Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional damage to ischemic myocardial tissue; this forces to seek therapies of cardioprotection to reduce this additional damage. There are many cardioprotective agents; within these, cannabinoids have shown to have beneficial effects, mainly cannabidiol (CBD). CBD is a non psychoactive cannabinoid. To evaluate the effect in experimental models of CBD in myocardial ischemia reperfusion in rats, twelve‐week‐old male rats have been used. The animals were divides in 3 groups: control(C), ischemia reperfusion (IR) and CBD pretreatment (1/day/5mg/kg /10days). Langendorff organ isolate studies were performed, and the area of infarction was assessed with triphenyl tetrazolium, in addition to molecular analysis of AT1 and AT2 receptors and Akt and Erk proteins and their phosphorylated forms related to RISK pathways. It was observed that there is an improvement with the use of CBD increasing inotropism and cardiac lusitropism, improving considerably the cardiovascular functionality. These could be related to the reduction of the area of infarction and activation of the AT2 receptor and the RISK pathway with absence of activation of the AT2 receptor (these could relate the reduction of the infarct area and the restoration of cardiovascular function with the activation of the AT2 receptor and the RISK pathway with the absence of activation of the AT2 receptor). The use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.

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Objective. In the pathogenesis of pterygium, the protective role of glutathione and nitric oxide production is unclear. These are important factors for homeostasis in the redox state of cells. The aim of this study was to determine the levels of these and related parameters in pterygium tissue. Patients and Methods. The study sample consisted of 120 patients diagnosed with primary or recurrent pterygium. Five groups of tissue samples were examined: control, primary pterygium, recurrent pterygium, and two groups of primary pterygium given a one-month NAC presurgery treatment (topical or systemic). The levels of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), 3-nitrotyrosine (3NT), reduced and oxidized glutathione (GSH and GSSG), and catalase (CAT) were evaluated in tissue homogenates. Results. Compared with the control, decreased levels of eNOS, NO, and 3-nitrotyrosine as well as the degree of oxidation of GSH (GSSG%) were observed in primary and recurrent pterygium. 3-Nitrotyrosine and GSSG% were reduced in the other pterygium groups. GSH and CAT were enhanced in recurrent pterygium and systemic-treated primary pterygium but were unchanged for topical-treated primary pterygium. There was a strong positive correlation of eNOS with NO and 3NT, GSSG% with NO and 3NT, and GSH with GSSG and CAT. Women showed a higher level of GSH and catalase in primary pterygium, whereas a lower level of GSH and a higher level of NO in recurrent pterygium. Conclusion. The results are congruent with the following proposed sequence of events leading to a protective response of the organism during the pathogenesis of primary pterygium: a decreased level of eNOS provokes a decline in the level of NO in pterygium tissue, which then leads to reduced S-nitrosylation of GSH or other thiols and possibly to the modulation of the intracellular level of GSH through synthesis and/or mobilization from other tissues.

Background There was not investigated the participation of glutathione (GSH), endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) in pterygium pathogenesis and the effects of the precursor of GSH synthesis N-acetylcysteine in treatment prior to surgery.Methods The levels of eNOS, NO, 3-nitrotyrosine, reduced and oxidized GSH (GSSG) and catalase were measured in tissue homogenates of 120 patients with primary or recurrent pterygium, and systemic or topical pretreatment with N-acetylcysteine, compared to control group.Results A decrease in eNOS, NO, 3-nitrotyrosine, and GSH oxidation degree (GSSG%) was observed in primary pterygium, which remained decreased in other pathological groups in case of GSSG% and 3-nitrotyrosine. The levels of GSH and catalase increased in recurrent pterygium, even more, they increased in the group with systemic treatment, while topical treatment did not affect them, compared with control or primary pterygium groups. High positive correlation in groups of the study was observed between behavior of eNOS with NO or GSSG%, while GSH showed it with GSSG or catalase. Women showed a higher level of GSH and catalase in primary pterygium group, lower its level and a higher level of NO in recurrent pterygium. It was observed in women positive correlation in groups of study of GSSG% with 3-nitrotyrosine alone, while in men with NO.Conclusions Study data do not contradict the assumption about the following possible sequence of events in pathogenesis of the primary pterygium: decrease in the activity of eNOS and consequently of NO, decrease in S-nitrosation of GSH, possible modulation of the intracellular level of GSH through synthesis and/or mobilization from other tissues.

Background: In the pathogenesis of pterygium, the protective role of glutathione and nitric oxide production is unclear. These are important factors for homeostasis in the redox state of cells. The aim of this study was to determine the levels of these and related parameters in pterygium tissue. Methods: Five groups of tissue samples were examined: control, primary pterygium, recurrent pterygium and two groups of primary pterygium given a one-month NAC pre-surgery treatment (topical or systemic). The levels of endothelial nitric oxide synthase (e-NOS), nitric oxide (NO), 3-nitrotyrosine (3NT), reduced and oxidized glutathione (GSH and GSSG), and catalase (CAT) were evaluated in tissue homogenates. Results: Compared to the control, decreased levels of eNOS, NO and 3-nitrotyrosine as well as the degree of oxidation of GSH (GSSG%) were observed in primary and recurrent pterygium. 3-Nitrotyrosine and GSSG% were also reduced in the other pterygium groups. GSH and CAT were enhanced in recurrent pterygium and systemic-treated, but were unchanged for topical-treated primary pterygium. There was a strong positive correlation of eNOS with NO and 3NT, GSSG% with NO and 3NT, and GSH with GSSG and CAT. Conclusions: The results are congruent with the following proposed sequence of events leading to a protective response of the organism during the pathogenesis of primary pterygium: a decreased level of eNOS provokes a decline in the level of NO in pterygium tissue, which then leads to the modulation of the intracellular level of GSH through synthesis and/or mobilization from other tissues.

One therapy that has demostrated that it normalize the cardiovascular responses of angiotensin receptor in one experimental model, is the hyperbaric oxygen therapy. It has been described the wide use of dexametasone during the neonatal period of time, having different and controversial responses. Dexametasone has been used commonly due to the improvement in the lung function into the respiratory difficulty syndrome. Some studies reports that the use of steroid during the neonatal period could have some beneficial effects but also it could induce cardiovascular and renal disorder during the development. As it has been described one of the main pathway involved is the renin‐aldosterone‐angiotensin system. Some researchers describe that steroids regulate the angiotensin II receptor and function.Objetivethe main idea is to analize the modification of the expression of angiotensin II receptor in rat with administration neonatal of dexametasone with/without hyperbaric oxygen therapy.Methodologyneonatal rat (2 days) were administrated with dexametasone and were divided in 2 groups one with hyperbaric oxygen therapy and the other without therapy. At the age of 6 weeks the animals were sacrificed, and the expression of the receptor At1 were measured in the heart and the kidney by PCR and inmunohistochemistry.ResultsThe group only with dexametasone showed has major expression of At1 receptor, however the group with dexametasone and hyperbaric oxygen therapy has a reduction in the expression of this receptor.ConclusionThis results could suggest that the hyperbaric oxygen therapy could normalize the expresion in this rats with dexametasone treatment, being beneficial because it could reduce the possibility of one cardiovascular pathology like and infarct.Support or Funding InformationSIP, COFAA, IPNThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Gulf War illness (GWI) afflicts ~30% of US retired military personnel whom served at Persian Gulf War (GW) of 1990–91 (~450,000 men and women). GWI comprises a gathering of symptoms mainly affecting nervous and skeletal muscle (SkM) systems. The syndrome includes cognitive deficits, depression, muscle pain, weakness, intolerance to exercise and fatigue. Affected Veterans continue to experience altered behavior and other symptoms after 25 years of exposure to suspect chemicals. Co‐exposure to specific chemical agents and stress are suspected to be the cause of such disorder. GW military personnel consumed daily pyridostigmine (PB) tablets as a prophylactic treatment to protect from nerve gas attacks during the war. In addition, to reduce the risk of infection by communicable (insect borne) diseases troop/staff members were also exposed to insecticides and insect repellents, most commonly permetrim (PM) and N;N‐diethyl‐m‐toluamide (DEET). VA investigators have developed and validated rodent models of GWI like exposure by providing them with equivalent doses of chemicals for limited periods of time (up to 4 weeks). Whereas a significant amount of knowledge is available about the effects of such treatments on neurological structure and function, very little is known about the effects on skeletal muscle (SkM). We implemented a rat model of GWI to examine changes in SkM structure and function including tissue wasting pathways. Three month old male Wistar rats (n=9) were provided orally with PB 1.3 mg/kg/day, PM 0.13 mg/kg/day (back skin) and DEET 40 mg/kg/day (back skin), and physically restricted them for five minutes for a total of 3 weeks. An additional 3 week period was allowed to develop the intoxication (intox) profile. A control group (n=9), were administered vehicles and did not receive physical restraint. After the intoxication period, animals were subjected to treadmill and limb strength testing. Afterwards, animals were euthanized and SkM (gastrocnemius) samples collected and processed for histological, biochemical and Western blot analysis. Prior to euthanasia, GWI animals did not evidence significant changes in body weight vs. controls. In contrast, grastrocnemius weight and size from intoxicated animals was ~35% significantly lower vs. controls, which was consistent with recorded significant decreases in SkM myofiber area, limb strength (see figure) and treadmill distance (~30–50%). SkM immunostaining of GWI samples evidence the MyHC (α/β) ratio increase vs. controls. Western blot analysis of follistatin, ACTA‐1, CKm, MYH protein levels were significantly decreased (up to 80%) in the GWI group. Wasting pathway related proteins levels such as myostatin, MURF1, FAbx, atrogin and proteasome 20s were significantly increased (up to 80%) in GWI rats. Altogether, results indicate that exposure of rodents to equivalent human doses of associated GWI chemicals can activate muscle atrophy pathways leading to a severe loss of organ function. Further studies are needed to identify the specific causal agent(s) and risks of human exposure.Support or Funding InformationNIH DK98717 to FVThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.