Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.

Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity.

Kaolin exogenous application boosts antioxidant capacity and phenolic content in berries and leaves of grapevine under summer stress.

Heat waves, high light intensities and water deficit are becoming important threats in many important viticultural areas worldwide, so the implementation of efficient and cost-effective mitigation strategies is crucial for the production of premium wines while maintaining productivity. In this context, the foliar application of kaolin, a chemically inert mineral with excellent reflective properties, is being developed and experimented as a strategy to reduce the impact of heat and drought in Douro vineyards (Northern Portugal), already revealing promising results. In the present study we investigated if an improved antioxidant capacity is part of the beneficial effects of kaolin, by studying changes in the enzymatic and nonenzymatic antioxidant system in leaves and berries (cv Touriga Nacional). Results showed that mature grape berries contained higher amounts of total phenols (40%), flavonoids (24%), anthocyanins (32%) and vitamin C (12%) than fruits from control vines, and important changes were also measured in leaves. In parallel, kaolin application improved the antioxidant capacity in berries, which was correlated with the observed increased content in secondary metabolites. Kaolin application also regulated secondary metabolism at the transcriptional level through the increase in the transcript abundance of genes encoding phenylalanine ammonia lyase and chalcone synthase.

Mast cell curve-response in partial Achilles tendon rupture after 830 nm phototherapy.

OBJECTIVE: The aim of this study was to quantify mast cells at different time intervals after partial Achilles tendon rupture in rats treated with low-level laser therapy (LLLT). BACKGROUND DATA: There is a high incidence of lesions and ruptures in the Achilles tendon that can take weeks and even months to heal completely. As the mast cells help in the healing repair phase, and LLLT has favorable effects on this tissue repair process, study of this modality on the quantity of mastocytes in the ruptured tendon is relevant. METHODS: Sixty Wistar rats were subjected to partial Achilles' tendon rupture by direct trauma, randomized into 10 groups, and then divided into the group treated with 80 mW aluminum gallium arsenide infrared laser diode, continuous wave, 2.8 W/cm(2) power density, 40 J/cm(2) energy density, and 1.12 J total energy, and the simulation group. Both the groups were subdivided according to the histological assessment period of the sample, either 6 h, 12 h, 24 h, 2 days, or 3 days after the rupture, to quantify the mastocytes in the Achilles' tendon. RESULTS: The group subjected to LLLT presented a greater quantity of mastocytes in the periods of 6 h, 12 h, 24 h, 2 days, and 3 days after rupture, compared with the simulation groups, but differences were detected between the sample assessment periods only in the simulation group. CONCLUSIONS: LLLT was shown to increase the quantity of mastocytes in the assessment periods compared with the simulation groups.

What is better in TRAM flap survival: LLLT single or multi-irradiation?

Low-level laser therapy (LLLT) has been used with the aim of improving vascular perfusion of the skin and musculocutaneous flaps. This study evaluated the effect of LLLT on transverse rectus abdominis musculocutaneous flap (TRAM) viability, vascular angiogenesis, and VEGF release. Eighty-four Wistar rats were randomly divided into seven groups with 12 rats in each group. Group 1 received sham laser treatment; group 2, 3 J/cm(2) at 1 point; group 3, 3 J/cm(2) at 24 points; group 4, 72 J/cm(2) at 1 point; group 5, 6 J/cm(2) at 1 point; group 6, 6 J/cm(2) at 24 points; and group 7, 144 J/cm(2) at 1 point. All experimental groups underwent LLLT immediately after the TRAM operation and on the following 2 days; thus, animals underwent 3 days of treatment. The percentage of skin flap necrosis area was calculated on the fourth postoperative day using the paper template method, and two skin samples were collected using a 1-cm(2) punch to evaluate alpha smooth muscle actin (1A4) and VEGF levels in blood vessels. Significant differences were found in necrosis percentage, and higher values were seen in group 1 than in the other groups. Statistically significant differences were not found among groups 3 to 7 (p<0.292). Groups 5 and 7 showed significantly higher VEGF levels compared to other groups. Groups 3 and 5 had an increase in levels of blood vessels compared to other groups. LLLT at energy densities of 6 to 144 J/cm(2) was efficient to increase angiogenesis and VEGF levels and promote viability in TRAM flaps in rats.

Effect of low-level laser therapy on mast cells in viability of the transverse rectus abdominis musculocutaneous flap.

OBJECTIVE: To assess the effect of low-level laser therapy (LLLT) on viability of mast cells of the transverse rectus abdominis musculocutaneous (TRAM) flap. BACKGROUND DATA: LLLT has been recently used on the TRAM flap to stimulate mast cells. MATERIALS AND METHODS: Eighty-four Wistar rats were randomly divided into seven groups of 12 rats in each: group 1 (sham laser therapy); group 2 received 3 J/cm(2) at one point; group 3 received 3 J/cm(2) at 24 points; group 4 received 72 J/cm(2) at 1 point; group 5 received 6 J/cm(2) at 1 point; group 6 received 6 J/cm(2) at 24 points; and group 7 received 144 J/cm(2) at 1 point. All experimental groups underwent LLLT immediately after TRAM surgery and on the next two following days, for three sessions in total. The percentage of the area of skin flap necrosis was calculated on the fourth postoperative day and two samples of skin were collected from each rat with a 1-cm(2) punch to perform mast cell evaluations with toluidine blue dye. RESULTS: Statistically significant differences were found in the percentage of necrosis, and higher values were seen in group 1 than in all other groups. Among groups 3-7 no statistically significant differences were found (p < 0.292). For mast cells, when group 1 was compared to groups 5 (6 J/cm(2) at 1 point) and 7 (144 J/cm(2) at 1 point), it had fewer mast cells. CONCLUSION: LLLT at a wavelength of 670 nm was effective at reducing the necrotic area, and we found that it can stimulate mast cells growth to increase vascular perfusion.

Effect of application site of low-level laser therapy in random cutaneous flap viability in rats.

OBJECTIVE: This study aimed to investigate the effect of diode laser (830 nm) irradiation on the viability of ischemic random skin flaps in rats, as well as to determine the most effective site for applying laser radiation to speed healing. BACKGROUND DATA: Low-level laser therapy (LLLT) has recently been used to improve the viability of ischemic random skin flaps in rats. MATERIALS AND METHODS: Seventy Wistar rats were used and divided into seven groups of 10 rats each: group 1, sham laser treatment; group 2, which received irradiation at 1 point 5 cm from the flap's cranial base; group 3, which received irradiation at 2 points (5 and 7.5 cm from the flap's base); group 4, which received irradiation at 3 points (2.5, 5 and 7.5 cm from the flap's base); group 5, which received irradiation at 1 point 2.5 cm from the flap's base; group 6, which received irradiation at 2 points (2.5 and 5 cm from the flap's base); and group 7, which received irradiation at 1 point 7.5 cm from the flap's base. The animals were subjected to laser therapy at an energy density of 36 J/cm(2) for 72 sec immediately after surgery, and one time on each of the four subsequent days. The percentage of necrotic skin flap area was calculated on the seventh postoperative day using a paper template. RESULTS: The results showed that the rats in group 5 had the highest increase in skin flap viability, with a statistically significant difference compared to the other groups. Statistically significant differences were not seen between any of the other groups. CONCLUSION: The diode laser was effective in increasing skin flap viability in rats, and laser irradiation of a point 2.5 cm from the cranial base flap was found to be the most effective.

Helium-neon laser in viability of random skin flap in rats.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the role of helium-neon (He-Ne) laser random skin flap viability in rats. STUDY DESIGN/MATERIALS AND METHODS: Experimentally controlled randomized study. Forty-eight Wistar-EPM rats were used, weighed, and divided into 4 groups with 12 rats each. The random skin flap was performed measuring 10 x 4 cm, with a plastic sheet interposed between the flap and the donor site. The Group 1 (control) underwent sham irradiation with He-Ne laser. The Group 2 was submitted to laser irradiation, using the punctual contact technique on the skin flap surface. The Group 3 was submitted to laser irradiation surrounding the skin flap, and the Group 4 was submitted to laser irradiation both on the skin flap surface and around it. The experimental groups were submitted to He-Ne laser irradiation with 3 J/cm(2) energy density immediately after the surgery and for the four subsequent days. The percentage of necrotic area of the four groups was calculated at the 7th post-operative day, through a paper-template method. RESULTS: Group 1 reached an average necrotic area of 48.86%; Group 2, 38.67%; Group 3, 35.34%; and Group 4, 22.61%. After the statistic analysis, results showed that all experimental groups reached statistically significant values when compared to the control group, and Group 4 was the best one, when compared to all groups of this study (P<0.001). CONCLUSION: The He-Ne laser irradiation was efficient to increase random skin flap viability in rats.