Nitric Oxide–Containing Nanoparticles as an Antimicrobial Agent and Enhancer of Wound Healing

Nitric oxide (NO) is known to be involved in wound healing and to have antimicrobial actions. Developing a means of delivering a diatomic, gaseous free radical has been a technical challenge. Using a combination of techniques, Martinez and colleagues have developed an ingenious method of storing NO, and they demonstrate its efficacy in treating infected wounds

Rash morphology as a predictor of COVID-19 severity:A systematic review of the cutaneous manifestations of COVID-19

Approximately 6% of those with COVID‐19 will experience cutaneous manifestations. Examining data from this cohort could provide useful information to help with the management of COVID‐19. To that end, we conducted a systematic review primarily to assess rash morphologies associated with COVID‐19 and their relationship with disease severity. Secondary outcomes include demographics, distribution, dermatological symptoms, timeline, diagnostic method and medication history. The literature was searched for all patients with skin manifestations thought to be related to suspected or confirmed COVID‐19. Patients with a history of dermatological, rheumatological or occupational skin disorders were excluded. Of the 2056 patients selected, the most common morphologies were chilblain‐like lesions (54.2%), maculopapular (13.6%) and urticaria (8.3%). Chilblain‐like lesions were more frequent in the younger population (mean age 21.5, standard deviation ± 10.8) and were strongly linked with milder disease, not requiring an admission (odds ratio [OR] 35.36 [95% confidence interval {CI} 23.58, 53.03]). Conversely, acro‐ischaemia and livedo reticularis were associated with worse outcomes, including a need for ICU (OR 34.01 [95% CI 16.62, 69.57] and OR 5.57 [95% CI 3.02, 10.30], respectively) and mortality (OR 25.66 [95% CI 10.83, 60.79] and OR 10.71 [95% CI 4.76, 24.13], respectively). Acral lesions were the most common site (83.5%). 35.1% experienced pruritus, 16.4% had pain and 4.7% reported a burning sensation. 34.1% had asymptomatic lesions. Rash was the only symptom in 20.9% and occurred before or alongside systemic symptoms in 12.4%. 28.3% had a positive polymerase chain reaction nasopharyngeal swab and 5.4% had positive antibodies, while 21.9% tested negative and 45.1% were not tested. In conclusion, COVID‐19 causes a variety of rashes, which may cause symptoms and add to morbidity. Rash type could be helpful in determining COVID‐19 prognosis

Is sunlight good for our heart?

Humans evolved being exposed for about half of the day to the light of the sun. Nowadays, exposure to sunlight is actively discouraged for fear of skin cancer, and contemporary lifestyles are associated with long hours spent under artificial light indoors. Besides an increasing appreciation for the adverse effects of these life-style-related behavioural changes on our chronobiology, the balance between the beneficial and harmful effects of sunlight on human health is the subject of considerable debate, in both the scientific and popular press, and the latter is of major public health significance. While there is incontrovertible evidence that ultraviolet radiation (UVR) in the form of sunlight is a significant predisposing factor for non-melanoma and melanoma skin cancers in pale skinned people,1 a growing body of data suggest general health benefits brought about by sunlight.2 These are believed to be mediated either by melatonin or vitamin D. Melatonin is produced from serotonin by the pineal gland located in the centre of the brain during periods of darkness, and its release is suppressed as a function of the visible light intensity sensed through ocular photoreceptors. Vitamin D is formed by ultraviolet B (UVB)-mediated photolysis of 7-dehydrocholesterol in the skin. Both melatonin and vitamin D are pleiotropic hormones that exert a multitude of cellular effects by interacting with membrane and nuclear receptors, and receptor-independent actions. People with more heavily pigmented skin require higher doses of UVB to produce adequate amounts of vitamin D, and this may have been an evolutionary driver to the variation of human skin colour with latitude and intensity of solar irradiation. Our degree of exposure to sunlight is easily modified by behavioural factors such as the use of clothing, sunglasses, and sun-blocking creams, and time spent outdoors. Balancing the carcinogenic risks with the requirement for vitamin D has led to advice on moderating sun exposure, while supplementing food with vitamin D. Guidance on such behaviour is part of the public health campaigns in most countries with Caucasian populations. Following these suggestions, we may, however, be missing out on other health benefits provided by natural sunlight that are less obvious and unrelated to the above classical mediators

UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase

The incidence of hypertension and cardiovascular disease correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are abundant in human skin we hypothesised that exposure to UVA may mobilise NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers irradiation of the skin with 2 Standard Erythemal Doses of UVA lowered BP, with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO-synthase activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labelled with the NO-imaging probe DAF2-DA revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent fashion, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability which may account for the latitudinal and seasonal variations of BP and cardiovascular disease.Journal of Investigative Dermatology accepted article preview online, 20 January 2014

Complement Receptor Type 1 (CR1, CD35) Is a Receptor for C1q

AbstractMolecular definition of the cellular receptor for the collagen domain of C1q has been elusive. We now report that C1q binds specifically to human CR1 (CD35), the leukocyte C3b/C4b receptor, and the receptor on erythrocytes for opsonized immune complexes. Biotinylated or radioiodinated C1q (*C1q) bound specifically to transfected K562 cells expressing cell surface CR1 and to immobilized recombinant soluble CR1 (rsCR1). *C1q binding to rsCR1 was completely inhibited by unlabeled C1q and the collagen domain of C1q and was partially inhibited by C3b dimers. Kinetic analysis in physiologic saline of the interaction of unlabeled C1q with immobilized rsCR1 using surface plasmon resonance yielded an apparent equilibrium dissociation constant (Keq2) of 3.9 nM. Thus, CR1 is a cellular C1q receptor that recognizes all three complement opsonins, namely, C1q, C3b, and C4b

Does Incident Solar Ultraviolet Radiation Lower Blood Pressure?

Background Hypertension remains a leading global cause for premature death and disease. Most treatment guidelines emphasize the importance of risk factors, but not all are known, modifiable, or easily avoided. Population blood pressure correlates with latitude and is lower in summer than winter. Seasonal variations in sunlight exposure account for these differences, with temperature believed to be the main contributor. Recent research indicates that UV light enhances nitric oxide availability by mobilizing storage forms in the skin, suggesting incident solar UV radiation may lower blood pressure. We tested this hypothesis by exploring the association between environmental UV exposure and systolic blood pressure (SBP) in a large cohort of chronic hemodialysis patients in whom SBP is determined regularly. Methods and Results We studied 342 457 patients (36% black, 64% white) at 2178 US dialysis centers over 3 years. Incident UV radiation and temperature data for each clinic location were retrieved from the National Oceanic and Atmospheric Administration database. Linear mixed effects models with adjustment for ambient temperature, sex/age, body mass index, serum Na+/K+ and other covariates were fitted to each location and combined estimates of associations calculated using the DerSimonian and Laird procedure. Pre-dialysis SBP varied by season and was ≈4 mm Hg higher in black patients. Temperature, UVA and UVB were all linearly and inversely associated with SBP. This relationship remained statistically significant after correcting for temperature. Conclusions In hemodialysis patients, in addition to environmental temperature, incident solar UV radiation is associated with lower SBP. This raises the possibility that insufficient sunlight is a new risk factor for hypertension, perhaps even in the general population.</p