3,3′-Diindolylmethane nanoencapsulation improves its antinociceptive action.

PMID: 

Colloids Surf B Biointerfaces. 2019 Sep 1 ;181:295-304. Epub 2019 May 25. PMID: 31154140

Abstract Title: 

3,3'-Diindolylmethane nanoencapsulation improves its antinociceptive action: Physicochemical and behavioral studies.

Abstract: 

This study aimed to characterize the physicochemical properties of 3,3'-diindolylmethane (DIM)-loaded nanocapsules (NCs) as well as the antinociceptive effect using distinct animal models (hot plate test, formalin-induced nociception and complete Freud's adjuvant induced paw inflammation). The DIM-loaded NCs (composed by primula oil and ethylcellulose) were characterized using differential scanning calorimetry, thermogravimetric analysis, Fourier-transformed infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. The physicochemical characterization demonstrated that DIM could be molecularly dispersed into the NCs, whose size was nanometric with a spherical shape. An improvement in DIM thermal stability was achieved by its encapsulation and there were no interactions among the formula components. For the nociceptive evaluation, male adult Swiss mice were pretreated with the NCs or free DIM by the intragastric route at the dose of 10 mg/Kg (time-response curve), 5 or 2.5 mg/Kg (dose-response curve). The behavioral tests were performed over an experimental period of 0.5-8 h. Both free and nanoencapsulated DIM reduced the mechanical hypernociception induced by CFA, mitigated nociceptive behavior of formalin-induced neurogenic and inflammatory pain and increased paw withdrawal latency assessed by the hot-plate test. Importantly, the DIM nanoencapsulation promoted a rapid initiation and prolonged the bioactive antinociceptive action (up to 8 h) as well as reduced the effective dose in comparison to its free form. In summary, this study reported that the NCs had adequate nanometric size, increased DIM stability and its antinociceptive action in different animal models, suggesting that the formulation may be a possible therapeutic alternative to the management of pain and inflammatory-related pathologies.

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Statin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients.

PMID: 

Eur Heart J. 2019 Jul 30. Epub 2019 Jul 30. PMID: 31362307

Abstract Title: 

Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France.

Abstract: 

AIMS: The role of statin therapy in primary prevention of cardiovascular disease in persons older than 75 years remains a subject of debate with little evidence to support or exclude the benefit of this treatment. We assessed the effect of statin discontinuation on cardiovascular outcomes in previously adherent 75-year-olds treated for primary prevention.METHODS AND RESULTS: A population-based cohort study using French national healthcare databases was performed, studying all subjects who turned 75 in 2012-14, with no history of cardiovascular disease and with a statin medication possession ratio≥80% in each of the previous 2 years. Statin discontinuation was defined as three consecutive months without exposure. The outcome was hospital admission for cardiovascular event. The hazard ratio comparing statin discontinuation with continuation was estimated using a marginal structural model adjusting for both baseline and time-varying covariates (cardiovascular drug use, comorbidities, and frailty indicators). A total of 120 173 subjects were followed for an average of 2.4 years, of whom 17 204 (14.3%) discontinued statins and 5396 (4.5%) were admitted for a cardiovascular event. Theadjusted hazard ratios for statin discontinuation were 1.33 [95% confidence interval (CI) 1.18-1.50] (any cardiovascular event), 1.46 (95% CI 1.21-1.75) (coronary event), 1.26 (95% CI 1.05-1.51) (cerebrovascular event), and 1.02 (95% CI 0.74-1.40) (other vascular event).CONCLUSION: Statin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients. Future studies, including randomized studies, are needed to confirm these findings and support updating and clarification of guidelines on the use of statins for primary prevention in the elderly.

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Oral supplementation of L-glutathione prevents UVB-induced melanogenesis and oxidative stress.

PMID: 

Exp Anim. 2019 Jun 26. Epub 2019 Jun 26. PMID: 31243189

Abstract Title: 

Oral supplementation of L-glutathione prevents UVB-induced melanogenesis and oxidative stress in BALB/c mice.

Abstract: 

Dietary antioxidant supplements such as L-glutathione have gained considerable attention in dermatology and cosmeceutical fields. L-Glutathione possesses antiaging, antimelanogenic, antioxidant, and anticancer properties. This study aimed to investigate the inhibitory effects of L-glutathione on melanogenesis activity and oxidative stress in UVB-irradiated BALB/c mice. Eighteen female BALB/c mice were randomly divided into 3 groups: a control group (n=6), a group without UVB irradiation and L-glutathione administration; a UVB irradiated group (n=6), a group irradiated with a UVB dose of 250 mJ/cmfor 3 minutes; and a treatment group (n=6), a group irradiated with UVB and treated with 100 mg/kg of L-glutathione by oral gavage. Treatment was given for 14 days, and UVB irradiation was given on days 9, 11, and 13. Oral L-glutathione significantly (p

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N-acetyl-cysteine supplementation improves functional connectivity within the cingulate cortex in early psychosis.

PMID: 

Int J Neuropsychopharmacol. 2019 Aug 1 ;22(8):478-487. PMID: 31283822

Abstract Title: 

N-Acetyl-Cysteine Supplementation Improves Functional Connectivity Within the Cingulate Cortex in Early Psychosis: A Pilot Study.

Abstract: 

BACKGROUND: There is increasing evidence that redox dysregulation, which can lead to oxidative stress and eventually to impairment of oligodendrocytes and parvalbumin interneurons, may underlie brain connectivity alterations in schizophrenia. Accordingly, we previously reported that levels of brain antioxidant glutathione in the medial prefrontal cortex were positively correlated with increased functional connectivity along the cingulum bundle in healthy controls but not in early psychosis patients. In a recent randomized controlled trial, we observed that 6-month supplementation with a glutathione precursor, N-acetyl-cysteine, increased brain glutathione levels and improved symptomatic expression and processing speed.METHODS: We investigated the effect of N-acetyl-cysteine supplementation on the functional connectivity between regions of the cingulate cortex, which have been linked to positive symptoms and processing speed decline. In this pilot study, we compared structural connectivity and resting-state functional connectivity between early psychosis patients treated with 6-month N-acetyl-cysteine (n = 9) or placebo (n = 11) supplementation with sex- and age-matched healthy control subjects (n = 74).RESULTS: We observed that 6-month N-acetyl-cysteine supplementation increases functional connectivity along the cingulum and more precisely between the caudal anterior part and the isthmus of the cingulate cortex. These functional changes can be partially explained by an increase of centrality of these regions in the functional brain network.CONCLUSIONS: N-acetyl-cysteine supplementation has a positive effect on functional connectivity within the cingulate cortex in early psychosis patients. To our knowledge, this is the first study suggesting that increased brain glutathione levels via N-acetyl-cysteine supplementation may improve brain functional connectivity.

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Baru almond supplementation increased the GPx activity in overweight and obese women.

PMID: 

Nutrients. 2019 Jul 30 ;11(8). Epub 2019 Jul 30. PMID: 31366053

Abstract Title: 

Baru Almonds Increase the Activity of Glutathione Peroxidase in Overweight and Obese Women: A Randomized, Placebo-Controlled Trial.

Abstract: 

BACKGROUND: Obesity-induced inflammation is frequently associated with higher oxidative stress. In vitro and experimental studies have considered baru almonds (Dipteryx alata Vog) as a legume seed with high antioxidant capacity. The aim of this study was to evaluate whether baru almonds are capable of improving the inflammatory and antioxidant status in overweight and obese women.METHODS: In a parallel-arm, randomized placebo-controlled trial, 46 overweight and obese women (age: 40± 11 years; body mass index: 33.3 ± 4.3) were randomly assigned to receive advice to follow a normocaloric and isoenergetic diet with placebo (PLA,= 22) or similar advice plus 20 g baru almonds (BARU,= 24) for 8 wk. Malondialdehyde (MDA), adiponectin, tumor necrosis factor-α, interleukin-6, interleukin-10, antioxidant enzymes activities (catalase-CAT; glutathione peroxidase-GPx; superoxide dismutase-SOD), and minerals were analyzed in plasma samples.RESULTS: At baseline, groups were similar regarding the body composition, oxidative, and inflammatory parameters. The BARU group increased the activity of GPx (+0.08 U/mg, 95%CI + 0.05 to +0.12 vs. -0.07, 95%CI -0.12 to -0.03,

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Liposomal glutathione as a promising candidate for immunological rheumatoid arthritis therapy.

PMID: 

Heliyon. 2019 Jul ;5(7):e02162. Epub 2019 Jul 27. PMID: 31384691

Abstract Title: 

Liposomal glutathione as a promising candidate for immunological rheumatoid arthritis therapy.

Abstract: 

Nano-medicine can passively accumulate in chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or by being conjugated with a ligand that can bind to receptors over expressed by cells inside chronic inflammatory tissues, contributing to reduced systemic side-effects and increased efficacy. This article highlights the utilization of nanomedicine for potential treatment of rheumatoid arthritis. Rheumatoid arthritis was induced in rat model via 2 weeks intradermal injection of pristane at the base of the tail in a daily dose of 150μl. Susceptible rat strains developed severe arthritis with a sudden onset 3 weeks post pristane injection. Three weeks post pristane administration; rats were treated intravenously with glutathione or liposomal-glutathione in a dose of 5 mg/kg daily for 30 days. Concomitant supplementation with the aforementioned antioxidants effect on proinflammatory marker C-reactive protein (CRP) was assessed. On the other hand, oxidative stress biomarker malondialdehyde (MDA) and rheumatoid factor (RF) compared with pristane treated group was also investigated. The results elucidated that glutathione andliposomal -glutathione significantly reduced rheumatoid factor, malondialdehyde and C-reactive protein levels with the superiority of liposomal -glutathione in this side reflecting its pronounced effect as anti-rheumatoid agent.

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Effects of N-acetyl cysteine, vitamin E and vitamin C on liver glutathione levels following amiodarone treatment in rats.

PMID: 

Kardiochir Torakochirurgia Pol. 2019 Jul ;16(2):88-92. Epub 2019 Jun 28. PMID: 31410096

Abstract Title: 

Effects of N-acetyl cysteine, vitamin E and vitamin C on liver glutathione levels following amiodarone treatment in rats.

Abstract: 

Introduction: Amiodarone, a pharmaceutical extensively used to suppress atrial and ventricular tachyarrhythmias, is also known to cause many side effects on many tissues. N-acetyl-cysteine (NAC), vitamin E and vitamin C are known as antioxidants for their ability to minimize oxidative stress. In the peer-reviewed literature, there is no study reporting on the protective effects of these antioxidant agents against its hepatotoxicity.Aim: We investigated the oxidative effects of NAC, vitamins E and C on liver tissue after amiodarone treatment.Material and methods: Rats were randomly assigned to: control; amiodarone group; amiodarone + NAC treated group; amiodarone + Vit. E group and amiodarone + Vit. C group. Liver tissues were isolated from animals and total glutathione levels were measured.Results: In all time intervals, the level of glutathione increased. When all time intervals were compared, the amiodarone group revealed the lowest levels. The antioxidant co-administered group was studied; the glutathione levels were statistically significantly higher than the sole amiodarone group. When vitamins E, C or N-acetyl cysteine were examined, there was no statistically significant difference among them.Conclusions: In this study we found that hepatotoxicity capacity of amiodarone may be reduced by taking up antioxidants. In addition, the effect documented here may be reproducible and may be applied to clinical settings.

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Mindfulness meditation training can effectively alleviate the symptoms of anxiety and depression and improve the quality of sleep in perimenopausal women.

PMID: 

Nan Fang Yi Ke Da Xue Xue Bao. 2019 Aug 30 ;39(8):998-1002. PMID: 31511223

Abstract Title: 

[Effect of mindfulness meditation training on anxiety, depression and sleep quality in perimenopausal women].

Abstract: 

OBJECTIVE: To explore the effect of mindfulness meditation training for improving anxiety, depression and sleep disorders in perimenopausal women.METHODS: Intervention by menopause meditation training was delivered in 121 perimenopausal women with anxiety, depression or sleep disorders in Baiyun District, Guangzhou. Before and after the intervention, the Self-rating Anxiety Scale, Self-rating Depression Scale and Pittsburg Sleep Quality Index were used for assessment of changes in the conditions of the women.RESULTS: After menopausal meditation training, the perimenopausal women showed significant improvement in the mean scores of Self-rating Anxiety Scale (48.26± 6.47;=3.865,< 0.01), Selfrating Depression Scale (50.27± 6.54;=4.541,< 0.01) and Pittsburgh Sleep Questionnaire (10.64± 4.38;=5.596,< 0.01). The symptom remission rates differed significantly among the women with different self-practice frequencies (< 0.01). The remission rates of anxiety, depression and sleep disorder increased significantly with the frequency of self-exercise (< 0.01).CONCLUSIONS: Mindfulness meditation training can effectively alleviate the symptoms of anxiety and depression and improve the quality of sleep in perimenopausal women, and the frequency of the exercise is positively correlated with the improvements. Mindfulness meditation training can be an effective intervention for improving the mental health of perimenopausal women.

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The sour side of vitamin C might mediate neuroprotective, anticonvulsive and antidepressant-like effects.

PMID: 

Med Hypotheses. 2019 Oct ;131:109320. Epub 2019 Jul 20. PMID: 31443769

Abstract Title: 

The sour side of vitamin C might mediate neuroprotective, anticonvulsive and antidepressant-like effects.

Abstract: 

In animal experiments, neuroprotective, anticonvulsive and antidepressant-like properties have been increasingly attributed to administrations of ascorbic acid (AA, vitamin C) in at least medium (low millimolar) doses, which however await validation in well controlled clinical studies. In mammalian cortical and subcortical neurons, small to modest acidification (

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These results suggest that cranberry ameliorates high fat diet-induced metabolic disturbances.

PMID: 

Biol Pharm Bull. 2019 ;42(8):1295-1302. PMID: 31366865

Abstract Title: 

Cranberry Attenuates Progression of Non-alcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice.

Abstract: 

Obesity is characterized by abnormal or excessive fat accumulation, which leads to the development of metabolic syndrome. Because oxidative stress is increased in obesity, antioxidants are regarded as suitable agents for preventing metabolic syndrome. Here, we examined the impact of cranberry, which contains various antioxidants, on metabolic profiles, including that during the progression of non-alcoholic fatty liver disease (NAFLD), in high-fat diet (HFD)-fed C57BL/6 mice. We observed that oxidative stress was diminished in mice that were fed HFD diets supplemented with 1 and 5% cranberry powder as compared with that in HFD-fed control mice. Notably, from 1 week after beginning the diets to the end of the study, the body weight of mice in the cranberry-treatment groups was significantly lower than that of mice in the HFD-fed control group; during the early treatment phase, cranberry suppressed the elevation of serum triglycerides; and adipocytes in the adipose tissues of cranberry-supplemented-HFD-fed mice were smaller than these cells in HFD-fed control mice. Lastly, we examined the effect of cranberry on NAFLD, which is one of the manifestations of metabolic syndrome in the liver. Histological analysis of the liver revealed that lipid-droplet formation and hepatocyte ballooning, which are key NAFLD characteristics, were both drastically decreased in cranberry-supplemented-HFD-fed mice relative to the levels in HFD-fed control mice. Our results suggest that cranberry ameliorates HFD-induced metabolic disturbances, particularly during the early treatment stage, and exhibits considerable potential for preventing the progression of NAFLD.

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