genetic factors contribute to the antiinflammatory efficacy of MTX, and a single locus involved in MTX-induced adenosine up-regulation is likely responsible for the observed resistance to MTX in DBA/1J mice.

Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors.

Recent evidence indicates that topical application of adenosine A(2A) receptor agonists, unlike growth factors, increases the rate at which wounds close in normal animals and promotes wound healing in diabetic animals as well as growth factors, yet neither the specific adenosine receptor involved nor the mechanism(s) by which adenosine receptor occupancy promotes wound healing have been fully established. To determine which adenosine receptor is involved and whether adenosine receptor-mediated stimulation of angiogenesis plays a role in promotion of wound closure we compared the effect of topical application of the adenosine receptor agonist CGS-21680 (2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosine) on wound closure and angiogenesis in adenosine A(2A) receptor knockout mice and their wild-type littermates. There was no change in the rate of wound closure in the A(2A) receptor knockout mice compared to their wild-type littermates although granulation tissue formation was nonhomogeneous and there seemed to be greater inflammation at the base of the wound. Topical application of CGS-21680 increased the rate of wound closure and increased the number of microvessels in the wounds of wild-type mice but did not affect the rate of wound closure in A(2A) receptor knockout mice. Similarly, in a model of internal trauma and repair (murine air pouch model), endogenously produced adenosine released into areas of internal tissue injury stimulates angiogenesis because there was a marked reduction in blood vessels in the walls of healing air pouches of A(2A) receptor knockout mice compared to their wild-type controls. Inflammatory vascular leakage and leukocyte accumulation in the inflamed air pouch were similarly reduced in the A(2A) receptor knockout mice reflecting the reduced vascularity. Thus, targeting the adenosine A(2A) receptor is a novel approach to promoting wound healing and angiogenesis in normal individuals and those suffering from chronic wounds.