The effect of combined application of pentoxifylline and vitamin E for the treatment of osteoradionecrosis of the jaws: a meta-analysis

Zhang Z, Xiao W, Jia J, Chen Y, Zong C, Zhao L, Tian L

Oral Surg Oral Med Oral Pathol Oral Radiol. 2020 Mar;129(3):207-214. doi: 10.1016/j.oooo.2019.08.005. Epub 2019 Aug 29.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the effect of combined application of pentoxifylline and vitamin E (PENTO) for the treatment of osteoradionecrosis of the jaws (ORNJ) by performing a meta-analysis.

STUDY DESIGN:

We searched for trials in 4 electronic databases (PubMed, Cochrane library, EMbase, and Web of Science) for studies that compared the effect of PENTO with those of other treatment methods. The range of exposed bone was chosen as the index to assess the effects of the different treatment methods. We performed the meta-analysis by using Review Manager 5.3.

RESULTS:

We identified 5 trials, which included 184 patients in the PENTO group and 180 patients in the “other treatment methods” (OTHER) group, and we performed a meta-analysis by using the random effect model. PENTO had a better effect compared with all the other treatment methods, and a statistically significant difference was noted (odds ratio [OR] = 4.54; 95% confidence interval [CI] 2.89-7.12; P < .01). PENTO was statistically different from antibiotics (OR = 7.02; 95% CI 1.33-37.01; P < .05) and hyperbaric oxygen therapy (OR = 20.06; 95% CI 1.74-230.78; P < .05) in terms of treatment effect. However, we could not confirm that PENTO was more effective than local surgery (OR = 6.50; 95% CI 0.80-53.09; P < .1).

CONCLUSIONS:

The results of this meta-analysis suggest that the application of PENTO for the treatment of ORNJ shows superior efficiency relative to the other treatment methods.

Read More

Association of Circulating Retinol and α-TOH Levels with Cognitive Function in Aging Subject with Type 2 Diabetes Mellitus

Huang X, Guo Y, Li P, Ma X, Dong S, Hu H, Li Y, Yuan L.

J Nutr Health Aging. 2020;24(3):290-299. doi: 10.1007/s12603-020-1328-1.

Abstract

OBJECTIVES:

Malnutrition of vitamin A (retinol) and vitamin E (α-tocopherol, α-TOH) was observed in type 2 diabetes mellitus (T2DM) or dementia patients. However, how these vitamins affect cognitive function of subjects with T2DM was seldom reported. The objective of this study was to determine the association of circulating retinol and α-TOH with cognition in aging subjects with T2DM.

METHODS:

A total of 448 T2DM subjects and 448 age, gender and education matched control subjects (aged 55-75 years) were included in the study. Demographic characters of the participants were collected. Food frequency questionnaire (FFQ) method was used to collect dietary intake information. To assess the status of cognition, the MoCA test was used. Circulating retinol and α-TOH levels were compared between T2DM and non-T2DM subjects. Correlation of circulating retinol and α-TOH levels with cognitive function was analyzed in T2DM subjects. The effect of serum retinol and α-TOH levels on the risk of MCI in T2DM patients was explored.

RESULTS:

We found that T2DM-MCI subjects demonstrate lower serum retinol level than T2DM-nonMCI subjects (P < 0.01). Serum retinol level was positively correlated to cognitive function in T2DM subject (P < 0.05). T2DM subjects with higher circulating retinol level demonstrate higher cognitive scores in visual and executive, attention, language, memory and delayed recall domains (P < 0.05).

CONCLUSION:

Diminished circulating retinol predicts an increased risk of MCI in T2DM patients. Our findings provide suggestions that optimal retinol nutritional status might benefit cognition and decrease the risk of MCI in aging subjects with T2DM.

Read More

The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients: A double-blinded randomized clinical trial

Pirhadi-Tavandashti N, Imani H, Ebrahimpour-Koujan S, Samavat S, Hakemi MS

Complement Ther Med. 2020 Mar;49:102357. doi: 10.1016/j.ctim.2020.102357. Epub 2020 Feb 26.

Abstract

OBJECTIVES:

The present study was aimed to investigate the effect of alpha-tocopherol supplementation on biomarkers of endothelial function (Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Protein 1) and inflammatory markers (Interleukin 6 and high-sensitivity C-reactive protein) among the hemodialysis patients.

METHODS:

To conduct this randomized, double-blinded, and placebo-controlled clinical trial, 49 hemodialysis patients, aged 20-60 years, were recruited and randomly divided into the intervention and control groups. The intervention group (n = 25) received 600 IU alpha-tocopherol soft gels (200 IU three times daily), while the controls (n = 24) consumed the identical placebo soft gels for 10 weeks. At the baseline and end of the study, 7 ml pre-dialysis blood samples were taken from all participants to measure their serum concentrations of ICAM-1, VCAM-1, IL-6, and hs-CRP.

RESULTS:

Alpha-tocopherol supplementation reduced the serum levels of ICAM-1 and VCAM-1 significantly (-140.67 ± 57.25 ng/ml vs. -15.97 ± 79.19 ng/ml, P = 0.001 for ICAM-1 and –6.79 ± 4.76 ng/ml vs. 1.02 ± 3.22 ng/ml, P = 0.019 for VCAM-1). However, no significant difference was observed between the two groups regarding the serum levels of hs-CRP (-0.15 ± 0.19 mg/l vs. 0.02 ± 0.12 mg/l; P = 0.32) and IL-6 (-0.03 ± 0.1 pg/ml vs. – 0.06 ± 0.11 pg/ml; P = 0.65).

CONCLUSIONS:

Our results showed that 10 weeks of supplementation with 600 IU alpha-tocopherol improved ICAM-1 and VCAM-1 levels, but did not have any effect on the serum concentration of IL-6 and hs-CRP in hemodialysis patients. Further studies are required to confirm these findings.

Read More

Pharmacological correction of alterations of apoptosis of the neurons of the hypothalamus suprachiasmatic nucleus and pinealocytes during aging and stress

Khuzhakhmetova LK, Teply DL, Bazhanova ED

Adv Gerontol. 2019;32(6):915-922.

Abstract

As is known, the pineal gland plays an important role in adaptogenesis, and the hypothalamus is one of the main links of the stress-reactive system and is involved in the regulation of the involution of the whole organism. So, the study of changes in these organs during stress and aging is very interesting. The aim of the work is to study the mechanisms of apoptosis of pinealocytes and neurosecretory cells of the suprachiasmatic nucleus of the hypothalamus during aging, stress, and under the conditions of pharmacological correction of involutional processes and stress response (antioxidant alpha-tocopherol acetate, immunomodulator cycloferon). We used Wistar rats as model, young (2-4 months) and old (30 months). Age-related features of the apoptosis dynamics of pinealocytes and neurosecretory cells of the hypothalamic suprachiasmatic nucleus were studied using TUNEL and immunohistochemistry, and the possibilities of pharmacological correction of apoptotic processes are determined. An age-dependent increase of apoptosis level of cells of suprachiasmatic nucleus and epiphysis in rats was revealed. The stress effect (immobilization) led to the intensification of cell death, more significant in older animals. The pineal gland and suprachiasmatic nucleus, traditionally regarded as regulators of circadian rhythms, are at the same time actively involved in general adaptation processes. The studied drugs (α-tocopherol-acetate, cycloferon, and their combination) have a pronounced anti-apoptotic, cytoprotective effect under physiological conditions during aging, as well as during non-specific emotional stress (immobilization) in young and old animals. The regulatory effect is accomplished by activating the expression of the anti-apoptotic protein Bcl-2 in the neurosecretory cells of the suprachiasmatic nucleus and pinealocytes.

Read More

Application of ɑ-Tocotrienol-Loaded Biocompatible Precirol in Attenuation of Doxorubicin Dose-Dependent Behavior in HUH-7 Hepatocarcinoma Cell Line

Tupal A, Sabzichi M, Bazzaz R, Fathi Maroufi N, Mohammadi M, Pirouzpanah SM, Ramezani F

Nutr Cancer. 2020;72(4):653-661. doi: 10.1080/01635581.2019.1650191. Epub 2019 Aug 8.

Abstract

Tumor-targeted nanoparticle delivery system has been known as a substitute and capable achievement in cancer treatment compared to conventional methods. In this study, we examined potential application of ɑ-tocotrienol-Precirol formulation to enhance efficiency of doxorubicin (DOX) in induction of apoptosis in HUH-7 hepatocarcinoma cells. ɑ-tocotrienol-loaded nanoparticles were characterized at the point of zeta potential, particle size, scanning electron microscope (SEM), and cell internalization. To evaluate antiproliferative effects of formulation, apoptosis, cell cycle procedure, flow cytometry, and MTT assays were employed. Optimum size of the ɑ-tocotrienol formulation revealed narrow size distribution with mean average of 78 ± 3 nm. IC50 values for ɑ-tocotrienol and ɑ-tocotrienol-nano structured lipid carriers after 24 h were 15 ± 0.6 and 10 ± 0.03 µM, respectively. After incubation of cells with ɑ-tocotrienol-loaded careers, the rate of cell proliferation decreased from 53 ± 6.1 to 34 ± 7.1% (P < 0.05). A significant improvement in the apoptosis percentage was revealed after treatment of the HUH-7 cell line with DOX and ɑ-tocotrienol careers (P < 0.05). Gene expression results demonstrated a marked decrease in survivin and increase in Bid and Bax levels. Our findings suggest that ɑ-tocotrienol-loaded nanoparticles elevate DOX efficacy in HUH-7 hepatocarcinoma cell.

Read More

Vitamin E-based prodrug self-delivery for nanoformulated irinotecan with synergistic antitumor therapeutics

Ling L, Ismail M, Shang Z, Hu Y, Li B

Int J Pharm. 2020 Mar 15;577:119049. doi: 10.1016/j.ijpharm.2020.119049. Epub 2020 Jan 23.

Abstract

Irinotecan (Ir) is a potent antitumor chemotherapeutics in clinic and used for the treatment of a various cancers, but the degree of its application is critically limited by toxic side-effects and marked heterogeneities. Nano-formulation of prodrugs, based on “all-in-one” carrier-free self-assemblies offers an effective approach to alter pharmacokinetics and safety profiles of cytotoxic agents. In this study, a novel vitamin E succinate-based formulation of Ir (VES-Ir) combined with nanoscaled characteristics and synergistic combination was constructed through esterification. The conjugation makes amphiphilic VES-Ir prodrug self-assemble into nanoparticles with a fine diameter (VES-Ir NPs, 75.4 nm) of spherical morphology. Furthermore, VES-Ir NPs with a 1:1 drug-to-drug ratio was demonstrated to possess respectable physiological stability within 72 h test, while can react to pH/esterase-sensitive drug release in lysosomes internalized into tumor cells, potentially highlighting their alleviating side effects. Compared with single and mixture drugs administration, the nanoformulated VES-Ir NPs codelivered both VES and Ir with different anticancer mechanisms to induce the highest suppress proliferation of MCF-7 (IC50 0.18 μM) and A549 (IC50 0.29 μM) cells in a synergistic way (CI < 1). More importantly, the formulating nanoparticulate Ir is to significantly enhance its bioavailability in vivo with long retention time in bloodstream and thereby, resulting the superior tumor inhibitory rate (TIR) of 85.2% versus controls. This simple nanoformulation of Ir drug deprived from VES conjugation, together with self-delivery and synergistic property, may provide an effective strategy for multiple chemotherapeutics delivery to treat cancers or other diseases.

Read More

The inhibitor-evoked shortage of tocopherol and plastoquinol is compensated by other antioxidant mechanisms in Chlamydomonas reinhardtii exposed to toxic concentrations of cadmium and chromium ions

Nowicka B, Fesenko T, Walczak J, Kruk J

Ecotoxicol Environ Saf. 2020 Mar 15;191:110241. doi: 10.1016/j.ecoenv.2020.110241. Epub 2020 Jan 31.

Abstract

One of the major mechanisms of heavy metal toxicity is the induction of oxidative stress. Redox-active heavy metals, like chromium, can induce it directly, whereas redox-inactive metals, like cadmium, play an indirect role in the generation of reactive oxygen species (ROS). Living organisms defend themselves against oxidative stress taking advantage of low-molecular-weight antioxidants and ROS-detoxifying enzymes. Tocopherols and plastoquinol are important plastid prenyllipid antioxidants, playing a role during acclimation of Chlamydomonas reinhardtii to heavy metal-induced stress. However, partial inhibition of synthesis of these prenyllipids by pyrazolate did not decrease the tolerance of C. reinhardtii to Cr- and Cd-induced stress, suggesting redundancy between antioxidant mechanisms. To verify this hypothesis we have performed comparative analyses of growth, photosynthetic pigments, low-molecular-weight antioxidants (tocopherols, plastoquinol, plastochromanol, ascorbate, soluble thiols, proline), activities of the ascorbate peroxidase (APX), catalase and superoxide dismutase (SOD) and cumulative superoxide production in C. reinhardtii exposed to Cd2+ and Cr2O72- ions in the presence or absence of pyrazolate. The decreased α-tocopherol and plastoquinol content resulted in the increase in superoxide generation and APX activity in pyrazolate-treated algae. The application of heavy metal ions and pyrazolate had a pronounced impact on Asc and total thiol content, as well as SOD and APX activities (the latter only in Cd-exposed cultures), when compared with algae grown in the presence of heavy metal ions or pyrazolate alone. The superoxide production in cultures exposed to heavy metal ions and pyrazolate decreased when compared to the cultures exposed to either heavy metal ions or an inhibitor alone.

Read More

Actions of annatto-extracted tocotrienol supplementation on obese postmenopausal women: study protocol for a double-blinded, placebo-controlled, randomised trial

Aryaie A, Tinsley G, Lee J, Watkins BA, Moore L, Alhaj-Saleh A, Shankar K, Wood SR, Wang R, Shen CL

BMJ Open. 2020 Mar 8;10(3):e034338. doi: 10.1136/bmjopen-2019-034338.

Abstract

INTRODUCTION:

Obesity is a major health concern in postmenopausal women, and chronic low-grade inflammation contributes to the development of obesity. Cellular studies and high-fat-diet-induced obese mouse model mimicking obesity show the antiobesity effect of annatto-extracted tocotrienols (TT) with antioxidant capability. We aim to assess the safety and efficacy of TT consumption for lipid-related parameters in obese postmenopausal women.

METHODS AND ANALYSIS:

Eligible obese postmenopausal women will be randomly assigned to placebo group (430 mg olive oil) and TT group (DeltaGold Tocotrienol 70%) for 24 weeks. In the present study, the primary outcome is total/regional fat mass and visceral adipose tissue. The secondary outcomes include lipid profile in serum, mRNA expression of fatty acid synthase and carnitine palmitoyltransferase 1A in fat tissue, oxylipins and endocannabinoids in plasma and adipose tissue, abundance and composition of intestinal microbiome in faeces, high-sensitivity C-reactive protein (hs-CRP) in serum and leptin in serum. Every participant will be evaluated at 0 (prior to starting intervention) and 24 weeks of intervention, except for serum lipid profile and hs-CRP at 0, 12 and 24 weeks. ‘Intent-to-treat‘ principle is employed for data analysis. Hierarchical linear modelling is used to estimate the effects of dietary TT supplementation while properly accounting for dependency of data and identified covariates. To our knowledge, this is the first randomised, placebo-controlled, double-blinded study to determine dietary TT supplementation on an obese population. If successful, this study will guide the future efficacy TT interventions and TT can be implemented as an alternative for obese population in antiobesity management.

ETHICS AND DISSEMINATION:

This study has been approved by the Bioethics Committee of the Texas Tech University Health Sciences Center, Lubbock. An informed consent form will be signed by a participant before enrolling in the study. The results from this trial will be actively disseminated through academic conference presentation and peer-reviewed journals.

Read More

Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels

Pirhadi-Tavandashti N, Imani H, Ebrahimpour-Koujan S, Samavat S, Hakemi MS

J Stroke Cerebrovasc Dis. 2020 Mar 6:104747. doi: 10.1016/j.jstrokecerebrovasdis.2020.104747. [Epub ahead of print]

Abstract

OBJECTIVES:

Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH.

METHODS:

At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be “cryptogenic” (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data.

RESULTS:

All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups.

CONCLUSIONS:

In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient’s pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.

Read More

Retinol and α-tocopherol in pregnancy: Establishment of reference intervals and associations with CBC

Liu J, Zhan S, Jia Y, Li Y, Liu Y, Dong Y, Tang G, Li L, Zhai Y, Cao Z

Matern Child Nutr. 2020 Mar 5:e12975. doi: 10.1111/mcn.12975. [Epub ahead of print]

Abstract

Profound physiological changes during pregnancy may affect the requirement of retinol and tocopherol, which are essential micronutrients for the maintenance of maternal health and foetal development. However, the current reference intervals (RIs) of retinol and tocopherol are based on non-pregnant population. In the present study, a liquid chromatography-tandem mass spectrometry quantitation method for serum retinol and α-tocopherol was established and validated. In addition, we established trimester-specific RIs of retinol and α-tocopherol using the data from paired screening test for 31,301 outpatients who participated in the prenatal vitamins A/E evaluation program at our hospital using the Hoffmann method, which is a simple indirect RI estimation method that does not require the recruitment of healthy subjects. Further, to explore the associations between the levels of retinol and α-tocopherol and the parameters of complete blood count (CBC), the results of retinol, α-tocopherol, and CBC of 1,977 pregnant outpatients in the third trimester were analysed. The testing interval between the levels of vitamins and CBC was no more than 7 days. Although no significant changes were noticed in the levels of retinol, the α-tocopherol levels continuously increased with normal physiological changes throughout pregnancy. Lower retinol levels were associated with the higher incidence of anaemia, whereas higher levels of retinol and lower levels of α-tocopherol were associated with higher platelet count.

Read More

Page 1 of 13112345...102030...Last »