Antioxidant enzyme activities and immune responses in rainbow trout (Onchorhynchus mykiss) juveniles fed diets supplemented with dandelion (Taraxacum officinalis) and lichen (Usnea barbata) extracts.

In the present study, antioxidant activity, immune responses, and growth performance of rainbow trout (Onchorhynchus mykiss) juveniles fed with diets supplemented with dandelion (Taraxacum officinalis) and lichen (Usnea barbata) extracts were assessed. Four different concentrations of aqueous methanolic extract of the plants (0% (control), 0.1%, 0.5%, and 1% (D, dandelion; L, lichen) were added to the diets, and fish were fed for 75 days. On the 15th, 45th, and 75th day of the study, liver antioxidant enzyme activities were determined, and immune responses were determined every 15th day. The results showed that SOD activity increased in the fish group of 0.1% D on the 15th and 45th day compared to control; however, it was lower in all the lichen extract-treated groups than in control at almost all sampling times, except on the 15th day in the 0.1% L group. CAT activity showed an increased value (P < 0.05) in 0.5% L and 1% L treated fish groups on the 15th day, in fish of 1% D and 1% L groups on 45th and on 75th day in 0.1% D group. GPX activity increased on the 15th day of the study in fish of 0.1% D group, on the 45th day in 1% D and 1% L groups and on the 75th day in fish of 0.5% D, 0.1% D, and 0.5% L groups (P < 0.05). G6PDH enhanced in all treatment groups compared to control on the 15th day, except in 0.1% L and 0.5% L groups. An elevated G6PDH activity was also observed on the 75th day of the study in 0.5% D, 1% D, and 0.5% L fish groups. An increase on lipid peroxidation (LP) was observed in all L groups on the 45th day of the study. Lysozyme activity was determined to be the highest in 0.5% and 1% L on the 45th day, in 0.1% L on the 60th day and in the 0.5% L fish group on the 75th day compared to control (P < 0.05). Myeloperoxidase was found to be the highest at the end of the study in 1% L fish group compared to the control (P < 0.05). In conclusion, we suggest the use of dandelion to combat oxidative stress and to lower FCR and the use of lichen to modulate the immune response in rainbow trout. The use of such products will be economical for aquaculture and harmless for the environment.

Acute effect of a maximum incremental test until exhaustion on malondialdehyde and antioxidant vitamins in plasma and erythrocytes in athletes / Efecto agudo de un test incremental máximo hasta la extenuación sobre el malondialdehído y las vitaminas antioxidantes en plasma y eritrocitos en atletas

BACKGROUND: it is well known that moderate or vigorous physical exercise produces an increase in free radicals. AIM: the aims of this study were to observe changes in malondialdehyde and antioxidant vitamins after a maximum incremental test, and to relate malondialdehyde and antioxidant vitamin values to performance parameters. METHODS: eighty-four male athletes participated in this study. Participants performed a maximum incremental test until exhaustion on a treadmill. Malondialdehyde in plasma and antioxidant vitamins in plasma and erythrocytes were determined before and after the test. RESULTS: in plasma, there was a decrease in malondialdehyde after the test. In erythrocytes, results showed increases in vitamin C and decreases in vitamin E after the test. Maximal oxygen uptake values were associated positively with vitamin C and negatively with malondialdehyde levels before the test. On the other hand, maximal oxygen uptake, total test time, and total test distance were positively related to the malondialdehyde values obtained after the test. CONCLUSIONS: a maximum incremental test did not produce any changes in plasma vitamins in athletes. However, it increased the levels of vitamin C in erythrocytes and decreased malondialdehyde values in plasma and vitamin E in erythrocytes. The levels of malondialdehyde, vitamin C and vitamin E were related to performance parameters. These results may be linked to the adaptation of antioxidant systems due to regular training

INTRODUCCIÓN: es sabido que el ejercicio físico moderado o vigoroso produce un aumento de radicales libres. OBJETIVOS: los objetivos del estudio fueron: observar los cambios del malondialdehído y las vitaminas antioxidantes después de un test incremental máximo y relacionar los niveles de malondialdehído y vitaminas antioxidantes con parámetros de rendimiento. MÉTODOS: ochenta y cuatro atletas masculinos participaron en el estudio. Los participantes realizaron un test incremental hasta la extenuación en un tapiz rodante. El malondialdehído en plasma y las vitaminas antioxidantes en plasma y en eritrocitos se determinaron antes y después del test incremental. RESULTADOS: en el plasma hubo una disminución del malondialdehído después de la prueba incremental. En los eritrocitos, los resultados mostraron un aumento de la vitamina C y un descenso de la vitamina E después de la prueba. El consumo máximo de oxígeno se asoció positivamente con la vitamina C e inversamente con el malondialdehído antes del test. Por otro lado, el consumo máximo de oxígeno, el tiempo total del test y la distancia total durante el test se asociaron positivamente con los valores de malondialdehído obtenidos tras el test máximo. CONCLUSIÓN: un test incremental máximo hasta la extenuación no produjo cambios en las vitaminas antioxidantes del plasma. Sin embargo, sí aumentó los niveles de vitamina C en los eritrocitos y redujo los niveles de malondialdehído en el plasma y los de vitamina E en los eritrocitos. Los niveles de malondialdehído, vitamina C y vitamina E se relacionaron con los parámetros de rendimiento. Estos resultados podrían estar relacionados con la adaptación de los sistemas antioxidantes debido al entrenamiento regular

Idiopathic myalgic pain (fibromyalgia): supportive management and prevention with Pycnogenol®.

BACKGROUND: The aim of this registry study was the prospective evaluation of the efficacy of Pycnogenol® in idiopathic fibromyalgia (FM), over 4 weeks in comparison with the standard management (SM). METHODS: A SM and a Pycnogenol®+SM group were formed. Pycnogenol® supplementation was used at the dose of 150 mg/day (4 weeks). The study considered the most important/frequent symptoms of FM. RESULTS: Fifty patients with idiopathic fibromyalgia were included: 26 in the Pycnogenol® group and 24 served as controls. The two groups were comparable at inclusion. No other disease or condition was present. All subjects were otherwise healthy women (BMI<26), not using any drug. All subjects had an elevated level of oxidative stress (OS) at inclusion. All routine blood tests - and all inflammatory and rheumatic tests - were within the normal range at inclusion and at the end of the study. No safety or tolerability problems were observed. The percentage of patients using NSAIDs (non-steroidal anti-inflammatory drugs) as rescue medications in the observation period was significantly higher in the SM management group (P<0.05) in comparison with the supplement group. The percentage of patients using corticosteroids as rescue medication was significantly higher in the SM group (P<0.05). The percentage of subjects with the symptoms/complaints decreased significantly, considering each symptom, with Pycnogenol® after 4 weeks in comparison with the SM (P<0.05). CONCLUSIONS: Pycnogenol® supplementation appears to control and reduce the intensity of common symptoms and complaints - especially pain-related - associated with FM. Pycnogenol® could be a 'soft', safe supplementation and prevention method to manage the symptoms of most of these patients, even for longer periods, reducing the need for drugs.

The effect of selected drugs on the mitigation of myocardial injury caused by gamma radiation.

Radiation damage of healthy tissues represents one of the complications of radiotherapy effectiveness. This study is focused on the screening of potentially effective drugs routinely used in medical practice and involved in the mechanism of radiation injury, namely for radiation-induced production of free radicals in the body. Experiments in rats revealed significant reduction of oxidative stress (malondialdehyde) and inflammatory marker (tumor necrosis factor α) in 10 Gy irradiated groups after administration of atorvastatin and a slight decrease after tadalafil administration, which indicates that one of the possible mechanisms for mitigation of radiation-induced cardiac damage could be the modulation of nitric oxide (NO) in endothelium and phosphodiesterase 5. In addition, miRNAs were analyzed as potential markers and therapeutically effective molecules. Expression of miRNA-21 and miRNA-15b showed the most significant changes after irradiation. Atorvastatin and tadalafil normalized changes of miRNA (miRNA-1, miRNA-15b, miRNA-21) expression levels in irradiated hearts. This screening study concludes that administration of specific drugs could mitigate the negative impact of radiation on the heart, but more detailed experiments oriented to other aspects of drug effectiveness and their exact mechanisms are still needed.

Reliability of a point-of-care device to determine oxidative stress in whole blood before and after acute exercise: A practical approach for the applied sports sciences.

Measuring alterations in redox homoeostasis in athletes can provide insights into their responses to training such as adaptations or fatigued states. However, redox monitoring is impractical in athletes given the time burden of venepuncture and subsequent laboratory assays. The ability of point-of-care tests (POC): 1) Free Oxygen Radical Test (FORT) and 2) Free Oxygen Radical Defence (FORD), to reliably measure whole blood oxidative stress between days and after exercise is unknown as well as their relationship with laboratory measures (F2-isoprostanes, total antioxidant capacity; TAC). Participants completed two trials performed on separate days comprising blood sampling at rest (n=22) and after treadmill-running (n=14). Between-day CVs for FORT (4.6%) and FORD (4.8%) were acceptable at rest. There was no difference in the between-day magnitude of change in any biomarker from pre- to post-exercise (p>0.05), yet the within-trial change in FORD was variable (trial one: +4.5%, p=0.15; trial two: +6.3%, p<0.05). TAC and FORD were significantly correlated pre- and post-exercise (r=~0.53, p<0.05), whereas F2-isoprostanes and FORT had a significant correlation pre-exercise only (r=0.45, p=0.03). Overall, the POC tests are reliable and could be used for baseline longitudinal redox monitoring. More data is required on POC tests for assessing redox perturbations induced by exercise.

In Vitro Interaction of 5-Aminoorotic Acid and Its Gallium(III) Complex with Superoxide Radical, Generated by Two Model Systems.

Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO2), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex.

Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.

AIM: Clinical trials on the effect of pycnogenol supplementation on cardiometabolic health have been controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the potential effect of pycnogenol supplementation on cardiometabolic profile. METHODS: PubMed, Scopus, and ISI Web of Science databases were searched until October 2018. RCTs that evaluated the effects of pycnogenol on cardiometabolic parameters were included. DerSimonian and Laird random-effect models were used to compute the weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Twenty-four RCTs including 1594 participants were included in the meta-analysis. Pycnogenol significantly reduced fasting blood glucose (WMD: -5.86 mg/dl; 95% CI: -9.56, -2.15), glycated hemoglobin (WMD = -0.29%, 95%CI: -0.56, -0.01), systolic blood pressure (WMD: -2.54 mmhg; 95% CI: -4.08, -0.99), diastolic blood pressure (WMD: -1.76 mmhg; 95% CI: -3.12, -0.41), body mass index (WMD: -0.47 kg/m2; 95% CI: -0.90, -0.03), LDL cholesterol (WMD: -7.12 mg/dl; 95% CI: -13.66, -0.58) and increased HDL cholesterol (WMD: 3.27 mg/dl; 95% CI: 0.87, 5.66). CONCLUSION: This meta-analysis suggests that pycnogenol may have a role in preventing cardiometabolic disease. However, further well-designed RCTs are recommended to evaluate its long-term effects and explore the optimal duration of use and dosage.

Features of clinical manifestations, free radical, coagulation and aggregation properties of blood in patients with craniocerebral trauma.

OBJECTIVE: Introduction: In recent years in Ukraine, as in the entire world, there has been an increase in cases of domestic injuries with a raise in the number of patients with craniocerebral trauma and its consequences. The aim of our research was to study clinical symptoms, the state of free radical oxidation, aggregate and hemocoagulative properties of blood in patients with mild craniocerebral trauma. PATIENTS AND METHODS: Materials and methods: We conducted comprehensive clinical and laboratory examination of 34 patients with mild craniocerebral trauma and 20 apparently healthy patients (the control group). The diagnosis was made under ICD-10. The verification of the diagnosis was based on data from clinical examination, neurological status of neuroimaging (computer tomography and magnetic resonance imaging). The study group included 24 men and 10 women aged from 19 to 40. In addition, 20 apparently healthy individuals of the same age were examined, who comprised the control group (14 men and 6 women). In the blood parameters of all patients, we examined free radical oxidation, hemostasis and aggregation properties of platelets. RESULTS: Results: The conducted study revealed clinical disturbances, changes in the parameters of free radical lipid oxidation, coagulation and microcirculatory hemostasis. CONCLUSION: Conclusions: All patients with mild craniocerebral trauma, develop disturbances in the form of symptoms of microorganic lesion of the central nervous system: convergence weakness in 100% of patients, Mann's symptom (76.4%), disruption of the function of the cranial nerves (58.8%), signs of pyramidal insufficiency (68.4%), vestibular disorders (94.1%), autonomic vascular dysfunction (100%). Mild craniocerebral trauma is accompanied by the activation of free radical lipid oxidation processes, decreased activity of antioxidant enzymes, hypercoagulation, and increased aggregation properties of platelets.

Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders.

Cholestane-3ß,5α,6ß-triol (3ß,5α,6ß-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7ß-hydroxycholesterol (7ß-HC) can also be formed by free radical oxidation of cholesterol. Here we investigate how 3ß,5α,6ß-triol, 7-OC and 7ß-HC are metabolised to bile acids. We show, by monitoring oxysterol metabolites in plasma samples rich in 3ß,5α,6ß-triol, 7-OC and 7ß-HC, that these three oxysterols fall into novel branches of the acidic pathway of bile acid biosynthesis becoming (25R)26-hydroxylated then carboxylated, 24-hydroxylated and side-chain shortened to give the final products 3ß,5α,6ß-trihydroxycholanoic, 3ß-hydroxy-7-oxochol-5-enoic and 3ß,7ß-dihydroxychol-5-enoic acids, respectively. The intermediates in these pathways may be causative of some phenotypical features of, and/or have diagnostic value for, the lysosomal storage diseases, Niemann Pick types C and B and lysosomal acid lipase deficiency. Free radical derived oxysterols are metabolised in human to unusual bile acids via novel branches of the acidic pathway, intermediates in these pathways are observed in plasma.

The effects of ketamine and lidocaine on free radical production after tourniquet-induced ischemia-reperfusion injury in adults.

BACKGROUND: The primary aim of this study was to compare the effects of a small-dose infusion of 2 antioxidant agents, ketamine and lidocaine, on ischemia-reperfusion injury (IRI) in patients undergoing elective lower limb surgery. Ischemia-modified albumin (IMA), lactate, and blood gas levels were all measured and assessed. METHODS: A total of 100 patients who underwent lower extremity surgery were randomized into 3 groups. After spinal anesthesia, the ketamine group (Group K, n=33) was given a ketamine infusion, a lidocaine infusion was administered to the lidocaine group (Group L, n=33), and in the control group (Group C), 0.9% a sodium chloride infusion was performed. Blood samples were obtained for IMA analysis before anesthetic administration (baseline), at 30 minutes of tourniquet inflation (ischemia), and 15 minutes after tourniquet deflation (reperfusion). Arterial blood gas measurements were determined before anesthetic administration and 15 minutes after tourniquet deflation. RESULTS: The lactate and IMA levels at reperfusion were significantly lower in both the ketamine group and the lidocaine group when compared with the control group. CONCLUSION: The administration of both ketamine and lidocaine infusions significantly decreased skeletal muscle IRI-related high lactate and IMA levels. These results suggest the possibility of the clinical application of ketamine or lidocaine infusions in cases of skeletal muscle-related IRI.

PycnoRacer®, a fitness drink including Pycnogenol®, improves recovery and training in the Cooper test.

BACKGROUND: This study evaluates the effects of training (on running distance measured with a Cooper test) in 3 weeks in non-professional athletes using PycnoRacer®, a fitness drink (FD) including Pycnogenol® during the training period. METHODS: Pycnogenol® has been used in preclinical conditions and prevention. PycnoRacer® is a liquid combination of Pycnogenol® (15 mg), L-leucine (0.6 g), L-arginine (0.3 g), L-isoleucine (0.3 g), and L-valine (0.3 g). Two comparable groups (one using the FD) were formed: 60 training athletes were requested to drink one bottle 4 times/day, while 65 controls did not use PycnoRacer® or other comparable sports drinks. All subjects had a strong athletic background and advanced knowledge of the procedures of the tests. Two daily training sessions were completed. The sessions consisted in warming up and running a Cooper test. RESULTS: 125 subjects completed the three weeks according to plans. There were nine dropouts due to logistical or working problems. Subjects using the FD improved on average by 18.83% (range 12-23%) in their running distance with training. The difference with controls was significant (P<0.05) at 3 weeks (controls improved on average by 8.9%; range 3-17.4%). The difference between the two groups was on average 9.93% (P<0.05). A comparable increase in VO2max was observed in the groups. In the FD group the increase was on average by 10.05 mL/kg/min compared to 4.95 mL/kg/min in controls, with a difference of 5.1 mL/kg/min (P<0.05). A VAS score showed comparable values. Lower values (concerning muscular pain and cramps) were observed in FD subjects (P<0.05) at the end of the 3 weeks of training. The level of plasma free radicals (PFR) values after the last Cooper test was significantly lower at 3 weeks in the FD group (P<0.05). No intolerance problem was observed by subjects using the FD. CONCLUSIONS: In conclusion, the use of PycnoRacer® improved training, running distance, VO2max and PFR decreasing muscular pain and cramps.

Marcadores lipídicos en suero y síndrome coronario agudo en pacientes egresados del servicio de cardiología. Hospital Faustino Pérez / Lipid markers in serum and acute coronary syndrome in patients discharged from service of cardiology. Hospital Faustino Pérez

RESUMEN Introducción: las enfermedades cardiovasculares actualmente son la principal causa de muerte en los países industrializados y se espera que también lo sean en los países en vías de desarrollo en el año 2020. Entre ellas la enfermedad arterial coronaria es la manifestación más prevalente, y se asocia a alta morbimortalidad. La ateroesclerosis es su principal génesis y por tanto los trastornos del metabolismo de los lípidos. Objetivo: determinar el perfil lipídico en pacientes egresados por síndrome coronario agudo. Materiales y métodos: se realizó una investigación descriptiva, transversal, correlacional en los pacientes egresados del servicio de cardiología del hospital Faustino Pérez en el período comprendido entre enero y diciembre del 2015. Resultados: se observó un aumento de los lípidos colesterol, triglicéridos, LDL-c, VLDL y Lp (a) en más del 50% de los pacientes estudiados. Los índices de Apo B/Apo A y Col/HDL-c marcaron como indicador de alto riesgo en un 67,5 y 58,75 % respectivamente. La HDL-c considerada como factor protector, resultó disminuida en más del 50% de los pacientes. Conclusiones: se detectó correlación entre el síndrome coronario agudo y trastornos en el metabolismo de los lípidos. Se recomienda realizar estudios observacionales epidemiológicos para determinar la verdadera influencia de estos factores como agente causal de síndrome coronario agudo (AU).

ABSTRACT Introduction: Currently, cardiovascular diseases are the main cause of death in developed countries, and it is believed that they also will be the same in developing countries in 2020 year. Among them, coronary arterial disease is the most prevalent manifestation, and is associated to high morbi-mortality. Atherosclerosis is its most important cause and consequently the disorders of the lipids metabolism. Objective: determining the lipid profile in patients discharged for acute coronary syndrome. Materials and methods: a descriptive, cross-sectional, correlational research was carried out in patients discharged from the service of Cardiology of the hospital Faustino Perez in the period from January to December 2015. Results: it was found an increase of the lipids cholesterol, triglycerides, LDL-c, VLDL and Lp(a) in more than 50 % of the studied patients. The indexes of Apo B/Apo A and Col/HDL-c were high risk indicators in 67.5 and 58.75 % respectively. HDL-c, considered as a protecting factor, was diminished in more than 50 % of the patients. Conclusions: a correlation was found between the acute coronary syndrome and disturbances in the lipids metabolism. We recommend performing epidemiologic, observational studies to determine the real influence of these factors as causal agent of the acute coronary syndrome (AU).

Marcadores lipídicos en suero y síndrome coronario agudo en pacientes egresados del servicio de cardiología. Hospital Faustino Pérez / Lipid markers in serum and acute coronary syndrome in patients discharged from service of cardiology. Hospital Faustino Pérez

RESUMEN Introducción: las enfermedades cardiovasculares actualmente son la principal causa de muerte en los países industrializados y se espera que también lo sean en los países en vías de desarrollo en el año 2020. Entre ellas la enfermedad arterial coronaria es la manifestación más prevalente, y se asocia a alta morbimortalidad. La ateroesclerosis es su principal génesis y por tanto los trastornos del metabolismo de los lípidos. Objetivo: determinar el perfil lipídico en pacientes egresados por síndrome coronario agudo. Materiales y métodos: se realizó una investigación descriptiva, transversal, correlacional en los pacientes egresados del servicio de cardiología del hospital Faustino Pérez en el período comprendido entre enero y diciembre del 2015. Resultados: se observó un aumento de los lípidos colesterol, triglicéridos, LDL-c, VLDL y Lp (a) en más del 50% de los pacientes estudiados. Los índices de Apo B/Apo A y Col/HDL-c marcaron como indicador de alto riesgo en un 67,5 y 58,75 % respectivamente. La HDL-c considerada como factor protector, resultó disminuida en más del 50% de los pacientes. Conclusiones: se detectó correlación entre el síndrome coronario agudo y trastornos en el metabolismo de los lípidos. Se recomienda realizar estudios observacionales epidemiológicos para determinar la verdadera influencia de estos factores como agente causal de síndrome coronario agudo (AU).

ABSTRACT Introduction: Currently, cardiovascular diseases are the main cause of death in developed countries, and it is believed that they also will be the same in developing countries in 2020 year. Among them, coronary arterial disease is the most prevalent manifestation, and is associated to high morbi-mortality. Atherosclerosis is its most important cause and consequently the disorders of the lipids metabolism. Objective: determining the lipid profile in patients discharged for acute coronary syndrome. Materials and methods: a descriptive, cross-sectional, correlational research was carried out in patients discharged from the service of Cardiology of the hospital Faustino Perez in the period from January to December 2015. Results: it was found an increase of the lipids cholesterol, triglycerides, LDL-c, VLDL and Lp(a) in more than 50 % of the studied patients. The indexes of Apo B/Apo A and Col/HDL-c were high risk indicators in 67.5 and 58.75 % respectively. HDL-c, considered as a protecting factor, was diminished in more than 50 % of the patients. Conclusions: a correlation was found between the acute coronary syndrome and disturbances in the lipids metabolism. We recommend performing epidemiologic, observational studies to determine the real influence of these factors as causal agent of the acute coronary syndrome (AU).

Supplementation with Robuvit® in post-traumatic stress disorders associated to high oxidative stress.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated to recurrent, obsessive recollection of severe traumatic events. This condition is still not completely understood. Elective treatment of PTSD is psychotherapy. Standardized supplements, used for improving chronic fatigue syndrome (i.e. Robuvit®, Horphag Research Ltd) can also be used to control some of the symptoms associated to PTSD, as well as to control the associated increased oxidative stress, present in many of these patients. The aim of this open registry was to evaluate the effects of supplementary Robuvit® 300 mg/day, added to standard management (SM), in subjects with PTSD over a period of 4 weeks, both on the psychological and the inflammatory level. METHODS: Otherwise healthy individuals with a diagnosis of PTSD were included in this registry. A clear main traumatic event occurred with different modalities in all subjects during or just after major earthquakes in Central Italy. SM included exposure therapy and psychotherapy. Supportive psychotherapy was used in all affected subjects. Subjects autonomously decided which group to enter (either SM or SM + Robuvit®), without any pre-defined group allocation or randomization. No placebo was used. RESULTS: The two groups were comparable: 18 subjects (11 females; age range 25-49) were included in the SM group, and 16 subjects (8 females; age range 26-52) using SM in combination with Robuvit® supplementation. BMI of all subjects was below 25 kg/m2. After 4 weeks, the percentages of subjects with recurrent memories and dreams, transient walking-dissociative states and reactive flashbacks/hallucinations, alarm reactions and intense emotional distress, emotional numbness, social disinterest and detachment were significantly lower in the subjects treated with Robuvit® (P<0.05%). Sleeping problems, irritability, and fatigue were also significantly reduced with supplementation. CONCLUSIONS: The results of our preliminary, pilot registry show that symptoms of PTSD as well as the high oxidative stress-related to the condition can be controlled and improved using Robuvit® as a supplementary management. The improvement with Robuvit® is faster and larger than that seen with standard management only. Supplementation is safe and well tolerated and may represent an important option in PTSD treatment.

Definitions and pathophysiology of vasoplegic shock.

Vasoplegia is the syndrome of pathological low systemic vascular resistance, the dominant clinical feature of which is reduced blood pressure in the presence of a normal or raised cardiac output. The vasoplegic syndrome is encountered in many clinical scenarios, including septic shock, post-cardiac bypass and after surgery, burns and trauma, but despite this, uniform clinical definitions are lacking, which renders translational research in this area challenging. We discuss the role of vasoplegia in these contexts and the criteria that are used to describe it are discussed. Intrinsic processes which may drive vasoplegia, such as nitric oxide, prostanoids, endothelin-1, hydrogen sulphide and reactive oxygen species production, are reviewed and potential for therapeutic intervention explored. Extrinsic drivers, including those mediated by glucocorticoid, catecholamine and vasopressin responsiveness of the blood vessels, are also discussed. The optimum balance between maintaining adequate systemic vascular resistance against the potentially deleterious effects of treatment with catecholamines is as yet unclear, but development of novel vasoactive agents may facilitate greater understanding of the role of the differing pathways in the development of vasoplegia. In turn, this may provide insights into the best way to care for patients with this common, multifactorial condition.

Temporary kidney dysfunction: Robuvit® supplementation in initial, transient kidney insufficiency and micro-macro albuminuria.

BACKGROUND: The aim of this study was to evaluate the efficacy of Robuvit® (French oak extract, Horphag Research) in improving kidney function in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. METHODS: Fifty-seven subjects with TKD were included in the registry. Subjects were divided into two goups according to albumin levels in the urine. Plasma free radicals were measured in order to evaluate a possible connection with alterations in kidney function. Robuvit® was used at the dose of three capsules/day (300 mg/day) for 4 weeks. RESULTS: Subjects with micro-albuminuria treated with Robuvit® improved significantly more than controls treated with standard management, achieving a full normalization of albumin levels in the urine (P<0.05). In subjects with macroalbuminuria, the decrease in albumin loss was also significant after four weeks, with better overall results in Robuvit® supplemented patients (P<0.05) than in controls. CONCLUSIONS: Albuminuria, as a significant marker of TKD, can be significantly and safely improved with Robuvit® supplementation.

Epidermal barrier and oxidative stress parameters improve during in 311 nm narrow band UVB phototherapy of plaque type psoriasis.

BACKGROUND: Psoriasis is a multi-systemic inflammatory disease that results from dysregulation between epidermal keratinocyte homeostasis and both innate and acquired immunity. Epidermal barrier defect has been described in psoriatic lesions. Furthermore an imbalance between pro-oxidative stress and antioxidant defense mechanisms are known in psoriasis patients. AIM: The aim of this study was to address the link between disease activity, epidermal barrier and systemic oxidative stress in the course of 311 nm narrow band ultraviolet B (NB-UVB) therapy of psoriasis. The dynamic of systemic oxidative stress parameters as well as local transepidermal water loss (TEWL) and stratum corneum hydration (SCH) was characterized before and after 311 nm NB-UVB therapy on the plaques of psoriasis vulgaris in comparison to untreated non-affected volar forearm sites of the same patients. MATERIAL AND METHODS: 22 patients with plaque type psoriasis vulgaris and 25 gender- and age-matched healthy controls were enrolled. We assessed the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) for monitoring disease activity, severity and self-perceived DLQI impact as patient related outcome parameter. We measured non-invasively TEWL (Tewameter TM 300) and SCH (Corneometer CM 825) and the end product of lipid peroxidation - malondialdehyde (MDA), Reactive oxygen species (ROS), ascorbyl radicals (Asc) and detoxifying activity of catalase (CAT) were measured in the peripheral blood with spectrophotometric and EPR spectroscopy methods. RESULTS: Disease activity improved in all patients compared to baseline witnessed by significant decrease in PASI; (from 14.1 to 10.4; p < 0.0001) and DLQI (from 11.7 to 8.1; p < 0.0001). At baseline TEWL-values were significantly (p < 0.0001) higher on psoriatic plaques (16.8 g/h/m2) in comparison to uninvolved skin (5.3 g/h/m2); with a decrease at both sites after NB-UVB phototherapy. SCH was significantly lower at psoriatic plaque s (4.7AU) compared to uninvolved sskin (42.4AU) and increased after treatment (8.6AU) (p < 0.0001). Interestingly, SCH decrease slightly during therapy at uninvolved skin (40.6AU). ROS and Asc declined during therapy in parallel to a decrease in MDA. A mild decrease in the antioxidative enzyme CAT activity which did not reach the significance was observed. CONCLUSION: The presented data is shows that a clinical improvement of psoriatic plaques under NB-UVB therapy, shown in with a decreased PASI and reflected by an increase in quality of life has beneficial effects on epidermal barrier function, SCH and improvement of systemic oxidative stress parameters (ROS, MDA and Asc). We assume that the general improvement in the oxidative stress parameters along with epidermal barrier parameters reflects mainly the improvement of disease activity which overwrites the possible negative pro-oxidative effects of the UV treatment.

Glutathione Conjugation at the Blood-CSF Barrier Efficiently Prevents Exposure of the Developing Brain Fluid Environment to Blood-Borne Reactive Electrophilic Substances.

Exposure of the developing brain to toxins, drugs, or deleterious endogenous compounds during the perinatal period can trigger alterations in cell division, migration, differentiation, and synaptogenesis, leading to lifelong neurological impairment. The brain is protected by cellular barriers acting through multiple mechanisms, some of which are still poorly explored. We used a combination of enzymatic assays, live tissue fluorescence microscopy, and an in vitro cellular model of the blood-CSF barrier to investigate an enzymatic detoxification pathway in the developing male and female rat brain. We show that during the early postnatal period the choroid plexus epithelium forming the blood-CSF barrier and the ependymal cell layer bordering the ventricles harbor a high detoxifying capacity that involves glutathione S-transferases. Using a functional knock-down rat model for choroidal glutathione conjugation, we demonstrate that already in neonates, this metabolic pathway efficiently prevents the penetration of blood-borne reactive compounds into CSF. The versatility of the protective mechanism results from the multiplicity of the glutathione S-transferase isoenzymes, which are differently expressed between the choroidal epithelium and the ependyma. The various isoenzymes display differential substrate specificities, which greatly widen the spectrum of molecules that can be inactivated by this pathway. In conclusion, the blood-CSF barrier and the ependyma are identified as key cellular structures in the CNS to protect the brain fluid environment from different chemical classes of potentially toxic compounds during the postnatal period. This metabolic neuroprotective function of brain interfaces ought to compensate for the liver postnatal immaturity.SIGNIFICANCE STATEMENT Brain homeostasis requires a stable and controlled internal environment. Defective brain protection during the perinatal period can lead to lifelong neurological impairment. We demonstrate that the choroid plexus forming the blood-CSF barrier is a key player in the protection of the developing brain. Glutathione-dependent enzymatic metabolism in the choroidal epithelium inactivates a broad spectrum of noxious compounds, efficiently preventing their penetration into the CSF. A second line of detoxification is located in the ependyma separating the CSF from brain tissue. Our study reveals a novel facet of the mechanisms by which the brain is protected at a period of high vulnerability, at a time when the astrocytic network is still immature and liver xenobiotic metabolism is limited.

Feline Toxoplasmosis: Tumor Necrosis Factor, Nitric Oxide, and Free Radicals in Seropositive Cats.

Toxoplasma gondii is a cosmopolitan protozoan that causes disease in several species, including humans. In cats, these infections are usually asymptomatic, but in other species they can lead to high levels of inflammatory and cell damage markers, causing cellular damage. Therefore, the aim of this study was to measure levels of tumor necrosis factor (TNF-α), reactive oxygen species (ROS), and nitric oxide (nitrite/nitrate-NOx) in the serum of cats seropositive for T. gondii. Initially, we investigated the presence of antibodies against T. gondii in cats in the city of Concordia, Santa Catarina, Brazil, with the use of indirect immunofluorescence (IFA), and found 30 cats seropositive for T. gondii and 30 seronegative cats. In this study, seropositive cats showed higher levels of TNF-α, ROS, and NOx compared to seronegative cats. Although cats do not show clinical signs of disease, constant inflammatory response can cause cell damage, which over time may adversely affect the animal.