Tryptophan intrinsic fluorescence from wound healing correlates with re-epithelialization in a rabbit model.

BACKGROUND: Wound healing monitoring and timely decision-making are critical for wound classification. Tryptophan (Tr) intrinsic fluorescence, detected at 295/340 nm, provides a noninvasive approach for wound assessment. Our previous work demonstrated that this autofluorescence is associated with keratinocytes in a highly proliferative state in vitro. OBJECTIVE: We investigated the correlation between Tr fluorescence and key wound healing parameters, including re-epithelialization, fibrosis, neovascularization, and acute and chronic inflammation, using a rabbit model. METHODS: Seven rabbits underwent wound healing assessment over a 15-day period. We employed histological analysis from central and marginal biopsies, and UV fluorescence imaging captured by a monochromatic near-UV sensitive camera equipped with a passband optical filter (340 nm/12 nm). Excitation was achieved using a 295 nm LEDs ring lamp. Normalized fluorescence values were correlated with histological measurements using Pearson correlation. RESULTS: The UV fluorescence strongly exhibited a strong correlation with re-epithelization (r = 0.8) at the wound edge, with peak intensity observed between the sixth and ninth days. Notably, wound-healing dynamics differed between the wound center and edge, primarily attributed to variations in re-epithelialization, neovascularization, and chronic inflammation. CONCLUSION: Our findings highlight the presence of autofluorescence at 295/340 nm during wound healing, demonstrating a robust association with re-epithelialization. This excitation/emission signal holds promise as a valuable noninvasive strategy for monitoring wound closure, re-epithelialization, and other biological processes where Tr plays a pivotal role.

Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

Linfocitos T citotóxicos CD8+ en la leishmaniasis cutánea / CD8+ cytotoxic lymphocytes in cutaneous leishmaniasis

OBJETIVO: Examinar la bibliografía relacionada con la participación de los linfocitos T CD8+ en la reacción inmunitaria a especies de Leishmania causantes de leishmaniasis cutánea. En esta enfermedad se ha resaltado la intervención de macrófagos, células dendríticas, NK y células T CD4+; sin embargo, es poco lo que se conoce de las células T CD8+. Los trabajos en modelos murinos señalan que la participación de las células CD8+ sucede a través de la producción de IFN-gamma, aunque su capacidad citotóxica puede desempeñar una función importante, como lo demuestran los hallazgos en seres humanos. La forma como se activan las células citotóxicas CD8+ es un enigma. Es posible que las células dendríticas realicen esa labor a través de mecanismos que incluyen transpresentación de antígenos. Comprender la contribución de este subtipo celular en la respuesta inmunitaria a Leishmania aportará novedosos conocimientos sobre la fisiopatogenia de la leishmaniasis, lo cual hará posible desarrollar nuevos enfoques terapéuticos para esta parasitosis.

OBJECTIVE: Review of the literature on the role of CD8+ T cell in the immune response against Leishmania species that cause cutaneous leishmaniasis. The role of macrophages, dendritic cells, CD4 T cells and NK cells has been extensively analyzed in leishmaniasis, yet very little knowledge has been gained on CD8+ T cells in this disease. Murine models of leishmaniasis suggest that CD8+ T cells participate through IFNg production, yet their cytotoxic capacity may also play a crucial role, as has been found in human disease. It is an enigma what mechanisms underlie the CD8+ T cell activation. It is possible that dendritic cells activate CD8+ T cells through mechanisms that include antigen traspresentation. A better understanding of CD8+ T cells in the immune response against Leishmania will undoubtedly provide new insights into the physiopathogenesis of the disease that could lead to new therapeutic approaches against leishmaniasis.