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Background: Adolescent and young adults (AYA) with Type 1 Diabetes (T1D) experience more difficulty with glycemic control than patients in all other age groups. The shared medical appointment (SMA) model has been effective in multiple healthcare populations, but the feasibility and effectiveness of SMA in AYA patients with T1D is unclear., Methods: This research leverages the team's multidisciplinary expertise to develop an engaging intervention toolkit and test the implementation of the Team Clinic care model for the treatment of T1D among middle school adolescents in a large urban children's hospital serving an economically, racially and ethnically diverse population. In Phase 1, the team will manualize the Team Clinic care model into an engaging, age-appropriate educational and intervention toolkit. In Phase 2, the team will conduct a randomized clinical trial to test the feasibility and usability of the toolkit from the provider perspective (team member satisfaction; clinical efficiency; compliance with American Diabetes Association, American Association of Diabetes Educators, and California Children's Services standards; and payor-level cost data) and the preliminary efficacy of the intervention toolkit on patient- and family-level outcomes (attendance, acceptability/satisfaction with care, patient-level cost data, diabetes outcomes, diabetes family conflict, diabetes distress, and depression)., Discussion: AYA patients with T1D often receive care in clinics and institutions with limited resources and time. This research tests the feasibility and efficacy of an innovative and potentially cost-effective SMA model to address the unique needs of underserved populations, while meeting national and state clinical standards. Trial registration The study is registered with ClinicalTrials.gov (Protocol Record: NCT04190368)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest or competing interests pertinent to this study. The authors have no financial relationships relevant to this article to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alternative and sustainable protein sources (e.g., algae, duckweed, insects) are required to produce (future) foods. However, introduction of new food sources to the market requires a thorough risk assessment of nutritional, microbial and toxicological risks and potential allergic responses. Yet, the risk assessment of allergenic potential of novel proteins is challenging. Currently, guidance for genetically modified proteins relies on a weight-of-evidence approach. Current Codex (2009) and EFSA (2010; 2017) guidance indicates that sequence identity to known allergens is acceptable for predicting the cross-reactive potential of novel proteins and resistance to pepsin digestion and glycosylation status is used for evaluating de novo allergenicity potential. Other physicochemical and biochemical protein properties, however, are not used in the current weight-of-evidence approach. In this study, we have used the Random Forest algorithm for developing an in silico model that yields a prediction of the allergenic potential of a protein based on its physicochemical and biochemical properties. The final model contains twenty-nine variables, which were all calculated using the protein sequence by means of the ProtParam software and the PSIPred Protein Sequence Analysis program. Proteins were assigned as allergenic when present in the COMPARE database. Results show a robust model performance with a sensitivity, specificity and accuracy each greater than ≥85%. As the model only requires the protein sequence for calculations, it can be easily incorporated into the existing risk assessment approach. In conclusion, the model developed in this study improves the predictability of the allergenicity of new or modified food proteins, as demonstrated for insect proteins., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Platelet rich plasma (PRP) is rich in growth factors and has been shown to improve healing in a variety of wounds. We determined the effects of PRP on healing and scarring in full thickness porcine burns with and without tangential excision and grafting (TEG)., Methods: Standardized full thickness 5cm by 5cm burns were created on each of the backs and flanks of 10 anesthetized female pigs (25kg) using a validated model. The burns were created with a heating device that emits heat at a temperature of 400°C for a period of 30s. The burns were randomized to one of six treatments: no TEG or PRP, no TEG+PRP, early (day 2) TEG and no PRP, early TEG+PRP, late (day 14) TEG and no PRP, and late TEG+PRP. Tangential excision was performed down to viable tissue and autografts were 0.2mm thick. When used, a thin layer of autologous PRP was applied below the graft. All wounds were then treated with a topical antibiotic ointment 3 times weekly for 42 days. Digital images and full thickness biopsies were taken at 9, 11, 14, 18, 21, 28, 35 and 42days after injury to determine percentage reepithelialization, scar depth, and scar contraction. Tissue sections were stained with H&E and viewed by a dermatopathologist masked to treatment assignment., Results: There was no reduction in platelet and white blood cell concentrations in PRP and blood samples for the first 14days after-full thickness burns. A total of 120 burns were created on 10 animals evenly distributed between the six treatment groups. Burns undergoing early TEG reepithelialized fastest and with the thinnest scars followed by late TEG. Burns that did not undergo TEG had the slowest reepithelialization and greatest amount of scarring. Application of PRP had no additional effects on reepithelialization, scar depth, or scar contraction in any of the treatment groups., Conclusions: Addition of PRP had similar effects on reepithelialization and scarring of full thickness porcine burns as standard topical antibiotic ointment regardless of whether the burns underwent excision or grafting or the timing of excision and grafting., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

It is known in humans and mouse models, that drinking water exposures to arsenite (As +3 ) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As +3 , and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As +3 via drinking water for 30d. Oxidation State Specific Hydride Generation- Cryotrapping- Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA +3 ) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA +3 levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As +3 and MMA +3 revealed that bone marrow cells are most sensitive to As +3 treatment, and MMA +3 is more genotoxic than As +3 . These results suggest that the differential sensitivities of the three immune organs to As +3 exposure are due to the different intracellular arsenic species and concentrations, and that MMA +3 may play a critical role in immunotoxicity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Genetically modified (GM) crops have achieved success in the marketplace and their benefits extend beyond the overall increase in harvest yields to include lowered use of insecticides and decreased carbon dioxide emissions. The most widely grown GM crops contain gene/s for targeted insect protection, herbicide tolerance, or both. Plant expression of Bacillus thuringiensis (Bt) crystal (Cry) insecticidal proteins have been the primary way to impart insect resistance in GM crops. Although deemed safe by regulatory agencies globally, previous studies have been the basis for discussions around the potential immuno-adjuvant effects of Cry proteins. These studies had limitations in study design. The studies used animal models with extremely high doses of Cry proteins, which when given using the ig route were co-administered with an adjuvant. Although the presumption exists that Cry proteins may have immunostimulatory activity and therefore an adjuvanticity risk, the evidence shows that Cry proteins are expressed at very low levels in GM crops and are unlikely to function as adjuvants. This conclusion is based on critical review of the published literature on the effects of immunomodulation by Cry proteins, the history of safe use of Cry proteins in foods, safety of the Bt donor organisms, and pre-market weight-of-evidence-based safety assessments for GM crops., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Current methods of assessing burn depth are limited and are primarily based on visual assessments by burn surgeons. This technique has been shown to have only 60% accuracy and a more accurate, simple, noninvasive method is needed to determine burn wound depth. Forward-looking infrared (FLIR) thermography is both noninvasive and user-friendly with the potential to rapidly assess burn depth. The purpose of this paper is to determine if early changes in burn temperature (first 3 days) can be a predictor of burn depth as assessed by vertical scarring 28 days after injury., Methods: While under general anesthesia, 20 burns were created on the backs of two female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150g aluminum bar, for a total of 40 burns. FLIR imaging was performed at both early (1, 2 and 3 days) and late (7, 10, 14, 17, 21, 24 and 28 days) time points. Burns were imaged from a height of 12 inches from the skin surface. FLIR ExaminIR(©) software was used to examine the infrared thermographs. One hundred temperature points from burn edge to edge across the center of the burn were collected for each burn at all time points and were exported as a comma-separated values (CSV) file. The CSV file was processed and analyzed using a MATLAB program. The temperature profiles through the center of the burns generated parabola-like curves. The lowest temperature (temperature minimum) and a line midway between the temperature minimum and ambient skin temperature at the burn edges was defined and the area of the curve calculated (the "temperature half-area")., Results: Half-area values 2 days after burn had higher correlations with scar depth than did the minimum temperatures. However, burns that became warmer from 1 day to 2 days after injury had a lower scar depth then burns that became cooler and this trend was best predicted by temperature minima. When data were analyzed as a diagnostic test for sensitivity and specificity using >3mm scarring, i.e. a full-thickness burn, as a clinically relevant criterion standard, temperature minima at 2 days after burn was found to be the most sensitive and specific test., Conclusions: FLIR imaging is a fast and simple tool that has been shown to predict burn wound outcome in a porcine vertical injury progression model. Data showed that more severe burn wounds get cooler between 1 and 2 days after burn. We found four analytic methods of FLIR images that were predictive of burn progression at 1 and 2 days after burn; however, temperature minima 2 days after burn appeared to be the best predictive test for injury progression to a full-thickness burn. Although these results must be validated in clinical studies, FLIR imaging has the potential to aid clinicians in assessing burn severity and thereby assisting in burn wound management., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: In order to be useful, animal models should be reproducible and consistent regardless of sampling bias, investigator creating burn, and burn location. We determined the variability in burn depth based on biopsy location, burn location and investigator in a porcine model of partial thickness burns., Methods: 24 partial thickness burns (2.5 cm by 2.5 cm each) were created on the backs of 2 anesthetized pigs by 2 investigators (one experienced, one inexperienced) using a previously validated model. In one of the pigs, the necrotic epidermis covering each burn was removed. Five full thickness 4mm punch biopsies were obtained 1h after injury from the four corners and center of the burns and stained with Hematoxylin and Eosin and Masson's trichrome for determination of burn depth by a board certified dermatopathologist blinded to burn location and investigator. Comparisons of burn depth by biopsy location, burn location and investigator were performed with t-tests and ANOVA as appropriate., Results: The mean (SD) depth of injury to blood vessels (the main determinant of burn progression) in debrided and non-debrided pigs pooled together was 1.8 (0.3)mm, which included 75% of the dermal depth. Non-debrided burns were 0.24 mm deeper than debrided burns (P<0.001). Burn depth increased marginally from cephalic to caudal in non-debrided burns, but showed no statistical differences for these locations, in debrided burns. Additionally, there were also no statistical differences in burn depths from midline to lateral in either of these burn types. Burn depth was similar for both investigators and among biopsy locations., Conclusions: Burn depth was greater for caudal locations in non-debrided burns and overall non-debrided burns were deeper than debrided burns. However, burn depth did not differ based on investigator, biopsy site, and medial-lateral location., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

The measurement of endogenous allergens is required by the European Commission (EC) as part of the compositional analysis for GM products from host plants that are common causes of food allergy, such as soybean (EC Implementing Regulation No. 503/2013). In each case, the EC Implementing Regulation indicates that analysis be conducted on identified allergens as specified in the Organization of Economic Cooperation and Development (OECD) consensus documents on compositional considerations for new plant varieties. This communication discusses the methods available to measure endogenous allergens as well as the endogenous soybean allergens that should be analyzed. It is suggested herein that in conjunction with the 2012 OECD consensus document on soybean, any list of soybean allergens should be based on clinically relevant data among publicly available allergen databases and peer-reviewed scientific publications, and the ability to measure the identified allergen. Based on a detailed analysis of the scientific literature, the following key points are recommended: (1) the acceptance of serum-free, quantitative analytical method data as an alternative to traditional IgE reactivity qualitative or semi-quantitative data for evaluation of endogenous soybean allergen content; (2) eight of the 15 potential allergens listed in the OECD soybean consensus document (Gly m 3, Gly m 4, Gly m Bd28K, Gly m Bd30K, Gly m 5, Gly m 6, Gly m 8, and Kunitz trypsin inhibitor) have both appropriate supporting clinical data and sufficient sequence information to be evaluated in comparative endogenous soybean allergen studies; and (3) the remaining seven proteins (Gly m 1, Gly m 2, unknown 50kDa protein, unknown 39kDa protein, P-22-25, lipoxygenase and lectin) lack sufficient data for clear classification as confirmed allergens and/or available sequence information and should not be currently included in the measurement of endogenous soybean allergens in the compositional analysis for the EU., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Precise content of gliadin (Glia) and glutenin (Glu) proteins in wheat grain are largely unknown despite their association with celiac disease, various allergies, and physical processing properties of wheat. Developing methods to quantitatively measure clinically relevant proteins could support advancement in understanding exposure thresholds and clinical study design. The aim of this study was to use a data-independent mass spectrometry (MS(E)) approach for quantifying gliadin and glutenin proteins in wheat grain. The biologically replicated analysis yielded concentrations for 34 gliadin and 22 glutenin proteins. The primary focus of this survey was on measuring celiac disease proteins and baker's asthma associated proteins along with the proteins associated with viscoelastic properties of wheat flour and grain texture. The technical coefficients of variation ranged from 0.12 to 1.39 and indicate that MS(E) proteomics is a reproducible quantitative method for the determination of gliadin and glutenin content in the highly complex matrix of protein extracts from wheat grain. This article is part of a Special Issue entitled: Translational Plant Proteomics., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Global regulatory agencies require bioinformatic sequence analysis as part of their safety evaluation for transgenic crops. Analysis typically focuses on encoded proteins and adjacent endogenous flanking sequences. Recently, regulatory expectations have expanded to include all reading frames of the inserted DNA. The intent is to provide biologically relevant results that can be used in the overall assessment of safety. This paper evaluates the relevance of assessing the allergenic potential of all DNA reading frames found in common food genes using methods considered for the analysis of T-DNA sequences used in transgenic crops. FASTA and BLASTX algorithms were used to compare genes from maize, rice, soybean, cucumber, melon, watermelon, and tomato using international regulatory guidance. Results show that BLASTX for maize yielded 7254 alignments that exceeded allergen similarity thresholds and 210,772 alignments that matched eight or more consecutive amino acids with an allergen; other crops produced similar results. This analysis suggests that each nontransgenic crop has a much greater potential for allergenic risk than what has been observed clinically. We demonstrate that a meaningful safety assessment is unlikely to be provided by using methods with inherently high frequencies of false positive alignments when broadly applied to all reading frames of DNA sequence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Thermal stability has been reported as a shared characteristic among some of the major food allergens and appears to have originated from the observation that some cooked foods retain their ability to cause allergic reactions by Immunoglobulin E (IgE) binding and the subsequent cascade of events that mediate allergic reactions. Based on this observation, the thermal stability of novel food proteins, like those in transgenic crops, is considered correlative with allergenic risk and has prompted requests from some regulatory agencies for additional testing to address safety concerns. Because human testing and serum IgE screening are not feasible nor are they necessarily useful for evaluating the thermal stability of a novel food protein, a protein function assay is often used to assess the thermal stability in the context of an allergenicity risk assessment. Some regulatory authorities also require immunodetection using polyclonal IgG antibodies and gel based methods. Here we review why heat stability as measured by these functional and immunodetection assays does not correlate with allergenicity and provides no useful safety information in assessing the allergenic potential of novel food proteins., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Bioinformatic tools are being increasingly utilized to evaluate the degree of similarity between a novel protein and known allergens within the context of a larger allergy safety assessment process. Importantly, bioinformatics is not a predictive analysis that can determine if a novel protein will ''become" an allergen, but rather a tool to assess whether the protein is a known allergen or is potentially cross-reactive with an existing allergen. Bioinformatic tools are key components of the 2009 CodexAlimentarius Commission's weight-of-evidence approach, which encompasses a variety of experimental approaches for an overall assessment of the allergenic potential of a novel protein. Bioinformatic search comparisons between novel protein sequences, as well as potential novel fusion sequences derived from the genome and transgene, and known allergens are required by all regulatory agencies that assess the safety of genetically modified (GM) products. The objective of this paper is to identify opportunities for consensus in the methods of applying bioinformatics and to outline differences that impact a consistent and reliable allergy safety assessment. The bioinformatic comparison process has some critical features, which are outlined in this paper. One of them is a curated, publicly available and well-managed database with known allergenic sequences. In this paper, the best practices, scientific value, and food safety implications of bioinformatic analyses, as they are applied to GM food crops are discussed. Recommendations for conducting bioinformatic analysis on novel food proteins for potential cross-reactivity to known allergens are also put forth., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In 2001, the FAO/WHO suggested a procedure for performing FASTA or BLAST searches, and a threshold of greater than 35% identity in 80 or greater amino acids to identify potential allergenic cross-reactivity of transgene encoded proteins in genetically enhanced crops. Transgene encoded proteins meeting or exceeding this threshold would require additional in vitro evaluation for allergy safety. In work described herein, a method to calculate an E-score threshold is proposed for utilizing the full capability of bioinformatics to accurately identify potential cross-reactive allergens. The threshold E-score, 3.9E-07, was produced using a test dataset of 7695 corn protein sequences and a method that entailed FASTA searches of the FARRP 7 allergen database with each of the dataset sequences using a conventional full length and an 80 amino acid sliding window FASTA comparison followed by an evaluation of E-score distribution. The results show that this E-score threshold identifies known corn allergens and it displays a false positive rate for known allergens that is comparable to that obtained from the 2001 FAO/WHO guidance. Furthermore, the E-score threshold is of sufficient stringency that it rejects the majority of false positive, composition-based anomalies and is 100% effective at identifying Bet v 1 cross-reactive allergens.

The biochemical characterization of protein structures has led to a better understanding of allergens, their structure/function relationship, and can be very powerful in identifying protein sequences with significant structural similarity to known allergens. However, for scientists, regulators and food manufacturers there exists a need for acquiring additional data on potential allergenicity of proteins, particularly, biotechnology derived molecules in food products for which minimal or no prior human exposure information is available. Since human exposure testing, while direct, is unacceptable, understanding allergy in animals has been used to investigate the allergic response on a molecular level as well as test the potential in vivo allergenicity of food proteins. Rodents seem to be the most likely candidate for assessing allergenicity. For development of an animal test system for allergenicity characterization and testing, a number of criteria are required for qualification for a model of human allergy including acceptable immunization protocols, allergic response measurements, and for standardization and validation of materials and procedures. If an animal test system can minimally provide a basis for measuring the relative physiological response to known allergens, this should be enough to establish a model that produces a relative measure of potential allergenicity. Our article will consider development of an adequate animal model for allergenicity determination that can be validated as a tool in safety assessments.

Caveolin-1 is the principal protein component of caveolae membrane domains, which are located at the cell surface in most cell types. Evidence has accumulated suggesting that caveolin-1 may function as a suppressor of cell transformation in cultured cells. The human CAV-1 gene is located at a putative tumor suppressor locus (7q31.1/D7S522) and a known fragile site (FRA7G) that is deleted in a variety of epithelial-derived tumors. Mechanistically, caveolin-1 is known to function as a negative regulator of the Ras-p42/44 MAP kinase cascade and as a transcriptional repressor of cyclin D1, possibly explaining its transformation suppressor activity in cultured cells. However, it remains unknown whether caveolin-1 functions as a tumor suppressor gene in vivo. Here, we examine the tumor suppressor function of caveolin-1 using Cav-1 (-/-) null mice as a model system. Cav-1 null mice and their wild-type counterparts were subjected to carcinogen-induced skin tumorigenesis, using 7,12-dimethylbenzanthracene (DMBA). Mice were monitored weekly for the development of tumors. We demonstrate that Cav-1 null mice are dramatically more susceptible to carcinogen-induced tumorigenesis, as they develop skin tumors at an increased rate. After 16 weeks of DMBA-treatment, Cav-1 null mice showed a 10-fold increase in tumor incidence, a 15-fold increase in tumor number per mouse (multiplicity), and a 35-fold increase in tumor area per mouse, as compared with wild-type littermate mice. Moreover, before the development of tumors, DMBA-treatment induced severe epidermal hyperplasia in Cav-1 null mice. Both the basal cell layer and the suprabasal cell layers were expanded in treated Cav-1 null mice, as evidenced by immunostaining with cell-type specific differentiation markers (keratin-10 and keratin-14). In addition, cyclin D1 and phospho-ERK1/2 levels were up-regulated during epidermal hyperplasia, suggesting a possible mechanism for the increased susceptibility of Cav-1 null mice to tumorigenesis. However, the skin of untreated Cav-1 null mice appeared normal, without any evidence of epidermal hyperplasia, despite the fact that Cav-1 null keratinocytes failed to express caveolin-1 and showed a complete ablation of caveolae formation. Thus, Cav-1 null mice require an appropriate oncogenic stimulus, such as DMBA treatment, to reveal their increased susceptibility toward epidermal hyperplasia and skin tumor formation. Our results provide the first genetic evidence that caveolin-1 indeed functions as a tumor suppressor gene in vivo.

In order to determine whether the enhanced reepithelialization of second-degree burns treated with octylcyanoacrylate (OCA) was due to its occlusive nature we compared reepithelialization (REP) and infection rates of second degree burns treated with OCA and polyurethane film (Tegaderm) in swine. Forty-four standardized partial thickness burns were created by applying an aluminum bar preheated to 80 degrees C to the backs of pigs for 20 s and randomly treated with OCA or Tegaderm. Full thickness biopsies were taken at 7, 10 and 14 days for blinded histopathological evaluation of rates of infection and reepithelialization. T-tests and chi(2) tests were used for group comparisons. There were no between group difference in the rates of reepithelialization and infection. All wounds were reepithelialized by day 14 and there were no infections in either group. We conclude that treatment of partial thickness burns with OCA spray or Tegaderm results in similar rates of reepithelialization and infection, suggesting that the beneficial effects of OCA on reepithelialization are due to its occlusive nature.

During wound repair a 3-day lag occurs between injury and granulation tissue development. When full-thickness, 8-mm-round, excisional wounds were made in the paravertebral skin of outbred Yorkshire pigs and harvested at various times, no granulation tissue was observed before day 4. Day 4 wounds were 3% filled with granulation tissue, day 5 wounds 48% filled, and day 7 wounds 88% filled. The prerequisites for granulation tissue induction are not known but hypothetically include fibrin matrix maturation or cell activation. To examine whether matrix maturation was necessary, wounds were allowed to heal for 5 or 7 days and then aggressively curetted, resulting in the formation of fresh fibrin clots in the newly formed wound spaces. In contrast to original wounds, no lag phase was observed; wounds curetted on day 5 were 23% filled with granulation tissue 1 day later and 99% filled 3 days later, whereas wounds curetted on day 7 were 47% filled 1 day later and completely filled within 2 days. Thus, granulation tissue formation resumed promptly and independently of fibrin clot matrix maturation. This observation suggested that mesenchymal cell activation might be the rate-limiting step in granulation tissue formation. To address this hypothesis more directly, cultured porcine or human fibroblasts, grown to 80% confluence in Dulbecco's minimal essential medium plus 10% fetal calf serum, were added to new wounds. These wounds were sealed with a freshly made exogenous fibrin clot. In some wounds, platelet releasate was added to the fibrin clot. Granulation tissue did not form in day 3 wounds, which had received either fibrin alone, fibrin and platelet releasate, or fibrin and fibroblasts. In contrast, granulation tissue was observed in wounds receiving fibrin, human fibroblasts, and platelet releasate. By day 4, wounds receiving cultured human fibroblasts, fibrin, and platelet releasate were 14% filled with granulation tissue compared with less than 4% granulation tissue in control wounds. Thus, fibroblast activation is a limiting step of granulation tissue formation, and continued cell stimulation is required for accelerated development.

A porphyrinic sensor was used to monitor nitric oxide release from vascular smooth muscle in response to exposure to ultraviolet light. Aortic rings exposed to UV light relaxed with a time course that parallels this observed NO release. With repeated UV light treatments, the magnitude of the relaxations diminished, suggesting that a store of NO was being exhausted. Photorelaxation in response to UV light was studied in aortic ring from two types of hypertensive rats, genetic (SHRSP) and nitroarginine-induced. These aortic rings showed greater photorelaxation and evidenced less tolerance than did aortic rings from control normotensive rats. Since NO synthase activity is depressed in both types of hypertension, it appears, paradoxically, that the UV light-releasable store of NO is augmented when NO synthase activity is depressed.